5 International Conference on Thalassemia

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24 - 25 November, 2012 New Delhi, India

Directorate of Health Services Govt. of NCT of Delhi

Official Support:

Organised by:
Thalassemics India

In Collaboration with:
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www.thalassemiaconference.in

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5th International Conference on

Thalassemia
New Delhi, India Diamond Sponsor

Gold Sponsor

Global Energy Pvt. Ltd.

Sliver Sponsor

UCO Bank Ltd., Kolkata

Special Thanks to
Thalassaemia International Federation, Cyprus Satia Industries Limited Forza Medi India Pvt. Ltd.

5th International Conference on Thalassemia

24th - 25th November, 2012 Hotel Hilton Eros, Nehru Place, New Delhi, India
Thalassemics India Thalassaemia International Federation Sir Ganga Ram Hospital Apollo Hospitals Indian Academic of Pediatrics, Delhi Branch Organised by: In Collaboration with:

Patrons Dr. D.S. Rana Chairman, Board of Management, Sir Ganga Ram Hospital Dr. Anupam Sibal Group Medical Director, Apollo Hospitals Group Advisory Committee Dr. Nica Cappellini, Italy Dr. M.B. Agarwal, Mumbai, India Dr. Roshan Colah, Mumbai, India Dr. V.P. Choudhary, Delhi, India Dr. I.C. Verma, Delhi, India Dr. Androulla Eleftheriou, Cyprus Dr. J.M. Walker, U.K. Scientific Committee Chairman Dr. V.K. Khanna Co - Chairman Dr. Sunil Gomber Secretary Dr. Amita Mahajan Dr. Jagdish Chandra Dr. Dharma Choudhary Dr. Nirmal Kumar Dr. Kirti Nanal Members Dr. Ritu Chawla Dr. A.P. Dubey Dr. Alka Mathur Dr. Ajay Sharma

Organizing Committee Chairman Deepak Chopra Co- chairman Dr. Gautam Bose Secretary Shobha Tuli Treasurer Arun Sehgal Rekha Arora Deepak Dhingra Ashwini Malik Anubha Taneja Members Hemant Bellani Rita Jain Gagandeep Singh Abhinav Wadhwa

Contents
Messages ...................................................................................................... 03 Conference Programme ................................................................................ 16 Abstracts........................................................................................................ 21 Posters........................................................................................................... 42 Donors and Well Wishers .............................................................................. 49 Advertisements.............................................................................................. 50

THALASSAEMIA INTERNATIONAL FEDERATION

In official relations with the World Health Organization
HEADQUARTERS: P.O. Box 28807, 2083 Nicosia,31 Ifigeneias str, 2007 Nicosia, Cyprus Tel: 357-22-319129, Fax: 357-22-314552 E-mail: thalassaemia@cytanet.com.cy Web-site: http://www.thalassaemia.org.cy
aemia

Foreword by the Thalassaemia International Federation President Panos Englezos

Dear Participants, Dear Friends, On behalf of the Board of Directors of TIF, I feel extremely privileged to welcome you all to the 5th International Conference on Thalassaemia in New Delhi, which coincides with the Silver Jubilee of TIF, earmarking a 25 year period of a concerted effort with devotion, diligence and hard work to achieve a better future for our children. I wish to thank the organisers of this conference and in particular, Mrs Shobha Tuli TIF Vice President, President of the Federation of Indian Thalassaemia Societies and Secretary of the Thalassaemics India, for their cordial invitation. This very significant educational event is concentrating participants from across the Indian Continent and beyond, aiming to promote networks of collaboration and create a forum for exchanging and sharing information, knowledge and experiences. In recent decades, we have all been witnessed to the remarkable progress with regards to health and social improvements pertaining to our patients. However, we can also still see big gaps, and the need for further major improvements in all areas including prevention, clinical management and psychosocial support to our patients and their families. Undeniably, this meeting is being held at a time when there is genuine promise and hope for a brighter future for patients with haemoglobin disorders, a hope that is based on advances on all aspects of medical research in this field. This event also occurs at a time when the global thalassaemia community, including the Indian, needs to get together to define how best to collaborate with each other, to determine the true extent of the thalassaemia problem and to educate governments about the true magnitude of the health burden it presents; by extend there is a need for a firm political commitment to addressing this very significant public health problem appropriately. The Indian Sub-continent constitutes one of the most densely populated countries in the world, where almost all forms of the haemoglobin disorders, mainly thalassaemia and sickle cell disease are highly prevalent and very heterogeneously spread across the country. Even though haemoglobin disorders are considered as Rare diseases, these are now both preventable and treatable, and TIFs presence at this conference reflects on its true commitment to lend its support and assistance to India, in a more systematic and focused way, as well as to reinforce the activities of each and every single thalassaemia association in this country. Indeed, every effort has been made by the Scientific Organising Committee to cover important topics and discuss issues of common and specific concern. I am confident that this abstract book, to which international and national experts have contributed, will provide participants not only with knowledge and information, but also provide food for thought and inspiration. Last but by no means least I would like to express my most sincere appreciation to the Central and individual states governments of India for the steps that have been taken so far in addressing this very significant public health problem, and to reiterate TIFs genuine interest to collaborating them even more closely in the future, in order to address this issue in a holistic manner. I wish everyone a most productive and rewarding meeting and an enjoyable stay in New Delhi, a city with a unique sense of hospitality.

Panos Englezos

President Thalassaemia International Federation

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Message.....
November 14, 2012

Message.....

Ms. Shobha Tuli Organizing Secretary A - 9, Nizamuddin West, New Delhi - 13

Dear Shobha Ji My heartiest congratulations to you for organizing the 5th International Conference on Thalassemia, being held in Delhi, on 24th and 25th November, 2012. It is through collective sharing of knowledge, skills, strategies and experience by diverse professionals working under varied environments, that perfection can be achieved in reaching finality. I am sure this collaborative effort will go a long way in sharpening the clinical acumen and knowledge of the delegates, furthering the ultimate cause of patient care for Thalassemic children. I am certain that this scientific deliberation will enhance the standard of care for our children with Thalassemia. I wish all the participants and organizers a fulfilling and enriching experience. With warm regards Your sincerely

Prof. Anupam Sibal

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Message ..... Message .....

Dear Friends,
The time has come when we meet again to see where we stand, where the advances have brought us and are steering us further in the field of thalassemia. The management of thalassemia does not have a defined end point or goal as in many other fields of medicine. The horizon widens with research and we strive to reach higher and more refined targets. This conference has been planned keeping in mind that our thalassemics require a multi-disciplinary approach and the topics have been selected accordingly. Experts from various super-specialties have been invited and they will tell us about their research work and provide us with guidelines for the best management of our thalassemics. Hoping to see you in this academic feast in vibrant Delhi.

Chairman Scientific Committee 5th International Conference on Thalassemia New Delhi

Dr. V.K. Khanna

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Welcome Message ..... WelcomeMessage .....

Dear Friends,
On behalf of the organizing committee, it gives me great pleasure to welcome you to the 5th International Conference on Thalassemia. Today, thalassemia is a very different disease. The last two decades have seen a number of developments that have translated into dramatic improvement in the life span and quality of life of patients with thalassemia who have access to optimal care. This has brought new challenges, which, we must now address. The Indian subcontinent has the largest number of patients with hemoglobinopathies. There are indeed huge gaps in access to optimal healthcare. Whilst we are committed to the long term aim of prevention of thalassemia, we must ensure optimal care to all patients. In this meeting, it is our endeavour to focus on the management of these patients and establish the standard of care in each aspect of patient management. The topics have been specifically selected to cover the practical aspects of clinical management of these patients. In addition, the conference aims to provide an insight into the future prospects of various advancements in the management of these patients. Doctors, parents and patients can look forward to hearing from and interacting with the leading medical professionals in this field. In addition, it will be an excellent opportunity to share our experiences, build new friendships and consolidate old ones. It is our sincere hope, that the conference will impact on the day to day management of our patients and take us closer to the aim of optimal care for each child and adult with thalassemia. Wishing you all a very rewarding meeting.

Secretary Scientific Committee 5th International Conference on Thalassemia New Delhi

Dr. Amita Mahajan

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Message ..... Message .....

Dear Delegates,
On behalf of the organizing committee, it gives me great pleasure to welcome you to the 5th International Conference on Thalassemia. This conference will help in educating Thalassemia patients, their families and all those who shall be attending the conference as delegates. We welcome all the doctors from India and abroad who are taking part in this meeting as Invited Speakers and Chairpersons. I hope that all the participating delegates will benefit from the proceedings of this conference. I am confident that the deliberations of this two day conference will enhance our commitment to create more awareness about this disorder and strive closer to a zero birth of Thalassemia Majors as well as give an overview to all those who are looking forward for the required breakthrough on Thalassemia, in medical science. We are grateful to the support extended to us by our well wishers, friends and corporates. Wishing all the delegates and faculty the very best.

Chairman Organising Committee 5th International Conference on Thalassemia New Delhi

Deepak Chopra

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Message ..... Message .....

Dear Participants,
On behalf of the Organising Committee, I feel extremely privileged to welcome you all to the 5th International Conference on Thalassemia. In continuation of Thalassemics Indias ongoing activities to spread information and to gain knowledge, this recent conference is being organised. Knowledge knows no boundaries. Mans ever lasting thirst for knowledge is the driving force behind every new discovery. It is with this spirit that we, as a parent group, are holding the 5th International Conference on Thalassemia in New Delhi on 24th-25th Nov., 2012. In India services for Thalassemia patients are quite well developed in few States but in other States, services are still lacking. It is noteworthy that 75% of the global annual affected births occur in the Asian nations and 80% of the patients with hematological disorders live in this region of the world. Overall, inherited diseases have been neglected by the health community. Knowing fully well that we, as an ngo, have to make sure that progress is made continuously in this filed and services for Thalassemia patients keep on improving till we match the European standards. This conference will therefore offer a scientific approach to touch various important aspects of Thalassemia, related to prevention, blood safety, chelation, BMT, Gene Therapy and other topics. The National and International faculty will dwell upon these subjects through presentations, panel discussions and debates. This meeting will also provide an opportunity for further developing collaborations and try to provide the information that may lead to far more actions and support for the management of Thalassemia. You are the ONE who hold the key to open new avenues for your childs bright future through this conference. My deep appreciation for your interest and for joining us here today! Let us all work together to make this event a successful one. Wishing you a pleasant stay in Delhi.

Best regards,
Org. Secretary 5th International Conference on Thalassemia New Delhi

Shobha Tuli

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5th International Conference on Thalassemia

Day 1

Scientific Program

Joint Session for Doctors / Parents / Patients

24th November, 2012

08:00 - 09:30 Registrations 09:30 - 10:00 Chairpersons: Dr. V.K. Khanna & Dr. Mohit Choudhary Safer blood to Minimize Transfusion Transmitted Viral Infections in Thalassemics Dr. Nico Lelie 10:00 - 10:30 Chairperson: Mr. Panos Englezos & Dr. Mohini Kumari Effective Programmes for the Prevention of Thalassemia in India: The Way Forward Prof. I.C. Verma 10:30 - 11:00 Chairpersons: Dr. S. Sudha Optimal Transfusion Therapy and Management of Transfusion Reactions Prof. Antonio Piga 11:00 - 12:00 Inauguration & Tea Break 12:00 - 12:30 Chairpersons: Dr. V. P. Choudhry, Dr Sunil Gomber, Dr. Amita Trehan Deferasirox: The journey so far Dr. Ali Taher 12:30 - 01:00 Chelation of Patients with Suboptimal Response to Deferasirox Dr. Maria D. Cappellini 01:00 - 01:30 The Place of Kelfer and Desferal in the Era of Deferasirox Dr. M.B. Agarwal 01:30 - 02:30 Lunch 02:30 - 03:15 Panel Discussion on Chelation Dr. John Porter, Prof. Antonio Piga, Dr. Ali Taher & Dr. M. B. Agarwal Moderator: Dr. V.K.Khanna 03:15 - 03:45 Chairpersons: Dr. Androulla Eleftheriou & Dr. Dinesh Kaul Infections and Immunisation in Thalassemics Dr. John Porter 03:45 - 04:15 Chairpersons: Dr.P.K. Gogoi, Dr. Dinesh Bhurrani & Dr. Alok Hemal Quality Control and Role of Generics in Chelation Dr. Mehran Karimi 04:15 - 04:45 Tea/Coffee Break 04:45 - 05:15 Chairpersons: Deepak Chopra, Vinay Shetty & Dr. Gautam Bose Patients Perspective You can still do it! My Experience Ajay Gandhi Employment Challenges Sukhsohit Singh Living with Thalassemia AnubhaTaneja 05:15 - 06:00 Open House Discussion Share your Personal Experiences

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Day 2

Joint Session for Doctors / Parents / Patients

25th November, 2012

09:00 - 09:30 Chairperson: Dr. Sharmila Chandra & Dr. A.P. Dubey Management of Adult Thalassemics Dr. Maria D Cappellini 09:30 - 10:15 Chairpersons: Dr. Anju Virmani & Dr. Sangeeta Yadav Assessment and Management of Endocrine Complications Dr. Ratna Chatterjee 10:15 - 10:45 Chairpersons: Dr. Anju Virmani & Dr. Ishita Sen Osteopathy in Thalassemia: Management Guidelines Dr. Rashid Merchant 10:45 - 11:15 Tea/Coffee Break 11:15 - 12:00 Chairpersons: Dr. Manvinder Sachdev & Dr. Neeraj Agarwal Cardiac Problems and solutions & The Role of T2 Star MRI Dr. Malcolm Walker 12:00 - 12:30 Chairpersons: Dr. Anupam Sibal & Dr. Neelam Mohan Overview of Hepatitis Associated Liver Disease Dr. Geoffrey M. Dusheiko 12:30 - 01:00 Chairpersons: Dr. A.P. Dubey & Dr. Nirmal Kumar Complication and Management of Non-Transfusion Dependent Thalassemia Dr. Ali Taher 01:00 - 01:45 Chairpersons: Dr. V. Kanwar, Dr. S.P. Yadav Stem Cell Transplant for Thalassemia Major - When and How? Dr. Alok Srivastava 01:45 - 02:30 Lunch 02:30 - 03:00 Chairpersons: Dr. Renu Saxena & Dr. Tulika Seth Thrombophilic Complications in Thalassemia Dr. Jagdish Chandra 03:00 - 03:30 Chairpersons: Dr. A.P. Dubey & Dr. Alka Mathur Monitoring of Thalassemia Patients Dr. John Porter 03:30 - 04:00 Chairpersons: Dr. Shubha Phadke & Dr. Pat Girondi Globin Gene Transfer for the Cure of Thalassemia: First US trial approved Dr. Michel Sadelain 04:00 - 04:30 Tea/Coffee Break 04:30 - 05:00 Chairpersons: Mr. Panos Englezos & Dr. J.S. Arora The Role of Patient Associations in Promoting the Thalassemia Services Countrywide Shobha Tuli 05:00 - 05:30 Chairpersons: Dr. L. Swasticharan, Dr. Rekha Bajoria & Dr. Pankaj Abrol Improving the Quality of Life of Patients with Thalassemia Prof. Antonio Piga 05:30 - 06:00 Open Discussions/ Questions-Answers 06.00 pm Vote of Thanks

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Day 2

Pre Lunch Session for Doctors

25th November, 2012

09:30 - 10:00 Chairpersons: Dr. Jagdish Chandra & Dr. K.K. Kaul Transfusion Therapy, Blood Safety & Transfusion Reactions Prof. Antonio Piga 10:00 - 10:30 Chairpersons: Dr. Ajay Sharma & Dr. Pranter Chakraberty Monitoring for Thalassemics Dr. John Porter 10:30 - 11:00 Chairpersons: Dr. V.P. Choudhary & Dr. Dharma Choudhary Stem Cell Transplant for Thalassemia Major - Continuing efforts to improve outcome Dr. Alok Srivastava 11:00 - 11:30 Tea/Coffee Break 11:30 - 12:15 Chairperson: Dr. Praveen Sobti & Dr. Kirti Nanal The 3Ds of Chelation Dr. Ali Taher 12:15 - 12:30 Chairpersons: Dr. Praveen Sobti & Dr. Kirti Nanal Fetal Chain Stimulation Dr. V.P. Choudhry 12:30 - 01:00 Chairperson: Dr. Anju Virmani FAQs on Endocrine Issues Dr. Ratna Chatterjee 01:00 - 01:30 Panel Discussion on Cardiac Issues Dr. J.M. Walker, Dr. Rashid Merchant, Dr. Manvinder Sachdev & Dr. Neeraj Agarwal Lunch

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The Organising Committee Sincerely Thanks Our Collaborators

Thalassaemia International Federation

Sir Ganga Ram Hospital

Apollo Hospitals

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Indian Academy of Pediatrics, Delhi Branch

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Notes

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Abstracts
Deferasirox: The journey so far
Ali T. Taher, MD and Joseph Maakaron, MD

Introduction

Iron overload is the main complication resulting from regular blood transfusions used to treat thalassemia and other congenital anemias. Chronic iron overload causes significant damage to the heart, liver and endocrine glands and can lead to premature death. More than half of all deaths in patients with thalassemia major (TM) were traditionally attributed to cardiac complications as a result of inadequate iron chelation. However, more recent studies are showing that with novel advances in iron overload detection and management the relative risk of death from iron-induced cardiomyopathy compared with infection has fallen. Although the subcutaneous iron chelator desferrioxamine (DFO) has served TM patients for more than four decades, the burden of prolonged and regular subcutaneous infusions reflected negatively on patients quality of life. Novel advances in oral iron chelation therapy became the highlight of TM management for the past two decades [1-8].

Deferasirox

Deferasirox is an oral iron chelator with a high affinity for iron. It efficiently and selectively mobilizes iron from liver and heart tissue, thereby promoting iron excretion. Deferasirox and its metabolites are mainly excreted in the faeces while renal excretion is minimal. Deferasirox can provide 24-hour chelation coverage with once daily administration, thus providing sustained protection from toxic labile iron. To date, deferasirox clinical experience extends over seven years, with more than 7,000 patients (age 2 years) investigated across several transfusion-dependent anemias (TM, SCD, MDS, and rare anemias). In a randomized phase 3 trial in 586 patients with TM, a deferasirox dose of 30 mg/kg/day was needed to reduce LIC and serum ferritin. The efficacy of deferasirox doses of 20 or 30 mg/kg/day was comparable with that of 40-60 mg/kg/day of DFO infused 5 days/week. The most common adverse events were gastrointestinal disturbances and rash. Mild, non-progressive increases in serum creatinine and liver enzyme levels were also observed. Serious side-effects, such as agranulocytosis, arthropathy, or growth failure, were not documented. For five years now, deferasirox has demonstrated longterm dose-dependent efficacy and an acceptable and clinically manageable safety profile. Similarly, studies targeting pediatric patients with TM (aged 216 years) showed that deferasirox provides dose-dependent efficacy for the treatment of iron overload in a wide range of iron-loading anemias. Deferasirox was also shown to be both safe and effective in patients who were heavily iron overloaded at baseline, and who eventually required dose escalation to > 30 mg/kg/day. In this study, a subset of the patients were either heavily iron overloaded or heavily transfused, or both. The dose of deferasirox was escalated to > 40 mg/kg/day to achieve adequate iron control. Comparison of occurrence of adverse events between patients taking doses < 30 mg/kg/day and those taking > 30 mg/kg/day revealed that they were comparable. Thus deferasirox is both safe and efficacious at doses > 30 mg/kg/day. In fact,

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it has recently received FDA approval for using a dose of 40 mg/kg in heavily iron overloaded patients [9-11] . The safety profile in patients achieving serum ferritin levels < 1,000 ng/ml during the core and extension study phases was also favourable. Deferasirox was associated with greater patient satisfaction. The EPIC (Evaluation of Patients Iron Chelation with Exjade) trial is currently the largest prospective trial of iron chelation therapy. The data confirmed the efficacy of deferasirox in achieving a reduction in iron load across a wide range of patients with transfusion-related iron overload with appropriate dosing. Deferasirox was also well tolerated with a safety profile consistent with data from previous clinical trials. The cardiac substudy of EPIC showed that deferasirox was effective in removing iron from the heart in patients with cardiac siderosis. The statistically significant improvement in cardiac T2* was associated with maintained normal cardiac function, and a concomitant significant decrease in hepatic and total body iron burden. Data also shows that cardiac T2* values continue to significantly improve and normalize over one two year extensions of the study[12-13]. The toxic effect of iron on the liver is well documented. A study evaluated the effect of deferasirox on liver fibrosis, liver inflammation, and liver enzymes in correlation with liver iron concentration after three years of treatment of deferasirox. The results showed that 83% of patients experienced either improvement in their liver fibrosis score or stabilization. These results were independent of whether or not their liver iron concentration met the response criteria defined by the trial. The improvement was also independent of hepatitis C exposure[14]. A 1-year study (US24T) explored the combined use of deferasirox and deferoxamine in patients with transfusion-dependent thalassemia who had failed standard chelation therapy with a single drug. The ability of the combined therapy to control systemic iron burden (serum ferritin and LIC) and myocardial overload (MRI T2*) was evaluated. Plasma non-transferrin bound iron (NTBI) and LPI were also measured. Median LIC declined by 48% from 10.8 mg/g (3.934.8 mg/g) to 5.7 (1.024.0 mg/g, P=0.003). Median ferritin fell by 43% from 2030 ng/mL (10005230 ng/mL) to 1150ng/mL (4315260 ng/mL, P=0.008). Deferasirox produced immediate and significant decline in plasma NTBI when administered during infusion of DFO: the median plasma NTBI on DFO alone was 2.46 M (0.925.90 M) which was decreased to 1.96 M (03.50 M) following administering of deferasirox (P<0.001). Myocardial iron in the 3 subjects who had T2*<20 ms at study entry showed an average improvement of 2.43 ms following treatment (P=0.027). All 3 subjects with left ventricular ejection fraction below 60% at baseline (47.558.1%) showed improvement at the end of study (60.664.4%). No significant toxicity or unusual adverse events observed with combined chelation therapy in this population. Elevation of serum creatinine or ALT was not observed. Two studies have investigated the efficacy of combination treatment with deferasirox and deferiprone, in patients inadequately compliant with or intolerant to deferasirox. The first study reports a case of a 34-year-old female with TM and refractory iron overload. Deferasirox was initiated in 2006 (final dose of 30 mg/kg/day). Despite progressive improvement, the continued presence of moderate liver and cardiac iron overload and a severe episode of atrial fibrillation led to the simultaneous addition of deferiprone (75 mg/kg/day) in 2009. One year following combination therapy, serum ferritin levels (397 ng/mL) and liver and cardiac MRI T2* (15.3 and 21.1 ms) were indicative of a significantly lower iron burden. An open-label, observational, single-center study investigated the efficacy and safety of deferasirox combined with deferiprone in 16 transfusiondependent TM patients over 2 years. Eligible patients had iron-related complications or required intensified chelation treatment at sporadic intervals. Combination therapy (deferasirox 2025 mg/kg/ day and deferiprone 75100 mg/kg/day) was associated with statistically significant improvements in serum ferritin, LIC, and liver/cardiac MRI T2* values. After 2 years of treatment, all patients demonstrated normalized liver T2*[15]. For patients not responding or not tolerating deferasirox, a regimen involving dividing the dose in two was tried. Eighteen patients (11 non-responders and 7 intolerant) were given deferasirox for 6 months in divided doses. For the non-responders, serum ferritin dropped from a median of 3,628 ng/ml to 2,185 ng/ml in 6 months. Five patients out of the seven who did not tolerate deferasirox experienced significant reduction in the severity of the adverse events reported[16].

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Deferasirox has also been shown to be safe and efficacious in non-transfusion dependent thalassemia (NTDT). The THALASSA trial is a prospective, randomized, double-blind, placebo-controlled Phase II study to evaluate efficacy and safety of deferasirox in non-transfusion dependent thalassemia patients with iron overload, conducted in 27 centres across 9 countries. Patients with high baseline LIc (>5 mg/g dw) were randomized into receiving 2 doses of deferasirox or placebo. Overall, 89.2% (n=148) of patients completed one year of treatment. LIC and SF increased by 0.38 mg Fe/ g dw (95% CI -0.59, 1.34) and 115 ng/mL, respectively over 1 year in patients randomized to placebo. Only six patients (10.7%) of these patients received transfusions during this time. This is equivalent to a body iron increase of 0.011 mg/kg/day. After 1 year of treatment, 56.4% of patients who received deferasirox 10 mg/kg/day and 32.7% of patients who received deferasirox 5 mg/kg/day achieved reductions in LIC of 3 mg/kg/ day. At Week 52, versus placebo, there were significantly greater decreases in liver iron concentration in both the 5 mg/kg/day (-2.33 0.70 mg Fe/ g dw; P=0.001) and 10 mg/kg/day (-4.18 0.69 mg Fe/ g dw; P<0.001) dose cohorts[17]. Recently, a boxed warning was added to the US deferasirox prescribing information, although this amendment has not been adopted by the European Health Authority or applied globally. The warning indicates that it may cause renal and hepatic impairment, including failure, and gastrointestinal hemorrhage. In some reported cases, these reactions were fatal. However, these reactions were observed in patients with advanced age, high risk myelodysplastic syndromes, underlying renal or hepatic impairment or low platelet counts. Moreover, many of the reported cases lacked apparent evidence of causality. Nevertheless, the search for more novel chelators with better safety and efficacy continues.

References
1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17.

Taher AT, Musallam KM, Inati A. Iron overload: consequences, assessment, and monitoring. Hemoglobin 2009; 33 Suppl 1:S46-57. Brittenham GM. Iron-chelating therapy for transfusional iron overload. N Engl J Med 2011; 364:146-156. Olivieri NF, Nathan DG, MacMillan JH, Wayne AS, Liu PP, McGee A, et al. Survival in medically treated patients with homozygous beta-thalassemia. N Engl J Med 1994; 331:574-578. Borgna-Pignatti C, Rugolotto S, De Stefano P, Zhao H, Cappellini MD, Del Vecchio GC, et al. Survival and complications in patients with thalassemia major treated with transfusion and deferoxamine. Haematologica 2004; 89:1187-1193. Modell B, Khan M, Darlison M, Westwood MA, Ingram D, Pennell DJ. Improved survival of thalassaemia major in the UK and relation to T2* cardiovascular magnetic resonance. J Cardiovasc Magn Reson 2008; 10:42. Delea TE, Edelsberg J, Sofrygin O, Thomas SK, Baladi JF, Phatak PD, et al. Consequences and costs of noncompliance with iron chelation therapy in patients with transfusion-dependent thalassemia: a literature review. Transfusion 2007; 47:1919-1929. Musallam K, Cappellini MD, Taher A. Challenges associated with prolonged survival of patients with thalassemia: transitioning from childhood to adulthood. Pediatrics 2008; 121:e1426-1429. Gabutti V, Piga A. Results of long-term iron-chelating therapy. Acta Haematol 1996; 95:26-36. Cappellini MD et al. A phase 3 study of deferasirox (ICL670), a once-daily oral iron chelator, in patients with betathalassemiaBlood 2006;107:34553462. Porter JB, Piga A, Cohen A, et al. Safety of deferasirox (Exjade) in patients with transfusion-dependent anemias and iron overload who achieve serum ferritin levels <1000 ng/ml during long-term treatment [abstract]. Blood. 2008;112:5423. Taher A, et al. Efficacy and safety of deferasirox doses of >30 mg/kg per d in patients with transfusion-dependent anaemia and iron overload. Br J Haematol. 2009;147(5):752-9. Cappellini MD, et al. Tailoring iron chelation by iron intake and serum ferritin: the prospective EPIC study of deferasirox in 1744 patients with transfusion-dependent anemias Haematologica. 2010;95:557-66. Pennell DJ et al. Deferasirox for up to 3 years leads to continued improvement of myocardial T2* in patients with -thalassemia major. Haematologica. 2012 Jun;97(6):842-8. Deugnier Y et al. Improvement in liver pathology of patients with -thalassemia treated with deferasirox for at least 3 years. Gastroenterology. 2011;141(4):1202-1211.e3. Lal A, Sweeters N, Ng V, et al. Combined chelation therapy with Deferasirox and Deferoxamine in transfusion dependent thalassemia [abstract]. Blood. 2011;116:4269. Chang HH, et al. Improved efficacy and tolerability of oral deferasirox by twice-daily dosing for patients with transfusion-dependent -thalassemia. Pediatr Blood Cancer. 2011;56:420-24. Taher AT, et al. Deferasirox reduces iron overload significantly in nontransfusion-dependent thalassemia: 1-year results from a prospective, randomized, double-blind, placebo-controlled study. Blood. 2012 Aug 2;120(5):970-7

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Hydroxyurea in Thalassemia Syndrome

V.P. Choudhry
Director, Former Head, Department of Hematology, AIIMS Consultant, Sunflag Pahuja Center for Blood Disorders, Sunflag Hospital, Sector 16 A, Faridabad - 121 002 Paras Hospital, C-1 Block, Sushant Lok, Phase-1, Gurgaon - 122 002 E-mail: vedpchoudhry@yahoo.co.in

Hydroxyurea in Thalassemia Intermedia Thalassemias are a heterogeneous group of disorders which results from imbalance between production of alpha and non-alpha globin chains in hemoglobin. Severity of the disease depends on the degree of imbalance in production of these globin chains. Therefore, the course of the disease can be modified by correcting the imbalance between the alpha and non-alpha globin chains. The drugs which correct the imbalance are called gene modifiers. Gene modifier works by increasing the expression of Hbf, which is possible in a proportion of patients. These gene modifying agents can be chemotherapeutic or non chemotherapeutic agents. Hydroxyurea appears to be the most effective drug for this purpose among chemotherapeutic agents. 5 azacytidine mycleran has also been used for this purpose. Among the non- chemotherapeutic agent recombinant human erythropoietin, haemin and butyrate derivatives have been tried with variable success. Hydroxyurea is an S-phase- specific and non DNA- hypomethylating chemotherapeutic agent which preferentially acts on dividing cells, permitting the emergence of primitive erthyroid progenitors more highly committed for HbF synthesis leading to increase in HbF levels. The dose of Hydroxyurea is usually 15-20 mg/Kg/day. The term Thalassemia Intermedia include a large spectrum of conditions of varying severity. Blood transfusion and chelation are necessary in some patients, especially during childhood, in order to promote growth and prevent bone deformities. Modalities used in treatment of this disease are splenectomy and gene modifier agents. Large series of Thalassemia Intermedia patients have been recently reported from Iran (Karimi et al, 2005) and India (Dixit et al, 2005: Panigrahi et al, 2005) (Table I). The results were impressive and many patients were reported to have become transfusion independent. In patients who were not transfused, the haemoglobin concentration increased. Studies from Europe had also documented a constant increase of the erythrocyte volume and in HbF, but only a modest effect on total haemoglobin concentration. Alpha deletions, the XmnI polymorphism (Panigrahi et al, 2005) and the Hb E / thalassemia (Singer et al, 2005) may be predictive of a good response of hydroxyurea. The improved sense of well- being, almost universally reported, reflects improvement in hemoglobin levels. It has been suggested that the efficacy of treatment could decrease over time (Mancuso et al, 2006). Older age, low baseline HbF level (<10%) and low baseline F cell percent were predictive for poor outcome. Response is usually evident in 4-6 weeks. Hydroxyurea have been used in these patients for long time and despite a thereotical risk of increasing hematolgic malignancies, no report of such cases has been found in literature.

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Table I: Hydroxycarbamide results in Thalassemia Intermedia

References Mancuso et al (2006) Karimi et al (2005) No. of patients 18 splenctomised untransfused 163 I group (receiving regular blood transfusion) II group ( no transfusion or longinterval transfusion Dixit et al (2005) 37 10-20 mg / kg Range; 4-36 months HU dose Median dosage 14.6mg/kg; range 5-30 mg/kg 8-12 mg/kg/day Length of therapy 1 year Results Average Hb 15 g/l; 11/18 Hb > 10 g/l 149 responded I group;83/106 became transfusion free;23 had 1-2 transfusions II group; 16/143 became transfusion free; 27 developed acceptable Hb levels 46% became transfusion free and Hb >20 g/l and transfusion need by 50% All patients total Hb in the first month of treatment. In TI patients Hb level rose from 65 to 105 g/l. the size of extramedullary erythropoietic masses and cured leg ulcers. 3/7 Hb level of 13, 19 and 20g/l Hb from 71 to 103 g/l Hb 30 g/l in 2; 10-20 g/l in 2; no response in 1

6 years

Bradai et al (2003)

7 (2 with TI)

Range 15-20 mg/kg/d

Range 13-21 months

Gamberini et al (2004)

1 g/d

90 d

De Paula et al (2003) Cianciulli et al (2000) Hoppe et al (1999)

7 1 5

10-20 mg/Kg/d 20mg/kg/d 3-10 mg/kg/d

6 months 6 months Length depends upon toxicity effects of HC

Hb, haemoglobin; HC, hydrocarbamide.

To conclude the hydroxyurea is an effective and safe agent which acts on stem cell and is able to improve the hemoglobin levels and quality of life in variety of conditions, such as Thalassemia Intermedia, in some cases of Thalassemia Major, sickle cell anemia, HbE- thalassemia. It has resulted in better quality of life and it should be considered as an option for treatment for above conditions.

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Complications and Management of Thalassemia Intermedia

Ali T. Taher, MD and Joseph Maakaron, MD

Introduction

The beta ()-thalassemia syndromes exhibit extremely diverse phenotypes ranging from the clinically silent -thalassemia minor to completely transfusion-dependent -thalassemia major (TM). The term -thalassemia intermedia (TI) was coined to describe patients who have clinical manifestations somewhere in between1. Although tremendous progress has been made over the past decade in characterizing these syndromes from a genotypic and molecular perspective, the diagnosis is still largely based on the clinical severity of the syndrome.

Clinical Perspective on -Thalassemia Intermedia

Ineffective erythropoiesis (IE), chronic hemolytic anemia, and iron overload associated with TI can result in a number of serious clinical sequelae that require proactive and comprehensive management2. The severity of anemia is determined by 2 main factors: the degree of IE and the extent of hemolysis of mature RBCs. Ineffective erythropoiesis is also associated with skeletal deformities and osteopenia attributed to erythroid marrow expansion,2 as well as compensatory extramedullary hematopoietic tumor formation3. Hemolysis is also associated with progressive splenomegaly and a hypercoagulable state, which may account for the high incidence of thromboembolic events in patients with TI,4-7 and may explain other complications associated with TI such as pulmonary hypertension (PHT)8-10. Ineffective erythropoiesis and chronic anemia also lead to an increase in gastrointestinal iron absorption that often results in nontransfusional iron overload, predominantly in the liver but with consequences affecting many organ systems11,12. Thus, despite being considered a milder form of -thalassemia at initial presentation and diagnosis, TI is associated with risk for a variety of serious complications that can increase with age. Therefore, optimal and early intervention is extremely important13. Unfortunately, despite a number of available treatment options, there are currently no clear treatment guidelines for TI. The OPTIMAL CARE study brought new clarity to the management of TI. This large retrospective overview of 584 patients with TI managed in the Middle East and Italy was designed to assess the rate of disease-associated complications in relation to current clinical practice14.

Currently Available Treatment Options

Splenectomy Even though splenectomy is indicated in certain situations,4 it can increase the risk of complications. In patients with nontransfusion-dependent TI who receive either no transfusions or sporadic transfusions, the size of the spleen inevitably increases with time, resulting in a gradual worsening of anemia and the requirement for RBC transfusion15. Neutropenia and thrombocytopenia also may worsen over time. Splenectomy typically reverses this process, resulting in a short-term increase in Hb levels by as much as 10-20 g/L, and reduces transfusion requirements in the majority of patients4,15. However, clinical observations suggest that splenectomy in patients with TI can contribute to an increased susceptibility to venous thrombosis,6,16 PHT,17,18 and silent brain infarcts19. Recently, the OPTIMAL CARE study confirmed an independent association between splenectomy and increased occurrence of thromboembolism, PHT, heart failure, iron-related endocrinopathy, and leg ulcers14. Splenectomy also increases the risk of infection, which carries a high mortality rate, especially in children with underlying hematologic disorders20. Recommendations from the British Committee for Standards in Haematology for the prevention of post-splenectomy infections21,22 include antibiotic prophylaxis; however, compliance with these regimens can be problematic. Immunization against Haemophilus influenzae and serogroup C meningococci also is recommended. Based on these considerations, a

26

guarded approach to splenectomy is advised, and the procedure should be delayed unless considered vitally necessary. Transfusion Therapy In patients with TI, the most challenging therapeutic decisions are whether and when to initiate regular transfusion therapy4,15. Many patients require intermittent RBC transfusions due to intercurrent infection or pregnancy, and more regular therapy often is indicated for growth failure, skeletal deformity, exercise intolerance, or when Hb levels decline due to progressive splenomegaly4,15,23. In addition, there may be clinical benefit to initiating transfusions earlier or prophylactically to reduce the risk of alloimmunization and to prevent complications that can occur with delayed initiation of transfusions4,24. In the OPTIMAL CARE study, patients who were placed on either intermittent or regular transfusion regimens had fewer complications (eg, EMH, PHT, and thrombosis), but had a higher rate of iron overload-related endocrinopathy14. Observational studies have confirmed that transfused patients with TI experience fewer thromboembolic events, PHT, and silent brain infarcts compared with transfusion-nave patients4,6,14,19,25. This may be due to correction of the underlying IE and resulting damaged RBCs with thrombogenic potential4,7. Although earlier introduction of RBC transfusions does increase iron accumulation, effective iron chelating agents are available, and the benefits of transfusion therapy may outweigh the cost and inconvenience of iron chelation therapy4. Patients in the OPTIMAL CARE study who received both transfusions and iron chelation therapy had a lower incidence of complications, including endocrinopathy, compared with patients who received no treatment or either treatment alone14. Moreover, a recent study comparing health-related quality of life (HRQoL) in patients with transfusion-independent TI and regularly transfused patients with TM showed that TI patients had worse HRQoL, possibly because of more frequent complications26. Iron Chelation Therapy Iron overloading in patients with TI can occur as a result of both increased intestinal absorption and transfusion therapy, but regardless of the source, iron overload can be monitored and chelation therapy can readily control this condition4,11,27. The initiation of chelation therapy in patients with TI depends primarily on the extent of iron overload and rate of accumulation but, as with other aspects of the management of TI, clear disease-specific guidelines are not available. Because of increased iron absorption, patients with TI may have a positive iron balance at 5 years of age,28 even in the absence of transfusions; thus, iron chelation therapy may be indicated4. The greatest challenge in these patients is monitoring iron levels because serum ferritin levels are not a good indicator of iron overload in patients with TI29. Therefore, direct assessment of liver iron concentration (LIC) either by biopsy or imaging every 1-2 years is recommended, and chelation therapy should be initiated in patients with elevated indices of iron overload4,11. In most cases, intermittent iron chelation with careful periodic assessment is sufficient in patients with TI. Data on iron chelation is limited in TI. The practical limitations and inconvenience of prolonged subcutaneous therapy with DFO can potentially affect quality of life and compliance,4,30,31 which has heightened interest in the use of oral iron chelators. The THALASSA study (NCT00873041) is a large, randomized, double-blind, placebo-controlled phase 2 trial of deferasirox in 166 patients with non transfusion-dependent thalassemia and iron overload (LIC 5 mg Fe/g dry weight and serum ferritin levels > 300 ng/mL). This is the first large study to evaluate the efficacy and safety of iron chelation therapy in this patient population. Preliminary results of this trial were presented at the 16th Congress of the European Hematology Association in June 201132; and efficacy outcomes were presented at the 2011 American Society of Hematology Annual Meeting21. Deferasirox significantly decreased LIC, the primary endpoint, compared with placebo after 1 year of treatment (P = 0.001 and P < 0.001 for 5 and 10 mg/kg/day deferasirox vs placebo, respectively). Deferasirox also significantly decreased mean serum ferritin levels compared with placebo (P < 0.001 for both doses vs placebo) and was associated with a manageable toxicity profile.

27

Fetal Hb Modulation A number of other medical interventions have been investigated in patients with TI to induce fetal Hb (HbF) production, overcome incomplete erythropoiesis, or manage complications, but results from these studies should be interpreted with caution. For example, hydroxycarbamide (also known as hydroxyurea) has been widely studied to induce HbF production and is commonly used in patients with TI based on evidence that it can increase Hb levels and reduce transfusion requirements. Indeed, the OPTIMAL CARE study documented the benefits of hydroxycarbamide in TI patients, especially when combined with transfusion and iron chelation therapy14. Although hydroxycarbamide is generally well tolerated with short- and medium-term use in patients with TI,33 results from recent studies suggest that the beneficial effects on HbF production are transient and attenuate with longer duration of therapy34. Studies to identify additional HbF inducers are ongoing. Findings from other studies35,36 suggest that hydroxyureaeither alone or in combination with L-carnitine or magnesiummay improve cardiac status and/or reduce PHT, but results are mixed. Hydroxyurea in combination with transfusion therapy also may decrease demand for EMH and reduce the risk of developing tumors. Paraspinal involvement is common and requires intervention due to the debilitating consequences of spinal compression3,4. In this setting, hydroxyurea often is used in conjunction with transfusion and radiotherapy to treat these tumors. Areas of Unmet Need Sildenafil Citrate, a selective smooth muscle relaxant, has been evaluated in the management of PHT, but available data are limited4. A National Heart, Lung, and Blood Institute study (NCT00872170) of sildenafil in 27 patients with thalassemia and PHT was recently completed. Studies of other therapeutic targets and interventions that could potentially ameliorate the disease burden in patients with hemoglobinopathy including TI are ongoing37-39.

References
1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15.

Sturgeon P, Itano HA, Bergren WR. Genetic and biochemical studies of intermediate types of Cooleys anaemia. Br J Haematol. Jul 1955;1(3):264-277. Taher A, Ismaeel H, Cappellini MD. Thalassemia intermedia: revisited. Blood Cells Mol Dis. Jul-Aug 2006;37(1):12-20. Haidar R, Mhaidli H, Taher AT. Paraspinal extramedullary hematopoiesis in patients with thalassemia intermedia. European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society. Jun 2010;19(6):871-878. Taher AT, Musallam KM, Cappellini MD, Weatherall DJ. Optimal management of beta thalassaemia intermedia. British journal of haematology. Mar 2011;152(5):512-523. Ataga KI, Cappellini MD, Rachmilewitz EA. Beta-thalassaemia and sickle cell anaemia as paradigms of hypercoagulability. Br J Haematol. Oct 2007;139(1):3-13. Taher A, Ismaeel H, Mehio G, et al. Prevalence of thromboembolic events among 8,860 patients with thalassaemia major and intermedia in the Mediterranean area and Iran. Thromb Haemost. Oct 2006;96(4):488-491. Taher AT, Otrock ZK, Uthman I, Cappellini MD. Thalassemia and hypercoagulability. Blood Rev. Sep 2008;22(5):283292. Aessopos A, Farmakis D, Karagiorga M, et al. Cardiac involvement in thalassemia intermedia: a multicenter study. Blood. Jun 1 2001;97(11):3411-3416. Taher A, Abou-Mourad Y, Abchee A, Zalouaa P, Shamseddine A. Pulmonary thromboembolism in beta-thalassemia intermedia: are we aware of this complication? Hemoglobin. May 2002;26(2):107-112. Karimi M, Musallam KM, Cappellini MD, et al. Risk factors for pulmonary hypertension in patients with beta thalassemia intermedia. European J Intern Med. Dec 2011;22(6):607-610. Taher A, Hershko C, Cappellini MD. Iron overload in thalassaemia intermedia: reassessment of iron chelation strategies. British journal of haematology. Dec 2009;147(5):634-640. Musallam KM, Cappellini MD, Wood JC, et al. Elevated liver iron concentration is a marker of increased morbidity in patients with {beta} thalassemia intermedia. Haematologica. Jul 26 2011;96(11):1605-1612. Taher AT, Musallam KM, El-Beshlawy A, et al. Age-related complications in treatment-naive patients with thalassaemia intermedia. British journal of haematology. Aug 2010;150(4):486-489. Taher AT, Musallam KM, Karimi M, et al. Overview on practices in thalassemia intermedia management aiming for lowering complication rates across a region of endemicity: the OPTIMAL CARE study. Blood. Mar 11 2010;115(10):18861892. Borgna-Pignatti C. Modern treatment of thalassaemia intermedia. Br J Haematol. Aug 2007;138(3):291-304.

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16. Cappellini MD, Robbiolo L, Bottasso BM, Coppola R, Fiorelli G, Mannucci AP. Venous thromboembolism and hypercoagulability in splenectomized patients with thalassaemia intermedia. Br J Haematol. Nov 2000;111(2):467473. 17. Aessopos A, Farmakis D. Pulmonary hypertension in beta-thalassemia. Ann N Y Acad Sci. 2005;1054:342-349. 18. Atichartakarn V, Likittanasombat K, Chuncharunee S, et al. Pulmonary arterial hypertension in previously splenectomized patients with beta-thalassemic disorders. Int J Hematol. Aug 2003;78(2):139-145. 19. Taher AT, Musallam KM, Nasreddine W, Hourani R, Inati A, Beydoun A. Asymptomatic brain magnetic resonance imaging abnormalities in splenectomized adults with thalassemia intermedia. J Thromb Haemost. Jan 2010;8(1):5459. 20. Bisharat N, Omari H, Lavi I, Raz R. Risk of infection and death among post-splenectomy patients. J Infect. Oct 2001;43(3):182-186. 21. Taher AT PJ, Viprakasit V, et al. Deferasirox significantly reduces liver iron concentration in non-transfusiondependent thalassemia patients with iron overload: results form the 1-year randomized, double-blind, placebocontrolled phase II THALASSA study. 53rd American Society of Hematology Annual Meeting. December 10-13, 2011; San Diego, California. Abstract 902. 22. Davies JM, Lewis MP, Wimperis J, Rafi I, Ladhani S, Bolton-Maggs PH. Review of guidelines for the prevention and treatment of infection in patients with an absent or dysfunctional spleen: prepared on behalf of the British Committee for Standards in Haematology by a working party of the Haemato-Oncology task force. British journal of haematology. Nov 2011;155(3):308-317. 23. Borgna-Pignatti C, Marsella M, Zanforlin N. The natural history of thalassemia intermedia. Ann N Y Acad Sci. Aug 2010;1202:214-220. 24. Eder AF, Chambers LA. Noninfectious complications of blood transfusion. Arch Pathol Lab Med. May 2007;131(5):708718. 25. Aessopos A, Kati M, Farmakis D. Heart disease in thalassemia intermedia: a review of the underlying pathophysiology. Haematologica. May 2007;92(5):658-665. 26. Musallam KM, Khoury B, Abi-Habib R, et al. Health-related quality of life in adults with transfusion-independent thalassaemia intermedia compared to regularly transfused thalassaemia major: new insights. Eur J Haematol. Jul 2011;87(1):73-79. 27. Kontoghiorghes GJ, Spyrou A, Kolnagou A. Iron chelation therapy in hereditary hemochromatosis and thalassemia intermedia: regulatory and non regulatory mechanisms of increased iron absorption. Hemoglobin. Jun 2010;34(3):251-264. 28. Cossu P, Toccafondi C, Vardeu F, et al. Iron overload and desferrioxamine chelation therapy in beta-thalassemia intermedia. Eur J Pediatr. Nov 1981;137(3):267-271. 29. Taher A, El Rassi F, Ismaeel H, Koussa S, Inati A, Cappellini MD. Correlation of liver iron concentration determined by R2 magnetic resonance imaging with serum ferritin in patients with thalassemia intermedia. Haematologica. Oct 2008;93(10):1584-1586. 30. Cappellini MD. Overcoming the challenge of patient compliance with iron chelation therapy. Semin Hematol. Apr 2005;42(2 Suppl 1):S19-21. 31. Treadwell MJ, Weissman L. Improving adherence with deferoxamine regimens for patients receiving chronic transfusion therapy. Semin Hematol. Jan 2001;38(1 Suppl 1):77-84. 32. Porter J, Cappellini M, Kattamis A, Viprakasit V, Lawniczek T, Ros J, Deng W, Taher A. Relationship between plasma non-transferrin-bound iron and markers of iron overload, anaemia and ineffective erythropoiesis in non-transfusiondependent thalassaemia syndromes [abstract]. Presented at the 16th Congress of the European Hematology Association. June 9-12, 2011. London, UK. Abstract 0536. 33. Karimi M, Cohan N, Moosavizadeh K, Falahi MJ, Haghpanah S. Adverse effects of hydroxyurea in beta-thalassemia intermedia patients: 10 years experience. Pediatr Hematol Oncol. Apr 2010;27(3):205-211. 34. Rigano P, Pecoraro A, Calzolari R, et al. Desensitization to hydroxycarbamide following long-term treatment of thalassaemia intermedia as observed in vivo and in primary erythroid cultures from treated patients. Br J Haematol. Dec 2010;151(5):509-515. 35. Karimi M, Mohammadi F, Behmanesh F, et al. Effect of combination therapy of hydroxyurea with l-carnitine and magnesium chloride on hematologic parameters and cardiac function of patients with beta-thalassemia intermedia. Eur J Haematol. Jan 1 2010;84(1):52-58. 36. Amoozgar H, Farhani N, Khodadadi N, Karimi M, Cheriki S. Comparative study of pulmonary circulation and myocardial function in patients with beta-thalassemia intermedia with and without hydroxyurea, a case-control study. Eur J Haematol. Jul 2011;87(1):61-67. 37. Gardenghi S, Ramos P, Marongiu MF, et al. Hepcidin as a therapeutic tool to limit iron overload and improve anemia in beta-thalassemic mice. J Clin Invest. Dec 1 2010;120(12):4466-4477. 38. Li H, Rybicki AC, Suzuka SM, et al. Transferrin therapy ameliorates disease in beta-thalassemic mice. Nat Med. Feb 2010;16(2):177-182. 39. Sankaran VG, Nathan DG. Reversing the hemoglobin switch. N Engl J Med. Dec 2 2010;363(23):2258-2260.

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40. Kaul DK, Liu XD, Zhang X, et al. Peptides based on alphaV-binding domains of erythrocyte ICAM-4 inhibit sickle red cell-endothelial interactions and vaso-occlusion in the microcirculation. American journal of physiology. Cell physiology. Nov 2006;291(5):C922-930. 41. Kaul DK, Liu X, Nagel RL. Ameliorating effects of fluorocarbon emulsion on sickle red blood cell-induced obstruction in an ex vivo vasculature. Blood. Nov 15 2001;98(10):3128-3131. 42. Kaul DK, Liu XD, Zhang X, Ma L, Hsia CJ, Nagel RL. Inhibition of sickle red cell adhesion and vasoocclusion in the microcirculation by antioxidants. American journal of physiology. Heart and circulatory physiology. Jul 2006;291(1):H167-175. 43. Kaul DK, Fabry ME. In vivo studies of sickle red blood cells. Microcirculation. Mar 2004;11(2):153-165. 44. Porter JB. Deferoxamine pharmacokinetics. Semin Hematol. Jan 2001;38(1 Suppl 1):63-68.

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No Bone Deserves a Break

Rashid Merchant1 M.D, D.C.H, Amruta Shirodkar2 D.C.H, D.N.B Pediatrics, Amish Udani3 D.C.H, D.N.B Pediatrics, Fellow Pediatric Nephrologist
1 2

Consultant Pediatrician, Dr. B. Nanavati Hospital, Vile Parle, Mumbai, India Assistant Professor, Dept. of Pediatrics, K. J. Somaiya Medical College, Sion, Mumbai, India 3 Consultant Pediatric Nephrologist, H. J. Doshi Ghatkopar Hindu Sabha Hospital & Parakh Hospital, Ghatkopar, Mumbai, India

Osteopathy in thalassemia major has emerged as a topic of interest since optimized transfusion regimens have increased life expectancy and improved quality of life in these children. It is clear that a large number of factors interact at the level of osteoblasts, osteoclasts, and other cells to regulate the balance between net bone resorption and formation. Due to chronic anemia and expansion of the bone marrow cavity there is loss of trabecular bone tissue resulting in osteopathy. The other factors are iron overload, iron chelators (especially deferoxamine) and genetic factors (polymorphisms of VDR gene and COL1 gene). Endocrine factors like hypogonadism, aberrant vitamin D and PTH axis and low IGF-1 also contribute significantly low bone mass. The important variables for evaluation of bone formation and resorption are 25-hydroxy-vitamin D, parathyroid hormone (PTH), insulin-like growth factor-1 (IGF-1), serum osteocalcin, and urine or serum crosslaps. The gold standard test for evaluation of osteoporosis and risk of fracture is bone mineral densitometry (BMD). In our experience with children suffering from thalassemia major between 10-25 years of age, six had fractures, nine had avascular necrosis of the head of the femur, two had tetany, two had hypocalcemic seizures and one hadbowing of legs. Dual energy X-ray absorptiometry (DEXA) revealed osteopenia/ osteoporosis in 81% of the children. All of them had high serum ferritin levels (mean 5344 ng/ml). Serum calcium levels were low in 16% and alkaline phosphatase was high in 37% cases only. 25-OH vitamin D was low in 62%, 38% had hyperparathyroidism, 55% had high urinary crosslaps, 52% had low IGF-1, and 36% had elevated serum osteocalcin.. Endocrine evaluation in these series showed low levels of FSH, LH, estradiol and free testosterone in 14%, 3%, 44% and 90% respectively. Advancing age shows a statistically significant increase in the incidence of osteoporosis. There is no statistically significant difference in any of the biochemical parameters studied between those with normal or abnormal DEXA. Pre-transfusion hemoglobin (Hb), transfusion requirement and chelation therapy used are factors that did not show any statistically significant difference between children with or without normal DEXA. We recommend that for prevention and management of osteoporosis in thalassemia it is important to maintain an adequate transfusion regimen to achieve Hb above 9 g/dL and appropriate chelation therapy to target serum ferritin below 1000 ng/ml. BMD is the gold standard test for diagnosis of osteoporosis as it is non-invasive and easy to interpret. BMD by DEXA should be evaluated annually from 10 years onwards and earlier if symptomatic. Age matched Z scores in young children and T scores in adults should be measured for diagnosis of osteopenia/osteoporosis. X-rays are indicated in symptomatic children for diagnosis of fractures, avascular necrosis or compression of spinal vertebrae. MRI may be useful to diagnose degenerative changes, extramedullary hematopoiesis and disc prolapse. Biochemical evaluation (serum calcium, phosphorus, alkaline phosphatase) should be monitored after receiving 2 years of transfusion every 3-6 months. Hormonal investigations (25 OH vitamin D, PTH, endocrine hormones) and if needed, serum osteocalcin and crosslaps, should be monitored once a year if the initial biochemical evaluation showed an abnormality, if the patient is symptomatic, or after 12 years of age. All children should receive daily calcium intake from dietary sources and supplements (0.5-1.0 g/day) upto 2.5 g/day. All children also should receive maintenance vitamin D (cholecalciferol) of 1000 IU/day. In case of deficiency (25 OH vitamin D levels <30 ng/dL), the child should be treated with 60,000 IU/ week for 2-6 months with monitoring for hypercalciuria and renal stone disease till vitamin D levels are within normal range. In children with hypogonadism and osteoporosis, hormone replacement therapy (HRT) is the first choice of treatment for 2 years with monitoring of correction of hypogonadism with trough sex steroid levels. Bisphosphonates should be used as second choice and in children without

31

hypogonadism for three to five years. Combination therapy with bisphosphonates and HRT can also be used in children with severe osteoporosis. Calcitonin nasal spray (200 IU/day) can be used to inhibit osteoclastic activity (elevated crosslaps or PTH levels) and especially in children with vertebral fractures. Teriparatide (iPTH) can be used in severe osteoporosis as an anabolic agent for 2 years in children older than 18 years not responding to above therapies.

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Stem Cell Transplant for Thalassemia Improved outcomes and newer possibilities
Alok Srivastava
Department of Haematology & Centre for Stem Cell Res. Christian Medical College, Vellore, India

Allogeneic blood or marrow stem cell transplantation (SCT) continues to be the only established and widely available cure for thalassaemia major and other severe haemoglobin diseases. While success has been high (85-90%) in patients who have been well transfused and iron chelated, this has not been the case for those who have not had such treatment. In India, more than half of the patients coming for SCT are in the high risk category. The success rate among these patients is about 60% with a subgroup of those >7 years of age and with >5cm enlarged liver (very high risk group) doing particularly worse, if treated with standard conditioning regimen of busulfan and cyclophosphamide (Bu/Cy). To improve results, within the first group we monitor the blood levels of busulfan among those receiving Bu/Cy and adjusting doses to target levels. For high risk patients, we now use a treosulfan based conditioning regimen with peripheral blood stem cells graft which has given excellent results of over 80% survival in a group which was ~30% earlier. However, this significantly increases the cost. The major limitation that prevents the vast majority of these patients from availing this treatment is the absence of a matched related donor. We have now started doing matched unrelated donor transplants for thalassemia major if there is at least a 9/10 HLA antigen matched donor. A significant number of patients from India are finding a match in the international donor registries and the initial results are very encouraging. However, caution is needed as we proceed with such donors as the chances of complications can be higher and the cost is indeed very high limiting this option for many patients in India. Even though good results have been reported in related matched cord blood transplants internationally, we prefer to avoid such transplants at present in India as most of our patients are in the high risk category. Among them, the risk of rejection can be high if cord blood alone is used. We therefore recommend that if there is a HLA matched sibling donor, then it is best to wait till enough bone marrow or peripheral blood stem cells can be harvested rather than go for cord blood transplant, even if cord blood has been preserved, particularly in high risk patients. We also do not recommend routine preservation of cord blood that may not be HLA matched or for autologous use, as is often advertised. Finally, it is important to remember that a successful transplant only takes care of one problem hemoglobin production. Iron overload needs to treated after SCT to bring serum ferritin down to normal levels and in older children, growth and development may need to be assessed and adequate hormonal replacement treatment provided, as necessary. All immunizations also need to initiated one year after SCT if there is no GVHD and completed by two years.

33

Effective Program for Prevention of Thalassemia in India: The Way Ahead

I. C. Verma
Director & Senior Consultant, Center of Medical Genetics, Sir Ganga Ram Hospital, New Delhi Email: icverma@yahoo.com

The need for prevention of thalassaemia is obvious due to high frequency of the condition in many states, the great expense and difficulty in providing optimal treatment for patients, and the innumerable fatalities from partially treated -thalassaemia. Prevention would be cost-effective, as the ratio of the cost of treatment to prevention is 4:1, as shown in studies from around the world. The strongest argument for prevention is that it would ensure the best possible care for the affected, by keeping their number as low as possible. Prevention can be implemented at a number of levels at the level of the individual obstetrician by screening every pregnant woman for carrier status of thalassemia, at the level of the family with an affected child by screening the other family members (cascade screening), on a wider scale in the city or state by making it a state plan. The first two strategies can be adopted immediately, the only cost being that of screening, and subsequently of prenatal diagnosis in the at risk couples. Prevention on a wider scale requires (i) Political and financial support, (ii) Prospective antenatal screening, (iii) Carrier screening in high schools or colleges, (iv) Counseling, (ii) Subsidized prenatal diagnosis in couples who have given birth to an affected child, as well as those identified to be at risk, (vii) Creating network of centers, and Regional working groups. Financial support is required for training and employing the manpower required for execution of the control program (social workers, technicians, doctors, counselors); purchase of equipment (electronic cell counters, HPLC machines, DNA diagnostic laboratories, and record keeping and information system in a confidential manner. Education of the professionals and the public should be done using all components of mass media newspapers, TV and films. The educational program should have three main messages - carrier state has no disadvantage, homozygous state is associated with a very severe disorder, that is eventually fatal with no curative therapy, and fetal diagnosis is available and safe. Experience around the world clearly indicates that carrier testing must be voluntary, and mandatory measures should be discouraged. Premarital screening has been advocated by many investigators in India as a preventive strategy. This is a good, perhaps the only option, in countries that do not allow termination of pregnancy, e.g., in Saudi Arabia, the Middle-east and Sri Lanka. In India this strategy has not met with much success. If the policy of premarital screening were to be successful, control of thalassaemia in India should have been achieved a long time ago, because this course of action has been available for decades. Over-emphasis on premarital screening should be avoided in India. What should be advocated is screening before or in early pregnancy. Strategy for a control program for -thalassaemia should be to sensitize the community to the problem, establish hematological technologies for screening, and molecular and obstetric techniques for prenatal diagnosis. However, the program should not begin until all components are in place. How should the carriers be identified? The technique to be used should be affordable, applicable, and accurate. The choice of using naked eye single tube red cell osmotic fragility test (NESTROFT), or electronic cell count, or HbA2 estimation using HPLC depends upon the resources available and the size of the population. No doubt Hb A2 estimation by HPLC is the ideal. The most important and difficult component is management and organization. This is only possible

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through Government involvement. Equally important is that every one (physicians and scientists) are willing to work as a group. Thalassemia major can be controlled in India! All the technological inputs required are available in the country, and the decision to control thalassemia has to be a political and administrative one. The Government has to be involved. A person has to be appointed to take charge of the program, an infrastructure created for implementation, and finances provided to carry out the plan, which can be easily developed.

Based on the Papers

1. 2.

Verma IC, Saxena R, Kohli S. Past, present & future scenario of thalassaemic care & control in India. Indian J Med Res. 2011 Oct;134:507-21. Verma IC, Saxena R, Kohli S. Hemoglobinopathies in India - clinical and laboratory aspects. Clin Lab Med. 2012 Jun;32(2):249-62.

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Overview of Hepatitis Associated Liver Disease in Thalassaemia and its Current Management
G. M. Dusheiko
Royal Free Hospital and University College London Medical School

Excessive iron absorbtion occurs in patients with Thalassaemia. Multiple transfusions can lead to secondary iron overload, although regular chelation therapy can delay but not completely avert the development of hepatic fibrosis. The iron loading that is encountered is similar to that seen in genetic haemochromatosis, but is exacerbation by the requirement for blood transfusions that lead to parenteral iron overload. Iron loading is observed at an early age, and necessitates aggressive prophylactic use of oral and parenteral iron chelation therapy with close regulation. Iron loading in the liver leads to liver damage, hypersplenism, thrombocytopaenia secondary to hypersplenism and portal hypertension. Patients with thalassaemia major require lifelong chelation therapy to prevent iron induced organ damage. There have been concerns regarding the effect of deferiprone induced progression of hepatic fibrosis but these have not been substantiated. Chronic hepatitis B infection and C infection remain an important cause of morbidity in thalassaemics worldwide. Before screening of blood, transfusion was a major risk factor for the acquisition of hepatitis C and many patients with thalassemia major became chronically infected. Thus these patients are at risk of developing hepatic fibrosis both from iron overload and from chronic HCV infection, emphasizing the need for effective antiviral therapy in addition to regular iron chelation. Coexistent hepatitis B or C infection can increase the risk of progressive fibrosis of the liver leading to cirrhosis, complications of cirrhosis, liver failure and hepatocellular carcinoma. Studies have shown that iron overload and hepatitis C infection are independent risk factors for liver fibrosis progression and their concomitant presence results in a striking increase in risk. Non invasive means of estimating fibrosis may assist in the identification of advanced liver disease. Between 25-35% of those chronically infected with hepatitis B develop progressive liver disease. Several stages of hepatitis B exist. Typically HBeAg positive patients are younger and may have high levels of hepatitis B replication, but relatively mild liver damage in the immunotolerant phase of the infection. Patients with pre-core mutant disease are anti-HBe positive, but replicate a variant of hepatitis B not expressing HBeAg. Inactive carriers of hepatitis B are anti-HBe positive, but have low levels of HBV replication and normal serum amintransferases. The goals of therapy are to reduce and preferably maintain suppression of HBV DNA to prevent sequelae of HBV infection. The advent of potent nucleoside analogues with low barriers to resistance has improved the outlook for patients with hepatitis. Cirrhosis develops within 10 years in about 10-20% of patients with chronic hepatitis C. Older age at infection, concomitant alcohol abuse, concurrent HBV or HIV infection and other illness may be important aggravating cofactors. The natural history after the first 20 years has not been fully defined in prospective studies. Combination treatment with interferon alpha (pegylated interferon) and ribavirin has been the mainstay of treatment. Iron overload does not prevent the possibility of a sustained virological response. The advent of new direct acting antiviral and host acting antivirals will hopefully translate into improved outcomes from hepatitis C in thalassaemics. The toxicities and drug -drug interactions of these new compounds will require special assessment in Thalassaemia.

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The Role of Thalassemia Associations in Promoting the Thalassemia Services Countrywide

Shobha Tuli
Secretary, Thalassemics India Vice-President, Thalassaemia International Federation President, Thalassemia International Federation

An NGO needs real leadership and commitment. NGOs play a lead role in providing access to health services in a country. The increasing role of NGOs in the area of public health has not only helped the patients but opened up new opportunities for building partnerships for mutual benefits. The state of health care in a particular city or state reflects the true picture of the NGO. In some countries, Non Government Organisations are so prominent and strong that they have set examples for others. The first and foremost duty of a Thalassemia NGO IS to be to give significant attention on promoting patient health care in their city/state and country. They should make sure that they are part of the working groups and are in constant dialogue with concerned authorities. It is time now for all Thalassemia NGOs to play an important role in furthering the patients rights. Article 25 of the UNs declaration of Human Rights states Everyone has the right to standard of living adequate for the health and well being of himself and of his family, including food, clothing, housing and medical care. One should not forget that Thalassemia is not considered as a priority health issue in some of the countries. Till all affected thalassemia patients start receiving free medical care and a prevention programme is in place, all Thalassemia NGOs should work hand in hand. We stand by TIFs motto Unity is our strength.

Reference
1.

Patients Rights, TIFs publication, No-7.

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Beyond Odds ......The Audacity to live A Struggle against MEDICAL APARTHEID. & A Quest for Dignity..
Sukhsohit Singh

It is sometimes difficult to talk about some things, and even more difficult to keep silent upon. Our tireless striving and vehement voice may be scuffled, but our silence would equally be fatal and selfdefeating. Adversities have a way of bringing out the best in Individuals and the worst in Institutions. And the road blocks and challenges that individuals afflicted of Thalassaemia have confronted in Employment related issues, amongst others, are a testimony of this. There is something common between me, Bayan, Mohammad Rouhi, Bashir and Sanna from Jordan , and 31 others from China, despite our diverse nationalities, and besides our medical status of Thalassaemia, all of us and many others unreported have been victimized by a form of medical apartheid. A report by Arab Reporters for Investigative Journalism highlights that in Jordan Article 3 of Annex 3 of the Medical Committees Regulation stipulates that those who had their spleen removed as a result of a disease shall not be employed in the government sector. A report in China Daily highlights that in 2009, some 31 applicants were denied government department jobs because they are Thalassaemia gene carriers, on the pretext that Under the general physical examination standard of government departments employment issued in 2007, applicants will be denied the job if he or she develops anemia, a condition caused by various mineral and vitamin deficiencies, contrary to experts and lawyers arguments that Thalassaemia gene carriers should not be regarded as anemia patients. While in India, the medical examinations rule that there should be nothing in the physical examination of the candidate or perspective employee reflective of an impaired constitution: a clause which is often evoked and which becomes the basis for rejection of candidates on medical grounds. Such and many other archaic rules and laws and there equally arbitrary interpretations culminate into discrimination and exclusion in employment matters, a reflection of a heartless and anemic system that disregards merit, a system that paralysis rather than promote, cripples rather than support. Our constitution (as elsewhere) Article 21 provides us a fundamental right to a dignified living and personal liberty. Yet practice denies it all too often. The United Nations Convention on the rights of persons with Disability 2007 recognizes blood related disorders as a form of disability and urges the global community to act in unison to promote, protect and ensure the full and equal enjoyment of all human rights and fundamental freedoms by all persons with disabilities, and to promote respect for their inherent dignity, individual autonomy including the freedom to make ones own choices, and independence of persons; Non-discrimination; Full and effective participation and inclusion in society; Respect for difference and acceptance of all as part of human diversity and humanity; and provide Equality of opportunity. India which has ratified the convention is in the process of adopting all appropriate legislative, administrative and other measures for the implementation of rights recognized in the convention, in the form of the Rights of Persons with Disability Bill 2012. It is hoped that the bill will soon graduate into a legislation and tangible executive action.

http://arij.net/en/thalassemia-patients-seeking-jobs-fall-victim-outdated-health-rules http://www.chinadaily.com.cn/china/2010-01/14/content_9317740.htm

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The medical science today has progressed in significant ways both in dimensions and magnitude, improving the chance of survival and life. With new treatment modalities for Thalassaemia, it is no longer fatal disease, but a chronic disease which can be managed well, given the free access to quality health care. While the Science has progressed, the Society and polity also must reengineer and refurbish to keep in tandem with the developments of science. Archaic laws call for a serious rethinking. As For the individuals and my fellow thals my message for them is... Never to feel small or belittled by catastrophes.each of us has a spark and the zeal withinand our endeavour should be to turn that spark into fire. turn into reality our dreams and desire..and to empower yourself with skills and knowledge. Never to allow the disease to turn into dis-ease. To have the tenacity and the constant will to win. The words of the famous British Theoretical Physicist Stephen Hawking who has amyotrophic lateral sclerosis (ALS) seem to be befitting here: We have a moral duty to remove the barriers to participation for the people with special conditions and to invest sufficient funding and expertise to unlock their vast potentials. It is my hope this will mark a turning point for inclusion of these people in the lives of their societies.

39

My Life as a Thalassemic
Anubha

I guess it is early to explain how life has been with thalassemia for the simple reason that life is not over yet and I am nowhere close to its end. Life has not been easy though. My parents tell me that they had not even heard about thalassemia before I was diagnosed with it. That alone speaks volumes about the distance we have traveled as a community. As a three month getting pricked repeatedly, as a nine years old sleeping with a pump on the belly, as a sixteen years old dealing with hepatitis, or as a twenty nine years old going for night transfusion shifts in order to avoid missing courts in the morning my experience has been very enriching indeed. My parents fortnightly struggle for getting blood, their invincible desire to treat me with the best medicines, their regular visits to thalassemia clinics and labs these things have contributed immensely towards making me who I am. Just because my family never allowed me to turn thalassemia into an excuse or a license and provided me with the best treatment available, today I work as the Deputy Director of the Confederation of Indian Industry (CII) after gathering experience from the office of the Additional Solicitor General and the leading Public Relations agency. My present situation is a reassurance that with proper management, a thalassemic can lead an extraordinary life, leave alone normal life. However, as a lawyer it very difficult for me to ignore the other side of the coin and I am more inclined towards talking about the journey ahead. While I acknowledge and appreciate the distance we have traveled in terms of awareness, treatment and management due to the unflinching efforts of the medical community and NGOs like Thalassemics India, I cannot help realizing that we have a long way to go. My exposure to the global scenario through various conferences may have inspired me to actively participate in blood donation camps and workshops, but more needs to be done in addition to these stray efforts. More than ever before, its now that we need an organized advocacy programme to enforce our rights as patients. These days, it is almost fashion to talk about rights. However, it is important to know the nature of that which we are demanding. Therefore, when we, as a community demand rights for patients, we must know the nature of those rights. First and foremost, we must be clear in our heads that what we are demanding is something that we are entitled to and not something that the State may chose to grant in the exercise of its discretion. All of us must know that our rights are the rights of every human being - to live with dignity and grace, without being discriminated against. In a nutshell, it is the right to life that we are asking for. Right to life is a fundamental right under Article 21 of the Constitution of India. Right to life under Article 21 is something more than mere survival or animal existence. It is something more than breathing. The Supreme Court held in Francis Vs. Union Territory (AIR 1981 SC 746) that right to life would include the right to live with human dignity. With this interpretation given to Article 21, the door was made open for various kinds of rights which would have to be read into the Right to life with human dignity. Various decisions of the Supreme Court have now imposed positive obligations on the State to take various steps for ensuring enjoyment of life by an individual with dignity. Thus every condition that is conducive for leading a better life with human dignity is brought within the fold of Article 21. The State is now enjoined to fulfill these positive obligations. This leads us to the irresistible conclusion that when we, patients of thalassemia, expect the State to provide us with free treatment including blood, blood transfusion centers, proper medication, education and employment we are not asking for something that we are not entitled to, we are demanding something that the Constitution of this country provides for. Understanding what we need is not sufficient though. It is equally important to understand how to get what we need. This is where advocacy comes into picture. Advocacy is not only about advocating a point of view, it is about advocating the right message before the right audience to get the right relief. There is nothing that Thalassemia International Federation and Thalassemics India have not done,

40

together and individually, to fight thalassemia in terms of prevention and treatment. It is time to evolve. We have spent adequate time on what to get, it is now time to devise means to get what we need. We know that we need cleen blood, we know that we need special transfusion centers, we also know the importance of chelation agents, we know what we need to do to avoid involvement of vital organs, we know that we can and must receive education and we also know that we can and must be employed to earn our bread and butter. What must be understood now is that all the needs which have been identified for us fall very much within the States responsibility. These needs are actually our rights which require to be enforced through the non confrontational and collaborative forum of advocacy. Devising an ideal advocacy programme for enforcing the rights of thalassemics will involve identifying key stakeholders including the Government (decision maker) and the Media (influencer), developing appropriate messages to be communicated to the identified stakeholders to get the desired results in the form of formulation of National Policy by the Government for enforcing the rights of thalassemics and the dissemination of correct information in the right proportion and on the right occasions by the Media to influence the Government in favour of such enforcement. Our fight for our rights is similar to any fight for independence that history has ever witnessed whether it be the French Revolution or the Indian struggle for independence. All the well meaning struggles have had conscious strategic engagement programs as their foundations without calling them so. We also need to do exactly the same. Recognition of rights is not enough, it is important to enforce those rights through an appropriate and evolved engagement strategy. I urge Thalassemia International Federation and Thalassemics India to adopt a strategic advocacy programme to enforce the rights thalassemics as provided by the law of the land. I also urge my thalassemic friends sitting here to come forward and recognize their duty towards themselves and towards the society, to realize and understand that we have spent enough time on mourning our medical inadequacyit is time to ensure that our medical inadequacy does not turn into a social and psychological defectit is time to save ourselves and save the world so that we dont have to despise our souls the way Kahlil Gibran despised his in the following lines: Seven times have I despised my soul: The first time when I saw her being meek that she might attain height. The second time when I saw her limping before the crippled. The third time when she was given to chose between the hard and the easy, and she chose the easy. The fourth time when she committed a wrong, and comforted herself that others also commit wrong. The fifth time when she forbore for weakness, and attributed her patience to strength. The sixth time when she despised the ugliness of a face, and knew not that it was one of her own masks. And the seventh time when she sang a song of praise, and deemed it a virtue.

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Posters
Psychosocial Problems of Children with Thalassemia
Agnes Fabiola1, Janet Parameshwara2, Abin Kottaram3
1 2

Medico-Social Worker, Dept. of Medico-Social Work, St. Johns Medical College Hospital, Bangalore Chief Social Welfare Officer, Kidwai Memorial Institute of Oncology, Bangalore 3 Medico-Social Worker, Blood Bank, St. Johns Medical College Hospital, Bangalore

Background

Children with Thalassemia require repeated blood transfusion. Hence the children and the parents undergo tremendous stress over a period of time. To study the parents awareness about the disease, the adjustment pattern of the thalassemia children and the burden on families of the affected children. The study was descriptive in nature. Written informed consent was obtained from the participants before the study. Out of 180 children, 50 children with Thalassemia, without any other chronic illnesses who are on regular blood transfusions at St. Johns Medical College Hospital, Bangalore were selected through purposive sampling for the study according to inclusion criteria. Tools used: Pre-adolescent adjustment scale (Pareek et al 1970) and Burden Assessment Scale (Thara et al 1999). Statistical Analysis: descriptive statistics, chi-square test, student t test and one-way ANOVA, Correlation Analysis. The age of children ranged from 8 15 years and the male female ratio was 3:2. Mean age was 11+2 years. The majority were Hindus (84%), hailing from nuclear family (78%), having 2 siblings (60%), coming from rural background (58%). The 50% of parents had primary school education. 84% of the children were having positive home adjustment. But in the school environment, one-third(28%) of them had negative school adjustment, 40% of them had negative peer adjustments and 60% of them negative adjustment with school teachers. The high home adjustment indicates the involvement of the parents irrespective of the level of the education. However, the negative adjustments in the school may be the result of lack of awareness among the teachers and the general population about the disease. As a result of the study, the Medico-Social Workers of the hospital started support group for thalassemia children and their parents for the past one year. These meetings have helped the parents to talk about their challenges and ways of coping and they are able to express their needs and support one another when in distress; parents have become lay counsellors to the newly diagnosed childs parents and guide them. Social group work for children has resulted in the formation of Thalassemia society, Karnataka, thalassemia patients have become office bearers of the society and the parents take lead role in the activities of the society.

Aim

Materials & Methods

Results

Comment and Outcome

42

Deferasirox in Thalassemia: Three year experience

Mayank Dhamija, Manas Kalra, Amita Mahajan
Apollo Center for Advanced Pediatrics Indraprastha Apollo hospitals, Sarita Vihar, New Delhi

Background

The traditional therapy for iron overload in patients with Thalassemia has been overnight infusion of desferoxamine and/or oral deferiprone. Both options have significant limitations and compliance issues. Deferasirox is a new once-daily oral tridentate chelator that mobilizes iron stores by binding selectively to the ferric form of iron. It has now become the drug of choice for iron chelation in Thalassemics across the world. To document our experience with deferasirox with regards to 1) Safety, 2) Efficacy, and 3) Compliance. A prospective analysis of the records of 50 children started on deferasirox was done over a period of 36 months (April 2008- April 2011) Age > 2 years starting on deferasirox as first chelator or switching from other chelators due to effectivity, toxicity or compliance issues Age < 2 years; Baseline creatinine > 1.2 mg/dl; Baseline SGOT/SGPT > 160 IU/dl Doses recommended were 20-40 mg/kg/day, depending on initial S ferritin levels and ferritin trends thereafter. Three monthly evaluation of S. ferritin, SGOT, SGPT, S. creatinine, and Urine albumin were done. Drug was discontinued if S. creatinine > 1 mg/dl or SGOT/SGPT > 200IU/dl Most of the patients (76%) experienced a significant fall (> 500ng/ml) in their ferritin levels at the end of 36 months (p 0.001). Median serum ferritin level at the start was 3555 and that after 12, 24 and 36 months of therapy were 2810, 2079 and 2271 respectively. S. Ferritin continued to rise steadily in 10% (n=5) and in rest 14%, ferritin is either stable or has a decline of < 500ng/ml. Deferasirox was well tolerated at a dose of 40mg/kg/day. Rash was noted in three patients (6%), Nausea and Diarrhoea in two patients each (4%). Fourteen patients (28%) developed transaminitis which eventually settled in all but one patient, who required temporary discontinuation of drug. Transient elevation in serum creatinine was observed in eleven patients (22%), of which, three patient required temporary discontinuation of therapy. Albuminuria was not seen. No patient required permanent discontinuation of drug. All patients and parents reported improved compliance with this chelator. Deferasirox represents a new approach to the management of chronic iron overload in transfusion dependant patients. According to this early data, it appears to be well tolerated even in the doses of 40mg/kg/day. Ongoing follow-up is required to confirm efficacy and safety of this new drug.

Aims & Objectives Study Design

Inclusion Criteria

Exclusion Criteria

Materials and Methods

Results

Conclusions

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Growth Status in -thalassemia Major: Experience at a tertiary care centre

Prasanna Kumar K, Lincy Mathew, Anand Prakash, Fulton DSouza, Phadke K
Department of Pediatrics, St.Johns Medical College Hospital, St. Johns National Academy of Health Sciences, Bangalore, India

Introduction

Growth failure in -thalassemia major has been recognised for many years, and has persisted despite major therapeutic advances. The increasing mean survival of these children urges the need for appropriate intervention strategies to aid in the improvement of growth status. To assess the growth status of children with -thalassemia major and to determine the predictors of growth status in these children. A prospective study conducted over 12 mths duration in children with -thalassemia major at St. Johns Medical College Hospital, Bangalore. Results were analysed using SPSS software, version 17.0 for Windows. Sixty-one children were included in the analysis. Mean age was 83.7yrs; 57% males. Mean age at diagnosis was 5mths. Pubertal changes were seen in 3 boys and 7 girls. One girl child had attained menarche. All subjects showed growth retardation with advancing age. In children below 9yrs, 17% were stunted and 60% were underweight. In children after 9yrs of age, 58% were stunted and 92% were underweight. Between genders, growth retardation was more pronounced after the age of 9 yrs in boys and 12 yrs in girls. Follow up data revealed, poor increments in growth. Height velocity in children <9yrs was 3.31.6cm/yr; >9yrs was 0.50.4 cm/yr, p=<0.001. Moreover, height velocity in children with pre-transfusion Hb>9gm/dL was 3.92.4cm/yr and those with Hb<9gm/dL was1.10.3cm/yr, p=0.004. Height velocity showed significant correlation with pre-transfusion Hb (r 0.506, p <0.001), volume of transfusion (r 0.526, p <0.001) and serum ferritin (r -0.475, p <0.001). Pre-transfusion Hb (R 0.881, R2 0.776, p <0.001) emerged to be the single best predictor of height velocity. This study has shown that children with -thalassemia major experienced growth retardation above 9 yrs of age with pre-transfusion hemoglobin being the single best predictor of growth. Hence, good maintanence of pre-transfusion hemoglobin could improve the growth status in these children.

Objective

Methods

Results

Growth Status

Univariate Analysis

Multivariate Analysis

Conclusion

44

Screening Tools to Detect Psychosocial Problems in Children with Thalassemia

Anand Prakash, Navya C J, Somu V, Fulton DSouza, Vijaya Raman1
Dept. of Paediatrics and Child Psychology1, St Johns Medical College Hospital

Abstract

Children with chronic disorders like thalassemia and their care givers are known to face various psychosocial problems. We attempted to use screening tests to detect these psychosocial issues so that prompt referral for counseling is possible. A Semi-structured demographic questionnaire, Pediatric symptom Checklist (PSC -17) and the Strengths and Difficulties Questionnaire (SDQ) were administered to 30 children with beta-thalassemia major, on regular treatment at our hospital. The same questionnaires were administered to age and sex matched controls. Parents were administered the General Health Questionnaire (GHQ). Thalassemic children scored higher on both PSC-17 ( 9.93 vs 4.87; p < 0.001) and SDQ ( 14.9 vs 10.9; p = 0.008). The parents of thalassemic children scored higher on the GHQ. ( 10.3 vs 8.0 ; p = 0.027). Psychosocial morbidity is higher in thalassemics and their care-givers. Screening tools help detect children and care givers in need for formal counseling.

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Mutational Spectrum of Thalassaemia of Northern Part of Odisha

Nibarana Satapathy, Bisnu Prasad Dash
Department of Bioscience and Biotechnology, Fakir Mohan University, Balasore, Odisha, India

Prevention of thalassaemia requires knowledge for diagnosing the molecular analysis in the population at risk. This knowledge is particularly necessary when prevention control is applied to a multiethnic population. For this purpose, we are analyzing different populations from northern part of Odisha. During the study, we encountered about 98 patients from District Head Quarter Hospital of Mayurbhanj and Balasore district. Molecular analysis of gene mutation showed that population showing IVS I-5(G-> C), cd 41/42(-CTTT), cd 8/9(+G), IVS I-1(G->T), cd 15(G->A), cd 30(G->C) as well as 619 bp deletion. In most cases we find the IVS 1-5(G-> C) mutation and cd 41/42(-CTTT) mutation. The novel 619 bp deletion is the first report being analyzed in northern part of Odisha. Apart from this we are also doing their biochemical analysis (i.e. Cholesterol, Bilirubin, Sodium, Potassium, Total Protein, creatinine,Alkaline Phpsphatase and albumin)for proper diagnostic purpose.

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Comparison between Deferasirox and Deferiprone in Treating Iron Overloads in Thalassemics Children
Mahantesh Matti, Pooja Gujjal Chebbi, Nijaguna, Rajashekhar Murthy G.R., Govindaraj M.
Indira Gandhi Institute of Child Health, Bangalore

Objective

To compare the efficacy of oral iron chelators - Deferasirox and Deferiprone in reducing serum ferritin levels and to compare and to compare their side effect profile. Prospective stratified randomized comparative study. Conducted at Thalassemia Day Care centre of Indira Gandhi institute of Child Health. Bengaluru, a tertiary care centre, studied for 1 year 41 children were included in the study after informed consent. Thalasemia children with, -S.ferritin>1000mcg/l -children not on chelation Children who are already on chelation therapy. -Children with pre-existing renal or hepatic disease The 41 children were divided in to two groups Group-1 had 19 children who received Deferasirox and group-2 had 22 children who received Deferiprone. Three children in Deferiprone group dropped from study because of severe arthalgia. Group-1 received 20mg/kg/day once a day dose of Deferasirox and Group-2 received 75mg/kg/day thrice a day dose of Deferiprone for a period of one year, their laboratory parameters were followed up. We found both the groups comparable with respect to age group, number of transfusions before chelation and initial ferritin levels. At the end of study we found no statistical significant difference either the mean fall in S.ferritin levels and or alteration Absolute neutrophil count, s. Creatinine, and liver enzymes. Compliance was better in the Deferasirox group and side effects lesser. Though Deferasirox appears costlier, there was not much difference in annual cost for each drug. Both drugs are equally effective in reducing serum ferritin levels. No rise in ALT, S. creatinine observed in both groups. Side effects, especially joint pain was significant with Deferiprone. Compliance was better with Deferasirox. Needs further larger randomized control studies to improve the accuracy of results and to obtain statistical significance, if any. Thalassemia, iron overload, Ferritin, chelators, Deferasirox, Deferipron

Design

Setting

Participants

Inclusion Criteria

Exclusion Criteria

Intervention

Results

Conclusion

Key Words

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Effectiveness of Cascade Screening in Detection of Thalassemia Carriers and Prevention of Thalassemia

Mahantesh Matti, Pooja Gujjal Chebbi, Nijaguna, Rajashekhar Murthy G.R., Govindaraj M., Shivananda
Indira Gandhi Institute of Child Health, Bangalore

Introduction

Beta Thalassemia is one of the most common hemoglobinopathy inherited by autosomal recessive pattern. It has high prevalence in Karnataka. It is an economical, social and psychological burden to the patient, family and health care set up. Thalassemia is basically a preventable disease by screening the population at large, but unfortunately there is no screening protocol and it is not cost effective to screen general population.

Aims and Objectives

Assessing the effectiveness of cascade screening in identifying the Thalassemia carrier status. Place: Thalassemia day care centre at Indira Gandhi Institute of Child Health, Bangalore. Method: Cascade screening is a method in which the relatives of index case are screened for carrier state detection. In this study, second and third degree relatives (n=138) of 20beta-thalassemia major patients were chosen for the study, after informed written consent persons were screened for carrier status by Hb electrophoresis.

Materials and Method

Results

Index cases of TThalassemia:20 Second and third degree relatives of index case: 138 Thalassemia carrier state detected in : 55(40%) out of 138 Male: 28 Female: 27 3 pregnant women were carriers, CVS done showed 2 foetus were carriers, 1 as Thalassemia major and it was aborted. For every Thalassemia patient studied, there were about 3 thalassemia carriers which is significantly high. Carrier rate of Thalassemiais about 1-3% in south India. High incidence of consanguineous marriages, along with high carrier status leads to increased incidence of Thalassemia major patients. The screening test for general population to detect Thalassemia carrier status is not being done and is not cost effective and not feasible also. Screening the relatives of Thalassemia index case is important step in bringing down the incidence by offering genetic counseling and prenatal diagnosis. Any screening programme created around family and relatives of index case is highly yielding. Cascade screening of Thalassemia is very effective in identifying the carriers and yield is high which was 40% in our study. This is cost effective and feasible, plays vital role in detection of Thalassemia carrier status, and finally helps to bring down the incidence of Thalassemia major patients.

Discussion

Conclusion

48

Our Worthy Donors and Well Wishers

APO Pharma Inc. Cryobanks India Bio Rad Laboratories Ltd. Brindavan Agro Industries (P) Ltd. Mittal Appliances Ltd. Sandhya Arora N.N. Keshwani V.P. Ahuja

49

Forza Medi India Pvt. Ltd.

166, Sector-4, IMT Manesar Gurgaon-122050, Haryana Phone: 0124-4365151 / 53 Fax: 0124-4365156 Email: fmi@forzamedi.com Website: www.forzamedi.com Manufacturer & Exporter of Aluminium Wheel Chairs

50

Xpert MTB Test

A WHO endorsed Rapid, Cost effective, Confirmatory Molecular test for diagnosis of Tuberculosis and detection of Rifampicin Resistance

51

52

 CONSTRUCTION PILLING READY MIX CONCRETE EQUIPMENT HIRING

RV AKASH GANGA INFRASTRUCTURE LTD.

206, 1st Floor, A-6, LSC, D.D.A. Complex, Block A-6, Paschim Vihar New Delhi - 110 063 Phone: +91-11-41700000, Fax: 011-41700011 Email: info@rvag.in, Website: www.rvaginfrastructure.com
53

IS:15622:2006

CM/L 9829610

India-proof. Anti-abrasion tiles by Somany.

We know what oors go through here. That's why we make tiles with our patented VC Shield HardCoat technology. So you get India's most durable tile.

Available in 600x600mm & 800x800mm size.

Visit us at:

Delhi Date: 6-9 Dec.12 Hall No.14 Stand No. A12-A13-A5

Somany Ceramics Ltd. Marketing Offices: AHMEDABAD: 079-65419885 BANGALORE: 080-23575736 BHUBANESHWAR: 0674-3254333 CHANDIGARH: 0172-2791921 CHENNAI: 044-23452104/08 KOCHI: 0484-4041435/36 KOLKATA: 033-22485668/7406 MUMBAI: 022-40398300 NAGPUR: 0712-2286197/ 2286753 NOIDA: 0120-4627900 | Visit us: www.somanyceramics.com | E-mail: marketing@somanyceramics.com Mobile Nos.: North Zone: 9268575306, East Zone: 9238422001, West Zone: 9223171882, South Zone: 9282248050 For more information / feedback, kindly SMS SOMANY <Suggestions> / <Complaint> < Your Text> and send it to 56070 TOLL FREE NO. 1800-103-0004

Size - 7.25 x 10

54

An elegant, comfortable & sturdy range of Carpets, Chairs & Tables for Tents, Banquets & Hotels
designer

Runner (size 3 x 100 ft) AVS 301

Rectangular Banquet Table

100% wood, size 2.5' x 5'

Royal (size 6 x 18, 5 x 15 ft) AVS 302

Floral (size 6 x 18, 5 x 15 ft) AVS 304 Diamond (size 6 x 18, 5 x 15 ft) AVS 303

AVS 501

plain

ribbed

Our speciality: customised designs, sizes and colours can be developed as per theme

Banquet Chair Light AVS 112

High Back Chair AVS 114

AVS DECOR PVT. LTD.

33, Church Road, Jangpura Bhogal, (Near Janta Bakery), New Delhi-14 Ph : 24371091, Telefax : 24371091 M: 9811683054, 9811643110, 9810119323 E-mail: avsdecor@rediffmail.com Website: www.avsdecor.com

55

ISO

invites Micro, Small

MSME Global M

MSME Global mart (www.msmemart.com) is a new endeavor of the Co the country and connect them with the buyers and suppliers all over the to Business) and B2C (Business to Consumer) marketing activities. Major features of the portal are Interactive and sector specific large alerts, Self web development tool and other B2B facilities, Paymen trusted International sources, Online buying/selling, Multi product ca support, etc. MSMEs can join this portal and avail the services on payment of Rs 5,00 Platinum membership (Unlimited access) respectively. Visit www.msmemart.com and contact your nearest NSIC offices (loc registration & payment facilities are also available on web portal. Conta

NATIONAL SMALL INDUS

(A Govt. of India E

Tel: 011-26927059, 26920906 Email : info@n

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O 9001 : 2008

l & Medium Enterprises to Join

Mart Web Portal

orporation to facilitate Marketing Services effectively to MSMEs across e world. The new portal provides an online platform for B2B (Business

e databases of MSMEs, Online Global & National Tender notices and nt gateway for membership subscription, Global Trade leads from art, Multiple payment options, MSME's Web Store, Multiple language

00/- per annum for Gold membership and Rs. 10,000/- per annum for

cations available on website) for further details on Membership. Online act :

STRIES CORPORATION

Enterprise)

6, 26382032, 1800111955 nsic.com.in

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58

SPECIALIST IN Hi-CLASS THEME EVENTS CELEBRITY MANAGEMENT SPECIAL JAI MALA THEMES INNOVATIVE GROOM ENTRY INNOVATIVE BRIDE ENTRY A NEW CREATIONS STAGE SET - UPS

(a coplete event factory)

Jeetu : - +91-9810497966 +91-9873004943

Shop No. 1, Gulabi Bagh, Delhi - 110 007. Tel No. : - 011-2364666 email :- events.jk@gmail.com
59

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With Best Compliments

Your One Stop Shop For All Your Financial Needs Car Loans Housing Loans Loan against Property Commercial Vehicle Loans Construction Equipment Loans Machinery Loans for Small & Medium Enterprises

RVAG Centurion Infra Solutions Ltd.

211, First Floor, A-6 Block Local Shopping Complex Paschim Vihar, New Delhi 110063 Phone Nos. : 011 25280683, 25280684 Commercial Vehicle / Construction Equipment Loans: Mr. Puneet Kaushik, 9899466831 Car Loans: Mr. Vishal Sethi, 9971422060 & Mr. Pawan Kumar, 8527587853 rajivgilani@gmail.com 9810046831

63

With Best Compliments

From

Sri Mohan Khaitan Charitable Trust

Khaitan House, B-1, Defence Colony New Delhi - 110 024 Tel.: 011-46501000

Trustees O P Khaitan Rekha Khaitan Gautam Khaitan Ritu Khaitan

64

With Best Compliments

from Rossell India Ltd.

1st Floor, DCM Building 16, Barakhamba Road, New Delhi - 110 001 Tel.: 011-23713262

65

With Best Compliments

From

Orient Refractories Limited

Manufacturer and Exporter of Slide Gate and other Concast Refractories, Low Cement Castables etc. Tel: 91-11-46425400 Fax: 91-11-26443859 E-mail: bhiwadi@oalindia.com

Regd. Office: 1307, Chiranjiv Tower 43, Nehru Place, New Delhi - 110 019, India Work: SP - 148, Industrial Area, Bhiwadi, Dist. Alwar, Rajasthan

66

Your One-Stop-Shop
for
Complete range of Neonatal / Paediatric products, Phototherapy, Warmers, Inclubators, Ventilator, Apnea Monitor, Oxygen Analyser, Bilimeters, Osmometer, Pulse Oxymeter, Infusion Pump, Multiparameter Monitor, Disposable BP Cuffs, SpO2 Probe etc...

With Best Compliments

GLOBAL MEDICAL SYSTEMS

B- 1/34, GND Floor, Model Town-II Delhi - 110 009, India Phone: +91-11-27215547, 27441442 Fax: +91-11-27115021 Email: globalmedicalsystems@yahoo.com

67

68

With Best Compliments

From

A1 EQUIPMENTS PVT. LTD.

5/102, First Floor, Facility Centre, Phase - II Mayapuri, New Delhi - 110 064 Mob.: 9313939802 E-mail: a1_equipments@yahoo.com

69

With Best Compliments

from Deepee Scientific & Chemical Company

4140, Naya Bazar, Delhi - 110 006

70

With Best Compliments

from

Global Energy Pvt. Ltd.

71

72

sector 85

new gurgaon

73

With Best Compliments

from

UNITECH MACHINES
Sector - 44, Plot No. -35, Gurgaon

74

75

What would you like to gift your child on the What would you like to OR first birthday? gift your child on the first birthday?

A thalassemia major requires blood transfusions every 15 to 30 days starting from 6 months of life. The birth of a thalassemia major child can be prevented. Thalassemia is a genetic blood disorder inherited at birth by the child from its parents who are both thalassemia carriers/or minors. 3-4 in every 100 Indians are carriers of thalassemia. A person who is a thalassemia minor is normal and healthy. A thalassemia major requires blood transfusions every You could be one of them and may be unaware about it. 15 to 30 days starting from 6 months of life. When two Thalassemia minors marry, the couple could give birth The of a thalassemia major child can be prevented. to a birth thalassemia major child. A thalassemia major is requires blood transfusions every Thalassemia a genetic blood disorder at birth by by HPLC) inherited can establish whether a A specific blood test (HbA 2 15 to 30the days starting from 6 months of life. child from its parents who are both thalassemia person is a thalassemia minor or not. carriers/or minors. major child can be prevented. The birth of a thalassemia Thalassemia has no CURE!!! but it can be prevented by a simple 3-4 in 100blood Indians are carriers of thalassemia. blood test. Thalassemia is every a genetic disorder inherited at birth by the childA from its parents who are both thalassemia person who is a thalassemia minor is normal and healthy. carriers/or minors. You could be one of them and may be unaware about it. 3-4 in every 100 Indians are carriers of thalassemia. When two Thalassemia minors marry, the couple could give birth to a thalassemia major child. A person who is a thalassemia minor is normal and healthy. 2 be by HPLC) can establish whether a be A specific bloodand test may (HbA You could one of them unaware about it. 2 person is a thalassemia minor orcouple not. could give birth When two Thalassemia minors marry, the to a thalassemia major child. CURE!!! but it can be prevented by a simple Thalassemia has no blood test. A specific blood test (HbA2 by HPLC) can establish whether a person is a thalassemia minor or not.

OR OR

Ask for a Hb A test by HPLC today.

Thalassemia has no CURE!!! but it can be prevented by a simple blood test.

Ask for a Hb A2 test by HPLC today. Ask for a Hb A2 test by HPLC today.
76

Ultra Premium Residencies Golf Course Extension Road Sec. 62, Gurgaon

Authorised Channel Partner

Setia Homes Pvt Ltd

D-111, Golf Course, Extn. Road, Sushant Lok-II, Gurgaon-122 009 M : +91 95601 61333; Email : info@setiahomes.in; Web : www.setiahomes.in
77

Sardari Lal & Company

Wholesale Pipes, Valves & PIPE Fitting Dealers

3367, Hauz Qazi, Delhi - 110 006 Phones: 011-23272794, 23263384 Fax: 011-23255926 E-mail: sardari57@yahoo.co.in Website: productsunlimited.in Mob.: 9310006244

With Best Compliments from

78

With Best Compliments

from
Vikas Arora, Director

Shib dass & sons pvt. ltd.

4997-98, Hauz qazi, delhi-110006
Phone : 43748200 (30 Lines) 23212095, 23212097, 23210489 23214533, 23213823, 23215770 Fax : 23215048 E-mail : enquiry@shibdass.com Website : wwww.shibdass.com

Dharam Engineersing Company

G.T. Road, Batala - 143505 Telefax: 01871-242516
79

B.L. Hansraj & Sons

3649/8, Gali Rura Achar Wali, Chawri Bazar, Delhi-110 006 Ph.: (0) 23265156, 23278270 Fax: 23272617 Mob.: 9810235785, 9999062886 E-mail: blhrsklinger@gmail.com

Marck-Hawa & IVEE Valves

ISO 9002
Also MFG iBR PIPE Fitting

Authorised Distributors & Stockists

U L UNI Klinger Ltd.

Spiral Wound Gaskets Steam Jointing Sheets Boiler Gauge Glass Piston Valve, Traps, Stainers

EIL, Mecon, TDC, PDIL IOCL, BV, LLOYDS & Many others

Approved

Non Asbestos Gland Packing

Manufacturers: Gate, Globe, Check, Ball, Butterfly, Control Valves & Expansion Bellows (Manual, Pneumatic & Motorized) Specialist In Investment Casting Ball Values, MOC: Caststeel, Stainless Steel, Alloy Steel, Cast Iron

High Pressure Port Glass Kit

Sant
Gun Metal Valves & Cocks

Industrial Valves & Components

H-893, RIICO Industrial Area Phase - III, Bhiwadi (Raj.) Tel.: 011-23271450, 23252139 (F) 011-23281032 E-mail: ivc_val@yahoo.co.in
80

Borosil
Sight & Gauge Glasses

Vivek Arora, Director

Shib Dass Metal Pvt. Ltd.

Distributors for Jindal Stainless Ltd., Hisar Jindal Pipes Ltd., Ghaziabad Maharashtra Seamless Ltd., / Ismt Stockist of: STAINLESS STEEL SHEET, PLATE, COIL, PIPE & PIPE FITTING IN ALL GRADE & SPECIFICATION Head Office: 4996, Hauz Qazi, Delhi - 110 006 Ph. Off.: 23212097/95, 23215654, 55432144, Fax: 23233549 E-mail: sds_metal@yahoo.com Mob.: 9810014625 Bahadurgarh Off: 951276395459 Fax: 267440

Jai Khandelwal M. No.: +91-9311192688

Super Classic (India)

Distributor of: MISR AMERICAN CARPET MILLS, CAIRO(EGYPT) Wholesalers of:EXCLUSIVE BEDSHEETS, CURTAIN NET FABRICS, DOOR MATS, CARPET, CUSHION COVER & SHOWER CURATINS ALL FURNISHING ACCESSORIES ETC.

Show Room: 2724/23, Basement, Main Saraswati Marg, Karol Bagh, New Delhi - 110 005 (INDIA) Fax : 0091-11-28721799 : Tel No.: - 011-28721599,1699 email.: mobile09811192788@gmail.com

81

abc
Mobile : 9811222882

Ashok Kumar: - +91-9811096711

ABC Catering Service

Caterers of All Functions
20, Jawahar Market, Lancer Road, Mall Road, Delhi - 110009 Telefax: - +91-11-23813529 email: - abc_catering@yahoo.com

Tele (O) : 27674845 27671114

Pawan Chhabra

A XF ADARSH FRUITS
Fruit Merchants & Commision Agents
Off. : C-65, New Subzi Mandi, Azadpur, Delhi - 110033 Br. Off.: Ram Sheela, Akhara Bazar, Kullu (H.P.) Ph: 222434
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