Dx & Mx of

CML
Diagnosis :
FBP
NAP score
+- BMA
Cytogenetic study
Biochemical parameters (done for pt mx)
Diagnosis :
1)FBP (chronic phase):
Leucocyte count at dx usually btw 50-
200x10
9
/l
full spectrum of cells in granulocytes series,
ranging from blast-neutrophils-myelocytes.
If blast count >12% may be pt in
acceleration / transformed phase
Diagnosis :
1)FBP (chronic phase):
increased in basophils & eosinophils.
platelet also usually increased 300-
600x10
9
/l
occ NRBC may be present.

FBP-increased leucocytes including immature
granulocytes, basophils & occ blast.

Diagnosis :
1)FBP (advanced phase):
the picture is variable
blast may be increased disproportionately.
platelet is greatly increased >1000x10
9
/l @
reduced < 100x10
9
/l

FBP of CML pt with lymphoid blast
transformation.

Diagnosis:
2)NAP score:
normal value:-
in CML:- low value
alkaline phosphatase content of neutrophils
cytoplasm is diminished @ absent.
Diagnosis:
3)BMA (chronic phase):
- not necessary to confirm the dx of CML.
- However it is carried out to assess the degree
of fibrosis and to exclude transformation.
- BMA- hypercellular fragments & the trails
composition resembling the CML blood
picture.







Diagnosis:
3)BMA (chronic phase):
- blast is around 2-10%
- Prominent eosinophils & basophils
mega are small, hypolobulated & numerous
- Reticulin may be normal / increased.






BMA:showing granulocytic hyperplasia, mega with
hypolobulated nuclei.

Trephine-granulocytic hyperplasia.

Diagnosis:
3)BMA (advanced phases):
- increased number of blast cells / increased
fibrosis.
- Transformation phase is define as blast >
30%
- 70% of pt have myeloid blast
- 20% have lymphoid blast
- 10% have mixed myeloid & lymphoid blast.
Diagnosis:
4) Cytogenetics study:
To detect Ph chromosome, t(9;22) @ bcr-abl
gene.


5)biochemical parameters:
Non specific
Serum uric acid- slightly raised
Sr alkaline phosphatase- N/slightly raised
LDH- raised
Potassium- spurious raised dt intracellular
leakage
B12 & B12 binding capacity-
dttranscobalamine 1.
5)biochemical parameters:
Transformation phase-
uric acid
LFT are abnormal
Hypercalcaemia dt bone destruction
Management of CML:
Chronic phase:
Alpha interferon
Hydroxyurea
Busulphan
BMT
STI 571
Advanced phase.
1) Alpha interferon:
Glycoprotein family with antiviral &
antiproliferative properties.
It will reduce the leucocyte count &
reversing the features of CML in 70-80%
of pt.
5-15% of pt will sustained reduction in Ph
positive marrow metaphase.
1) Alpha interferon:
It has two imp effect:
It identifies the haematological & cytogenetic
response subgp of people who will survive
longer than the others.
Prolongs the survival by 1-2 years in majority
of pt.
1) Alpha interferon:
IFN should be offered to all newly dx pt
who are not candidates for BMT.
SE:
Fever, ms aches, flu like features, lethargy,
malaise, anorexia, LOW, depression &
alopecia.
2) Hydroxyurea.
Ribonucleotide reductase inhibitors.
Targets mature myeloid progenitors in
proliferative phase.
Pharmaco action is rapid & reversible.
Started with 1-2g/d y mouth & cont
indefinitely.

2) Hydroxyurea.
Leococyte count starts to fall within days &
spleen reduces in size.
Within 4-8wks, features of CML is being
reversing.
Has relative few SE:
Nausea, diarrhea, buccal mucosa ulcer &
other GIT sx.
3) Busulphan.
Polyfunctional alkylating agent.
Targets primitive stem cell.
The dosage should be reduced/ stop before
leucocyte count fall below20x10
9
/l because
it can cause profound leucopenia.
Gonadal failure invariably occur within a
year & almost irreversible.
3) Busulphan.
Other SE:
Cutaneous pigmentation, pulmonary fibrosis
& wasting syndrome.
This drug is useful in older pt & also a major
component of some conditioning regime
before BMT.
4) BMT
Younger pt with HLA identical sibling
should be offered allogeneic BMT.
Pt are condition with cyclophosphamide
followed by total body irradiation/ with
combination of busulphan & cyclo
infusion of donor marrow reasonable
marrow fx is achieved 3-4 wks later.

4) BMT
SE:
GVHD.
Reactivation of infection with CMV
Idiophatic pneumonitis
Veno occlusive dz of the liver.




4) BMT
5 yr leukaemia free survival is 60-70%.
20% chance of transplant related mortality
15% chance of relapse.
About 10-30% of allogeneic BMT pt
relapse within 1
st
3 years insidious &
characterized by rising levels of BCR-ABL
, then by rising Ph-positive marrow and
haemato features of CML.

5) STI571- Gleevec
Antiproliferative agent, discovered by Dr.
Brian Druker.
Called as signal transduction inhibitors
(STI) which interfere with the pathway that
signal the growth of tumour cells.
Is targeted to the specific biochem abn
found predominantly in CML.

5) STI571- Gleevec
Claimed to be less Se tan other cytotoxic
drugs.
It is in a pill form
Also effective against GI stroma tumour.
Mx in advanced phase dz.
The tx is to prolong their life but cure is no hope.
If pt has myeloid transformation, he can be
treated with with drugs appropriate to the
induction of AML daunorubicin, cytosine
arabinoside with or without 6-thioguanine or
etoposide.
Blast cell will reduce substantially but increased
again within 3-6 wks.
Mx in advanced phase dz.
Pt in lymphoid transformation is treated
with drugs applicable to the tx of adult
ALL- prednisolone, vincristine &
danourubicin with or without L-aspara.
Pt who achieve 2
nd
chronic phase should
received neuroprophylaxis with intrathecal
methotrexate.
Variants of CML.
Ph negative CML
Chronic myelomonocytic leukaemia.
Juvenile CML
Eosiniphilic leukaemia.
1) Ph-negative CML.
About 5% of CML pt lack of Ph chromo.
There are 2 types of pt:
BCR-ABL gene
No BCR-ABL gene
Pt with BCR-ABL gene- that is molecularly
identical to the BCR-ABL gene of Ph positive
CML.
The gene morphologically normal on chromo 22
but can be found on chromo 9.







1) Ph-negative CML.
Such pt have clinical course similar to those
with Ph positive dz.
Pt with no BCR-ABL gene have haemato
features different from Ph positive dz.
This pt lack of basophilia, lack of blast &
myelocyte peaks in the differential
count/show dysplastic features.
They respond poorly to IFN/hydroxyurea &
survival poorer than Ph positive CML.




2) Chronic myelomonocytic
leukaemia
Rare condition affecting elderly man.
CF- anemia, haemorrhage with splenomegaly.
No Ph chromosome.
FBP- prominent monocytosis (50x10
9
/l), absent
basophilia & eosinophilia, dysplastic features in
granulocyte & erythroid series.
This dz is included in MDS classification.

3)Juvenile CML.
Rare dz affecting children below 12 y/o
CF- anemia, lymphadenopathy,
hepatosplenomegaly with variety of skin
rashes.
FBP- increased in leukocyte with variable
blast cells.
BM- hypercellular but lack of chromo abn.
Respond poorly to cytotoxic drugs.
4)Eosinophilic leukaemia.
It consist predominantly eosinophils.
Must be distinguish from reactive eosinophils.
CF- anemia, hepatosplenomegaly tissue
damage(myocardium) dt release of eosinophils
content.
FBP-eosinophils,neutrophils / monocytes.
Eosinophils can be abn such as degranulation,
cytoplasmic vacuolation, hypolobulation /
hyperlobulation.


BMA-increased in eosinophils & some with
abnormal nuclear shape with several blast cells.

Thank you