ALL

DEFINITION
Acute lymphoblastic leukemia (ALL) is a malignant
(clonal) disease of the bone marrow in which early
lymphoid precursors proliferate and replace the normal
hematopoietic cells of the marrow:

Acute lymphoblastic leukemia (ALL) may be

distinguished from other malignant lymphoid
disorders by the:
immunophenotype of the cells, which is
similar to B- or T-precursor cells.

Immunochemistry,

cytochemistry, and

cytogenetic markers may also aid in

categorizing the malignant lymphoid clone.

Bone marrow aspiration and biopsy

Aspiration slides should be stained for morphology with either Wright or Giemsa stain.
The diagnosis of acute lymphoblastic leukemia (ALL) is made when at least 20%
lymphoblasts (World Health Organization [WHO] classification) are present in the bone
marrow and/or peripheral blood.

In addition, slides should be stained with myeloperoxidase (or Sudan black) and terminal
deoxynucleotidyl transferase (TdT), unless another method is used, such as flow
cytometry.

Bone marrow samples should also be sent for cytogenetics and flow cytometry.
Approximately 15% of patients with acute lymphoblastic leukemia (ALL) have a t(9;22)
translocation (ie, Philadelphia [Ph] chromosome), but other chromosomal abnormalities
may also occur, such as t(4;11), t(2;8), and t(8;14).
A negative myeloperoxidase stain and a positive
TdT is the hallmark of the diagnosis of most
cases of acute lymphoblastic leukemia (ALL).

-flow cytometric demonstration of lymphoid

antigens: CD3 (T-lineage ALL) or CD19 (B-lineage
ALL

Studies for bcr-abl analysis by polymerase chain

reaction (PCR) or cytogenetics may help
distinguish patients with Philadelphia
chromosome–positive ALL from those with the
lymphoid blastic phase of chronic myelogenous
leukemia (CML). Most patients with Ph+ ALL
have the p190 type of bcr-abl, whereas patients
with lymphoid blastic CML have the p210 type of
bcr-abl.

L1 – Small cells with homogeneous chromatin, regular

nuclear shape, small or absent nucleolus, and scanty
cytoplasm; subtype represents 25-30% of adult
cases
L2 – Large and heterogeneous cells,
heterogeneous chromatin, irregular nuclear
shape, and nucleolus often large; subtype
represents 70% of cases (most common)
L3 – Large and homogeneous cells with multiple
nucleoli, moderate deep blue cytoplasm, and
cytoplasmic vacuolization that often overlies
the nucleus (most prominent feature); subtype
represents 1-2% of adult cases

Cytogenetic abnormalities occur in approximately 70% of cases of acute lymphoblastic

LEUKEMIA.
L-1
L-2
L-3
Induction therapy

Standard induction therapy typically involves either a 4-drug regimen of

vincristine, prednisone, anthracycline, and
cyclophosphamide/AND/ or L -asparaginase or

Using this approach, complete remissions (CRs)

are obtained in 65-85% of patients. The rapidity
with which a patient's disease enters CR is
correlated with treatment outcome.

Consolidation therapy
Because most studies have showed a benefit to consolidation therapy, regimens using a
standard 4- to 5-drug induction usually include consolidation therapy with Ara-C
in combination with an anthracycline or
epipodophyllotoxin.

Maintenance therapy
-daunorubicin or mitoxantrone, vincristine, prednisone, and methotrexate induction
followed by 4 intensifications

CNS prophylaxis
In contrast to patients with AML, patients with acute lymphoblastic leukemia (ALL)
frequently have meningeal leukemia at the time of relapse. A minority of patients have
meningeal disease at the time of initial diagnosis.
-early intrathecal chemotherapy is necessary to achieve the lowest risk of CNS relapse.
Newer approaches

-Burkitt ALL cells are CD20 positive. This allows for the addition of targeted therapy
with rituximab.

-Treatment of Philadelphia chromosome–positive ALL

The addition of imatinib to chemotherapy has resulted in significantly improved
outcomes.
Transplantation
-matched related allogeneic transplantations for acute lymphoblastic leukemia (ALL) in
first complete CR provide the most potent antileukemic therapy and considerable survival
benefit for standard-risk patients.
However, the transplantation-related mortality for high-
risk older patients was unacceptably high and abrogated
the reduction in relapse risk.

most authorities agree that allogeneic transplantation

should be offered to young patients with high-risk
features whose disease is in first remission.

Young patients without adverse features should receive

induction, consolidation, and maintenance therapy.

In these patients, transplantation is

reserved for relapse.
Older patients whose disease is in CR may be considered for such investigational