and Treatment - Acute Lymphocytic Leukemia
fluid examination, X-ray chest and other test are required
to assess the extent of the disease and immunophenotyping of
B-precursor ALL: B-cell precursor (or B-lineage) ALL,
defined by the expression of CD19, HLA-DR, CD10 (cALLa), and
other B-cell associated antigens, represents 80% to 85% of
childhood ALL. Approximately 80% of B-precursor ALL express
the cALLa, CD10 antigen. The lack of cALLa expression has
also been shown in some series to be associated with a worse
prognosis. For example, CD10 negativity is observed in a
higher proportion of infants with B-precursor ALL and is
associated with poor outcome.
are 3 major subtypes of B-precursor ALL
pre-B (no surface or cytoplasmic immunoglobulin)-
Approximately 75% of patients with B-precursor ALL have
the early pre-B phenotype and have the best prognosis.
(presence of cytoplasmic immunoglobulin)- The leukemic
cells of patients with pre-B ALL contain cytoplasmic
immunoglobulin (cIg), an intermediate stage of B-cell
differentiation. Twenty-five percent of patients with
pre-B ALL have the t(1;19) translocation.
Approximately 3% of patients have transitional
pre-B ALL expression of surface immunoglobulin heavy
chain without light chain, without C-MYC gene
involvement or L3 morphology. Patients with this
phenotype respond well to therapy used for B-cell
(presence of surface immunoglobulin) - Approximately 2%
of patients present with B-cell ALL (surface Ig
expression, generally with FAB L3 morphology and C-MYC
gene translocation). B-cell ALL is a systemic
manifestation of Burkitt?s and Burkitt?s-like non-Hodgkin?s
lymphoma, and its treatment is completely different from
that for other forms of childhood ALL. Rare cases of ALL
that express surface Ig but lack C-MYC gene
translocations are appropriately treated as B-precursor
ALL rather than B-cell ALL.
T-cell ALL: T-ALL is defined by the leukemic cell
expression of the T-cell-associated antigens CD2, CD7, CD5,
or CD3. Approximately 12% of children with newly diagnosed
ALL have the T-cell phenotype.
clinical features for T-cell ALL include
appropriately intensive therapy, however, children with
T-cell ALL have an outcome similar to that for children with
Myeloid antigen expression: About 33% of childhood ALL
cases have leukemia cells that express myeloid-associated
surface antigens. There is no independent adverse prognostic
significance for myeloid-surface antigen expression.
of Acute Lymphocytic Leukemia:
Hyperdiploidy (>50 chromosomes per cell or DNA index
>1.16) is the presence of additional copies of whole
chromosomes and occurs in 20% to 25% of cases of
B-precursor ALL. Hyperdiploidy generally occurs in cases
with favorable prognostic factors and is itself
associated with favorable prognosis.
-Children with trisomies of chromosomes 4, 10 and 17
have better prognosis.
1% of children with ALL have leukemia cells showing
hypodiploidy with less than 45 chromosomes. These
patients are at high risk for treatment failure.
Philadelphia chromosome t(9;22) is present in
approximately 3% of pediatric ALL patients and confers
an unfavorable prognosis.
(t(12;21) cryptic translocation): is present in 20% to
25% of cases of B-precursor ALL. Patients with the
TEL-AML1 fusion have an excellent outcome.
involving the MLL (11q23) gene occur in approximately 8%
of childhood ALL cases, and are generally associated
with increased risk for treatment failure.
t(1;19) translocation occurs in 5% to 6% of childhood
ALL, and involves fusion of the E2A gene on chromosome
19 to the PBX1 gene on chromosome 1. Patients with this
translocation usually have a relatively inferior
for Acute lymphocytic leukemia :
treatment of children with ALL requires the control of
systemic disease (marrow, liver and spleen, lymph nodes,
etc.) as well as the treatment (or prevention) of
extramedullary disease particularly in the central nervous
system (CNS). Only 3% of patients have detectable CNS
involvement by conventional criteria at diagnosis (≥5
WBC/μL with lymphoblast cells present), however, unless
specific therapy is directed toward the CNS, 50% to 70% or
more of children will eventually develop overt CNS leukemia.
Therefore all children with ALL should receive systemic
combination chemotherapy together with some form of CNS
prophylaxis. At present, most groups treat patients with
documented CNS leukemia at diagnosis with intrathecal
therapy followed by cranial irradiation with or without
concurrent spinal radiation.
for children with ALL is divided into stages:
induction: Three-drug induction therapy using
vincristine, Prednisone/dexamethasone, plus L-asparaginase
in conjunction with intrathecal therapy (IT), results in
complete remission rates of greater than 95%. High risk
patients generally receive induction therapy that includes
an anthracycline (e.g., daunomycin) along with the other
sanctuary therapy generally provided in each stage -
Every patient with ALL receives intrathecal chemotherapy
with methotrexate alone or methotrexate with cytarabine plus
hydrocortisone. Children with ALL who present with CNS
disease at diagnosis (defined as ≥5 white cells/μL
in cerebral spinal fluid (CSF) with lymphoblasts present)
generally receive cranial radiation (1,200-1,800 cGy) in
addition to appropriate systemic and intrathecal
intensity of both induction therapy and postinduction
therapy is determined by the clinical and biologic
prognostic factors utilized for risk-based treatment
assignment and some type of early response assessment (day 7
and/or day 14 marrow blast percentage, day 7 peripheral
blood blast count, end induction minimal residual disease
burden as measured by polymerase chain reaction [PCR],
and/or flow cytometry). The average duration of maintenance
therapy for children with ALL ranges between 2 and 3 years.
Stem Cell Transplant
recently, blood stem cell transplants were known as bone
marrow transplants, because marrow was the only source of
blood stem cells used to treat diseases. The three sources
of stem cells now being used for transplants are marrow,
circulating blood (also known as peripheral blood) and
umbilical cord blood.
a blood stem cell transplant, the patient is first given a
pre-transplant treatment of chemotherapy and/or radiation
therapy to destroy the patient's leukemia cells and immune
system. Blood stem cells are then put into the patient's
blood to restore the patient's immune system and blood
are two types of blood stem cell transplants that can be
used to treat ALL patients:
blood stem cell transplants use the patient's own blood
blood stem cell transplants use the blood stem cells of
a donor, either someone from the patient's family or an
for Acute Lymphocytic Leukemia - 75% to 80% of children
with ALL attain remission and survive free of leukemia
recurrence at least 5 years from diagnosis with current
treatments that incorporate systemic therapy (e.g.,
combination chemotherapy) and specific central nervous
system (CNS) preventive therapy (i.e., intrathecal
chemotherapy with or without cranial irradiation).