Thrombocytopenia.
WBC is usually elevated, with lymphocytosis and neutropenia, but approximately 50% of children have WBC counts <10,000 at presentation.
Lymphoblasts are usually identified on the peripheral blood smear (PBS).
Bone marrow generally shows >50% lymphoblasts. It should be obtained before starting therapy to determine immunophenotype, cytogenetics, and overall cellularity. Peripheral blood may be sufficient for these studies in cases with high peripheral blood blast count. Once the diagnosis of leukemia is confirmed, definitive assignment to the subtype of B-ALL, as provided by immunophenotyping and cytogenetic studies, is mandatory before deciding on therapeutic protocol.
Immunophenotype
Seventy percent to 80% of childhood ALL are of the B-precursor lineage. The expression of markers on the leukemic lymphoblasts does not correlate strictly with normal lymphoid maturation. B-ALL lymphoblasts are positive for CD19; cytoplasmic CD79a; and cytoplasmic and surface CD22, CD24, PAX5, and TdT. The expression of CD34, CD10 (CALLA antigen), and CD20 is variable. Myeloid markers CD13 and CD33 may also be present. The aberrant immunophenotype serves to identify minimum residual disease in the bone marrow following therapy.
A simple classification is offered below
:
Mature B-cell phenotype (1–2% of cases in children and 5% in adults). Surface monoclonal immunoglobulins. Indistinguishable from Burkitt lymphoma.
B-progenitor ALL present in 80–85% of childhood B-ALL. Eighty to 90% express CD10. The majority have an immunoglobulin gene rearrangement, predominantly involving the IgH gene. Different subsets are based on various cell markers: pro-B ALL (CD10−, no cytoplasmic Ig [cIg]), early pre-B ALL (CD10+, but no cIg), and pre-B ALL (CD10+, cIg positive). The prognosis among these various forms of immature B-ALL depends mostly on their genetic etiology as reflected in karyotypes or by interphase FISH (see below).
Cytogenetic/Genetic Analysis
In addition to immunophenotype, cytogenetic and molecular genetic abnormalities are used in the prognostic evaluation and therapy of B-ALL. Both numerical and structural abnormalities of the chromosomes are associated with prognosis and influence treatment.
t(9;22)(q34;q11.2); BCR-ABL (the Ph chromosome) is present in ≤25% of adults and 3% of children. Its presence denotes poor prognosis in B-ALL patients, but patients may respond to tyrosine kinase inhibitors.
t(12;21)(p13;q22); tETV6-RUNX1: favorable prognosis.
t(1;19)(q23;p13.3); E2A-PBX1 intermediate to poor prognosis.
MLL (11q23) rearrangements, most commonly t(4;11)(q21;q23) with AFF1(AF4)/MLL and t(11;19)(q23;p13.3) with (MLL; MLLT1(ENL); poor prognosis.
