Precursor B-Cell Leukemia-Lymphoma
178 Part III • White Cell Disorders
In addition to immunophenotype, certain chromosomal alterations have been identified in B-ALL that are considered prognostically important (see Table 11-8). While these abnormalities are not as consistently associated as the Philadelphia chromosome seen in CML, they do provide additional information that can help to refine the treatment regimen. Two abnormalities that have been associated with a good prognosis are (1) hyperploidy greater than 50 and (2) t(12;21)(p13;q22). Other cytogenetic findings have been linked to a poor prognostic outcome (Table 11.10).
Precursor T Lymphoblastic Leukemia/ Lymphoblastic Lymphoma
Precursor T lymphoblastic leukemia/lymphoma is a malignancy of lymphoblasts with pre-T markers predominating in the bone marrow (T-ALL). When there is primary involvement of lymph nodes or extranodal sites, it is termed T lymphoblastic lymphoma. As in BALL, greater than 25% of bone marrow cells must be identified as lymphoblasts to meet the WHO definition of acute lymphoblastic leukemia; however, the bone marrow aspirate typically consists of almost entirely lymphoblasts at diagnosis. When the leukemic process is limited to a mass lesion and at least 25% lym-phoblasts are seen in the marrow, the designation lymphoma is used.19
T-ALL represents approximately 15% to 20% of all childhood ALL, is more prevalent in adolescents than young children, and is seen more frequently in males than females. T-ALL accounts for 25% of adult cases. T-lymphoblastic lymphoma (T-LBL) is the subtype of 85% to 90% of lymphoblastic lymphomas19 and is seen more frequently in males.
The bone marrow and blood will manifest blasts in all cases of T-ALL. Both T-ALL and T-LBL patients often present with large mediastinal or other tissue masses; other sites of involvement include lymph nodes, liver, spleen, skin, CNS, and gonads.
The leukocyte count may be quite high in precursor TALL (>100 X 109/L). The lymphoblasts often have L2 morphology, medium-size blasts with a moderate amount of cytoplasm and prominent nucleoli, occasional nuclear clefting; or, less frequently, have L1 morphology with smaller blasts, a high nucleus-to-cytoplasm ratio, scant cytoplasm, and indistinct cytoplasm. Sometimes, a mixture of both L1 and L2 morphology is observed in the same case (see Table 11.9 and Fig. 11.15). The number of mitotic blast cells is usually higher in T-ALL than in B-ALL.
Most precursor T-ALL malignancies have an immuno-phenotype that corresponds to an immature thymocyte
Table 11.10 O Prognostic Factors in Acute Lymphoblastic Leukemia
Risk Factors Favorable Unfavorable
Response to treatment CNS leukemia Immunophenotype Cytogenetic
<10 X 109/L <10 g/dL 2 to 9 years White Female <14 days Absent
Precursor B-cell Hyperploidy >50 t(12;21)(p13;q22)
>28 days Present
Precursor T-cell or mixed lineage Hypoploidy
Translocations, especially t(9;22)(q34;q11.2) t(1;19)(q23;p13.3) t(4;11)(q21;q23)
(prothymocyte) stage, originating in the bone marrow. The B-LBL or lymphoma phenotypes correspond to the more mature state of differentiation.49 The lym-phoblasts in T-ALL are TdT, cytoplasmic CD3 and CD7 positive, and variably express CD1, CD2, CD4, CD5, CD8, and CD10. Of interest is the fact that the myeloid-associated antigens CD13 and CD34 are often present, and this may still be consistent with the diagnosis of T-ALL/LBL (Fig. 11.16).
Reciprocal translocations of the T-cell receptor loci have been detected in about one-third of patients with T-ALL/LBL.19 These translocations arise from mistakes in the normal recombination mechanisms that generate antigen receptor genes. These cellular rearrangements that occur in T-ALL cases affect the proteins that have vital functions in cell proliferation, differentiation, or survival.50 The association of clinical findings, specific lymphoblast phenotype with particular chromosomal abnormalities has been shown to have prognostic significance. For a detailed discussion of the genes affected by chromosomal translocations in B-ALL and T-ALL, the reader is referred to Williams Hematology, 6th ed. Chapter 97, New York: McGraw-Hill, 2001.
In the pediatric age group, children with ALL have an overall complete remission rate of close to 95%; however, the disease-free, long-term response rate is about
Figure 11.16 T-lineage antigen expression. T-cell development originates with prothymocytes in the bone marrow. Further development takes place after these cells migrate to the thymus, where the maturation of the thymocyte can be classified, using specific CD markers, according to the various membrane antigens that are expressed.
Mature T-Cell (peripheral)
Mature T-Cell (peripheral)
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