IMMUNOPHENOTYPIC CHANGES BETWEEN DIAGNOSIS AND RELAPSE IN CHILDHOOD ACUTE LYMPHOBLASTIC-LEUKEMIA

To get more insight into the phenotypic changes of childhood acute lym phoblastic leukemia (ALL) at relapse, a detailed morphological and imm unophenotypic study in 40 childhood ALL cases (32 precursor B-ALL and 8 T-ALL) was performed. Expression patterns of non-lineage specific ma rkers (terminal deoxynucleotidyl transferase (TdT), CD34, and HLA-DR), B-lineage markers (CD10, CD19, CD20, and CD22), T-lineage markers (CD 1, CD2, CD3, CD4, CD5, CD7, and CD8), and cross-lineage myeloid marker s (CD14, CD15, and CD33) were compared at diagnosis and relapse. In ca se of low blast counts (less than or equal to 70%) at relapse, double labeling for membrane markers and TdT was used in order to define the precise immunophenotype of the TdT(+) leukemic cells. An immunological marker-shift was defined as either a conversion from positive to nega tive and vice versa or a difference in positivity of greater than or e qual to 50%. Morphological differences between diagnosis and relapse w ere detected in 34% of precursor B-ALL and 14% of T-ALL. Differences i n immunological marker expression were found in 72% of precursor B-ALL and in 75% of T-ALL, and generally concerned minor shifts with loss o r acquisition of a few markers. The morphological shifts and immunophe notypic shifts were not correlated. Immunophenotypic shifts were found for all markers tested in precursor B-ALL, except for HLA-DR. Shifts in CD10 expression (16% of cases) were only observed in relapses occur ring 30 months or more after diagnosis. In four precursor B-ALL an int ra-lineage shift was found at relapse (one common ALL to null ALL and three pre-B-ALL to common ALL or null ALL) and two precursor B-ALL cas es were diagnosed as acute non-lymphocytic leukemia at relapse based o n morphology and immunophenotype. In T-ALL, neither intra-lineage nor inter-lineage shifts were observed, although shifts were detected in a ll T cell markers tested, except for the lineage specific CD3 and T ce ll receptor (TcR) markers. In conclusion, immunophenotypic shifts at r elapse frequently occur in precursor B-ALL and T-ALL, in a small perce ntage leading to an intralineage shift (10%) or inter-lineage shift (5 %). Therefore immunophenotypic monitoring of minimal residual disease in ALL patients should be based on multiple marker combinations, prefe rably together with polymerase chain reaction analysis of rearranged i mmunoglobulin and/or TcR genes or chromosome aberrations.