Regeneration pattern of precursor-B-cells in bone marrow of acute lymphoblastic leukemia patients depends on the type of preceding chemotherapy

Immunofluorescence stainings for the CD10 antigen and terminal deoxynucleot idyl transferase (TdT) can be used far the detection of leukemic blasts in CD10(+) precursor-B-acute lymphoblastic leukemia (precursor-B-ALL) patients , but can also provide insight into the regeneration of normal precursor-B- cells in bone marrow (BM). Over a period of 15 years, we studied the regene ration of CD10(+), TdT(+), and CD10(+)/TdT(+) cells in BM of children with (CD10(+)) precursor-B-ALL during and after treatment according to three dif ferent treatment protocols of the Dutch Childhood Leukemia Study Group (DCL SG) which differed both in medication and time schedule. This study include d a total of 634 BM samples from 46 patients who remained in continuous com plete remission (CCR) after treatment according to DCLSG protocols VI (1984 -1988; n = 8), VII (1988-1991; n = 10) and VIII (1991-1997; n = 28). After the cytomorphologically defined state of complete remission with CD10(+) an d CD10(+)/TdT(+) frequencies generally below 1% of total BM cells, a 10-fol d increase in precursor-B-cells was observed in protocol VII and protocol V III, but not in protocol VI. At first sight this precursor-B-cell regenerat ion during treatment resembled the massive regeneration of the precursor-B- cell compartment after maintenance treatment, and appeared to be related to the post-induction or post-central nervous system (CNS) therapy stops in p rotocols VII and VIII. However, careful evaluation of the distribution betw een the 'more mature' (CD10(+)/TdT(-)) and the 'immature' (CD10(+)/TdT(+)) precursor-B-cells revealed major differences between the post-induction/pos t-re-induction precursor-a-cell regeneration (low 'mature/immature' ratio: generally <1.0), the post-CNS treatment regeneration (moderate 'mature/imma ture' ratio: 1.2-2.8), and the post-maintenance regeneration (high 'mature/ immature' ratio: 5.7-7.6). We conclude that a therapy stop of approximately 2 weeks is already sufficient to induce significant precursor-B-cell regen eration even from aplastic BM after induction treatment. Moreover, differen ces in precursor-B-cell regeneration patterns are related to the intensity of the preceding treatment block, with lower 'mature/immature' ratios after the highly intensive treatment blocks. This information is essential for a correct interpretation of flow cytometric immunophenotyping results of BM samples during follow-up of leukemia patients. Particularly in precursor-B- ALL patients, regeneration of normal precursor-B-cells should not be mistak en for a relapse.