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

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Abstract
Immunofluorescence stainings for the CD10 antigen and terminal deoxynucleotidyl transferase (TdT) can be used for 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 regeneration of CD10+, TdT+, and CD10+/TdT+ cells in BM of children with (CD10+) precursor-B-ALL during and after treatment according to three different treatment protocols of the Dutch Childhood Leukemia Study Group (DCLSG) which differed both in medication and time schedule. This study included a total of 634 BM samples from 46 patients who remained in continuous complete 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+ and CD10+/TdT+ frequencies generally below 1% of total BM cells, a 10-fold increase in precursor-B-cells was observed in protocol VII and protocol VIII, but not in protocol VI. At first sight this precursor-B-cell regeneration 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 protocols VII and VIII. However, careful evaluation of the distribution between the ‘more mature’ (CD10+/TdT−) and the ‘immature’ (CD10+/TdT+) precursor-B-cells revealed major differences between the post-induction/post-re-induction precursor-B-cell regeneration (low ‘mature/immature’ ratio: generally <1.0), the post-cns treatment regeneration (moderate ‘mature/immature’ 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 regeneration even from aplastic bm after induction treatment. moreover, differences 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 mistaken for a relapse.

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