Detection of abnormalities in B‐cell differentiation pattern is a useful tool to predict relapse in precursor‐B‐ALL

Abstract

Summary. Immunophenotypic investigation of minimal residual disease (MRD) has traditionally been based on the investigation of phenotypic aberrants at diagnosis to be used later as a target for MRD detection. This approach has several shortcomings (it is only applicable to patients with aberrant phenotypes, requires a diagnostic sample, and is patient-specific) and therefore a search for simpler alternatives is warranted. The present study is based on the hypothesis that in precursor-B-ALL patients the persistence of residual leukaemic cells may induce abnormalities in the precursor-B-cell compartment in bone marrow (BM) and these could be used as a criteria to predict relapse.These abnormalities may include: (1) the presence of an increase in the frequencies of immature B cells (CD34 þ / CD19 þ or CD20 ¹ /CD19 þ ) or (2) the existence of an altered B-cell differentiation pathway due to a blockade or to the presence of B cells outside the normal pathway. A total of 180 BM samples from 45 consecutive precursor-B-ALL patients who achieved morphological complete remission (CR) were analysed by multiparametric flow cytometry. Our results show that a significant increase in immature B-cell subsets or an altered B-cell differentiation predicts a high relapse rate (P < 0·01) and a shorter disease-free survival (P < 0·01). Moreover, abnormalities in either of these two criteria detected at specific time points during follow-up (end of induction, maintenance, or after treatment) were associated with a significantly shorter disease-free survival (P < 0·01).In summary, the investigation of abnormalities in B-cell differentiation is a relatively simple and cheap approach for predicting relapse in precursor-B-ALL patients.

Flow cytometric follow-up of minimal residual disease in bone marrow gives prognostic information in children with acute lymphoblastic leukemia

“…Moreover, studies of normal B cell precursor differentiation patterns in regenerating bone marrow may facilitate distinction between MRD and B cells regenerating after chemotherapy. 45 In some patients recurrences may develop even from very small populations present at diagnosis, which may be interpreted as the phenotype switch. This was the case with one of our T-ALL patients, who demonstrated AML phenotype at relapse and during follow-up did not show TdT/cyCD3 positive population but persisting small CD34 + /CD7 + /CD33(dim) population.…”

Immunophenotyping of acute leukemias and myelodysplastic syndromes

“…These studies provided a detailed definition of the exact sequence of expression of multiple antigens along the normal B-cell maturation pathways in the BM (34 -38). Accordingly, at present it is well accepted that the first B-cell associated antigens to be expressed after commitment of an early CD34ϩ hematopoietic precursor into the B-lymphoid lineage are CD22, CD10, and CD19 (on the cell membrane), nTdt, and cytoplasmic CD79a (cCD79a) (35)(36)(37)(38). Immediately after, the B-cell precursors sequentially start losing CD34 and nTdt, decrease CD10 expression, and display reactivity for CD20 (35)(36)(37).…”

Immunophenotypic analysis of hematogones (B-lymphocyte precursors) in 662 consecutive bone marrow specimens by 4-color flow cytometry

“…The reports of increased hematogones in specific diseases are mostly retrospective studies based on relatively small patient cohorts, lacking broad control populations. [3][4][5]9,13 Furthermore, in most flow cytometry studies hematogones have been reported as the percent of total lymphocytes or of B lymphocytes 8,17,26,[34][35][36] and in only a few reports as a percent of total events. 9,10,37 Finally, prior studies have not addressed the effects of the specimen-processing method and marrow involvement with neoplastic cells on the percentage of hematogones.…”