Minimal residual disease detection in childhood precursor–B-cell acute lymphoblastic leukemia: relation to other risk factors. A Children's Oncology Group study

Abstract

Minimal residual disease (MRD) can be detected in the marrows of children undergoing chemotherapy either by flow cytometry or polymerase chain reaction. In this study, we used four-color flow cytometry to detect MRD in 1016 children undergoing therapy on Children's Oncology Group therapeutic protocols for precursor-B-cell ALL. Compliance was excellent, with follow-up samples received at the end of induction on nearly 95% of cases; sensitivity of detection at this time point was at least 1/10,000 in more than 90% of cases. Overall, 28.6% of patients had detectable MRD at the end of induction. Patients with M3 marrows at day 8 were much more likely to be MRD positive (MRD+) than those with M2 or M1 marrows. Different genetically defined groups of patients varied in their prevalence of MRD. Specifically, almost all patients with BCR-ABL had high levels of end-of-induction MRD. Only 8.4% of patients with TEL-AML1 were MRD+40.01% compared with 20.3% of patients with trisomies of chromosomes 4 and 10. Our results show that MRD correlates with conventional measures of slow early response. However, the high frequency of MRD positivity in favorable trisomy patients suggests that the clinical significance of MRD positivity at the end of induction may not be the same in all patient groups.

Minimal residual disease (MRD) analysis in the non-MRD-based ALL IC-BFM 2002 protocol for childhood ALL: is it possible to avoid MRD testing?

“…With regard to this, it is not surprising that the proportion of M1 and M2 marrows in the Children's Oncology Group study is significantly higher. 29 In our study, BCP-ALL patients with M3 BM d8 were more likely to be MRD positive at both d33 and w12. This trend was even preserved in SRG.…”

Comparative analysis of minimal residual disease detection using four-color flow cytometry, consensus IgH-PCR, and quantitative IgH PCR in CLL after allogeneic and autologous stem cell transplantation

“…In accordance with the literature on MRD in acute leukemias, [34][35][36][37] we defined that at least 20 CLL cells forming a population in light scatter were required as evidence for MRD (absolute specificity threshold). In addition, a sample was judged as MRD positive only if the CLL cell number exceeded the relative specificity threshold.…”

“…38 In accordance with reports on MRD flow for acute leukemias, we defined 20 events as absolute specificity threshold. [34][35][36][37] A second prerequisite for specific MRD detection is that the number MRD-positive cells is higher than the expected number of false positive events per 100 000 leukocytes analyzed (relative specificity threshold). The relative specificity threshold is particularly dependent on debris and unspecific antibody binding.…”

Bone marrow minimal disseminated disease (MDD) and minimal residual disease (MRD) in childhood T‐cell lymphoblastic lymphoma stage III, detected by flow cytometry (FC) and real‐time quantitative polymerase chain reaction (RQ‐PCR)

“…Early treatment response, expressed by levels of minimal residual disease (MRD) in bone marrow (BM)/peripheral blood (PBL), has proven to be a powerful predictor of treatment outcome [18][19][20][21][22][23][24] and was introduced to recent ALL treatment protocols for risk-group stratification [24,25]. The sensitive and specific methodologies used are real-time quantitative polymerase chain reaction (RQ-PCR) for evaluating clonal immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangements [26][27][28][29][30][31][32][33][34] and multiparameter Flow Cytometry (FC) for tracing the leukemic-specific immunophenotype [35][36][37][38][39].…”