Prognostic Value of Minimal Residual Disease Quantification Before Allogeneic Stem-Cell Transplantation in Relapsed Childhood Acute Lymphoblastic Leukemia: The ALL-REZ BFM Study Group

Abstract

MRD is an important predictor for post-transplantation outcome. As a result, new strategies with modified stem-cell transplantation procedures will be evaluated in ALL-BFM trials.

Impact of pretransplant minimal residual disease after cord blood transplantation for childhood acute lymphoblastic leukemia in remission: an Eurocord, PDWP–EBMT analysis

“…To this date, the impact of MRD before transplantation in childhood ALL has only been addressed in studies with a relatively small number of patients. 19,26,27 In this study, including 170 patients with a median follow-up of 4 years, we have shown that MRD before UCBT is a strong predictive Leukemia Free Survival Figure 2. The estimated 4-year probability of LFS in children with ALL in remission by MRD status before UCBT.…”

“…In fact, Bader et al 19 analyzed MRD by PCR in 91 children with ALL, finding that the 5-year event-free survival probability was 27% in those with a MRD value of 10 À 4 or more, compared with 60% in those with a MRD value of o10 À 4 . Others 27 reported 31 children with ALL in remission studied by MFC.…”

“…18 The impact of MRD evaluation performed before allogeneic, either related or unrelated hematopoietic stem cell transplantation has been reported in patients with ALL and acute myeloid leukemia and found to be associated with outcomes. 19,20 In order to verify whether MRD determination before the allograft has prognostic significance in patients given UCBT, we conducted a retrospective analysis on children with ALL transplanted from an unrelated cord blood donor and reported to the Eurocord registry.…”

Prognostic and therapeutic implications of minimal residual disease at the time of transplantation in acute leukemia

“…Nevertheless, these studies uniformly found excellent long-term outcomes for patients without detectable MRD (that is, 'MRD À ' patients) undergoing myeloablative AlloHCT, with 2-5 year estimates of EFS, relapse-free survival and OS often in the 70-80% range, and more recent series suggesting even better outcomes. [29][30][31][34][35][36][37][39][40][41][42][43][46][47][48][49] Almost without exception, the outcomes for patients with detectable MRD (that is, 'MRD þ ' patients) were significantly inferior, with long-term estimates of EFS of 0-30% and OS of 30-50%, respectively. Although data are more limited for AutoHCT, available information suggests that MRD À patients may have relatively good disease control that appears to approach that seen after AlloHCT, at least in the subset of leukemias that do not harbor the Philadelphia chromosome; on the other hand, MRD þ ALL patients experience exceedingly high rates of relapse after AutoHCT.…”

“…53,57,61,62 However, MRD appears to bear significance as an independent prognostic marker, as suggested by multivariate regression modeling in many of the studies. [27][28][29]36,37,39,[42][43][44][47][48][49]53,54,57,[59][60][61] The association between MRD and risk of BM relapse is likely 'dose-dependent' in ALL 27,28,36,37,41,42,44,47,63 and, possibly, AML, 53,54,60 while MRD assessments may fail to predict extramedullary relapse accurately. 32,45 Interestingly, evidence from logistic regression models suggests that the relative level of MRD has more impact on survival in ALL than in AML.…”