Allogeneic but Not Autologous Stem Cell Transplant Attenuates the Negative Prognostic Impact Dictated By Pretransplant MRD Positivity

Multiparametric flow cytometry (MPFC) detection of minimal residual disease (MRD) represents a robust surrogate for the quality of complete remission (CR) and reliably predicts clinical outcome. In our experience, MRD detection provides prognostically relevant information when assessed at the post-consolidation time point. Ten years ago we demonstrated that the amount of MRD before autologous stem cell transplant (AuSCT) affected outcome. More recently, other authors have extended this observation to allogeneic stem cell transplant (ASCT) showing that pre-transplant MRD is a major determinant of prognosis regardless of graft-versus-leukemia (GVL) effect. The aim of our study was to evaluate, in an extended series of patients submitted to AuSCT or ASCT, the impact of a pre-transplantation MRD positive (MRD^pos) or negative (MRD^neg) status on overall survival (OS) and disease free survival (DFS). We analyzed 173 MRD^pos and 53 MRD^neg patients of whom 67 were submitted to AuSCT and 51 to ASCT. Eighty-two patients received no transplant because of age, poor performance status or insufficient stem cell harvest whereas 26, all in the MRD^pos group, relapsed before transplant delivery. In the AuSCT group, before transplant, 32/67 (48%) were MRD^neg and 35/67 (52%) MRD^pos, with MRD^neg group showing a superior OS (55% vs 20%, p=0.007). In the ASCT group, before transplant, 45/51 (88%) were MRD^pos and 6/51 (12%) MRD^neg. For 21 out of 51 (41%) sources of stem cells were matched unrelated donors (12) or haploidentical donors (9). In this subgroup, MRD^pos and MRD^neg patients shared a comparable 5-years OS (60% vs 56%, p=NS), with a 36% survival gain for those MRD^pos who received ASCT as compared to AuSCT. Among MRD^neg patients, no survival differences were demonstrated between those submitted to AuSCT or ASCT (55% vs 60%, p=NS). Such a lack of difference is likely due to the higher treatment related mortality (ASCT 3/6, 50% vs AuSCT 2/32, 6%, p=0.003) which counterbalanced the lower relapse rate in the ASCT group (ASCT 0/6, 0% vs AuSCT 11/32, 34%, p=NS). In conclusion, ASCT confers a significant survival advantage to MRD^pos patients, attenuating the negative prognostic impact of pre-transplant MRD positivity. ASCT may expose MRD^neg patients to an excess of toxicity suggesting that in these patients the allogeneic option should be postponed after a second remission. In MRD^pos patients, AuSCT does not represent a valid therapeutic choice and ASCT, which should be timely delivered, also considering alternative sources of stem cells.