Comparison of minimal residual disease as outcome predictor for AML patients in first complete remission undergoing myeloablative or nonmyeloablative allogeneic hematopoietic cell transplantation

Abstract

Minimal residual disease (MRD) is associated with adverse outcome in AML after myeloablative (MA) hematopoietic cell transplantation (HCT). We compared this association with that seen after nonmyeloablative (NMA) conditioning in 241 adults receiving NMA (n=86) or MA (n=155) HCT for AML in first remission with pre-HCT bone marrow aspirates assessed by flow cytometry. NMA patients were older and had more comorbidities and secondary leukemias. Three-year relapse estimates were 28% and 57% for MRDneg and MRDpos NMA patients, and 22% and 63% for MA patients. Three-year overall survival (OS) estimates were 48% and 41% for MRDneg and MRDpos NMA patients and 76% and 25% for MA patients. This similar OS after NMA conditioning was largely accounted for by higher non-relapse mortality (NRM) in MRDneg (30%) compared to MRDpos (10%) patients, whereas the reverse was found for MRDneg (7%) and MRDpos (23%) MA patients. A statistically significant difference between MA and NMA patients in the association of MRD with OS (P<0.001) and NRM (P=0.002) but not relapse (P=0.17) was confirmed. After adjustment, the risk of relapse was 4.51-times (P<0.001) higher for MRDpos patients. These data indicate that the negative impact of MRD on relapse risk is similar after NMA and MA conditioning.

Pre-transplantation minimal residual disease with cytogenetic and molecular diagnostic features improves risk stratification in acute myeloid leukemia

“…Our results were comparable to those recently reported showing that the presence of MRD determined by MFC increases the risk of relapse not only after myeloablative conditioning but also after reduced intensity conditioning regimens and it signifies a poor prognosis in addition to that conferred by other patient-and disease-related characteristics including cytogenetics. 27 Moreover, our results suggest that the impact of MRD at HCT on RI differs in distinct prognostic groups defined by using diagnostic cytogenetics and molecular findings.…”

Comparison of Intensive Chemotherapy and Hypomethylating Agents before Allogeneic Stem Cell Transplantation for Advanced Myelodysplastic Syndromes: A Study of the Myelodysplastic Syndrome Subcommittee of the Chronic Malignancies Working Party of the European Society for Blood and Marrow Transplant Research

“…A minimal pre-transplantation disease burden is considered important for posttransplantation outcomes [17,18], and the presence of more than 5% blasts at time of HSCT is reported to contribute to poor results [19]. Whether this reflects the pre-transplantation therapy or an inherent biological sensitivity that is more likely to result in favorable outcomes after HSCT remains uncertain.…”

Acute myeloid leukemia—Major progress over four decades and glimpses into the future

“…Today, all patients with AML in whom MRD is detected in CR should be considered for a change of therapy, for example, referral to allogeneic SCT; or consideration of investigational approaches including more intensified chemotherapy regimens, epigenetic-targeted therapies, other targeted therapies (e.g., CD123 or CD33 monoclonal antibodies), or immune therapies (e.g., checkpoint inhibitors), even among patients with MRD under consideration for allogeneic SCT [55].…”