Conditioning Intensity, Pre-Transplant Flow Cytometric Measurable Residual Disease, and Outcome in Adults with Acute Myeloid Leukemia Undergoing Allogeneic Hematopoietic Cell Transplantation

Abstract

How conditioning intensity is related to outcomes of AML patients undergoing allografting in morphologic remission is an area of great ongoing interest. We studied 743 patients in morphologic remission and known pre-transplant measurable residual disease (MRD) status determined by multiparameter flow cytometry (MFC) who received a first allograft after myeloablative, reduced intensity, or nonmyeloablative conditioning (MAC, RIC, and NMA). Overall, relapse-free survival (RFS) and overall survival (OS) were longer after MAC than RIC or NMA conditioning, whereas relapse risks were not different. Among MRDpos patients, 3-year estimates of relapse risks and survival were similar across conditioning intensities. In contrast, among MRDneg patients, 3-year RFS and OS were longer for MAC (69% and 71%) than RIC (47% and 55%) and NMA conditioning (47% and 52%). Three-year relapse risks were lowest after MAC (18%) and highest after NMA conditioning (30%). Our data indicate an interaction between conditioning intensity, MFC-based pre-transplant MRD status, and outcome, with benefit of intensive conditioning primarily for patients transplanted in MRDneg remission. Differing from recent findings from other studies that indicated MAC is primarily beneficial for some or all patients with MRDpos pre-HCT status, our data suggest MAC should still be considered for MRDneg AML patients if tolerated.

Conditioning intensity and peritransplant flow cytometric MRD dynamics in adult AML

“…Data from 714 of the 810 patients in the final study cohort, including 264 patients examined for early post-HCT MRD clearance after MAC, have been partially reported. 7,[9][10][11][12][13][14][15][16][17] The HCT-specific comorbidity index was calculated as previously described. 18 Related or unrelated donors were selected by high-resolution HLA typing.…”

Dose intensity for conditioning in allogeneic hematopoietic cell transplantation: can we recommend “when and for whom” in 2021?

“…In light of these results that suggest benefits of more intensive conditioning primarily for some or all AML patients who were MRD-positive prior to HSCT, a recent analysis suggested that MAC should also be considered for MRD-negative AML patients if tolerated. 49 In an analysis of 287 patients with MDS, 50 of whom one quarter had >5% marrow blasts and more than a half were MRD-positive at HSCT, as determined by multiparameter flow cytometry and cytogenetics on marrow aspirates, it was found that the risk of overall mortality was higher with lower intensity retimens than with higher intensity regimens among the MRD-positive patients. On the other hand, MRD-negative patients had similar risks of mortality.…”

“…In light of these results that suggest benefits of more intensive conditioning primarily for some or all AML patients who were MRD-positive prior to HSCT, a recent analysis suggested that MAC should also be considered for MRD-negative AML patients if tolerated. 49 …”

Eradication of Measurable Residual Disease in AML: A Challenging Clinical Goal

“…More recently another study confirmed these results [83]. More currently, and in contrast with the above studies, the Fred Hutchinson Cancer Research Center reported that MAC determines longer RFS and OS but similar RR in comparison to RIC and NMA conditioning [84]. Importantly, in MRD+ patients, MAC determined RR and OS similar to RIC and NMA, whereas in MRD− patients, it determined a better clinical outcome in comparison to RIC and NMA (3-y OS and RFS 69% and 71% vs. 47% and 55% for RIC vs. 47% and 52% for NMA; 3-y RR 18% vs. 30% for RIC and NMA).…”