Comparative analysis of total body irradiation (TBI)-based and non-TBI-based myeloablative conditioning for acute myeloid leukemia in remission with or without measurable residual disease

Abstract

Myeloablative allogeneic hematopoietic cell transplantation (HCT) is commonly used in adults with acute myeloid leukemia (AML) in morphologic remission [1, 2]. Numerous conditioning regimens are available for this purpose, some containing total body irradiation (TBI) [3]. Despite several prospective randomized trials and large retrospective analyses, the benefit of high-dose TBI (HD-TBI; TBI doses ≥12 Gy) remains controversial [4]. Moreover, whether the relative value of HD-TBIversus non-HD-TBI-based myeloablative conditioning differs depending on the pre-HCT measurable residual disease (MRD) status is unknown. These questions prompted us to compare outcomes among adults ≥18 years with AML (based on 2016 WHO criteria [5]) who underwent a first allogeneic transplant in first or second morphologic remission at our institution after myeloablative conditioning using peripheral blood or bone marrow as a stem cell source. We included all transplants between 4/2006, when a refined multiparameter flow cytometry (MFC)-based MRD assay was introduced, and 1/2019. Patients were treated on Institutional Review Board-approved research protocols or standard treatment protocols and gave consent in accordance with the Declaration of Helsinki. Follow-up was current as of April 29, 2019. We used the refined MRC/NCRI criteria [6] to assign cytogenetic risk. Three-tube, 10-color MFC was performed routinely on marrow aspirates before HCT as described [7–11]. MRD was identified as a cell population showing deviation from the normal patterns of antigen expression found on specific cell lineages at specific stages of maturation as compared with either normal or regenerating marrow. The assay detects MRD in the large majority of cases down to a level of 0.1% and in progressively smaller subsets of patients as the level of MRD decreases below that level. Any measurable level of MRD was considered MRD [7–11]. MRD-test results were available to transplant teams. Unadjusted probabilities of relapse-free survival (RFS) and overall survival (OS) were estimated using the These author contributed equally: Linde M. Morsink, Evandro D. Bezerra