Risk Factors for Early Relapse after Allogeneic Hematopoietic Cell Transplantation in Acute Myeloid Leukemia

Abstract Background While allogeneic hematopoietic cell transplantation (alloHCT) can be curative for patients with acute myeloid leukemia (AML), relapse remains a significant challenge. Previous work has suggested that disease status at time of transplant and cytogenetics are important predictors of relapse. However, it is unclear if common somatic mutations or dimorphisms of MHC class I chain-related gene A (MICA), a ligand of the natural killer (NKG2D) receptor on immune effector cells that helps mediate NK cell alloreactivity, also contribute. Moreover, the mechanisms of early relapse are an area of ongoing investigation. We assessed risk factors for relapse within 6 and 12 months after alloHCT. Methods We conducted a single center, retrospective analysis of adults with AML who underwent a first alloHCT. Analysis was restricted to patients with T-cell replete HLA-8/8 matched related or unrelated donor. In addition to cytogenetic risk group stratification by European LeukemiaNet criteria (Dohner H, et al, Blood 2016), a subset of patients had a 36-gene somatic mutation panel assessed prior to alloHCT by next-generation sequencing. Dimorphisms at the MICA-129 position have previously been categorized as weaker (valine/valine: V/V), heterozygous (methionine/valine: M/V), or stronger (methionine/methionine: M/M) receptor binding affinity. Risk factors for early relapse were assessed with Fine and Gray competing risk regression with results as hazard ratios (HR) and 95% confidence intervals (CI). Results From 2000 - 2017, 319 adult AML patients were identified meeting inclusion criteria. Median age at transplant was 51 years (range, 18-74), with 95% Caucasian. The distribution of low, intermediate, and high HCT-CI scores was 28%, 28%, and 44%, respectively. 75% of patients were transplanted ≤12 months from diagnosis. Disease status at transplant included 48% in first complete remission (CR1), 19% in second CR (CR2), 33% in third CR or relapsed/refractory or untreated (collectively, In univariable analysis, non-Caucasian race, disease status Conclusion Relapse after alloHCT for AML remains a challenge. In our study, the strongest risk factors for early relapse after alloHCT remains absence of CR1 disease status at transplant and adverse-risk cytogenetics. We observed no prognostic effect of somatic mutations nor MICA dimorphisms prior to transplant on 6 or 12-month relapse post-transplant. Further interrogation of pre-transplant or post-transplant persistence of somatic mutations in a larger series may better risk stratify subjects who may benefit from more intensive or innovative approaches to prevent post-transplant relapse. Disclosures Nazha: MEI: Consultancy. Advani: Amgen: Research Funding; Pfizer: Honoraria, Research Funding; Novartis: Consultancy; Glycomimetics: Consultancy. Carraway: Novartis: Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees; Balaxa: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; FibroGen: Consultancy; Jazz: Speakers Bureau; Agios: Consultancy, Speakers Bureau. Gerds: Celgene: Consultancy; Apexx Oncology: Consultancy; Incyte: Consultancy; CTI Biopharma: Consultancy. Sekeres: Celgene: Membership on an entity's Board of Directors or advisory committees; Opsona: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Opsona: Membership on an entity's Board of Directors or advisory committees. Maciejewski: Apellis Pharmaceuticals: Consultancy; Alexion Pharmaceuticals, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Apellis Pharmaceuticals: Consultancy; Ra Pharmaceuticals, Inc: Consultancy; Ra Pharmaceuticals, Inc: Consultancy; Alexion Pharmaceuticals, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Majhail: Atara: Honoraria; Incyte: Honoraria; Anthem, Inc.: Consultancy.