Impact of Pre-Transplant Measurable Residual Disease on Outcome of Allogeneic Hematopoietic Cell Transplantation in Adult Monosomal Karyotype AML

Allogeneic hematopoietic cell transplantation (HCT) is often unsuccessful for monosomal karyotype (MK) acute myeloid leukemia (AML). To what degree failures are associated with pre-transplant measurable residual disease (MRD) – a dominant adverse risk factor – is unknown. We therefore studied 606 adults with intermediate- or adverse-risk AML in morphologic remission who underwent allogeneic HCT between 4/2006 and 1/2019. Sixty-eight (11%) patients had MK AML, the majority of whom with complex cytogenetics. Before HCT, MK AML patients more often tested MRD(pos) by multiparameter flow cytometry (49% vs. 18%; P<0.001) and more likely had persistent cytogenetic abnormalities (44% vs. 13%; P<0.001) than non-MK AML patients. Three-year relapse/overall survival estimates were 46%/43% and 72%/15% for MRD(neg) and MRD(pos) MK AML patients, respectively, contrasted to 20%/64% and 64%/38% for MRD(neg) and MRD(pos) non-MK AML patients, respectively. After multivariable adjustment, MRD(pos) remission status but not MK remained statistically significantly associated with shorter survival and higher relapse risk. Similar results were obtained in several patient subsets. In summary, while our study confirms higher relapse rates and shorter survival for MK-AML compared to non-MK AML patients, these outcomes are largely accounted for by the presence of other adverse prognostic factors, in particular higher likelihood of pre-HCT MRD.