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The measurable residual disease (MRD) assessment provides an attractive predictor of allogeneic hematopoietic cell transplnat (alloHCT) outcomes. Cell-free DNA (cfDNA) has been applied to diagnosis, early detection, and disease burden monitoring in various tumors, but its utility as an MRD test in myeloid malignancies has not been systematically evaluated. We sought to determine the differential sensitivity between bone marrow (BM) and cfDNA MRD and to assess the effect of cfDNA MRD on alloHCT outcomes. The technical and clinical validation cohorts, including 82 patients participating in clinical trials (Bone Marrow Transplant Clinical Trials Network-0201 and 0402), were used. Ultradeep error-corrected targeted sequencing was performed on plasma and BM-derived DNA. We demonstrated that 94.6% (range, 93.9-95.3) of cfDNA was derived from hematopoietic tissue. The mutant allele fraction was congruent between BM and cfDNA (rho = 0.8; P < .0001); however, cfDNA seemed to be more sensitive in detecting clones with a variant allele frequency (VAF) of <0.26%. cfDNA-MRD clearance by day 90 after alloHCT (D90) was associated with improved relapse-free survival (RFS, median survival not reached vs 5.5 months; P < .0001) and overall survival (OS, median survival not reached vs 7.3 months; P < .0001) when compared with patients with persistent MRD. Irrespective of pre-alloHCT MRD, D90 cfDNA MRD was associated with inferior 2-year OS (16.7% vs 84.8%; P < .0001) and RFS (16.7% vs 80.7%; P < .0001). cfDNA seems to be an accurate, minimally invasive alternative to BM aspirates in MRD assessment and confers important prognostic implications in patients with myeloid malignancies undergoing alloHCT., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

To characterize the outcomes of patients who developed a particular subsequent solid cancer after hematopoietic cell transplantation (HCT), age at cancer diagnosis, survival, and causes of death were compared with the respective primary cancer in the general population, using data from the national HCT registry and population-based cancer registries in Japan. Among 31 867 patients who underwent a first HCT between 1990 and 2013 and had progression-free survival at 1 year, 713 patients developed subsequent solid cancer. The median age at subsequent solid cancer diagnosis was 55 years, which was significantly younger than the 67 years for primary cancer patients in the general population ( P < .001). The overall survival probability was 60% at 3 years after diagnosis of subsequent solid cancer and differed according to cancer type. Development of most solid cancers was associated with an increased risk of subsequent mortality after HCT. Subsequent solid cancers accounted for 76% of causes of death. Overall survival probabilities adjusted for age, sex, and year of diagnosis were lower in the HCT population than in the general population for colon, bone/soft tissue, and central nervous system cancers and did not differ statistically for other cancers. In conclusion, most subsequent solid cancers occurred at younger ages than primary cancers, emphasizing the need for cancer screening at younger ages. Subsequent solid cancers showed similar or worse survival compared with primary cancers. Biological and genetic differences between primary and subsequent solid cancers remain to be determined., (© 2018 by The American Society of Hematology.)