PURPOSE Patients with acute myeloid leukemia (AML) in remission remain at risk for relapse even after allogeneic hematopoietic cell transplantation (alloHCT). AML measurable residual disease (MRD) status before alloHCT has been shown to be prognostic. Whether modulation of the intensity of the alloHCT conditioning regimen in patients with AML who test positive for MRD can prevent relapse and improve survival is unknown. METHODS Ultra-deep, error-corrected sequencing for 13 commonly mutated genes in AML was performed on preconditioning blood from patients treated in a phase III clinical trial that randomly assigned adult patients with myeloid malignancy in morphologic complete remission to myeloablative conditioning (MAC) or reduced-intensity conditioning (RIC). RESULTS No mutations were detected in 32% of MAC and 37% of RIC recipients; these groups had similar survival (3-year overall survival [OS], 56% v 63%; P = .96). In patients with a detectable mutation (next-generation sequencing [NGS] positive), relapse (3-year cumulative incidence, 19% v 67%; P < .001) and survival (3-year OS, 61% v 43%; P = .02) was significantly different between the MAC and RIC arms, respectively. In multivariable analysis for NGS-positive patients, adjusting for disease risk and donor group, RIC was significantly associated with increased relapse (hazard ratio [HR], 6.38; 95% CI, 3.37 to 12.10; P < .001), decreased relapse-free survival (HR, 2.94; 95% CI, 1.84 to 4.69; P < .001), and decreased OS (HR, 1.97; 95% CI, 1.17 to 3.30; P = .01) compared with MAC. Models of AML MRD also showed benefit for MAC over RIC for those who tested positive. CONCLUSION This study provides evidence that MAC rather than RIC in patients with AML with genomic evidence of MRD before alloHCT can result in improved survival.

Data Sharing Statements: De-identified participant data for BMT CTN 1203 will be deposited in the NHLBI Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC) (https://biolincc.nhlbi.nih.gov/home/); a publicly available database. Study documents including the study protocol, informed consent form, data dictionary, case report forms for data collection are also available via the repository. Data will become accessible 3 years after the end of clinical activity and 2 years after the primary publication, as anticipated in 2020. Instructions on specimen or data requests and contact information for BioLINCC are also available.

Background Race/ethnicity remains an important barrier in clinical care. We investigated differences in autologous hematopoietic cell transplantation (AHCT) utilization in multiple myeloma (MM) and outcomes based on race/ethnicity in the United States. Methods The CIBMTR database identified 28,450 patients who underwent AHCT for MM from 2008–2014. Using SEER 18, the incidence of MM was calculated. A stem cell transplant utilization rate (STUR) was derived. Among patients 18–75 years undergoing melphalan-conditioned peripheral cell grafts (N=24,102), we analyzed post-AHCT outcomes. Results The STUR increased across all groups from 2008 to 2014. The increase was substantially lower among Hispanics (8.6% to 16.9%) and non-Hispanic Blacks (12.2% to 20.5%) than for non-Hispanic Whites (22.6% to 37.8%). There were 18,046 non-Hispanic Whites, 4123 non-Hispanic Blacks and 1933 Hispanic patients. The Hispanic group was younger (p <0.001). Fewer patients over 60 were transplanted in Hispanic (39%) and non-Hispanic Blacks (42%) vs. non-Hispanic Whites (56%). A Karnofsky score <90 and HCT-CI>3 were more common in non-Hispanic Blacks compared to Hispanic and non-Hispanic Whites (p<0.001). More Hispanic (57%) vs. non-Hispanic Blacks (54%) and non-Hispanic Whites (52%) (p<0.001) had stage III disease. More Hispanics (48%) vs. non-Hispanic Blacks (45%) and non-Hispanic Whites (44%) were in ≥very good partial response pre-transplant (p=0.005). Race/Ethnicity did not impact post-AHCT outcomes. Conclusions Although increasing, STUR remains low and significantly lower among Hispanic followed by non-Hispanic Blacks compared to non-Hispanic Whites. Race/ethnicity does not impact transplant outcomes. Efforts to increase transplant utilization for eligible MM patients, with emphasis on groups underutilizing transplant are warranted.

The COVID-19 pandemic has created significant barriers to timely donor evaluation, cell collection, and graft transport for allogeneic hematopoietic stem cell transplantation (allo-HCT). To ensure availability of donor cells on the scheduled date of infusion, many sites now collect cryopreserved grafts before the start of pretransplantation conditioning. Post-transplantation cyclophosphamide (ptCY) is an increasingly used approach for graft-versus-host disease (GVHD) prophylaxis, but the impact of graft cryopreservation on the outcomes of allo-HCT using ptCY is not known. Using the Center for International Blood and Marrow Transplant Research (CIBMTR) database, we compared the outcomes of HCT using cryopreserved versus fresh grafts in patients undergoing HCT for hematologic malignancy with ptCY. We analyzed 274 patients with hematologic malignancy undergoing allo-HCT between 2013 and 2018 with cryopreserved grafts and ptCY. Eighteen patients received bone marrow grafts and 256 received peripheral blood stem cell grafts. These patients were matched for age, graft type, disease risk index (DRI), and propensity score with 1080 patients who underwent allo-HCT with fresh grafts. The propensity score, which is an assessment of the likelihood of receiving a fresh graft versus a cryopreserved graft, was calculated using logistic regression to account for the following: disease histology, Karnofsky Performance Score (KPS), HCT Comorbidity Index, conditioning regimen intensity, donor type, and recipient race. The primary endpoint was overall survival (OS). Secondary endpoints included acute and chronic graft-versus-host disease (GVHD), nonrelapse mortality (NRM), relapse/progression and disease-free survival (DFS). Because of multiple comparisons, only P values <.01 were considered statistically significant. The 2 cohorts (cryopreserved and fresh) were similar in terms of patient age, KPS, diagnosis, DRI, HCT-CI, donor/graft source, and conditioning intensity. One-year probabilities of OS were 71.1% (95% confidence interval [CI], 68.3% to 73.8%) with fresh grafts and 70.3% (95% CI, 64.6% to 75.7%) with cryopreserved grafts (P = .81). Corresponding probabilities of OS at 2 years were 60.6% (95% CI, 57.3% to 63.8%) and 58.7% (95% CI, 51.9% to 65.4%) (P = .62). In matched-pair regression analysis, graft cryopreservation was not associated with a significantly higher risk of mortality (hazard ratio [HR] for cryopreserved versus fresh, 1.

BACKGROUND In hematopoietic cell transplantation (HCT), current risk adjustment strategies are based upon clinical and disease-related variables. Though patient reported outcomes (PROs) predict mortality in multiple cancers, PROs have been less well studied within HCT. Improvements in risk adjustment strategies in HCT would inform patient selection, patient counseling, and quality reporting. Our objective was to determine whether pre-HCT PROs, in particular physical health, predict survival among patients undergoing autologous or allogeneic transplantation. METHODS In this secondary analysis, we studied pre-HCT PROs that were reported by 336 allogeneic and 310 autologous HCT recipients enrolled in the BMT CTN 0902 trial, a study with broad representation of patients transplanted in the US. RESULTS Among allogeneic HCT recipients, the pre-HCT SF-36 physical component summary score (PCS) independently predicted overall mortality (HR 1.40 per 10 point decrease, p<0.001) and performed at least as well as currently used, non-PRO risk indices. Survival probability estimates at one year for the first, second, third, and fourth quartiles of the baseline PCS were 50%, 65%, 75%, and 83%. Early post-HCT decreases in PCS were associated with higher overall and treatment-related mortality. When adjusted for patient variables included in the US Stem Cell Therapeutic Outcomes Database model for transplant center-specific reporting, the SF-36 PCS retained independent prognostic value. CONCLUSIONS PROs have the potential to improve prognostication in HCT. We recommend the routine collection of PROs prior to HCT, and consideration of incorporation of PROs into risk adjustment for quality reporting.