After more than 60 years of research in allogeneic hematopoietic cell transplantation (HCT), this therapy has advanced from one that was declared dead in the 1960s to a standard treatment of otherwise fatal malignant and non-malignant blood diseases. To date, close to 1.5 million hematopoietic cell transplants have been performed in more than 1,500 transplantation centers worldwide. This review will highlight the enormous efforts by numerous investigators throughout the world who have brought the experimental field of HCT to clinical reality, examine ongoing challenges, and provide insights for the future.

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How conditioning intensity is related to outcomes of AML patients undergoing allografting in morphologic remission is an area of great ongoing interest. We studied 743 patients in morphologic remission and known pre-transplant measurable residual disease (MRD) status determined by multiparameter flow cytometry (MFC) who received a first allograft after myeloablative, reduced intensity, or nonmyeloablative conditioning (MAC, RIC, and NMA). Overall, relapse-free survival (RFS) and overall survival (OS) were longer after MAC than RIC or NMA conditioning, whereas relapse risks were not different. Among MRDpos patients, 3-year estimates of relapse risks and survival were similar across conditioning intensities. In contrast, among MRDneg patients, 3-year RFS and OS were longer for MAC (69% and 71%) than RIC (47% and 55%) and NMA conditioning (47% and 52%). Three-year relapse risks were lowest after MAC (18%) and highest after NMA conditioning (30%). Our data indicate an interaction between conditioning intensity, MFC-based pre-transplant MRD status, and outcome, with benefit of intensive conditioning primarily for patients transplanted in MRDneg remission. Differing from recent findings from other studies that indicated MAC is primarily beneficial for some or all patients with MRDpos pre-HCT status, our data suggest MAC should still be considered for MRDneg AML patients if tolerated.

Conditioning with fludarabine and low-dose total-body irradiation before allogeneic hematopoietic cell transplantation (HCT) enabled treating older or medically infirm patients with advanced hematologic malignancies in the outpatient setting. Between December 1997 and June 2017, 1037 patients with hematologic malignancies received peripheral blood stem cell (PBSC) grafts from HLA-matched or 1 HLA antigen/allele-mismatched related or unrelated donors. Median age was 58 (range, 18 to 80) years. Serious comorbidities with Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI) scores 3 were present in 52% of patients. We found that 47% of patients were either never hospitalized or only had an overnight hospital stay for infusion of late-arriving PBSCs while 53% were admitted for a median of 6 days. Main reasons for admission were infection, fever, graftversus-host disease, and regimen-related toxicity. Two thirds of admissions occurred within 3 weeks of HCT. The 5-year risk of nonrelapse mortality (NRM) was 26% among hospitalized patients and 13% among nonhospitalized patients. Significant risk factors for hospitalization included unrelated transplants, 1 HLA antigen-mismatched transplant, high HCT-CI scores, and diagnosis of nonmyeloma malignancies. Significant risk factors for NRM were hospitalization, older age, unrelated transplants, and high HCT-CI scores. Ambulatory allogeneic HCT is feasible and safe.