A novel and safe protocol for patients with severe comorbidity who undergo haploidentical hematopoietic stem cell transplantation: A single-center prospective study.

Background and Objectives: Haploidentical stem cell transplantation (haplo-HSCT) has demonstrated promising results in patients without severe comorbidities. There is also an increasing need for haplo-HSCT in patients with severe comorbidities. However, the high risk of treatment-related mortality (TRM) hindered its extensive application. We aimed to investigate a novel conditioning regimen (Bu/Flu/Cy/ATG) followed by haplo-HSCT in patients with severe comorbidities. Methods: This prospective, single-arm clinical trial was performed at Peking University Institute of Hematology, China. Patients were enrolled if they were (1) diagnosed with acute leukemia, myelodysplastic syndrome (MDS), or chronic myelomonocytic leukemia (CMML); (2) patients with no HLA-matched sibling donor or matched unrelated donor available but with a haplo-HSCT donor; (3) patients with hematopoietic cell transplantation comorbidity index (HCT-CI) scores ≥3. The primary endpoint was 2-year TRM. Results: From June 2018 to November 2022, a total of 72 patients were enrolled. All patients achieved neutrophil engraftment. The cumulative incidence of grade II-IV acute graft-versus-host disease (aGVHD) at day 100 was 20.8%. The cumulative incidences of cytomegalovirus (CMV) viremia and Epstein‒Barr (EB) viremia at day 100 were 72.2% and 31.9%, respectively. The cumulative incidence of 2-year TRM was 25.1%. The cumulative incidence of 2-year relapse was 8.6%. The probabilities of 2-year overall survival and leukemia-free survival were 71.9% and 65.6%, respectively. Conclusion: This study suggested that a novel conditioning regimen followed by haploidentical HSCT might be a promising option for patients with severe comorbidities. The study was registered as a clinical trial (NCT03412409).