Allogeneic hematopoietic stem cell transplantation in high-altitude hypoxia preserves graft-versus-leukemia without acute gvhd

Abstract

Abstract Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative treatment for many high-risk hematologic malignancies and bone marrow failure syndromes. However, the feasibility and safety of allo-HSCT in high-altitude, hypobaric hypoxic environments remain unknown. Xining, China (altitude ~2300 meters), represents the highest site where allo-HSCT has been systematically performed. Hypoxia is known to modulate immune responses and hematopoiesis, but its clinical implications in allo-HSCT remain unexplored. Methods: We conducted a prospective single-center study of 7 consecutive patients undergoing allo-HSCT at Qinghai University Affiliated Hospital between September 2023 and December 2024. All patients were long-term residents of regions >2500m. A parallel comparator cohort of 186 patients undergoing allo-HSCT at a sea-level transplant center in the National Longitudinal Cohort of Hematological Diseases (NIECH-BMT, NCT04645199,elevation 5 meters) during the same period was used for outcome benchmarking. Conditioning regimens, graft source, GVHD prophylaxis, and supportive care were harmonized between cohorts. Clinical endpoints included overall survival (OS), disease-free survival (DFS), graft-versus-host disease (GVHD), relapse, infection rates, engraftment kinetics, and immune reconstitution. Results: At a median follow-up of 12 months, no relapse occurred in the high-altitude group at 1 year (0% vs. 9.6%; P=0.39). Grade 2–4 and 3–4 acute GVHD were absent in high-altitude patients (0% vs. 18.4% and 9.9% respectively; P=0.22 and 0.38). Chronic GVHD at 1 year was observed in 16.7% of high-altitude patients versus 24.4% in controls (P=0.95). Neutrophil engraftment was significantly faster in high-altitude patients (median 11 vs. 14 days, P=0.037), while platelet engraftment was similar. CMV infection rates did not differ significantly. Conclusions: Allo-HSCT is feasible and safe in high-altitude hypoxic environments, with favorable engraftment, reduced GVHD, and excellent early disease control. This study provides the first clinical evidence for transplantation care delivery in chronic hypoxia and expands transplant accessibility in geographically challenging regions.