A nationwide retrospective analysis of allogeneic hematopoietic stem cell transplantation for adult hemophagocytic lymphohistiocytosis.

[BACKGROUND/OBJECTIVE]: Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening disorder characterized by systemic hyperinflammation. Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only potentially curative treatment for primary and relapsed/refractory HLH, the optimal strategy has not been established. [STUDY DESIGN]: We retrospectively analyzed 56 adult patients (≥ 18 years) with primary and secondary HLH (mainly consisting of Epstein-Barr virus-associated HLH) who underwent allo-HSCT using the registry database of the Japanese Society for Transplantation and Cellular Therapy, including 26 patients who underwent cord blood transplantation (CBT). One-fourth of patients received myeloablative conditioning (MAC), mainly consisting of total body irradiation-based regimens. [RESULTS]: The 3-year overall survival (OS) was 40.6%, while the 3-year cumulative incidences of relapse and non-relapse mortality (NRM) were 19.8% and 39.6%, respectively. In univariable analysis, age at allo-HSCT (the 3-year OS: 27.5% for ≥ 25 years old vs 58.0% for < 25 years old, P = 0.030), conditioning intensity (7.1% for MAC vs 51.8% for reduced-intensity conditioning (RIC), P = 0.003), and donor source (26.0% for CBT vs 52.9% for bone marrow or peripheral blood stem cell transplantation (BMT/PBSCT), P = 0.033) were associated with significantly inferior OS. In multivariable analysis, older age at allo-HSCT (≥ 25 years old) (Hazard ratio [HR], 2.37; 95% CI, 1.01-5.58; P = 0.048), MAC (HR, 2.45; 95% CI, 1.09-5.53; P = 0.031), and CBT (HR, 2.21; 95% CI, 1.04-4.71; P = 0.040) were independently associated with worse OS. In addition, only conditioning intensity predicted higher NRM (the 3-year NRM: 78.6% for MAC vs 26.6% for RIC), while no factors were associated with the relapse rate. [CONCLUSION]: This study includes the largest number of adult HLH patients undergoing CBT. Although the use of CBT is acceptable, BMT/PBSCT are more favorable strategies in allo-HSCT in adult HLH. Regarding conditioning intensity, RIC regimens are more beneficial in this setting.

Informations de copyright

Copyright © 2024. Published by Elsevier Inc.

Déclaration de conflit d'intérêts

Declaration of competing interest MS owns stock in Celaid Therapeutics. KF received honoraria from Janssen Pharmaceutical. TI received consultant fee from AbbVie, Nippon Shinyaku, and Nihon Kayaku. TI received grants from AbbVie, Nippon Shinyaku, Repertoire Genesis, Asahi Kasei, Chugai Pharmaceutical, CBL Behring, Daiichi Sankyo, Eisai, Kyowahakko Kirin, Ono Pharmaceutical, Otsuka Pharmaceutical, Sumitomo Dainippon Pharma, Takeda Pharmaceutical, and Zenyaku Kogyo. TI received honoraria from Bristol-Myers Squibb, Eisai, FUJIFILM Wako Chemicals, Kyowahakko Kirin, Novartis Pharma, Ono Pharmaceutical and Pfizer. YA received lecture fee from Otsuka Pharmaceutical, Chugai Pharmaceutical, Novartis Pharma, and AbbVie. YA received consultant fee from JCR Pharmaceuticals and Kyowa Kirin. YA received honoraria from Meiji Seika Pharma. KK received honoraria from Ono Pharmaceutical, Eisai, Astellas Pharma, Novartis, Chugai Pharmaceutical, AstraZeneca, Sumitomo Pharma, Kyowa Kirin, Janssen Pharmaceutical, Takeda Pharmaceutical, Otsuka Pharmaceutical, SymBio Pharmaceuticals, Bristol Myers Squibb, Pfizer, Nippon Shinyaku, Daiichi Sankyo, Alexion Pharmaceuticals, AbbVie, Meiji Seika Pharma, Sanofi, Sysmex, Mundipharma, Incyte Corporation, and Kyorin Pharmaceutical. KK received research support from Otsuka Pharmaceutical, Chordia Therapeutics, Chugai Pharmaceutical, Takeda Pharmaceutical, and Meiji Seika Pharma. KK received scholarship from Asahi Kasei Pharma, Eisai, Otsuka Pharmaceutical, Ono Pharmaceutical, Kyowa Kirin, Shionogi, Takeda Pharmaceutical, Sumitomo Dainippon Pharma, Chugai Pharmaceutical, Teijin Pharma, Japan Blood Products Organization, Mochida Pharmaceutical, JCR Pharmaceuticals, and Nippon Shinyaku. KK owns stock in Asahi Genomics. KK has a patent for Genetic alterations as a biomarker in T-cell lymphomas and a patent for PD-L1 abnormalities as a predictive biomarker for immune checkpoint blockade therapy. The other authors declare no competing interests.