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Comparison of hematopoietic cell transplant conditioning regimens for hemophagocytic lymphohistiocytosis disorders

Lookup NU author(s): Professor Andrew GenneryORCiD


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© 2021 American Academy of Allergy, Asthma & ImmunologyBackground: Allogeneic hematopoietic cell transplantation for hemophagocytic lymphohistiocytosis (HLH) disorders is associated with substantial morbidity and mortality. Objective: The effect of conditioning regimen groups of varying intensity on outcomes after transplantation was examined to identify an optimal regimen or regimens for HLH disorders. Methods: We studied 261 patients with HLH disorders transplanted between 2005 and 2018. Risk factors for transplantation outcomes by conditioning regimen groups were studied by Cox regression models. Results: Four regimen groups were studied: (1) fludarabine (Flu) and melphalan (Mel) in 123 subjects; (2) Flu, Mel, and thiotepa (TT) in 28 subjects; (3) Flu and busulfan (Bu) in 14 subjects; and (4) Bu and cyclophosphamide (Cy) in 96 subjects. The day 100 incidence of veno-occlusive disease was lower with Flu/Mel (4%) and Flu/Mel/TT (0%) compared to Flu/Bu (14%) and Bu/Cy (22%) (P < .001). The 6-month incidence of viral infections was highest after Flu/Mel (72%) and Flu/Mel/TT (64%) compared to Flu/Bu (39%) and Bu/Cy (38%) (P < .001). Five-year event-free survival (alive and engrafted without additional cell product administration) was lower with Flu/Mel (44%) compared to Flu/Mel/TT (70%), Flu/Bu (79%), and Bu/Cy (61%) (P = .002). The corresponding 5-year overall survival values were 68%, 75%, 86%, and 64%, and did not differ by conditioning regimen (P = .19). Low event-free survival with Flu/Mel is attributed to high graft failure (42%) compared to Flu/Mel/TT (15%), Flu/Bu (7%), and Bu/Cy (18%) (P < .001). Conclusions: Given the high rate of graft failure with Flu/Mel and the high rate of veno-occlusive disease with Bu/Cy and Flu/Bu, Flu/Mel/TT may be preferred for HLH disorders. Prospective studies are warranted.

Publication metadata

Author(s): Marsh RA, Hebert K, Kim S, Dvorak CC, Aquino VM, Baker KS, Chellapandian D, Davila Saldana B, Duncan CN, Eckrich MJ, Georges GE, Olson TS, Pulsipher MA, Shenoy S, Stenger E, Lugt MV, Yu LC, Gennery AR, Eapen M

Publication type: Article

Publication status: Published

Journal: Journal of Allergy and Clinical Immunology

Year: 2022

Volume: 149

Issue: 3

Pages: 1097-1104.e2

Print publication date: 01/03/2022

Online publication date: 08/08/2021

Acceptance date: 30/07/2021

ISSN (print): 0091-6749

ISSN (electronic): 1097-6825

Publisher: Elseiver


DOI: 10.1016/j.jaci.2021.07.031

PubMed id: 34375618


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