Comparison of hematopoietic cell transplant conditioning regimens for hemophagocytic lymphohistiocytosis disorders

Rebecca A. Marsh*, Kyle Hebert, Soyoung Kim, Christopher C. Dvorak, Victor M. Aquino, K. Scott Baker, Deepak Chellapandian, Blachy Dávila Saldaña, Christine N. Duncan, Michael J. Eckrich, George E. Georges, Timothy S. Olson, Michael A. Pulsipher, Shalini Shenoy, Elizabeth Stenger, Mark Vander Lugt, Lolie C. Yu, Andrew R. Gennery, Mary Eapen

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


Background: 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.

Original languageEnglish (US)
Pages (from-to)1097-1104.e2
JournalJournal of Allergy and Clinical Immunology
Issue number3
StatePublished - Mar 2022


  • BMT
  • HCT
  • HLH
  • HSCT
  • Hemophagocytic lymphohistiocytosis
  • allogeneic hematopoietic cell transplantation
  • bone marrow transplantation
  • hematopoietic stem cell transplantation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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