Rebecca A Marsh1, Kyle Hebert2, Soyoung Kim2, Christopher C Dvorak3, Victor M Aquino4, K Scott Baker5, Deepak Chellapandian6, Blachy Dávila Saldaña7, Christine N Duncan8, Michael J Eckrich9, George E Georges5, Timothy S Olson10, Michael A Pulsipher11, Shalini Shenoy12, Elizabeth Stenger13, Mark Vander Lugt14, Lolie C Yu15, Andrew R Gennery16, Mary Eapen2. 1. University of Cincinnati and Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio. Electronic address: Rebecca.marsh@cchmc.org. 2. Center for International Blood and Marrow Transplant Research, Division of Hematology/Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisc. 3. Division of Pediatric Allergy, Immunology, and Bone Marrow Transplantation, University of California San Francisco, Benioff Children's Hospital, San Francisco, Calif. 4. UT Southwestern Medical Center, Dallas, Tex. 5. Fred Hutchinson Cancer Research Center, Seattle, Wash. 6. Center for Cell and Gene Therapy for Non-Malignant Conditions, Johns Hopkins All Children's Hospital, St Petersburg, Fla. 7. Division of Bone Marrow Transplant, Children's National Hospital, Washington, DC. 8. Dana-Farber Cancer Institute, Boston, Mass. 9. Sarah Cannon Pediatric Transplant and Cellular Therapy Program, Methodist Children's Hospital, San Antonio, Tex. 10. Department of Pediatrics, Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, Pa. 11. Children's Hospital Los Angeles, Los Angeles, Calif. 12. Department of Pediatrics, Washington University School of Medicine, St Louis, Mo. 13. Children's Hospital of Pittsburgh, Pittsburgh, Pa. 14. The University of Michigan, Ann Arbor, Mich. 15. Children's Hospital, New Orleans, La. 16. Newcastle University, Newcastle Upon Tyne, United Kingdom.
Abstract
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.
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.
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