TY - JOUR
T1 - Comparison of hematopoietic cell transplant conditioning regimens for hemophagocytic lymphohistiocytosis disorders
AU - Marsh, Rebecca A.
AU - Hebert, Kyle
AU - Kim, Soyoung
AU - Dvorak, Christopher C.
AU - Aquino, Victor M.
AU - Baker, K. Scott
AU - Chellapandian, Deepak
AU - Dávila Saldaña, Blachy
AU - Duncan, Christine N.
AU - Eckrich, Michael J.
AU - Georges, George E.
AU - Olson, Timothy S.
AU - Pulsipher, Michael A.
AU - Shenoy, Shalini
AU - Stenger, Elizabeth
AU - Lugt, Mark Vander
AU - Yu, Lolie C.
AU - Gennery, Andrew R.
AU - Eapen, Mary
N1 - Funding Information:
The CIBMTR is supported primarily by Public Health Service grant agreement 5U24-CA076518 from the National Cancer Institute (NCI), the National Heart, Lung, and Blood Institute (NHLBI), and the National Institute of Allergy and Infectious Diseases (NIAID), and contract HHSH250201200016C with Health Resources and Services Administration (HRSA/DHHS). The views expressed in this article do not reflect the official policy or position of the National Institute of Health, Health Resources and Services Administration, or any other agency of the US government.
Funding Information:
The CIBMTR is supported primarily by Public Health Service grant agreement 5U24-CA076518 from the National Cancer Institute (NCI), the National Heart, Lung, and Blood Institute (NHLBI), and the National Institute of Allergy and Infectious Diseases (NIAID), and contract HHSH250201200016C with Health Resources and Services Administration (HRSA/DHHS). The views expressed in this article do not reflect the official policy or position of the National Institute of Health, Health Resources and Services Administration, or any other agency of the US government.
Publisher Copyright:
© 2021 American Academy of Allergy, Asthma & Immunology
PY - 2022/3
Y1 - 2022/3
N2 - 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.
AB - 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.
KW - BMT
KW - HCT
KW - HLH
KW - HSCT
KW - Hemophagocytic lymphohistiocytosis
KW - allogeneic hematopoietic cell transplantation
KW - bone marrow transplantation
KW - hematopoietic stem cell transplantation
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U2 - 10.1016/j.jaci.2021.07.031
DO - 10.1016/j.jaci.2021.07.031
M3 - Article
C2 - 34375618
AN - SCOPUS:85114615522
SN - 0091-6749
VL - 149
SP - 1097-1104.e2
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
IS - 3
ER -