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 - 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
UR - http://www.scopus.com/inward/record.url?scp=85114615522&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85114615522&partnerID=8YFLogxK
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 -