title: Allogeneic hematopoietic cell transplantation for XIAP deficiency: an international survey reveals poor outcomes.
abstract: There have been no studies on patient outcome after allogeneic hematopoietic cell transplantation (HCT) in patients with X-linked inhibitor of apoptosis (XIAP) deficiency. To estimate the success of HCT, we conducted an international survey of transplantation outcomes. Data were reported for 19 patients. Seven patients received busulfan-containing myeloablative conditioning (MAC) regimens. Eleven patients underwent reduced intensity conditioning (RIC) regimens predominantly consisting of alemtuzumab, fludarabine, and melphalan. One patient received an intermediate-intensity regimen. Survival was poor in the MAC group, with only 1 patient surviving (14%). Most deaths were from transplantation-related toxicities, including venoocclusive disease and pulmonary hemorrhage. Of the 11 patients who received RIC, 6 are currently surviving at a median of 570 days after HCT (55%). Preparative regimen and HLH activity affected outcomes, and of RIC patients reported to be in remission from HLH, survival is 86% (P = .03). We conclude that MAC regimens should not be used for patients with XIAP deficiency. It is possible that the loss of XIAP and its antiapoptotic functions contributes to the high incidence of toxicities observed with MAC regimens. RIC regimens should be pursued with caution and, if possible, efforts should be made to ensure HLH remission before HCT in these patients.
authors.affiliation: Division of Bone Marrow Transplantation and Immunodeficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA. rebecca.marsh@cchmc.org
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Marsh
authors.forename: Kanchan
authors.initials: K
authors.lastname: Rao
authors.forename: Prakash
authors.initials: P
authors.lastname: Satwani
authors.forename: Kai
authors.initials: K
authors.lastname: Lehmberg
authors.forename: Ingo
authors.initials: I
authors.lastname: Müller
authors.forename: Dandan
authors.initials: D
authors.lastname: Li
authors.forename: Mi-Ok
authors.initials: MO
authors.lastname: Kim
authors.forename: Alain
authors.initials: A
authors.lastname: Fischer
authors.forename: Sylvain
authors.initials: S
authors.lastname: Latour
authors.forename: Petr
authors.initials: P
authors.lastname: Sedlacek
authors.forename: Vincent
authors.initials: V
authors.lastname: Barlogis
authors.forename: Kazuko
authors.initials: K
authors.lastname: Hamamoto
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Kanegane
authors.forename: Sam
authors.initials: S
authors.lastname: Milanovich
authors.forename: David A
authors.initials: DA
authors.lastname: Margolis
authors.forename: David
authors.initials: D
authors.lastname: Dimmock
authors.forename: James
authors.initials: J
authors.lastname: Casper
authors.forename: Dorothea N
authors.initials: DN
authors.lastname: Douglas
authors.forename: Persis J
authors.initials: PJ
authors.lastname: Amrolia
authors.forename: Paul
authors.initials: P
authors.lastname: Veys
authors.forename: Ashish R
authors.initials: AR
authors.lastname: Kumar
authors.forename: Michael B
authors.initials: MB
authors.lastname: Jordan
authors.forename: Jack J
authors.initials: JJ
authors.lastname: Bleesing
authors.forename: Alexandra H
authors.initials: AH
authors.lastname: Filipovich
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D005060:Europe; D040181:Genetic Diseases, X-Linked / Q000235:genetics / Q000401:mortality / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006470:Hemorrhage / Q000209:etiology; D006504:Hepatic Veno-Occlusive Disease / Q000209:etiology; D006801:Humans; D007223:Infant; D007564:Japan; D008168:Lung / Q000098:blood supply; D008232:Lymphoproliferative Disorders / Q000235:genetics / Q000401:mortality / Q000628:therapy*; D009154:Mutation; D017063:Outcome Assessment, Health Care / Q000706:statistics & numerical data; D012074:Remission Induction; D012189:Retrospective Studies; D016019:Survival Analysis; D015996:Survival Rate; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D014481:United States; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000235:genetics; D055815:Young Adult
chemical_list: D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human