Allogeneic hematopoietic cell transplantation for XIAP deficiency: an international survey reveals poor outcomes
Open Access
- 7 February 2013
- journal article
- Published by American Society of Hematology in Blood
- Vol. 121 (6), 877-883
- https://doi.org/10.1182/blood-2012-06-432500
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.This publication has 30 references indexed in Scilit:
- Making a definitive diagnosis: Successful clinical application of whole exome sequencing in a child with intractable inflammatory bowel diseaseGenetics in Medicine, 2011
- Clinical similarities and differences of patients with X-linked lymphoproliferative syndrome type 1 (XLP-1/SAP deficiency) versus type 2 (XLP-2/XIAP deficiency)Blood, 2011
- X-linked lymphoproliferative disease due to SAP/SH2D1A deficiency: a multicenter study on the manifestations, management and outcome of the diseaseBlood, 2011
- XIAP deficiency: a unique primary immunodeficiency best classified as X-linked familial hemophagocytic lymphohistiocytosis and not as X-linked lymphoproliferative diseaseBlood, 2010
- Phenotypic differences between mice deficient in XIAP and SAP, two factors targeted in X-linked lymphoproliferative syndrome (XLP)Cellular Immunology, 2009
- Defining the Intensity of Conditioning Regimens: Working DefinitionsTransplantation and Cellular Therapy, 2009
- XIAP discriminates between type I and type II FAS-induced apoptosisNature, 2009
- A rapid flow cytometric screening test for X‐linked lymphoproliferative disease due to XIAP deficiencyCytometry Part B: Clinical Cytometry, 2009
- Small molecule XIAP inhibitors cooperate with TRAIL to induce apoptosis in childhood acute leukemia cells and overcome Bcl-2–mediated resistanceBlood, 2009
- Allogeneic stem cell transplantation in X-linked lymphoproliferative disease: two cases in one family and review of the literatureBone Marrow Transplantation, 2005