Reduced-Intensity/Reduced-Toxicity Conditioning Approaches Are Tolerated in XIAP Deficiency but Patients Fare Poorly with Acute GVHD
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Reduced-Intensity/Reduced-Toxicity Conditioning Approaches Are Tolerated in XIAP Deficiency but Patients Fare Poorly with Acute GVHD. / Arnold, Danielle E; Nofal, Rofida; Wakefield, Connor; Lehmberg, Kai; Wustrau, Katharina; Albert, Michael H; Morris, Emma C; Heimall, Jennifer R; Bunin, Nancy J; Kumar, Ashish; Jordan, Michael B; Cole, Theresa; Choo, Sharon; Brettig, Tim; Speckmann, Carsten; Ehl, Stephan; Salamonowicz, Malgorzata; Wahlstrom, Justin; Rao, Kanchan; Booth, Claire; Worth, Austen; Marsh, Rebecca A.
In: J CLIN IMMUNOL, Vol. 42, No. 1, 01.2022, p. 36-45.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Reduced-Intensity/Reduced-Toxicity Conditioning Approaches Are Tolerated in XIAP Deficiency but Patients Fare Poorly with Acute GVHD
AU - Arnold, Danielle E
AU - Nofal, Rofida
AU - Wakefield, Connor
AU - Lehmberg, Kai
AU - Wustrau, Katharina
AU - Albert, Michael H
AU - Morris, Emma C
AU - Heimall, Jennifer R
AU - Bunin, Nancy J
AU - Kumar, Ashish
AU - Jordan, Michael B
AU - Cole, Theresa
AU - Choo, Sharon
AU - Brettig, Tim
AU - Speckmann, Carsten
AU - Ehl, Stephan
AU - Salamonowicz, Malgorzata
AU - Wahlstrom, Justin
AU - Rao, Kanchan
AU - Booth, Claire
AU - Worth, Austen
AU - Marsh, Rebecca A
N1 - © 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2022/1
Y1 - 2022/1
N2 - X-linked inhibitor of apoptosis (XIAP) deficiency is an inherited primary immunodeficiency characterized by chronic inflammasome overactivity and associated with hemophagocytic lymphohistiocytosis (HLH) and inflammatory bowel disease (IBD). Allogeneic hematopoietic cell transplantation (HCT) with fully myeloablative conditioning may be curative but has been associated with poor outcomes. Reports of reduced-intensity conditioning (RIC) and reduced-toxicity conditioning (RTC) regimens suggest these approaches are well tolerated, but outcomes are not well established. Retrospective data were collected from an international cohort of 40 patients with XIAP deficiency who underwent HCT with RIC or RTC. Thirty-three (83%) patients had a history of HLH, and thirteen (33%) patients had IBD. Median age at HCT was 6.5 years. Grafts were from HLA-matched (n = 30, 75%) and HLA-mismatched (n = 10, 25%) donors. There were no cases of primary graft failure. Two (5%) patients experienced secondary graft failure, and three (8%) patients ultimately received a second HCT. Nine (23%) patients developed grade II-IV acute GVHD, and 3 (8%) developed extensive chronic GVHD. The estimated 2-year overall and event-free survival rates were 74% (CI 55-86%) and 64% (CI 46-77%), respectively. Recipient and donor HLA mismatch and grade II-IV acute GVHD were negatively associated with survival on multivariate analysis with hazard ratios of 5.8 (CI 1.5-23.3, p = 0.01) and 8.2 (CI 2.1-32.7, p < 0.01), respectively. These data suggest that XIAP patients tolerate RIC and RTC with survival rates similar to HCT of other genetic HLH disorders. Every effort should be made to prevent acute GVHD in XIAP-deficient patients who undergo allogeneic HCT.
AB - X-linked inhibitor of apoptosis (XIAP) deficiency is an inherited primary immunodeficiency characterized by chronic inflammasome overactivity and associated with hemophagocytic lymphohistiocytosis (HLH) and inflammatory bowel disease (IBD). Allogeneic hematopoietic cell transplantation (HCT) with fully myeloablative conditioning may be curative but has been associated with poor outcomes. Reports of reduced-intensity conditioning (RIC) and reduced-toxicity conditioning (RTC) regimens suggest these approaches are well tolerated, but outcomes are not well established. Retrospective data were collected from an international cohort of 40 patients with XIAP deficiency who underwent HCT with RIC or RTC. Thirty-three (83%) patients had a history of HLH, and thirteen (33%) patients had IBD. Median age at HCT was 6.5 years. Grafts were from HLA-matched (n = 30, 75%) and HLA-mismatched (n = 10, 25%) donors. There were no cases of primary graft failure. Two (5%) patients experienced secondary graft failure, and three (8%) patients ultimately received a second HCT. Nine (23%) patients developed grade II-IV acute GVHD, and 3 (8%) developed extensive chronic GVHD. The estimated 2-year overall and event-free survival rates were 74% (CI 55-86%) and 64% (CI 46-77%), respectively. Recipient and donor HLA mismatch and grade II-IV acute GVHD were negatively associated with survival on multivariate analysis with hazard ratios of 5.8 (CI 1.5-23.3, p = 0.01) and 8.2 (CI 2.1-32.7, p < 0.01), respectively. These data suggest that XIAP patients tolerate RIC and RTC with survival rates similar to HCT of other genetic HLH disorders. Every effort should be made to prevent acute GVHD in XIAP-deficient patients who undergo allogeneic HCT.
KW - Genetic Diseases, X-Linked/etiology
KW - Graft vs Host Disease/prevention & control
KW - Hematopoietic Stem Cell Transplantation/adverse effects
KW - Humans
KW - Lymphoproliferative Disorders/etiology
KW - Retrospective Studies
KW - Transplantation Conditioning
KW - X-Linked Inhibitor of Apoptosis Protein/genetics
U2 - 10.1007/s10875-021-01103-6
DO - 10.1007/s10875-021-01103-6
M3 - SCORING: Journal article
C2 - 34586554
VL - 42
SP - 36
EP - 45
JO - J CLIN IMMUNOL
JF - J CLIN IMMUNOL
SN - 0271-9142
IS - 1
ER -
