Hematopoietic stem cell transplantation for adolescents and adults with inborn errors of immunity: an EBMT IEWP study

TY - JOUR

T1 - Hematopoietic stem cell transplantation for adolescents and adults with inborn errors of immunity: an EBMT IEWP study

AU - Albert, Michael H

AU - Sirait, Tiarlan

AU - Eikema, Dirk-Jan

AU - Bakunina, Katerina

AU - Wehr, Claudia

AU - Suarez, Felipe

AU - Fox, Maria Laura

AU - Mahlaoui, Nizar

AU - Gennery, Andrew R

AU - Lankester, Arjan C

AU - Beier, Rita

AU - Bernardo, Maria Ester

AU - Bigley, Venetia

AU - Lindemans, Caroline A

AU - Burns, Siobhan O

AU - Carpenter, Ben

AU - Dybko, Jaroslaw

AU - Güngör, Tayfun

AU - Hauck, Fabian

AU - Lum, Su Han

AU - Balashov, Dmitry

AU - Meisel, Roland

AU - Moshous, Despina

AU - Schulz, Ansgar

AU - Speckmann, Carsten

AU - Slatter, Mary A

AU - Strahm, Brigitte

AU - Uckan-Cetinkaya, Duygu

AU - Meyts, Isabelle

AU - Vallée, Tanja C

AU - Wynn, Robert

AU - Neven, Bénédicte

AU - Morris, Emma C

AU - Aiuti, Alessandro

AU - Maschan, Alexei

AU - Aljurf, Mahmoud

AU - Gedde-Dahl, Tobias

AU - Gurman, Gunhan

AU - Bordon, Victoria

AU - Kriván, Gergely

AU - Locatelli, Franco

AU - Porta, Fulvio

AU - Valcárcel, David

AU - Beguin, Yves

AU - Faraci, Maura

AU - Kröger, Nicolaus

AU - Kulagin, Aleksandr

AU - Shaw, Peter J

AU - Veelken, Joan Hendrik

AU - Diaz de Heredia, Cristina

AU - Fagioli, Franca

AU - Felber, Matthias

AU - Gruhn, Bernd

AU - Holter, Wolfgang

AU - Rössig, Claudia

AU - Sedlacek, Petr

AU - Apperley, Jane

AU - Ayas, Mouhab

AU - Bodova, Ivana

AU - Choi, Goda

AU - Cornelissen, J J

AU - Sirvent, Anne

AU - Khan, Anjum

AU - Kupesiz, Alphan

AU - Lenhoff, Stig

AU - Ozdogu, Hakan

AU - von der Weid, Nicolas

AU - Rovira, Montserrat

AU - Schots, Rik

AU - Vinh, Donald C

AU - Inborn Errors Working Party of the EBMT

N1 - © 2022 by The American Society of Hematology.

PY - 2022/10/6

Y1 - 2022/10/6

N2 - Allogeneic hematopoietic stem cell transplantation (HSCT) is the gold standard curative therapy for infants and children with many inborn errors of immunity (IEI), but adolescents and adults with IEI are rarely referred for transplant. Lack of published HSCT outcome data outside small, single-center studies and perceived high risk of transplant-related mortality have delayed the adoption of HSCT for IEI patients presenting or developing significant organ damage later in life. This large retrospective, multicenter HSCT outcome study reports on 329 IEI patients (age range, 15-62.5 years at HSCT). Patients underwent first HSCT between 2000 and 2019. Primary endpoints were overall survival (OS) and event-free survival (EFS). We also evaluated the influence of IEI-subgroup and IEI-specific risk factors at HSCT, including infections, bronchiectasis, colitis, malignancy, inflammatory lung disease, splenectomy, hepatic dysfunction, and systemic immunosuppression. At a median follow-up of 44.3 months, the estimated OS at 1 and 5 years post-HSCT for all patients was 78% and 71%, and EFS was 65% and 62%, respectively, with low rates of severe acute (8%) or extensive chronic (7%) graft-versus-host disease. On univariate analysis, OS and EFS were inferior in patients with primary antibody deficiency, bronchiectasis, prior splenectomy, hepatic comorbidity, and higher hematopoietic cell transplant comorbidity index scores. On multivariable analysis, EFS was inferior in those with a higher number of IEI-associated complications. Neither age nor donor had a significant effect on OS or EFS. We have identified age-independent risk factors for adverse outcome, providing much needed evidence to identify which patients are most likely to benefit from HSCT.

AB - Allogeneic hematopoietic stem cell transplantation (HSCT) is the gold standard curative therapy for infants and children with many inborn errors of immunity (IEI), but adolescents and adults with IEI are rarely referred for transplant. Lack of published HSCT outcome data outside small, single-center studies and perceived high risk of transplant-related mortality have delayed the adoption of HSCT for IEI patients presenting or developing significant organ damage later in life. This large retrospective, multicenter HSCT outcome study reports on 329 IEI patients (age range, 15-62.5 years at HSCT). Patients underwent first HSCT between 2000 and 2019. Primary endpoints were overall survival (OS) and event-free survival (EFS). We also evaluated the influence of IEI-subgroup and IEI-specific risk factors at HSCT, including infections, bronchiectasis, colitis, malignancy, inflammatory lung disease, splenectomy, hepatic dysfunction, and systemic immunosuppression. At a median follow-up of 44.3 months, the estimated OS at 1 and 5 years post-HSCT for all patients was 78% and 71%, and EFS was 65% and 62%, respectively, with low rates of severe acute (8%) or extensive chronic (7%) graft-versus-host disease. On univariate analysis, OS and EFS were inferior in patients with primary antibody deficiency, bronchiectasis, prior splenectomy, hepatic comorbidity, and higher hematopoietic cell transplant comorbidity index scores. On multivariable analysis, EFS was inferior in those with a higher number of IEI-associated complications. Neither age nor donor had a significant effect on OS or EFS. We have identified age-independent risk factors for adverse outcome, providing much needed evidence to identify which patients are most likely to benefit from HSCT.

KW - Adolescent

KW - Adult

KW - Bronchiectasis/etiology

KW - Child

KW - Graft vs Host Disease

KW - Hematopoietic Stem Cell Transplantation/adverse effects

KW - Humans

KW - Infant

KW - Middle Aged

KW - Retrospective Studies

KW - Transplantation, Homologous

KW - Young Adult

U2 - 10.1182/blood.2022015506

DO - 10.1182/blood.2022015506

M3 - SCORING: Journal article

C2 - 35344580

VL - 140

SP - 1635

EP - 1649

JO - BLOOD

JF - BLOOD

SN - 0006-4971

IS - 14

ER -