TY - JOUR
T1 - Hematopoietic stem cell transplantation for Wiskott-Aldrich syndrome
T2 - an EBMT Inborn Errors Working Party analysis
AU - Albert, Michael H.
AU - Slatter, Mary A.
AU - Gennery, Andrew R.
AU - Güngör, Tayfun
AU - Bakunina, Katerina
AU - Markovitch, Benyamin
AU - Hazelaar, Sheree
AU - Sirait, Tiarlan
AU - Courteille, Virginie
AU - Aiuti, Alessandro
AU - Aleinikova, Olga V.
AU - Balashov, Dmitry
AU - Bernardo, Maria Ester
AU - Bodova, Ivana
AU - Bruno, Benedicte
AU - Cavazzana, Marina
AU - Chiesa, Robert
AU - Fischer, Alain
AU - Hauck, Fabian
AU - Ifversen, Marianne
AU - Kałwak, Krzysztof
AU - Klein, Christoph
AU - Kulagin, Alexander
AU - Kupesiz, Alphan
AU - Kuskonmaz, Baris
AU - Lindemans, Caroline A.
AU - Locatelli, Franco
AU - Lum, Su Han
AU - Maschan, Alexey
AU - Meisel, Roland
AU - Moshous, Despina
AU - Porta, Fulvio
AU - Sauer, Martin G.
AU - Sedlacek, Petr
AU - Schulz, Ansgar
AU - Suarez, Felipe
AU - Vallée, Tanja C.
AU - Winiarski, Jacek H.
AU - Zecca, Marco
AU - Neven, Bénédicte
AU - Veys, Paul
AU - Lankester, Arjan C.
N1 - © 2022 by The American Society of Hematology.
PY - 2022/3/31
Y1 - 2022/3/31
N2 - Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative treatment for patients affected by Wiskott-Aldrich syndrome (WAS). Reported HSCT outcomes have improved over time with respect to overall survival, but some studies have identified older age and HSCT from alternative donors as risk factors predicting poorer outcome. We analyzed 197 patients undergoing transplant at European Society for Blood and Marrow Transplantation centers between 2006 and 2017 who received conditioning as recommended by the Inborn Errors Working Party (IEWP): either busulfan (n = 103) or treosulfan (n = 94) combined with fludarabine ± thiotepa. After a median follow-up post-HSCT of 44.9 months, 176 patients were alive, resulting in a 3-year overall survival of 88.7% and chronic graft-versus-host disease (GVHD)-free survival (events include death, graft failure, and severe chronic GVHD) of 81.7%. Overall survival and chronic GVHD-free survival were not significantly affected by conditioning regimen (busulfan- vs treosulfan-based), donor type (matched sibling donor/matched family donor vs matched unrelated donor/mismatched unrelated donor vs mismatched family donor), or period of HSCT (2006-2013 vs 2014-2017). Patients aged <5 years at HSCT had a significantly better overall survival. The overall cumulative incidences of grade III to IV acute GVHD and extensive/moderate/severe chronic GVHD were 6.6% and 2.1%, respectively. Patients receiving treosulfan-based conditioning had a higher incidence of graft failure and mixed donor chimerism and more frequently underwent secondary procedures (second HSCT, unconditioned stem cell boost, donor lymphocyte infusion, or splenectomy). In summary, HSCT for WAS with conditioning regimens currently recommended by IEWP results in excellent survival and low rates of GVHD, regardless of donor or stem cell source, but age ≥5 years remains a risk factor for overall survival.
AB - Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative treatment for patients affected by Wiskott-Aldrich syndrome (WAS). Reported HSCT outcomes have improved over time with respect to overall survival, but some studies have identified older age and HSCT from alternative donors as risk factors predicting poorer outcome. We analyzed 197 patients undergoing transplant at European Society for Blood and Marrow Transplantation centers between 2006 and 2017 who received conditioning as recommended by the Inborn Errors Working Party (IEWP): either busulfan (n = 103) or treosulfan (n = 94) combined with fludarabine ± thiotepa. After a median follow-up post-HSCT of 44.9 months, 176 patients were alive, resulting in a 3-year overall survival of 88.7% and chronic graft-versus-host disease (GVHD)-free survival (events include death, graft failure, and severe chronic GVHD) of 81.7%. Overall survival and chronic GVHD-free survival were not significantly affected by conditioning regimen (busulfan- vs treosulfan-based), donor type (matched sibling donor/matched family donor vs matched unrelated donor/mismatched unrelated donor vs mismatched family donor), or period of HSCT (2006-2013 vs 2014-2017). Patients aged <5 years at HSCT had a significantly better overall survival. The overall cumulative incidences of grade III to IV acute GVHD and extensive/moderate/severe chronic GVHD were 6.6% and 2.1%, respectively. Patients receiving treosulfan-based conditioning had a higher incidence of graft failure and mixed donor chimerism and more frequently underwent secondary procedures (second HSCT, unconditioned stem cell boost, donor lymphocyte infusion, or splenectomy). In summary, HSCT for WAS with conditioning regimens currently recommended by IEWP results in excellent survival and low rates of GVHD, regardless of donor or stem cell source, but age ≥5 years remains a risk factor for overall survival.
KW - Busulfan/therapeutic use
KW - Child, Preschool
KW - Graft vs Host Disease/etiology
KW - Hematopoietic Stem Cell Transplantation/adverse effects
KW - Humans
KW - Retrospective Studies
KW - Tissue Donors
KW - Transplantation Conditioning/methods
KW - Treatment Outcome
KW - Wiskott-Aldrich Syndrome/therapy
UR - http://www.scopus.com/inward/record.url?scp=85127136275&partnerID=8YFLogxK
U2 - 10.1182/blood.2021014687
DO - 10.1182/blood.2021014687
M3 - Article
C2 - 35100336
SN - 0006-4971
VL - 139
SP - 2066
EP - 2079
JO - Blood : the Journal of Hematology
JF - Blood : the Journal of Hematology
IS - 13
ER -