Excellent outcomes following hematopoietic cell transplantation for Wiskott-Aldrich syndrome: a PIDTC report
- 4 June 2020
- journal article
- research article
- Published by American Society of Hematology in Blood
- Vol. 135 (23), 2094-2105
- https://doi.org/10.1182/blood.2019002939
Abstract
Wiskott-Aldrich syndrome (WAS) is an X-linked disease caused by mutations in the WAS gene leading to thrombocytopenia, eczema, recurrent infections, autoimmune disease, and malignancy. Hematopoietic cell transplantation (HCT) is the primary curative approach, with the goal of correcting the underlying immunodeficiency and thrombocytopenia. HCT outcomes have improved over time, particularly for patients with HLA-matched sibling and unrelated donors. Here we report the outcomes of 129 patients with WAS who underwent HCT at 29 Primary Immune Deficiency Treatment Consortium centers between 2005 and 2015. Median age at HCT was 1.2 years. Most patients (65%) received myeloablative busulfan-based conditioning. With a median follow-up of 4.5 years, the 5-year overall survival (OS) was 91%. Superior 5-year OS was observed in patients <5 vs. ≥5 years old at the time of HCT (94% vs. 66%, overall p=0.0008). OS was excellent regardless of donor type even in cord blood recipients (90%). Conditioning intensity did not impact OS, but was associated with donor T-cell and myeloid engraftment post-HCT. Specifically, patients who received fludarabine/melphalan-based reduced-intensity regimens were more likely to have donor myeloid chimerism 95%) versus low-level (5%-49%) donor myeloid engraftment. In summary, HCT outcomes for WAS have improved since 2005 compared to prior reports. HCT at a younger age continues to be associated with superior outcomes supporting the recommendation for early HCT. High-level donor myeloid engraftment is important for platelet reconstitution following either myeloablative or busulfan-containing reduced intensity conditioning. (www.clinicaltrials.gov NCT02064933.)This publication has 46 references indexed in Scilit:
- Long-term outcome and lineage-specific chimerism in 194 patients with Wiskott-Aldrich syndrome treated by hematopoietic cell transplantation in the period 1980-2009: an international collaborative studyBlood, 2011
- Clinical spectrum, pathophysiology and treatment of the Wiskott–Aldrich syndromeCurrent Opinion in Hematology, 2011
- Stem-Cell Gene Therapy for the Wiskott–Aldrich SyndromeThe New England Journal of Medicine, 2010
- Defining the Intensity of Conditioning Regimens: Working DefinitionsTransplantation and Cellular Therapy, 2009
- Long-term outcome following hematopoietic stem-cell transplantation in Wiskott-Aldrich syndrome: collaborative study of the European Society for Immunodeficiencies and European Group for Blood and Marrow TransplantationBlood, 2008
- Stem cell transplantation for the Wiskott–Aldrich syndrome: a single-center experience confirms efficacy of matched unrelated donor transplantationBone Marrow Transplantation, 2006
- Once-daily intravenous busulfan and fludarabine: clinical and pharmacokinetic results of a myeloablative, reduced-toxicity conditioning regimen for allogeneic stem cell transplantation in AML and MDSBlood, 2004
- A multiinstitutional survey of the Wiskott-Aldrich syndromeThe Journal of Pediatrics, 1994
- Localization of the gene for the Wiskott-Aldrich syndrome between two flanking markers, TIMP and DXS255, on Xp11.22–Xp11.3Genomics, 1991
- BONE-MARROW TRANSPLANTATION IN A PATIENT WITH THE WISKOTT-ALDRICH SYNDROMEThe Lancet, 1968