Treosulfan-based conditioning for allogeneic HSCT in children with chronic granulomatous disease: a multicenter experience. Blood 2016 Jul 21;128(3):440-8
Date
05/25/2016Pubmed ID
27216217Pubmed Central ID
PMC4957165DOI
10.1182/blood-2016-03-704015Scopus ID
2-s2.0-84979529945 (requires institutional sign-in at Scopus site) 127 CitationsAbstract
Chronic granulomatous disease (CGD) can be cured by allogeneic hemopoietic stem cell transplantation (HSCT). Complications include graft failure, graft-versus-host disease (GVHD), infection, and transplant-related mortality; therefore, reduced-intensity conditioning regimens are being used to improve outcomes. In this retrospective study, the aim was to determine the outcome of treosulfan-based conditioning in HSCT for pediatric patients with CGD. The following data were collected: risk features pre-HSCT, additional conditioning agents, donor type and stem cell source, toxicity, engraftment, GVHD, chimerism, viral reactivation, post-HSCT complications, length of follow-up, and outcome. Seventy patients (median age, 107 months; interquartile range [IQR], 46-232 months) from 16 centers worldwide were transplanted between 2006 and 2015. Ninety-one percent had high-risk features. Fifty-seven HLA-matched donors, 12 HLA-mismatched donors, and 1 CD3(+)TCR αβ/CD19 depleted parental haploidentical transplants were performed. No major toxicity was reported. Median times to neutrophil and platelet engraftment were 17 (IQR, 15-35) and 16 (IQR, 13-50) days. At a median follow-up of 34 months (IQR, 13-102 months), the overall survival was 91.4%, and event-free survival was 81.4%. The cumulative incidence of acute grade III-IV GVHD was 12%. Nine patients developed chronic GVHD. When split cell chimerism was available, 95% or more myeloid donor chimerism was documented in 80% of surviving patients. Secondary graft failure occurred in 12% of patients. Treosulfan-containing conditioning regimens can be used safely in HSCT for children with CGD and high-risk clinical features, achieving excellent survival with high myeloid chimerism. Further studies are needed to compare with other regimens and evaluate the long-term outcome, particularly on fertility.
Author List
Morillo-Gutierrez B, Beier R, Rao K, Burroughs L, Schulz A, Ewins AM, Gibson B, Sedlacek P, Krol L, Strahm B, Zaidman I, Kalwak K, Talano JA, Woolfrey A, Fraser C, Meyts I, Müller I, Wachowiak J, Bernardo ME, Veys P, Sykora KW, Gennery AR, Slatter MAuthor
Julie-An M. Talano MD Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Acute DiseaseAdolescent
Adult
Allografts
Blood Platelets
Busulfan
Child
Child, Preschool
Disease-Free Survival
Female
Follow-Up Studies
Graft Survival
Graft vs Host Disease
Granulomatous Disease, Chronic
Hematopoietic Stem Cell Transplantation
Humans
Infant
Male
Neutrophils
Survival Rate
Transplantation Conditioning
