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.

Department of Microbiology and Immunology Department of Pediatrics University Hospitals Leuven KU Leuven Leuven Belgium;

Department of Paediatric Immunology Great North Children´s Hospital Newcastle Upon Tyne United Kingdom;

Department of Paediatric Immunology Great North Children´s Hospital Newcastle Upon Tyne United Kingdom; Institute of Cellular Medicine Newcastle University Newcastle Upon Tyne United Kingdom

Department of Pediatric Hematology and Oncology Teaching Hospital Motol Prague Czech Republic;

Department of Pediatrics University Medical Center Ulm Ulm Germany;

Fred Hutchinson Cancer Research Center Seattle WA; The University of Washington School of Medicine Seattle WA;

Hannover Medical School Hannover Germany;

Lady Cilento Children's Hospital Brisbane Australia;

Medical College of Wisconsin Milwaukee WI;

Paediatric Bone Marrow Transplant Great Ormond Street Hospital London United Kingdom;

Paediatric Bone Marrow Transplantation Schiehallion Unit Royal Hospital for Sick Children Glasgow United Kingdom;

Pediatric Haematology Oncology University Medical Centre Freiburg Germany;

Rambam Hospital Haifa Israel;

San Raffaele Telethon Institute for Gene Therapy Pediatric Immunohematology and Bone Marrow Transplantation Unit San Raffaele Scientific Institute Milan Italy; and

University Medical Center Hamburg Eppendorf Hamburg Germany;

University of Medical Sciences Poznan Poland;

Wroclaw Medical University Wroclaw Poland;

Blood. 2016 Jul 21;128(3):322-3. doi: 10.1182/blood-2016-06-719922. PubMed

Blood. 2016 Nov 24;128(21):2585. doi: 10.1182/blood-2016-10-745455. PubMed

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