Treosulfan-based conditioning for allogeneic HSCT in children with chronic granulomatous disease: a multicenter
Beatriz Morillo-Gutierrez1, Rita Beier2, Kanchan Rao3
1Department of Paediatric Immunology, Great North Children´s Hospital, Newcastle Upon Tyne, United Kingdom;
Insights
Treosulfan-based conditioning is safe and effective for pediatric patients undergoing hemopoietic stem cell transplantation (HSCT) for Chronic Granulomatous Disease (CGD). This approach achieves high survival rates and excellent donor chimerism in high-risk children.
Area of Science:
- Hematology
- Immunology
- Pediatric Oncology
Background:
- Allogeneic hemopoietic stem cell transplantation (HSCT) offers a cure for Chronic Granulomatous Disease (CGD).
- Reduced-intensity conditioning regimens are crucial for improving HSCT outcomes by mitigating complications like graft failure and GVHD.
Purpose of the Study:
- To evaluate the safety and efficacy of treosulfan-based conditioning regimens in pediatric patients with CGD undergoing HSCT.
- To analyze outcomes including engraftment, graft-versus-host disease (GVHD), chimerism, and survival rates.
Main Methods:
- Retrospective analysis of 70 pediatric CGD patients transplanted between 2006 and 2015 across 16 international centers.
- Data collection included pre-HSCT risk features, conditioning agents, donor types, stem cell sources, toxicities, engraftment, GVHD, chimerism, viral reactivation, complications, and survival.
- Focus on treosulfan-containing conditioning regimens, with analysis of HLA-matched, mismatched, and haploidentical transplants.
Main Results:
- High-risk features were present in 91% of patients; 91.4% overall survival and 81.4% event-free survival were observed at a median follow-up of 34 months.
- No major toxicity was reported. Median neutrophil and platelet engraftment occurred at 17 and 16 days, respectively.
- Cumulative incidence of acute grade III-IV GVHD was 12%, with 9 cases of chronic GVHD. 80% of surviving patients achieved ≥95% myeloid donor chimerism.
Conclusions:
- Treosulfan-based conditioning is a safe and effective strategy for HSCT in pediatric CGD patients, including those with high-risk features.
- The regimen achieves excellent survival rates and high myeloid chimerism, suggesting its suitability for this patient population.
- Further research is warranted to compare treosulfan regimens with others and assess long-term outcomes, particularly regarding fertility.
Abstract:
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.
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