Treosulfan based conditioning for allogeneic HSCT in children with chronic granulomatous disease: a multicentre experience

TY - JOUR

T1 - Treosulfan based conditioning for allogeneic HSCT in children with chronic granulomatous disease: a multicentre experience

AU - Morillo-Gutierrez, Beatriz

AU - Beier, Rita

AU - Rao, Kanchan

AU - Burroughs, Lauri

AU - Schulz, Ansgar

AU - Ewins, Anna-Maria

AU - Gibson, Brenda

AU - Sedlacek, Petr

AU - Krol, Ladislav

AU - Strahm, Brigitte

AU - Zaidman, Irina

AU - Kalwak, Krzysztof

AU - Talano, Julie-An

AU - Woolfrey, Ann

AU - Fraser, Chris

AU - Meyts, Isabelle

AU - Müller, Ingo

AU - Wachowiak, Jacek

AU - Bernardo, Maria Ester

AU - Veys, Paul

AU - Sykora, Karl-Walter

AU - Gennery, Andrew R

AU - Slatter, Mary

N1 - Copyright © 2016 American Society of Hematology.

PY - 2016/5/23

Y1 - 2016/5/23

N2 - Chronic granulomatous disease (CGD) can be cured by allogeneic haemopoietic stem-cell transplantation (HSCT). Complications include graft failure, graft-versus-host disease (GvHD), infection and transplant-related mortality (TRM); therefore, reduced-intensity conditioning (RIC) 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 paediatric 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; IQR 46-232) from 16 centres worldwide were transplanted between 2006 and 2015. Ninety-one % had high-risk features. Fifty-seven HLA-matched donor, 12 HLA-mismatched donor and 1 CD3+TCR alpha beta/CD19 depleted parental haploidentical transplants were performed. No major toxicity was reported. Median times to neutrophil and platelet engraftment were 17 (IQR15-35) and 16 (IQR13-50) days. At a median follow-up of 34 months (IQR13-102), the overall survival was 91.4% and EFS 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% 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.

AB - Chronic granulomatous disease (CGD) can be cured by allogeneic haemopoietic stem-cell transplantation (HSCT). Complications include graft failure, graft-versus-host disease (GvHD), infection and transplant-related mortality (TRM); therefore, reduced-intensity conditioning (RIC) 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 paediatric 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; IQR 46-232) from 16 centres worldwide were transplanted between 2006 and 2015. Ninety-one % had high-risk features. Fifty-seven HLA-matched donor, 12 HLA-mismatched donor and 1 CD3+TCR alpha beta/CD19 depleted parental haploidentical transplants were performed. No major toxicity was reported. Median times to neutrophil and platelet engraftment were 17 (IQR15-35) and 16 (IQR13-50) days. At a median follow-up of 34 months (IQR13-102), the overall survival was 91.4% and EFS 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% 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.

U2 - 10.1182/blood-2016-03-704015

DO - 10.1182/blood-2016-03-704015

M3 - SCORING: Journal article

C2 - 27216217

VL - 128

SP - 440

EP - 448

JO - BLOOD

JF - BLOOD

SN - 0006-4971

IS - 3

ER -