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

Morillo-Gutierrez, Beatriz ; Beier, Rita ; Rao, Kanchan ; Burroughs, Lauri ; Schulz, Ansgar ; Ewins, Anna-Maria ; Gibson, Brenda ; Sedlacek, Petr ; Krol, Ladislav LU orcid and Strahm, Brigitte , et al. (2016) In Blood 128(3). p.440-448
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;... (More)

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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type
Contribution to journal
publication status
published
subject
keywords
Acute Disease, Adolescent, Adult, Allografts, Blood Platelets/metabolism, Busulfan/administration & dosage, Child, Child, Preschool, Disease-Free Survival, Female, Follow-Up Studies, Graft Survival/drug effects, Graft vs Host Disease/blood, Granulomatous Disease, Chronic/blood, Hematopoietic Stem Cell Transplantation, Humans, Infant, Male, Neutrophils/metabolism, Survival Rate, Transplantation Conditioning/methods
in
Blood
volume
128
issue
3
pages
440 - 448
publisher
American Society of Hematology
external identifiers
  • scopus:84979529945
  • pmid:27216217
ISSN
1528-0020
DOI
10.1182/blood-2016-03-704015
language
English
LU publication?
no
id
836a0b8d-34f5-486b-a2e3-7b82a2a6f217
date added to LUP
2021-04-29 08:19:02
date last changed
2024-07-28 15:17:51
@article{836a0b8d-34f5-486b-a2e3-7b82a2a6f217,
  abstract     = {{<p>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.</p>}},
  author       = {{Morillo-Gutierrez, Beatriz and Beier, Rita and Rao, Kanchan and Burroughs, Lauri and Schulz, Ansgar and Ewins, Anna-Maria and Gibson, Brenda and Sedlacek, Petr and Krol, Ladislav and Strahm, Brigitte and Zaidman, Irina and Kalwak, Krzysztof and Talano, Julie-An and Woolfrey, Ann and Fraser, Chris and Meyts, Isabelle and Müller, Ingo and Wachowiak, Jacek and Bernardo, Maria Ester and Veys, Paul and Sykora, Karl-Walter and Gennery, Andrew R and Slatter, Mary}},
  issn         = {{1528-0020}},
  keywords     = {{Acute Disease; Adolescent; Adult; Allografts; Blood Platelets/metabolism; Busulfan/administration & dosage; Child; Child, Preschool; Disease-Free Survival; Female; Follow-Up Studies; Graft Survival/drug effects; Graft vs Host Disease/blood; Granulomatous Disease, Chronic/blood; Hematopoietic Stem Cell Transplantation; Humans; Infant; Male; Neutrophils/metabolism; Survival Rate; Transplantation Conditioning/methods}},
  language     = {{eng}},
  month        = {{07}},
  number       = {{3}},
  pages        = {{440--448}},
  publisher    = {{American Society of Hematology}},
  series       = {{Blood}},
  title        = {{Treosulfan-based conditioning for allogeneic HSCT in children with chronic granulomatous disease : a multicenter experience}},
  url          = {{http://dx.doi.org/10.1182/blood-2016-03-704015}},
  doi          = {{10.1182/blood-2016-03-704015}},
  volume       = {{128}},
  year         = {{2016}},
}