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

Beatriz Morillo-Gutierrez, Rita Beier, Kanchan Rao, Lauri Burroughs, Ansgar Schulz, Anna-Maria Ewins, Brenda Gibson, Petr Sedlacek, Ladislav Krol, Brigitte Strahm, Irina Zaidman, Krzysztof Kalwak, Julie-An Talano, Ann Woolfrey, Chris Fraser, Isabelle Meyts, Ingo Müller, Jacek Wachowiak, Maria Ester Bernardo, Paul VeysKarl-Walter Sykora, Andrew R. Gennery, Mary Slatter

Research output: Contribution to journalArticle

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.
Original languageEnglish
Pages (from-to)440 - 448
Number of pages9
JournalBlood
Volume128
Issue number3
DOIs
Publication statusPublished - Jul 21 2016

Fingerprint

treosulfan
Chronic Granulomatous Disease
Stem Cell Transplantation
Stem cells
Chimerism
Graft vs Host Disease
Grafts
Tissue Donors
Transplants
Transplantation (surgical)
Transplantation Conditioning
Toxicity
Survival
Disease-Free Survival
Fertility
Pediatrics
Neutrophils
Stem Cells
Blood Platelets
Retrospective Studies

ASJC Scopus subject areas

  • Immunology
  • Biochemistry
  • Hematology
  • Cell Biology

Cite this

Morillo-Gutierrez, B., Beier, R., Rao, K., Burroughs, L., Schulz, A., Ewins, A-M., ... Slatter, M. (2016). Treosulfan-based conditioning for allogeneic HSCT in children with chronic granulomatous disease: A multicenter experience. Blood, 128(3), 440 - 448. https://doi.org/10.1182/blood-2016-03-704015

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; Strahm, Brigitte; Zaidman, Irina; Kalwak, Krzysztof; Talano, Julie-An; Woolfrey, Ann; Fraser, Chris; Meyts, Isabelle; Müller, Ingo; Wachowiak, Jacek; Bernardo, Maria Ester; Veys, Paul; Sykora, Karl-Walter; Gennery, Andrew R.; Slatter, Mary.

In: Blood, Vol. 128, No. 3, 21.07.2016, p. 440 - 448.

Research output: Contribution to journalArticle

Morillo-Gutierrez, B, Beier, R, Rao, K, Burroughs, L, Schulz, A, Ewins, A-M, Gibson, B, Sedlacek, P, Krol, L, Strahm, B, Zaidman, I, Kalwak, K, Talano, J-A, Woolfrey, A, Fraser, C, Meyts, I, Müller, I, Wachowiak, J, Bernardo, ME, Veys, P, Sykora, K-W, Gennery, AR & Slatter, M 2016, 'Treosulfan-based conditioning for allogeneic HSCT in children with chronic granulomatous disease: A multicenter experience', Blood, vol. 128, no. 3, pp. 440 - 448. https://doi.org/10.1182/blood-2016-03-704015
Morillo-Gutierrez, Beatriz ; Beier, Rita ; Rao, Kanchan ; Burroughs, Lauri ; Schulz, Ansgar ; Ewins, Anna-Maria ; Gibson, Brenda ; Sedlacek, Petr ; Krol, Ladislav ; Strahm, Brigitte ; Zaidman, Irina ; Kalwak, Krzysztof ; Talano, Julie-An ; Woolfrey, Ann ; Fraser, Chris ; Meyts, Isabelle ; Müller, Ingo ; Wachowiak, Jacek ; Bernardo, Maria Ester ; Veys, Paul ; Sykora, Karl-Walter ; Gennery, Andrew R. ; Slatter, Mary. / Treosulfan-based conditioning for allogeneic HSCT in children with chronic granulomatous disease: A multicenter experience. In: Blood. 2016 ; Vol. 128, No. 3. pp. 440 - 448.
@article{06509b15f2f9474e839c3aca5cd12d5a,
title = "Treosulfan-based conditioning for allogeneic HSCT in children with chronic granulomatous disease: A multicenter experience",
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.",
author = "Beatriz Morillo-Gutierrez and Rita Beier and Kanchan Rao and Lauri Burroughs and Ansgar Schulz and Anna-Maria Ewins and Brenda Gibson and Petr Sedlacek and Ladislav Krol and Brigitte Strahm and Irina Zaidman and Krzysztof Kalwak and Julie-An Talano and Ann Woolfrey and Chris Fraser and Isabelle Meyts and Ingo M{\"u}ller and Jacek Wachowiak and Bernardo, {Maria Ester} and Paul Veys and Karl-Walter Sykora and Gennery, {Andrew R.} and Mary Slatter",
year = "2016",
month = "7",
day = "21",
doi = "10.1182/blood-2016-03-704015",
language = "English",
volume = "128",
pages = "440 -- 448",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "3",

}

TY - JOUR

T1 - Treosulfan-based conditioning for allogeneic HSCT in children with chronic granulomatous disease: A multicenter 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

PY - 2016/7/21

Y1 - 2016/7/21

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84979529945&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84979529945&partnerID=8YFLogxK

U2 - 10.1182/blood-2016-03-704015

DO - 10.1182/blood-2016-03-704015

M3 - Article

VL - 128

SP - 440

EP - 448

JO - Blood

JF - Blood

SN - 0006-4971

IS - 3

ER -