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. (© 2016 by The American Society of Hematology.)Eur Respir J. 2015 Jun;45(6):1613-23. (PMID: 25614174); Int J Hematol. 2009 Dec;90(5):571-5. (PMID: 19866337); Blood. 2005 Jan 15;105(2):879-85. (PMID: 15367433); Drug Discov Today. 2014 Oct;19(10):1572-86. (PMID: 24747172); Expert Rev Clin Immunol. 2012 Mar;8(3):255-66; quiz 267. (PMID: 22390490); Immunol Allergy Clin North Am. 2010 May;30(2):195-208. (PMID: 20493396); Pediatr Blood Cancer. 2015 Feb;62(2):359-361. (PMID: 25175046); Biol Blood Marrow Transplant. 2011 Jan;17(1 Suppl):S123-31. (PMID: 21195301); Clin Infect Dis. 2015 Apr 15;60(8):1176-83. (PMID: 25537876); Biol Blood Marrow Transplant. 2014 Dec;20(12 ):1996-2003. (PMID: 25196857); N Engl J Med. 2001 Mar 22;344(12):881-8. (PMID: 11259721); Lancet. 2014 Feb 1;383(9915):436-48. (PMID: 24161820); Ann Hematol. 2015 Feb;94(2):297-306. (PMID: 25231927); Clin Exp Immunol. 2008 May;152(2):211-8. (PMID: 18410635); Blood. 2002 Dec 15;100(13):4344-50. (PMID: 12393596); J Infect. 2014 Nov;69 Suppl 1:S32-5. (PMID: 25264161); Blood. 2011 Apr 21;117(16):4367-75. (PMID: 21325599); PLoS One. 2013 Apr 26;8(4):e61637. (PMID: 23637873); Br J Haematol. 2009 Apr;145(1):73-83. (PMID: 19222467); Bone Marrow Transplant. 2015 Dec;50(12):1536-41. (PMID: 26259076); Blood. 2016 Jan 28;127(4):503-12. (PMID: 26644451); J Clin Immunol. 2013 Jan;33(1):8-13. (PMID: 23011479); J Allergy Clin Immunol. 2013 Nov;132(5):1150-5. (PMID: 23870668); Br J Haematol. 2015 Sep;170(5):719-26. (PMID: 25974284). Linking ISSN: 00064971. Subset: MEDLINE; Grant Information: P01 HL122173 United States HL NHLBI NIH HHS Date of Electronic Publication: 2016 May 23. Current Imprints: Publication: 2021- : [New York] : Elsevier; Original Imprints: Publication: New York, Grune & Stratton [etc.] <br />