Outcome of chronic granulomatous disease - Conventional treatment vs stem cell transplantation.
chronic granulomatous disease (CGD)
conventional treatment
fungal infection
hematopoietic stem cell transplantation (HSCT)
outcome
Journal
Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology
ISSN: 1399-3038
Titre abrégé: Pediatr Allergy Immunol
Pays: England
ID NLM: 9106718
Informations de publication
Date de publication:
04 2021
04 2021
Historique:
revised:
01
08
2020
received:
26
05
2020
accepted:
19
10
2020
pubmed:
30
10
2020
medline:
19
8
2021
entrez:
29
10
2020
Statut:
ppublish
Résumé
Hematopoietic stem cell transplantation (HSCT) can cure chronic granulomatous disease (CGD), but it remains debated whether all conventionally treated CGD patients benefit from HSCT. We retrospectively analyzed 104 conventionally treated CGD patients, of whom 50 patients underwent HSCT. On conventional treatment, seven patients (13%) died after a median time of 16.2 years (interquartile range [IQR] 7.0-18.0). Survival without severe complications was 10 ± 3% (mean ± SD) at the age of 20 years; 85% of patients developed at least one infection, 76% one non-infectious inflammation. After HSCT, 44 patients (88%) were alive at a median follow-up of 2.3 years (IQR 0.8-4.9): Six patients (12%) died from infections. Survival after HSCT was significantly better for patients transplanted ≤8 years (96 ± 4%) or for patients without active complications at HSCT (100%). Eight patients suffered from graft failure (16%); six (12%) developed acute graft-vs-host disease requiring systemic treatment. Conventionally treated patients developed events that required medical attention at a median frequency of 1.7 (IQR 0.8-3.2) events per year vs 0 (IQR 0.0-0.5) in patients beyond the first year post-HSCT. While most conventionally treated CGD patients failed to thrive, catch-up growth after HSCT in surviving patients reached the individual percentiles at the age of diagnosis of CGD. Chronic granulomatous disease patients undergoing HSCT until 8 years of age show excellent survival, but young children need more intense conditioning to avoid graft rejection. Risks and benefits of HSCT for adolescents and adults must still be weighed carefully.
Sections du résumé
BACKGROUND
Hematopoietic stem cell transplantation (HSCT) can cure chronic granulomatous disease (CGD), but it remains debated whether all conventionally treated CGD patients benefit from HSCT.
METHODS
We retrospectively analyzed 104 conventionally treated CGD patients, of whom 50 patients underwent HSCT.
RESULTS
On conventional treatment, seven patients (13%) died after a median time of 16.2 years (interquartile range [IQR] 7.0-18.0). Survival without severe complications was 10 ± 3% (mean ± SD) at the age of 20 years; 85% of patients developed at least one infection, 76% one non-infectious inflammation. After HSCT, 44 patients (88%) were alive at a median follow-up of 2.3 years (IQR 0.8-4.9): Six patients (12%) died from infections. Survival after HSCT was significantly better for patients transplanted ≤8 years (96 ± 4%) or for patients without active complications at HSCT (100%). Eight patients suffered from graft failure (16%); six (12%) developed acute graft-vs-host disease requiring systemic treatment. Conventionally treated patients developed events that required medical attention at a median frequency of 1.7 (IQR 0.8-3.2) events per year vs 0 (IQR 0.0-0.5) in patients beyond the first year post-HSCT. While most conventionally treated CGD patients failed to thrive, catch-up growth after HSCT in surviving patients reached the individual percentiles at the age of diagnosis of CGD.
CONCLUSION
Chronic granulomatous disease patients undergoing HSCT until 8 years of age show excellent survival, but young children need more intense conditioning to avoid graft rejection. Risks and benefits of HSCT for adolescents and adults must still be weighed carefully.
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
576-585Informations de copyright
© 2020 The Authors. Pediatric Allergy and Immunology published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.
Références
Roos D. Chronic granulomatous disease. In: Knaus UG, Leto TL, eds. NADPH oxidases: methods and protocols. Methods in molecular biology. New York, NY: Springer New York; 2019:531-542. https://doi.org/10.1007/978-1-4939-9424-3_32
Arnadottir GA, Norddahl GL, Gudmundsdottir S, et al. A homozygous loss-of-function mutation leading to CYBC1 deficiency causes chronic granulomatous disease. Nat Commun. 2018;9(1):1-9. https://doi.org/10.1038/s41467-018-06964-x
van de Geer A, Nieto-Patlán A, Kuhns DB, et al. Inherited p40phox deficiency differs from classic chronic granulomatous disease. J Clin Invest. 2018;128(9):3957-3975. https://doi.org/10.1172/JCI97116
Harbort CJ, Soeiro-Pereira PV, von Bernuth H, et al. Neutrophil oxidative burst activates ATM to regulate cytokine production and apoptosis. Blood. 2015;126(26):2842-2851. https://doi.org/10.1182/blood-2015-05-645424
de Luca A, Smeekens SP, Casagrande A, et al. IL-1 receptor blockade restores autophagy and reduces inflammation in chronic granulomatous disease in mice and in humans. Proc Natl Acad Sci USA. 2014;111(9):3526-3531. https://doi.org/10.1073/pnas.1322831111
Kelkka T, Kienhöfer D, Hoffmann M, et al. Reactive oxygen species deficiency induces autoimmunity with type 1 interferon signature. Antioxid Redox Signal. 2014;21(16):2231-2245. https://doi.org/10.1089/ars.2013.5828
Magnani A, Mahlaoui N. Managing inflammatory manifestations in patients with chronic granulomatous disease. Paediatr Drugs. 2016;18(5):335-345. https://doi.org/10.1007/s40272-016-0182-4
Martire B, Rondelli R, Soresina A, et al. Clinical features, long-term follow-up and outcome of a large cohort of patients with chronic granulomatous disease: an Italian multicenter study. Clin Immunol. 2008;126(2):155-164. https://doi.org/10.1016/j.clim.2007.09.008
Cole T, Pearce MS, Cant AJ, Cale CM, Goldblatt D, Gennery AR. Clinical outcome in children with chronic granulomatous disease managed conservatively or with hematopoietic stem cell transplantation. J Allergy Clin Immunol. 2013;132(5):1150-1155. https://doi.org/10.1016/j.jaci.2013.05.031
Kuhns DB, Alvord WG, Heller T, et al. Residual NADPH oxidase and survival in chronic granulomatous disease. N Engl J Med. 2010;363(27):2600-2610. https://doi.org/10.1056/NEJMoa1007097
Cole T, McKendrick F, Titman P, et al. Health related quality of life and emotional health in children with chronic granulomatous disease: a comparison of those managed conservatively with those that have undergone haematopoietic stem cell transplant. J Clin Immunol. 2013;33(1):8-13. https://doi.org/10.1007/s10875-012-9758-0
Dunogué B, Pilmis B, Mahlaoui N, et al. Chronic granulomatous disease in patients reaching adulthood: a nationwide study in France. Clin Infect Dis. 2017;64(6):767-775. https://doi.org/10.1093/cid/ciw837
Horwitz ME, Barrett AJ, Brown MR, et al. Treatment of chronic granulomatous disease with nonmyeloablative conditioning and a T-cell-depleted hematopoietic allograft. N Engl J Med. 2001;344(12):881-888. https://doi.org/10.1056/NEJM200103223441203
Seger RA. Treatment of chronic granulomatous disease with myeloablative conditioning and an unmodified hemopoietic allograft: a survey of the European experience, 1985-2000. Blood. 2002;100(13):4344-4350. https://doi.org/10.1182/blood-2002-02-0583
Güngör T, Teira P, Slatter M, et al. Reduced-intensity conditioning and HLA-matched haemopoietic stem-cell transplantation in patients with chronic granulomatous disease: a prospective multicentre study. Lancet. 2014;383(9915):436-448. https://doi.org/10.1016/S0140-6736(13)62069-3
Morillo-Gutierrez B, Beier R, Rao K, et al. Treosulfan based conditioning for allogeneic HSCT in children with chronic granulomatous disease: a multicentre experience. Blood. 2016;128(3):440-448. https://doi.org/10.1182/blood-2016-03-704015
Marciano BE, Holland SM. Primary immunodeficiency diseases: current and emerging therapeutics. Front Immunol. 2017;8:937. https://doi.org/10.3389/fimmu.2017.00937
Glucksberg H, Storb R, Fefer A, et al. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors. Transplantation. 1974;18(4):295-304. https://doi.org/10.1097/00007890-197410000-00001
Shulman HM, Sullivan KM, Weiden PL, et al. Chronic graft-versus-host syndrome in man. A long-term clinicopathologic study of 20 Seattle patients. Am J Med. 1980;69(2):204-217. https://doi.org/10.1016/0002-9343(80)90380-0
Pulvirenti F, Sangerardi M, Plebani A, et al. Health-related quality of life and emotional difficulties in chronic granulomatous disease: data on adult and pediatric patients from italian network for primary immunodeficiency (IPINet). J Clin Immunol. 2020;40(2):289-298. https://doi.org/10.1007/s10875-019-00725-1
Åhlin A, Fugeläng J, de Boer M, Ringden O, Fasth A, Winiarski J. Chronic granulomatous disease - haematopoietic stem cell transplantation versus conventional treatment. Acta Paediatr. 2013;102(11):1087-1094. https://doi.org/10.1111/apa.12384
Parta M, Kelly C, Kwatemaa N, et al. Allogeneic reduced-intensity hematopoietic stem cell transplantation for chronic granulomatous disease: a single-center prospective trial. J Clin Immunol. 2017;37(6):548-558. https://doi.org/10.1007/s10875-017-0422-6
Yonkof JR, Gupta A, Fu P, Garabedian E, Dalal J, the United States Immunodeficiency Network Consortium. Role of allogeneic hematopoietic stem cell transplant for chronic granulomatous disease (CGD): a report of the United States immunodeficiency network. J Clin Immunol. 2019;39(4):448-458. https://doi.org/10.1007/s10875-019-00635-2
Lum SH, Flood T, Hambleton S, et al. Two decades of excellent transplant survival for chronic granulomatous disease: a supraregional immunology transplant center report. Blood. 2019;133(23):2546-2549. https://doi.org/10.1182/blood.2019000021
Chiesa R, Wang J, Blok H-J, et al. Haematopoietic cell transplantation in chronic granulomatous disease: a study on 712 children and adults. Blood. 2020;136(10):1201-1211. https://doi.org/10.1182/blood.2020005590
Oshrine B, Morsheimer M, Heimall J, Bunin N. Reduced-intensity conditioning for hematopoietic cell transplantation of chronic granulomatous disease. Pediatr Blood Cancer. 2015;62(2):359-361. https://doi.org/10.1002/pbc.25225
Hoenig M, Niehues T, Siepermann K, et al. Successful HLA haploidentical hematopoietic SCT in chronic granulomatous disease. Bone Marrow Transplant. 2014;49(10):1337-1338. https://doi.org/10.1038/bmt.2014.125
Tang X, Zhang Y, Jing Y, et al. Allogeneic hematopoietic stem cell transplantation using unrelated cord blood or unmanipulated haploidentical donors is effective in pediatric chronic granulomatous disease with inflammatory complications and severe infection. Bone Marrow Transplant. 2020;55(9):1875-1878. https://doi.org/10.1038/s41409-020-0864-y
Parta M, Hilligoss D, Kelly C, et al. Failure to prevent severe graft-versus-host disease in haploidentical hematopoietic cell transplantation with post-transplant cyclophosphamide in chronic granulomatous disease. J Clin Immunol. 2020;40(4):619-624. https://doi.org/10.1007/s10875-020-00772-z
Kohn DB, Booth C, Kang EM, et al. Lentiviral gene therapy for X-linked chronic granulomatous disease. Nat Med. 2020;26(2):200-206. https://doi.org/10.1038/s41591-019-0735-5