International study of BMT outcomes provides a wealth of data to assess individual risk for CGD transplants
The largest study ever conducted on the success rates of bone marrow transplant (BMT) in children and adults with CGD has been published recently in the journal Blood.
The work found excellent outcomes and a low incidence of graft failure and mortality and further underlines the importance of stem cell transplants as a cure for CGD.
The research involved analysis of the records of 712 patients who had received a stem cell transplant between 1993 and 2018 and was a major collaborative effort made possible through the European Society for Blood and Marrow Transplantation (EBMT) with information collected from 101 EBMT centres.
The study included 635 children, who were aged < 18 years old and 77 adult patients (older than 18 years of age) and included patients with X-linked CGD and autosomal recessive CGD. The average ages of these two groups at transplant were 5 years old (range: a few months old to 18 years of age) and 22 years old (range: 18 to 48 years of age). This large data set allowed analysis of the impact of age, type of donor and tissue match, health complications, pre-transplant conditioning treatments on outcomes such as overall survival rates, event free survival, donor engraftment, graft failure and graft versus host disease (GvHD), to be analysed.
Overall survival for the whole group at 3 years post-transplant was 85.7% (with 95% of patients falling between the range of 83 – 89%) and event free survival 75.8% (with 95% of patients falling between the range of 72 – 79%). The disease burden in the whole group was significant prior to transplant, with 47% of patients having a history of infections, 24% with chronic colitis and 9% and 5% with liver and kidney complications, respectively. There was a low incidence of graft failure and mortality for all age groups studied.
Dr Robert Chiesa, Consultant in Bone Marrow Transplantation, at the Great Ormond Street Hospital, and lead author on the paper said
"This is a pivotal study on outcomes of allogeneic haematopoietic stem cell transplant in children and adults affected by CGD. The richness of the data allows us, for the first time, a detailed analysis of the impact of age, donor type, degree of tissue-type mismatch and pre-transplant complications on different transplant outcomes. The study showed excellent survival rates and an acceptable incidence of acute and chronic graft versus host disease (GvHD). Interestingly, over 87% of the patients in this study had received a transplant after 2006, indicating a recent and significant change of practice in the management of patients with CGD.
The best survival rates were found in patients who had a stem cell transplant at a young age with a matched family donor and emphasises that transplant should be strongly considered at a younger age, especially when there is a well-matched donor available. Less favourable outcomes were found for older patients. However, adults, as we know, can benefit significantly from transplant and this should strongly be considered as a treatment option. Recipients of transplants with one tissue type mismatch also had poorer outcomes but with new graft manipulations such as T cell depletion the results are likely to improve over time.
The wealth of data in this study is invaluable for counselling CGD patients and their families about their individual risk when considering a stem cell transplant".
The research findings were published with an accompanying commentary by Professor Emma Morris, Director of the Division of Infection & Immunity and Professor of Clinical Cell & Gene Therapy at University College, London, entitled "HCT for CGD? Yes, and the sooner the better".
This article (click here for the link) discusses the results further and makes the conclusion that it is always best to transplant CGD patients early in a patients life.
Summary of other key findings
Best outcomes were achieved using a matched family donor with an overall survival rate of 89.4% and event-free survival of 85.3%.
Transplants using a 10/10 HLA matched unrelated donor had an overall survival rate of 87.7% and event-free survival of 74.4% due to a higher risk of graft failure.
Mismatched transplants (9/10 HLA matched) resulted in overall survival rates of 76% and event-free survival of 66%.
Overall survival rate was influenced by age, pre-transplant colitis and donor type (as above). Older age was associated with reduced survival and increased GvHD, with an overall 76% survival rate (with 95% of patients falling between the range of 66 – 86%).
The genetic pattern of CGD inheritance did not influence the survival rate post-transplant.
The most common pre-BMT conditioning regimen used was busulphan and fludarabine (45.5%) but the other types of conditioning, including busulphan/cyclophosphamide; treosulphan/fludarabine; treosulphan/ fludarabine/thiotepa, did not influence the overall survival or event free survival rates.
The incidence of graft failure was influenced by donor type, choice of conditioning regimen and type of stem cell source.
Ninety-eight patients underwent a second transplant because of graft rejection or progressive falling chimerism (a measure of monitoring disease relapse). For these patients, the overall survival rate at three years post-transplant was still quite good: 76%, with 95% of patients falling between the range of 67 – 86%.
Ninety-two patients died after transplant. This was due to infection (42%), GvHD (33%), toxicity/organ damage (11%), or other complications (14%).
Haematopoietic Cell Transplantation in Chronic Granulomatous Disease: a Study on 712 Children and Adults. Robert Chiesa, Junfeng Wang, Henric-Jan Blok, Sheree Hazelaar, Benedicte Neven, Despina Moshous, Ansgar S Schulz, Manfred Hoenig, Fabian Hauck, Amal Al Seraihy, Jolanta Gozdzik, Per T Ljungman, Caroline Lindemans, Juliana Fernandes, Krzysztof Kalwak Brigitte Strahm, Urs Schanz, Petr Sedlacek, Karl-Walter Sykora, Serap Aksoylar, Franco Locatelli, Polina Stepensky, Robert F Wynn, Su Han Lum, Marco Zecca, Fulvio Porta, Mervi H Taskinen, Brenda Es Gibson, Susanne Matthes-Martin, Musa Karakukcu, Mathias M Hauri-Hohl, Paul Veys, Andrew R Gennery, Giovanna Lucchini, Matthias Felber, Michael H Albert, Dmitry Balashov, Arjan C Lankester, Tayfun Güngör, Mary Slatter.
Blood 2020 Jul 2; blood.2020005590. doi: 10.1182/blood.2020005590. Online ahead of print.
The full paper can be found here : https://ashpublications.org/blood/article/136/10/1121/463530/HCT-for-CGD-Yes-and-the-sooner-the-better
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