Efficacy Of Allogeneic Hematopoietic Stem Cell Transplantation In 22 Chinese Children With Chronic Granulomatous Disease

Objective: In order to evaluate the efficacy of allo-HSCT in chronic granulomatous disease,this study is conducted to provide suggestion for clinical decision.Methods: Patients suffered from CGD who have performed allo-HSCT from 2012 May to 2018 January in our center were included.All of these patients have received allogeneic stem cell transplantation(allo-HSCT),patients were divided into reduced toxicity conditioning(RTC)group and non-RTC group according to condition related toxicity,the clinical manifestations were reviewed,we used myeloablative conditioning regimen and cyclosporine(CsA)plus mycophenolate mofetil(MMF)acted as the major prophylaxis for graft versus host disease(GVHD).Engraftment,overall survival(OS)and complications such as GVHD and condition related toxicity were analyzed.Results: All patients were boys with high risk factors,the median age at HSCT was 18(7,116)months,the median time for neutrophil and platelet engraftment were 11(9,19)days and 11(7,35)days post-transplantation.There is no significant difference in the time of neutrophil engraftment(11.07 Vs 12.57,p=0.158),but there is significant difference in the time of platelet engraftment(12 Vs 14,p=0.042)between HLA matched group and non-HLA matched group.All patients except for the one without engraftment showed 100% donor chimerism 1 year post-transplantation using an informative short tandem repeat(STR)-PCR technique and free of infection.In the median follow-up duration at 18(1,83)months,86.4% patients survived,there is no significant difference in overall survival between HLA matched group and non-HLA matched group(90.9% Vs 81.8%,p=0.507).The cumulative incidence of acute GVHD was 68.2%,the incidence of grade III aGVHD is 9.1%,a high incidence of cGVHD was observed(36.4%).The addition of ATG bears a significant positive prognostic value in avoiding aGVHD,while age at transplantation,HLA match,conditioning regimen,GVHD prophylaxis,dosage of stem cells,donor-recipient blood type,donor-recipient gender have no significant influence in the occurrence of aGVHD.Liver dysfunction(45.5%)and vomiting(54.5%)were major complications after conditioning,only one patient(4.5%)suffered from hemorrhagic cystitis,no VOD or neural toxicity was observed.The incidence of condition-related complications such as liver dysfunction,vomiting,mucositis and myocardial damage in RTC group and non-RTC group were different,but there is no significant difference between them.Conclusion: Myeloablative conditioning regimen obtained stable donor cell chimerism in allo-HSCT for pediatric patients with CGD,accompanied with good tolerance and safety.All patients with high risk factors should accept HSCT as soon as possible when diagnosis is defined to improve survival and quality of life,but multi-center large sample study and long term follow-up are still needed to vertify the conclusion.