Clinical efficacy and safety for pediatric patients with severe combined immunodeficiency disease treated with modified allo-haploidentical stem cell transplantation

Abstract

Abstract Purpose: Hematopoietic stem cell transplantation (HSCT) is the curative treatment for severe combined immunodeficiency disease (SCID). The natural survival age of this disease does not exceed 1 year, when the age is less than 3.5 months, before the onset of infection is the best time for performing HSCT. Here, we conducted a completely new treatment option for SCID patients without suitable donors using post-transplant cyclophosphamide (PT/Cy) as Graft versus host disease (GVHD) prophylaxis. It is necessary to observe its efficacy and safety, further more to observe the immunological reconstitution patterns of SCID patients under a new transplantation system. Methods: A total of 10 patients without a suitable donor were selected haplo-identical family donors as donor sources between March 2022 and March 2025. A modified transplant protocol with PTCy (25-35 mg/kg/day on days +3 and +4) was performed, including fludarabine 160 mg/m2 divided into 4 days on day -8 to -5, Melphalan 100 mg/m2divided into two days on day -3, -2, Cyclophosphamide 20mg/kg/day on day -5, -4 and porcrine anti-human lymphocyte immunoglobulin 25mg/kg/d on day -8 to -6. Low dose FK506 or CSA combined with MMF were added as GVHD prophylaxis. Results: From March 2022 to March 2024, 10 infants with newly diagnosed SCID were treated with this update conditioning regimen. Among these cases, there were 9 boys (90%) and 1 girl (10%), 9 cases of X-SCID (90%), and 1 case of Lig-IV (10%). All 10 cases were from haploidentical related donors, the median age at transplantation was 4 months (2～12). The median times for neutrophil and platelet engraftment were 15 (11～21) days and 32 (17～60) days, respectively. Three months post-transplantation, 10 cases (100%) achieved complete donor chimerism. In these group of patients，9 (90%) cases, we observed that the absolute count of NK lymphocytes returned to normal levels 2 months post-transplantation, and the absolute count of CD3+ lymphocytes was greater than 300 cells/ml 3 months post-transplantation. The median follow-up post-transplantation was 28 (30～50) months. Nine patients achieved long-term disease-free survival, and 1 patient died 27 months post-transplantation due to pulmonary fibrosis caused by COVID-19 infection, which was ineffective despite rescue efforts. We observed that the modified conditioning regimen for SCID patients showed lower toxicity, lower incidence of GVHD, and a significantly higher overall survival rate (90%) compared to traditional regimens.Conclusion: Our modified protocol provides a new treatment method for SCID patients without suitable donor, expanded donor pool. Using the reduced intensity conditioning regimen, reduced toxicity and heavy economic burden, lower rate of GVHD increased high quality of life. Due to the small sample size, further confirmation is needed with a larger number of cases.