Abstract
Background
Patients afflicted with rare non-malignant disorders endure the pain of the disease from birth. Receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT), especially umbilical cord blood transplantation (UCBT), as soon as possible has becomes the only cure opportunity for such patients. For infants under six months old, the toxicity caused by chemotherapy-based conditioning regimens is a key issue that needs to be focused on. Nevertheless, consensus regarding specific dosage adjustments for conditioning regimens in such infants remains elusive.
Objective
Our pilot study aimed to determine a noval dose-adjusted conditioning regimen suitable for infants under 6 months of age with rare non malignant diseases who underwent unrelated umbilical cord blood transplantation.
Methods
We reported the transplant outcomes of five infants under 6 months old with rare non-malignant disease who underwent UCBT at our center from 2021 to 2024. Patients received a conditioning regimen containing adjusted dose of cyclophosphamide, fludarabine, anti-thymocyte immunoglobulin, busulfan and thiotepa, using ≥ 8/10 UCB as the cell source.
Results
The median age of the patients was 4.2 months (range, 4.0 to 5.1) and the median weight of the patients was 5.5 kg (range, 3.5 to 7.5) at transplantation. These infants were diagnosed with Krabbe disease, very early onset inflammatory bowel disease (VEO-IBD), Shwachman-Diamond syndrome (SDS) and Methoxyvaleric aciduria. The median time for neutrophil engraftment and platelet engraftment in all patients was 24 days (range, 12–30 days) and 32 days (range, 26 to 46 days), respectively. The whole blood donor chimerism in all patients was > 95% at 100 days post-UCBT, and all patients achieved a durable complete donor chimerism. The primary diseases of all patients have been effectively corrected, determined by regularly monitoring the enzyme concentration or gene mutation recovery. All patients survived until the follow-up date, and the event free survival rate after UCBT was 100%. Two out of five patients developed acute GVHD, but none had progressed to grade IV aGVHD or chronic GVHD. All patients achieved good lymphocyte reconstruction, especially with CD4 + cells reaching over 200/uL in all patients at 100 days after UCBT. Moreover, natural killer cells and B cells also recover rapidly, with a immunoglobulin class switching.
Conclusions:
In summary, our preliminary research suggest that UCBT with this novel conditioning regimen offers a safe and effective option for infants under 6 months with rare non-malignant diseases, achieving early and rapid donor engraftment, good immune reconstitution with mild GVHD, and superior overall survival.