非恶性疾病患者的低强度训练 (RIC) 方案 (RIC)

This Phase II, single-institution, investigator-initiated pilot study evaluates reduced-intensity conditioning (RIC) strategies in the setting of allogeneic hematopoietic stem cell transplantation (HSCT) for non-malignant disorders. The study focuses on optimizing conditioning approaches to balance adequate immunosuppression for donor engraftment with minimization of regimen-related toxicity.

RIC regimens are designed to reduce the organ toxicity and late effects associated with traditional myeloablative conditioning while maintaining sufficient host immune suppression to allow durable donor cell engraftment. This approach is particularly relevant in patients with pre-existing organ dysfunction or increased vulnerability to treatment-related complications. In non-malignant diseases, full donor chimerism may not be required for therapeutic benefit, and stable mixed chimerism may be sufficient for disease correction.

The conditioning strategies evaluated in this protocol primarily differ in the timing and administration of alemtuzumab, an anti-CD52 monoclonal antibody used to deplete host lymphocytes and reduce the risk of graft rejection and graft-versus-host disease. Earlier ("distal") administration is intended to reduce prolonged exposure at the time of stem cell infusion, thereby preserving donor immune function, while more proximal administration provides more immediate immunosuppression but may increase the risk of delayed immune recovery.

Disease-specific modifications to conditioning intensity are incorporated for select populations. Patients with beta thalassemia major receive additional cytoreductive and immunosuppressive agents to address the higher risk of graft rejection associated with intact immunity and expanded marrow space. Infants with immunodeficiencies are treated with modified regimens designed to reduce toxicity while maintaining engraftment potential.

Following conditioning, patients undergo stem cell transplantation using donor sources that may include related or unrelated donors as well as cord blood or alternative donor options based on clinical circumstances. Standard supportive care and post-transplant immunosuppression are administered according to institutional guidelines.

Patients are monitored longitudinally for engraftment, donor chimerism, immune recovery, and transplant-related complications. The study also evaluates clinical management strategies such as donor lymphocyte infusions or second transplantation in cases of declining chimerism or graft failure.

This study is intended to inform optimal conditioning approaches for patients with non-malignant disorders undergoing HSCT, with the goal of improving transplant tolerability while maintaining effective and durable engraftment.