A Phase II Study of Reduced Intensity Conditioning in Pediatric Patients and Young Adults ≤55 Years of Age With Non-Malignant Disorders Undergoing Umbilical Cord Blood, Bone Marrow, or Peripheral Blood Stem Cell Transplantation

For some non-malignant diseases (NMD; i.e., thalassemia, sickle cell disease, most immune deficiencies) a hematopoietic stem cell transplant may be curative by healthy donor stem cell engraftment alone. HSCT in patients with NMD differs from that in malignant disorders for two important reasons: 1) these patients are typically naïve to chemotherapy and immunosuppression. This may potentially lead to difficulties with engraftment. And 2) RIC with subsequent bone marrow chimerism may be beneficial even in mixed chimerism and result in decreased transplant-related mortality (TRM). Nevertheless, any previous organ damage, as a result of the underlying disease, may remain present after the HSCT.

For other diseases (metabolic disorders, some immunodeficiencies, etc.), a transplant is not curative. For these diseases, the main intent of the transplant is to slow down, or stop, the progress of the disease. In select few cases/diseases, the presence of healthy bone marrow derived cells may even prevent progression and prevent neurological decline.

Research funds are not available to assist with enrollment on this trial.

In this research study, instead of using the standard myeloablative conditioning, the study doctor is using RIC, in which significantly lower doses of chemotherapy will be used. The lower doses may not eradicate every stem cell in the patient's bone marrow, however, in the presented combination, the intention is to eliminate already formed immune cells and provide maximum growth advantage to healthy donor stem cells. This paves the way to successful engraftment of donor stem cells. Engrafting donor stem cells can outcompete, and donor lymphocytes could suppress, the patients' surviving stem cells. With RIC, the side effects on the brain, heart, lung, liver, and other organ functions are less severe and late toxic effects should also be reduced.

The purpose of this study is to collect data from the patients undergoing reduced-intensity conditioning before HSCT, and compare it to the standard myeloablative conditioning. It is expected there will be therapeutic benefits, paired with better survival rate, less organ toxicity and improved quality of life, following the RIC compared to the myeloablative regimen.