Reduced Intensity Conditioning (RIC) Regimen for Patients With Non-malignant Disorders

This Phase II pilot study evaluates the safety and effectiveness of reduced-intensity conditioning (RIC) regimens prior to allogeneic hematopoietic stem cell transplantation (HSCT) in pediatric and young adult patients with non-malignant disorders, including immunodeficiencies and hemoglobinopathies. The study examines different conditioning approaches that vary in the timing and dosing of alemtuzumab (Campath), as well as disease-specific modifications for beta thalassemia major and infants. The primary objective is to assess donor engraftment and event-free survival at one year following transplant. The study aims to determine whether RIC regimens can reduce toxicity while maintaining successful engraftment and disease control.

Inclusion Criteria: 1. Age \>6 months- 25 years 2. Diseases eligible for Distal Alemtuzumab: * Immunodysregulation polyendocrinopathy enteropathy X-linked (IPEX) syndrome * Sickle cell disease (Neurologic: history of stroke or any neurologic defect lasting \>24 hours accompanied by infarct on MRI; or abnormal transcranial Doppler, or abnormal MRI with cerebral vasculature stenosis. OR minimum 2 episodes of acute chest syndrome in preceding 2 year period OR history 3 or more severe pain events/year in the 2 years prior to transplant.) * Thalassemia major * Bone marrow failure, including Kostmann's, amegakaryocytic thrombocytopenia, Blackfan-Diamond syndrome 3. Diseases eligible for Intermediate Alemtuzumab * Hemophagocytic lymphohistiocytosis other macrophage activation syndromes, severe Langerhans histiocytosis * Severe combined immune deficiency, adenosine deaminase deficiency, common variable immunodeficiency * Wiskott-Aldrich syndrome 4. Organ criteria: * Cardiac: Echocardiogram shortening fraction \>27% * Pulmonary: for those with pulmonary function tests: DLCO/VA \>40% If DLCO/VA is not reported this is considered inability to perform the test. In this case Pulse Ox and Respiratory Exam will be used as evaluation criteria. * Renal: Serum creatinine \