Alemtuzumab, Fludarabine, and Melphalan Reduced Intensity Conditioning Hematopoietic Cell Transplantation: Experience in over 200 Pediatric and Young Adult Patients with Primary Immune Deficiency, Metabolic, and Marrow Failure Disorders

Alemtuzumab, fludarabine, and melphalan reduced intensity conditioning regimens are increasingly used for the hematopoietic cell transplantation of pediatric and young adult patients with non-malignant diseases.  Data regarding large patient groups are limited.  We retrospectively analyzed the outcomes of 206 patients with primary immunodeficiencies, metabolic diseases, and non-fanconi anemia marrow failure disorders who underwent 210 RIC HCT procedures at Cincinnati Children’s Hospital.  Ninety-seven percent of patients engrafted.  Mixed donor and recipient chimerism developed in 46% of patients.  The risk was highest in patients who received proximal or higher dose/kg alemtuzumab schedules (all HR>2, all p<0.05) or cord blood grafts (HR 3.122, CI 1.236-7.888, p= 0.016).  Patients with marrow failure were protected against mixed chimerism (HR 0.208, CI 0.061-0.709, p=0.012).  The overall cumulative incidences of grades II-IV and III-IV acute GHVD were 25% (CI 20-32%) and 18% (CI 14%-25%).  Five percent of patients required re-transplantation.  One-year survival without re-transplantation was 75% (CI 69-81%).  Only 2 deaths were related to acute toxicities; the majority were related to infections.  Age, HLA match, and grades III-IV acute GVHD impacted survival.  Despite the high incidence of mixed chimerism, alemtuzumab, fludarabine, and melphalan RIC HCT offers minimal life-threatening acute toxicities and good outcomes for many patients.