A novel reduced-intensity stem cell transplant regimen for nonmalignant disorders

Bone marrow transplantation (BMT) benefits nonmalignant diseases but is limited by regimen-related toxicity, graft-versus-host disease (GVHD), donor availability, and graft rejection (GR). To overcome some of these barriers, we developed a new conditioning strategy for these patients. In total, 16 patients received Campath-1H (33/ 48 mg; days - 21 to - 19), fludarabine (150 mg/m(2); days - 8 to - 4), melphalan (140/70 mg/m(2); day - 3), and transplant using related/unrelated stem cells. GVHD prophylaxis included cyclosporine/methylprednisolone for cord cells. Other recipients also received methotrexate. Risk factors for GR included multiple transfusions ( 6), low stem cell numbers ( 1), and immunologic/ metabolic disorders ( 3). Donor engraftment was present in 14/16 recipients. Neutrophils (ANC >0.5 x 10(9)/l) and platelets (>50 x 10(9)/l) engrafted at a median of 13 and 24 days. Two patients died of Pseudomonas sepsis prior to engraftment, one of CMV disease, and another of intracranial hemorrhage. With median follow-up of 281 days (78 - 907), 12/16 are stable/improved, or cured. Acute GVHD was absent (n = 10) or mild and transient (grade 1 - 2 skin) (n = 4). There was no chronic GVHD. Toxicities were predominantly early infections within 100 days, and correlated with lymphopenia (CD4+ T and B cells). Stable engraftment and low incidence of significant GVHD, irrespective of age or stem cell source, make this reduced-intensity regimen attractive for nonmalignant disorders.