1. ¹Washington University School of Medicine, St Louis, MO, USA
2. ²St Louis Children's Hospital, St Louis, MO, USA
3. ³Louisiana State University Medical Center, New Orleans, LA, USA

Correspondence: Dr S Shenoy, Division of Pediatric Hematology-Oncology, Washington University School of Medicine, Box 8116, SLCH, 1 Children's Place, St Louis, MO 63110, USA. E-mail: shenoy@kids.wustl.edu

Received 26 July 2004; Accepted 27 October 2004; Published online 13 December 2004.

Abstract

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/m²; days -8 to -4), melphalan (140/70 mg/m²; 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>0.5 10⁹/l) and platelets (>50 10⁹/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 (grade1–2 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.