Summary:
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.
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Acknowledgements
We acknowledge assistance with data collection and compilation by Shannon Witty, CRA, Saint Louis Children's Hospital, St Louis, and transplant teams at participating institutions.
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Shenoy, S., Grossman, W., DiPersio, J. et al. A novel reduced-intensity stem cell transplant regimen for nonmalignant disorders. Bone Marrow Transplant 35, 345–352 (2005). https://doi.org/10.1038/sj.bmt.1704795
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DOI: https://doi.org/10.1038/sj.bmt.1704795
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