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Substitution of cyclophosphamide and busulfan by fludarabine, treosulfan and melphalan in a preparative regimen for children and adolescents with Shwachman–Diamond syndrome

2007; Springer Nature; Volume: 39; Issue: 3 Linguagem: Inglês

10.1038/sj.bmt.1705553

1476-5365

Martin G. Sauer, Cornelia Zeidler, Barbara Meissner, Klaus Rehe, Alexander Hanke, Karl Welte, P Lohse, K-W Sykora,

Neonatal Health and Biochemistry

Allogeneic hematopoietic stem cell transplantation (HSCT) is the only definitive treatment for severe bone marrow dysfunction and clonal disorders in patients diagnosed with Shwachman–Diamond syndrome (SDS). In an attempt to minimize regimen-related toxicity (RRT), we have initiated a fludarabine/treosulfan/melphalan-based pilot protocol avoiding the combination of busulfan and cyclophosphamide. Median age at transplantation was 9.6 years (range 1.5–17 years). All three patients received conditioning with fludarabine (30 mg/m2/day × 6), treosulfan (12 g/m2/day × 3) and melphalan (140 mg/m2/day × 1). CAMPATH-1H (0.1 mg/kg × 2) was added in two cases, while rabbit ATG (Genzyme; 3 × 2.5 mg/kg) was given to the cord blood recipient. One patient was transplanted with a non-manipulated marrow graft from an HLA-identical sibling, one with a marrow graft from a 10/10 matched unrelated donor, and one with a 9/10 matched unrelated umbilical cord blood (UCB) unit. Mean cell doses given were 3.6 × 108 nucleated cells/kg BW for the bone marrow recipients and 4.2 × 107 nucleated cells/kg BW for UCB recipient. Overall, two of three patients are alive and display 100% donor chimerism. Acute graft-versus-host disease grade II was seen in one patient, while no GVHD exceeding grade I occurred in the remaining two.