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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

High-dose cyclophosphamide with autologous lymphocyte-depleted peripheral blood stem cell (PBSC) support for treatment of refractory chronic autoimmune thrombocytopenia.

Patients with refractory chronic autoimmune thrombocytopenia ( AITP) have a significant risk of morbidity and mortality related to hemorrhage. High-dose (HD) cytotoxic therapy may produce remissions but entails risks related to myelosuppression. Hematopoietic stem cell support with lymphocyte-depleted grafts may accelerate hematologic recovery and concomitantly reduce repopulation by autoreactive immunocytes. Fourteen patients with chronic AITP, in whom multiple prior therapies including corticosteroids, splenectomy, intravenous immunoglobulin, and various cytotoxic or immunomodulatory regimens had failed, were treated with HD cyclophosphamide (50 mg/kg/d) and autologous granulocyte colony-stimulating factor (G-CSF)-mobilized leukocytes depleted of lymphocytes by immunomagnetic CD34(+) selection. There were no significant adverse events related to G-CSF, intravenous device insertion, or leukapheresis. Treatment-related complications included transient hemorrhagic cystitis (1 patient), vaginal bleeding (2 patients), gastrointestinal bleeding (1 patient), epistaxis (1 patient), and antibiotic-responsive febrile neutropenia (all patients). The mean time to absolute neutrophil count (ANC) more than 500/mm(3) was 9 +/- 0.6 days. Eight patients experienced antibiotic-responsive gram-positive bacteremia. A median of 2 platelet transfusions was required for stem cell mobilization, intravenous catheter insertion, and apheresis and a median of 9 platelet transfusions was required during hematopoietic recovery. Six patients obtained durable complete responses (platelet counts > 100 000/mm(3) without other therapy) with maximum follow-up of 42 months. Two additional patients obtained durable partial responses (platelet counts significantly increased over baseline with reduced medication requirements and cessation of bleeding complications). This therapeutic approach is feasible for patients with severe chronic AITP, a substantial proportion of whom may obtain durable remissions. Larger controlled trials are recommended.[1]


  1. High-dose cyclophosphamide with autologous lymphocyte-depleted peripheral blood stem cell (PBSC) support for treatment of refractory chronic autoimmune thrombocytopenia. Huhn, R.D., Fogarty, P.F., Nakamura, R., Read, E.J., Leitman, S.F., Rick, M.E., Kimball, J., Greene, A., Hansmann, K., Gratwohl, A., Young, N., Barrett, A.J., Dunbar, C.E. Blood (2003) [Pubmed]
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