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Peripheral Blood Stem Cells

Transplantation of highly purified HLA-identical sibling donor peripheral blood CD34+ cells without prophylactic post-transplant immunosuppression in adult patients with first chronic phase chronic myeloid leukemia: results of a phase II study

Abstract

The feasibility of transplantation using highly purified G-CSF-mobilized peripheral blood CD34+ cells from HLA-identical sibling donors without prophylactic post-transplant immunosuppression was prospectively studied in 10 adult first chronic phase chronic myeloid leukemia (CML) patients with special reference to graft engineering performance and follow-up studies of minimal residual disease and immune reconstitution. CD34+ cells were enriched by clinical-scale magnetic-activated cell separation (MACS) using iron-dextran beads bound to monoclonal anti-CD34 antibody. Grafts contained a median of 9.7 (range 1.7–16.6) × 106 CD34+ cells per kilogram of recipient body weight with a purity between 94.5% and 98.3% (median 97.2%). The median number of transfused CD3+ T lymphocytes was 1.0 (range 0.5–8.5) × 104/kg, corresponding to a log10 t lymphocyte depletion between 3.8 and 5.0 (median 4.6). all patients engrafted rapidly with a median duration to neutrophil counts >500/μl of 8 (range 8–19) days and to self-sustaining platelet counts >20 000/μl of 12 (range 9–25) days. Isolated skin acute graft-versus-host disease (GVHD) of stages I to II occurred in three patients. One patient developed secondary graft failure and was successfully salvaged by an unmanipulated blood stem cell graft from the same donor. All 10 patients are surviving in complete hematologic, cytogenetic and molecular remission (four patients after donor lymphocyte infusions) between 12 and 22 (median 16) months post transplant. In conclusion, transplantation of MACS-purified blood CD34+ cells from HLA-identical sibling donors in adult CML patients appears safe, effectively prevents acute GVHD without prophylactic post-transplant immunosuppression, and is capable of inducing complete cytogenetic and molecular remissions. Bone Marrow Transplantation (2000) 26, 823–829.

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Acknowledgements

We are indebted to the technicians of the blood cell separator unit and the experimental hematology and molecular biology laboratories at the Department of Bone Marrow Transplantation for their skillful expertise in performing the cell preparative work and analytical investigations. We further thank the technicians of the cytogenetic laboratory at the Department of Internal Medicine (Tumour Research) for performing the cytogenetic investigations. This work was supported in part by a grant from ‘Deutsche Krebshilfe’ (Project-No. 70–1669-EL I) and a grant from Amgen GmbH, München, Germany.

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Beelen, D., Peceny, R., Elmaagacli, A. et al. Transplantation of highly purified HLA-identical sibling donor peripheral blood CD34+ cells without prophylactic post-transplant immunosuppression in adult patients with first chronic phase chronic myeloid leukemia: results of a phase II study. Bone Marrow Transplant 26, 823–829 (2000). https://doi.org/10.1038/sj.bmt.1702635

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