The feasibility and efficacy of subcutaneous plerixafor for mobilization of peripheral blood stem cells in allogeneic HLA-identical sibling donors: results of the HOVON-107 study

皮下注射普乐沙福对异基因 HLA 相合兄弟姐妹供体外周血干细胞动员的可行性和有效性:HOVON-107 研究结果

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作者:Georgine E de Greef, Eric Braakman, Bronno van der Holt, Jeroen J W M Janssen, Eefke Petersen, Vladimir Vucinic, Nicole Thuss, Meriam Grootes, Jan J Cornelissen

Background

Plerixafor (PFX) mobilizes CD34+ cells into circulation by disrupting the CXCR4 binding of the hematopoietic stem cell in its bone marrow niche. Study design and

Conclusion

stem cell mobilization with sc PFX 0.320 mg/kg in allogeneic sibling donors is feasible with limited toxicity for donors. 14 allogeneic donors were mobilized with PFX 0.320 mg intravenously according to the same protocol. Due to the limited numbers, these results are in the supplementary section.

Methods

in the prospective HOVON-107 study (www.hovon.nl) 23 allogeneic HLA-identical sibling donors received one or two subcutaneous (sc) injections of plerixafor 0.320 mg/kg.The primary endpoint, was defined as feasibility to mobilize a minimum of 2.0 x106 CD34+ cells/kg recipient weight obtained by leukopheresis in at least 90% of the donors.

Results

median 3.3 x 106 CD34+ cells/kg (1.9-6.5) were collected after 1 (n=12) or 2 (n=10) sc injections of PFX. Side effects occurred in 15/23 (65%) donors: most were grade 1-2; in 5 donors grade 3 and all resolved. All grafts were directly transplanted. Compared to 10 grafts obtained with G-CSF the number of CD34+ cells was 2.4 fold lower but the percentage of phenotypically most immature CD34+ subset was higher (31% vs 15%). The total number of CD3+ cells in the graft seemed higher after PFX-mobilization, but CD4/CD 8 ratios, and frequencies of Th2, Th17 and regulatory T-cells or NK cells were comparable. All patients engrafted and no increase in incidence or severity of acute or chronic graft versus host disease was observed.

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