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• W2073729028 abstract "Since alloreactive NK cells have recently been described to exert an anti-leukemic effect, to reduce GvHD and to facilitate engraftment across HLA-barriers, we have designed a protocol to promote rapid engraftment of haploidentical stem cells after Reduced Intensity Conditioning (RIC) in patients with refractory hematological malignancies. Haploidentical donors (if available, NK-alloreactive donors were preferentially chosen and 5 out of 8 donors had a constellation of NK-alloreactivity) were mobilized using G-CSF and/or G+GM-CSF. In order to cotransplant large numbers of CD56+ NK cells together with stem cells, PBSCs were negatively depleted of T-lymphocytes using an anti-CD3 monoclonal antibody conjugated to magnetic microbeads and high gradient magnetic cell sorting utilizing the automated CliniMACS device (Miltenyi Biotec).The RIC regimen included Fludarabine (200 mg/m2), Thiotepa (10 mg/m2) and Melphalan (60 to 140 mg/m2). Rituximab (375 mg/m2) was given prior to the stem cell infusion. Immunosuppressive regimen included Muromonab-CD3 (OKT3) and Cyclosporine or Mycophenolate mofetil. We transplanted 8 patients (5 AML-relapse, 1 therapy-related secondary MDS, 1 Biphenotypic leukemia-CR2, 1 CML-blastic crisis). 5 patients have received a previous allogeneic HSCT. The mean total MNC, CD34+ and CD3+ cell counts per kg infused were 8.16 × 108(2.6 -15 × 108), 15.13 ×106(2.14–37.54 × 106) and 0.243 × 106 (0.01–0.476 × 106) respectively. The number of infused CD56+ NK cells ranged from 44 to 200 × 106/kg. All patients achieve early 100% peripheral blood donor chimerisms with a median of 14.5 (8–20) days. 7 patients achieve primary engraftment (ANC > 500) at a mean of 11.14 (7–14) days. One patient had only early lymphoid engraftment. He was successfully engrafted by day 45 after repeated plasmapheresis and a stem cell boost. No early transplant-related mortality was seen. 3 patients had transient grade 1–2 skin GVHD that was controlled with immunosuppression and 1 patient developed liver GvHD. 5 of the 8 patients are alive with short follow-up. Overall, patients tolerated the RIC well and achieved very rapid chimeric engraftment. Haploidentical transplantation of T-cell depleted PBSC after RIC might be a therapeutic option for patients with advanced malignant diseases and a platform for further exploiting the role of alloreactive NK cells in the reduction of GvHD and the facilitation of engraftment in patients with nonmalignant diseases." @default.
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• W2073729028 date "2004-02-01" @default.
• W2073729028 modified "2023-09-22" @default.
• W2073729028 title "Rapid conversion to full chimerism after reduced intensity conditioning (RIC) and transplantation of T-cell depleted large numbers of CD34+ stem and CD56+ natural killer (NK) cells obtained from mobilized haploidentical donors" @default.
• W2073729028 doi "https://doi.org/10.1016/j.bbmt.2003.12.285" @default.
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