期刊
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
卷 22, 期 4, 页码 705-709出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.bbmt.2015.12.028
关键词
Natural killer cell; Allogeneic transplantation; AML; MDS
资金
- National Institutes of Health [CA023766, HL088134, CA008748]
We conducted a phase 2 study to determine the efficacy of HLA-haploidentical related donor natural killer (NK) cells after cyclophosphamide-based lymphodepletion in patients with relapsed or progressive acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS) following allogeneic hematopoietic cell transplantation (HCT). Eight patients (2 with MDS and 6 with AML) were treated with cyclophosphamide 50 mg/kg on day -3 and day -2 before infusion of NK cells isolated from a haploidentical related donor. One patient also received fludarabine 25 mg/m(2)/day for 4 days. Six doses of 1 million units of interleukin-2 (IL-2) were administered on alternating days beginning on day 1. The median number of NK cells infused was 10.6 x 10(6)/kg (range, 4.3 to 22.4 x 10(6)/kg), and the median number of CD3 cells infused was 2.1 x 10(3)/kg (range, 1.9 to 40 x 10(3)/kg). NI( infusions were well tolerated, with a median time to neutrophil recovery of 19 days (range, 7 days to not achieved) and no incidence of graft-versus-host disease after NK infusion. One patient with AML and 1 patient with MDS achieved a complete response, but relapsed at 1.7 and 1.8 months, respectively. One patient with MDS experienced resolution of dysplastic features but persistence of clonal karyotype abnormalities; this patient was stable at 65 months after NK cell therapy. The median duration of survival was 12.9 months (range, 0.8 to 65.3 months). Chimerisrn analysis of CD3(-)/CD56(+) peripheral blood cells did not detect any circulating haploidentical NI( cells after infusion. NI( phenotyping was performed in 7 patients during and after IL-2 infusion. We found a slight trend toward greater expression of KIR2DL2/2DL3/2DS2 (5% versus 28%; P = .03) at 14 days in patients who survived longer than 6 months from NM cell infusion (n = 4) compared with those who died within 6 months of NK cell therapy (n = 3). In summary, our data. support the safety of haploidentical NK cell infusion after allogeneic HCT. (C) 2016 American Society for Blood and Marrow Transplantation.
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