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Choi, I.,Yoon, S.R.,Park, S.Y.,Kim, H.,Jung, S.J.,Kang, Y.L.,Lee, J.H.,Lee, J.H.,Kim, D.Y.,Lee, J.L.,Park, H.S.,Choi, E.J.,Lee, Y.S.,Kang, Y.A.,Jeon, M.,Seol, M.,Baek, S.,Yun, S.C.,Kim, H.J.,Lee, K.H. Kluge Carden Jennings Pub. Co 2016 BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION Vol.22 No.11
The optimum method of donor natural killer cell infusion (DNKI) after allogeneic hematopoietic cell transplantation (HCT) remains unclear. Fifty-one patients (age range, 19 years to 67 years) with refractory acute leukemia underwent HLA-haploidentical HCT and underwent DNKI on days 6, 9, 13, and 20 of HCT. Median DNKI doses were .5, .5, 1.0, and 2.0@?x@?10<SUP>8</SUP>/kg cells, respectively. During DNKI, 33 of the 45 evaluated patients (73%) developed fever (>38.3<SUP>o</SUP>C) along with weight gain (median, 13%; range, 2% to 31%) and/or hyperbilirubinemia (median, 6.2@?mg/dL; range, 1.0 mg/dL to 35.1@?mg/dL); the toxicity was reversible in 90% of patients. After transplantation, we observed cumulative incidences of neutrophil engraftment (≥500/@?L), grade 2 to 4 acute graft-versus-host disease (GVHD), chronic GVHD, and nonrelapse mortality of 84%, 28%, 30%, and 16%, respectively. The leukemia complete remission rate was 57% at 1 month after HCT and 3-year cumulative incidence of leukemia progression was 75%. When analyzed together with our historical cohort of 40 patients with refractory acute leukemia who underwent haploidentical HCT and DNKI on days 14 and 21 only, higher expression of NKp30 (>90%) on donor NK cells was an independent predictor of higher complete remission (hazard ratio, 5.59) and less leukemia progression (hazard ratio, .57). Additional DNKI on days 6 and 9 was not associated with less leukemia progression (75% versus 55%).
Lee, K.H.,Lee, J.H.,Lee, J.H.,Kim, D.Y.,Park, H.S.,Choi, E.J.,Ko, S.H.,Seol, M.,Lee, Y.S.,Kang, Y.A.,Jeon, M.,Baek, S.,Kang, Y.L.,Kim, S.H.,Yun, S.C.,Kim, H.,Jo, J.C.,Choi, Y.,Joo, Y.D.,Lim, S.N. Kluge Carden Jennings Pub. Co 2017 BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION Vol.23 No.9
To investigate the role of antithymocyte globulin (ATG)-containing reduced-intensity conditioning (RIC) in hematopoietic cell transplantation (HCT) from unrelated (UD) or haploidentical family donors (HFD), we conducted a phase 2 trial of 237 patients (age range, 16 to 69 years) with acute myeloid leukemia (AML) in remission. Patients undergoing UD-HCT (n@?=@?93) or HFD-HCT (n@?=@?59) received RIC comprising busulfan, fludarabine, and ATG, 9@?mg/kg, whereas those undergoing HCT from matched sibling donors (MSD, n@?=@?85) received myeloablative busulfan and cyclophosphamide conditioning or aforementioned RIC with ATG, 4.5@?mg/kg. For graft-versus-host disease (GVHD) prophylaxis, cyclosporine and methotrexate were administered. The median follow-up period was 44.7 months after HCT for 161 survivors. For UD-HCT versus HFD-HCT, there were no significant differences in leukemia recurrence, nonrelapse mortality, relapse-free survival, grades 2 to 4 acute GVHD, and moderate-to-severe chronic GVHD. Furthermore, when the outcomes of UD-HCT and HFD-HCT were combined and compared with those of MSD-HCT, there were no significant differences in leukemia recurrence (3-year cumulative incidence, 30% versus 29%), nonrelapse mortality (3-year cumulative incidence, 7% versus 8%), relapse-free survival (3-year estimate, 63% versus 63%), and grades 2 to 4 acute GVHD (120-day cumulative incidence, 16% versus 13%). Moderate-to-severe chronic GVHD, however, occurred less frequently in UD/HFD-HCT (2-year cumulative incidence, 22% versus 40%; P@?=@?.006). The addition of ATG to conditioning regimen was a significant predictor for less chronic GVHD (subdistribution hazard ratio, .59). In AML in remission, UD/HFD-HCT after ATG-containing RIC achieved leukemia control equivalent to that of MSD-HCT. Despite HLA disparity in UD/HFD-HCT, chronic GVHD occurred less frequently after ATG-containing RIC, suggesting a strong GVHD-modulating effect of ATG.