Törlén Johan, Ringdén Olle, Le Rademacher Jennifer, Batiwalla Minoo, Chen Junfang, Erkers Tom, Ho Vincent, Kebriaei Partow, Keever-Taylor Carolyn, Kindwall-Keller Tamila, Lazarus Hillard M, Laughlin Mary J, Lill Michael, O'Brien Tracey, Perales Miguel-Angel, Rocha Vanderson, Savani Bipin N, Szwajcer David, Valcarcel David, Eapen Mary
Centre for Allogeneic Stem Cell Transplantation, Karolinska University Hospital Huddinge, Stockholm, Sweden.
Centre for Allogeneic Stem Cell Transplantation, Karolinska University Hospital Huddinge, Stockholm, Sweden; Division of Therapeutic Immunology, Karolinska Institutet, Stockholm, Sweden.
Biol Blood Marrow Transplant. 2014 Sep;20(9):1418-25. doi: 10.1016/j.bbmt.2014.05.021. Epub 2014 Jun 2.
Reduced-intensity conditioning/nonmyeloablative conditioning regimens are increasingly used in allogeneic hematopoietic cell transplantation (HCT). Reports have shown CD34(+) dose to be important for transplantation outcome using myeloablative conditioning. The role of CD34(+) dose of peripheral blood progenitor cells (PBPC) has not been previously analyzed in a large population undergoing reduced-intensity conditioning/nonmyeloablative HCT. We studied 1054 patients, ages 45 to 75 years, with acute myeloid leukemia or myelodysplastic syndrome who underwent transplantation between 2002 and 2011. Results of multivariate analysis showed that PBPC from HLA-matched siblings containing <4 × 10(6) CD34(+)/kg was associated with higher nonrelapse mortality (hazard ratio [HR], 2.03; P = .001), overall mortality (HR, 1.48; P = .008), and lower neutrophil (odds ratio [OR], .76; P = .03) and platelet (OR, .76; P = .03) recovery. PBPC from unrelated donors with CD34(+) dose < 6 × 10(6) CD34(+)/kg was also associated with higher nonrelapse (HR, 1.38; P = .02) and overall mortality (HR, 1.20; P = .05). In contrast to reports after myeloablative HCT, CD34(+) dose did not affect relapse or graft-versus-host disease with either donor type. An upper cell dose limit was not associated with adverse outcomes. These data suggest that PBPC CD34(+) doses >4 × 10(6) CD34(+)/kg and >6 × 10(6) CD34(+)/kg are optimal for HLA-matched sibling and unrelated donor HCT, respectively.
减低强度预处理/非清髓性预处理方案在异基因造血细胞移植（HCT）中应用越来越广泛。报告显示，使用清髓性预处理时，CD34(+)剂量对移植结局很重要。外周血祖细胞（PBPC）的CD34(+)剂量在接受减低强度预处理/非清髓性HCT的大量人群中的作用此前尚未得到分析。我们研究了2002年至2011年间接受移植的1054例年龄在45至75岁之间的急性髓系白血病或骨髓增生异常综合征患者。多变量分析结果显示，来自HLA匹配同胞的PBPC中CD34(+)含量<4×10(6)/kg与较高的非复发死亡率（风险比[HR]，2.03；P = 0.001）、总死亡率（HR，1.48；P = 0.008）以及较低的中性粒细胞（优势比[OR]，0.76；P = 0.03）和血小板（OR，0.76；P = 0.03）恢复率相关。来自无关供者的PBPC中CD34(+)剂量<6×10(6)/kg也与较高的非复发率（HR，1.38；P = 0.02）和总死亡率（HR，1.20；P = 0.05）相关。与清髓性HCT后的报告相反，CD34(+)剂量对两种供者类型的复发或移植物抗宿主病均无影响。较高的细胞剂量上限与不良结局无关。这些数据表明，对于HLA匹配同胞和无关供者HCT，PBPC的CD34(+)剂量分别>4×10(6)/kg和>6×10(6)/kg是最佳的。
