Martin Paul S, Li Shuli, Nikiforow Sarah, Alyea Edwin P, Antin Joseph H, Armand Philippe, Cutler Corey S, Ho Vincent T, Kekre Natasha, Koreth John, Luckey C John, Ritz Jerome, Soiffer Robert J
Fred Hutchinson Cancer Research Center and University of Washington School of Medicine, Seattle, WA, USA
Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
Haematologica. 2016 Apr;101(4):499-505. doi: 10.3324/haematol.2015.134841. Epub 2016 Jan 14.
Mobilized peripheral blood is the most common graft source for allogeneic hematopoietic stem cell transplantation following reduced-intensity conditioning. In assessing the effect of donor cell dose and graft composition on major transplant outcomes in the reduced-intensity setting, prior studies focused primarily on CD34(+)cell dose and reported conflicting results, especially in relation to survival end-points. While the impact of total nucleated cell dose has been less frequently evaluated, available studies suggest higher total nucleated cell dose is associated with improved survival outcomes in the reduced-intensity setting. In order to further explore the relationship between CD34(+)cell dose and total nucleated cell dose on reduced-intensity transplant outcomes, we analyzed the effect of donor graft dose and composition on outcomes of 705 patients with hematologic malignancies who underwent reduced-intensity peripheral blood stem cell transplantation at the Dana Farber Cancer Institute from 2000 to 2010. By multivariable analysis we found that higher total nucleated cell dose (top quartile; ≥10.8 × 10(10)cells) was associated with improved overall survival [HR 0.69 (0.54-0.88),P=0.0028] and progression-free survival [HR 0.68 (0.54-0.85),P=0.0006]. Higher total nucleated cell dose was independently associated with decreased relapse [HR 0.66 (0.51-0.85),P=0.0012] and increased incidence of chronic graft-versus-host disease [HR 1.4 (1.12-1.77),P=0.0032]. In contrast, higher doses of CD34(+)cells (top quartile; ≥10.9 × 10(6)/kg) had no significant effect on graft-versus-host disease or survival outcomes. These data suggest total nucleated cell dose is a more relevant prognostic variable for reduced-intensity transplant outcomes than the more commonly studied CD34(+)cell dose.
动员外周血是减低预处理强度后异基因造血干细胞移植最常见的移植物来源。在评估供体细胞剂量和移植物组成对减低预处理强度情况下主要移植结局的影响时,既往研究主要聚焦于CD34(+)细胞剂量,且报道的结果相互矛盾,尤其是在生存终点方面。虽然对有核细胞总剂量的影响评估较少,但现有研究表明,在减低预处理强度情况下,较高的有核细胞总剂量与改善的生存结局相关。为了进一步探讨CD34(+)细胞剂量和有核细胞总剂量与减低预处理强度移植结局之间的关系,我们分析了2000年至2010年在达纳法伯癌症研究所接受减低预处理强度外周血干细胞移植的705例血液系统恶性肿瘤患者的供体移植物剂量和组成对结局的影响。通过多变量分析,我们发现较高的有核细胞总剂量(最高四分位数;≥10.8×10(10)个细胞)与改善的总生存[风险比0.69(0.54 - 0.88),P = 0.0028]和无进展生存[风险比0.68(0.54 - 0.85),P = 0.0006]相关。较高的有核细胞总剂量与复发减少[风险比0.66(0.51 - 0.85),P = 0.0012]和慢性移植物抗宿主病发生率增加[风险比1.4(1.12 - 1.77),P = 0.0032]独立相关。相比之下,较高剂量的CD34(+)细胞(最高四分位数;≥10.9×10(6)/kg)对移植物抗宿主病或生存结局无显著影响。这些数据表明,对于减低预处理强度的移植结局,有核细胞总剂量是比更常研究的CD34(+)细胞剂量更相关的预后变量。