Transplantation Biology Program, Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
JAMA. 2011 Nov 2;306(17):1874-83. doi: 10.1001/jama.2011.1558.
A minimally toxic nonmyeloablative regimen was developed for allogeneic hematopoietic cell transplantation (HCT) to treat patients with advanced hematologic malignancies who are older or have comorbid conditions.
To describe outcomes of patients 60 years or older after receiving minimally toxic nonmyeloablative allogeneic HCT.
DESIGN, SETTING, AND PARTICIPANTS: From 1998 to 2008, 372 patients aged 60 to 75 years were enrolled in prospective clinical HCT trials at 18 collaborating institutions using conditioning with low-dose total body irradiation alone or combined with fludarabine, 90 mg/m(2), before related (n = 184) or unrelated (n = 188) donor transplants. Postgrafting immunosuppression included mycophenolate mofetil and a calcineurin inhibitor.
Overall and progression-free survival were estimated by Kaplan-Meier method. Cumulative incidence estimates were calculated for acute and chronic graft-vs-host disease, toxicities, achievement of full donor chimerism, complete remission, relapse, and nonrelapse mortality. Hazard ratios (HRs) were estimated from Cox regression models.
Overall, 5-year cumulative incidences of nonrelapse mortality and relapse were 27% (95% CI, 22%-32%) and 41% (95% CI, 36%-46%), respectively, leading to 5-year overall and progression-free survival of 35% (95% CI, 30%-40%) and 32% (95% CI, 27%-37%), respectively. These outcomes were not statistically significantly different when stratified by age groups. Furthermore, increasing age was not associated with increases in acute or chronic graft-vs-host disease or organ toxicities. In multivariate models, HCT-specific comorbidity index scores of 1 to 2 (HR, 1.58 [95% CI, 1.08-2.31]) and 3 or greater (HR, 1.97 [95% CI, 1.38-2.80]) were associated with worse survival compared with an HCT-specific comorbidity index score of 0 (P = .003 overall). Similarly, standard relapse risk (HR, 1.67 [95% CI, 1.10-2.54]) and high relapse risk (HR, 2.22 [95% CI, 1.43-3.43]) were associated with worse survival compared with low relapse risk (P < .001 overall).
Among patients aged 60 to 75 years treated with nonmyeloablative allogeneic HCT, 5-year overall and progression-free survivals were 35% and 32%, respectively.
为治疗患有晚期血液系统恶性肿瘤、年龄较大或合并症的患者，开发了一种低毒非清髓性同种异体造血细胞移植（HCT）方案。
描述 60 岁及以上接受低毒非清髓性同种异体 HCT 治疗的患者的结局。
设计、地点和参与者：1998 年至 2008 年，在 18 个合作机构进行了前瞻性临床 HCT 试验，共纳入 372 名年龄在 60 岁至 75 岁之间的患者，采用低剂量全身照射联合氟达拉滨（90mg/m2）预处理，接受亲缘（n=184）或非亲缘（n=188）供者移植。移植后免疫抑制包括霉酚酸酯和钙调磷酸酶抑制剂。
采用 Kaplan-Meier 法估计总生存率和无进展生存率。采用累积发生率估计法评估急性和慢性移植物抗宿主病、毒性、完全供者嵌合、完全缓解、复发和非复发死亡率。采用 Cox 回归模型估计风险比（HR）。
总体而言，5 年非复发死亡率和复发率分别为 27%（95%CI，22%-32%）和 41%（95%CI，36%-46%），导致 5 年总生存率和无进展生存率分别为 35%（95%CI，30%-40%）和 32%（95%CI，27%-37%）。按年龄组分层，这些结果无统计学差异。此外，年龄增加与急性或慢性移植物抗宿主病或器官毒性的增加无关。多变量模型显示，HCT 特定合并症指数评分 1 至 2（HR，1.58[95%CI，1.08-2.31]）和 3 或更高（HR，1.97[95%CI，1.38-2.80]）与 HCT 特定合并症指数评分 0 相比，生存状况较差（P=0.003 总）。同样，标准复发风险（HR，1.67[95%CI，1.10-2.54]）和高复发风险（HR，2.22[95%CI，1.43-3.43]）与低复发风险（P<0.001 总）相比，生存状况较差。
在接受非清髓性同种异体 HCT 治疗的 60 至 75 岁患者中，5 年总生存率和无进展生存率分别为 35%和 32%。
