Long-term Outcomes Among Older Patients Following Nonmyeloablative Conditioning and Allogeneic Hematopoietic Cell Transplantation for Advanced Hematologic Malignancies
Long-term Outcomes Among Older Patients Following Nonmyeloablative Conditioning and Allogeneic Hematopoietic Cell Transplantation for Advanced Hematologic Malignancies
复制标题
DOI：
10.1001/jama.2011.1558
复制
发表时间：
2011-11-02
影响因子：
120.7
通讯作者：
Storb, Rainer
中科院分区：
文献类型：
--
作者：
Sorror, Mohamed L.;Sandmaier, Brenda M.;Storb, Rainer
背景一种最低毒性非清髓性异基因造血细胞移植（HCT）方案被开发用于治疗老年或有合并症的晚期恶性血液病患者。目的描述60岁或60岁以上患者接受最低毒性非清髓性异基因HCT后的结局。设计、设置和参与者从1998年到2008年，372例年龄在60 - 75岁之间的患者在18个合作机构参加了前瞻性临床HCT试验，在相关（n=184）或无关（n =188）供体移植前，使用单独或联合氟达拉滨（90 mg/m2）的低剂量全身照射预处理。移植后免疫抑制剂包括吗替麦考酚酯和钙调神经磷酸酶抑制剂。主要结果测量总生存率和无进展生存率采用Kaplan-Meier法。计算急性和慢性移植物抗宿主病、毒性、完全供体嵌合体的实现、完全缓解、复发和非复发死亡率的累积发生率估计值。从考克斯回归模型估计风险比（HR）。结果总体而言，5年累积非复发死亡率和复发率为27%（95% CI，22%-32%）和41%（95% CI，36%-46%），导致5年总体和无进展生存期分别为35%（95% CI，30%-40%）和32%（95% CI，27%-37%）。当按年龄组分层时，这些结局无统计学显著差异。此外，年龄的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。在多变量模型中，与HCT特异性合并症指数评分为0相比，HCT特异性合并症指数评分为1 - 2（HR，1.58 [95%CI，1.08-2.31]）和3或更高（HR，1.97 [95%CI，1.38-2.80]）与生存率更差相关（总体P= 0.003）。类似地，与低复发风险相比，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]）与较差的生存率相关（P
Context 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.Objective 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.Main Outcome Measures 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.Results 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