美国医学会杂志(JAMA)11月2日发表的一项分析表明，在应用非清髓性预处理继以异基因造血干细胞移植的方案时，老年晚期恶性血液病患者的远期预后与年轻患者一样好，其中半数在治疗期间或治疗后不需住院，并且2/3存活者的生理功能恢复正常或恢复至基本正常的水平。
这项分析由西雅图弗雷德哈钦森癌症研究中心移植生物学计划的Mohamed L. Sorror博士及其同事进行，分析的对象为1998 ~2008年在18个医学中心参与有关该治疗方案的前瞻性临床研究的372例60~75岁患者。患者罹患的疾病包括白血病、骨髓增生异常综合征、骨髓增生性疾病、多发性骨髓瘤和淋巴瘤等恶性血液病。由于老年患者不适合在大剂量异基因造血干细胞移植之前接受强细胞毒性预处理，因此这些患者转而接受了依赖于移植物抗肿瘤效应的非清髓性预处理来治愈癌症，包括移植前氟达拉滨治疗和小剂量全身照射，并在移植后应用霉酚酸酯和钙调磷酸酶抑制剂(环孢素或他克莫司)进行1个疗程的免疫抑制治疗。
结果显示，中位随访55个月(范围：12~133个月)后，133例患者仍存活。5年总生存率为35%，5年无进展生存率为32%。分析发现，60~64岁、65~69岁和≥70岁患者的5年总生存率分别为38%、33%和25%。不考虑年龄因素的话，5年生存率在合并症评分高且疾病风险高的患者中为23%，在合并症评分低且疾病风险低的患者中为69%。5年时约2/3存活者的移植物抗宿主病(GVHD)症状完全缓解，并且能够在中位2.5年后停用免疫抑制药物，这些老年患者的GVHD发生率和缓解率与在接受大剂量造血干细胞移植的年轻患者中观察到的结果相似。
在239例死亡中，135例由疾病进展和复发引起。1年和5年复发率分别为33%和41%。多数非复发性死亡是由多器官衰竭、GVHD和感染引起。
研究者指出，恶性血液病是老年人的主要疾病，其发生率在未来20年可能随人口老龄化而增至77%。然而，最新数据显示，近年来接受造血干细胞移植治疗的患者中，仅12%为60岁以上患者。这表明医生并不愿意对老年患者实施异基因造血干细胞移植。从上述分析结果来看，考虑对恶性血液病老年患者进行非清髓性移植是可行的。
在随刊述评中，密歇根大学安娜堡分校血液和骨髓移植计划的Shin Mineishi博士表示，上述结果对临床决策和医疗政策具有重要意义，尤其是在当前人口老龄化的形势下。老年患者在总生存率、无进展生存率和其他预后指标方面与年轻患者基本无异，应在老年患者中大力推广异基因造血干细胞移植方案，以使更多的患者获益。未来还需进行比较非清髓性与低强度异基因造血干细胞移植的随机研究。此外，老年患者确实有不同于年轻患者的问题，其一就是老年患者需要更多的资源来帮助康复，而医疗保险体系的覆盖面较小(JAMA 2011;306:1918-9)。
该研究获美国国立卫生研究院及白血病和淋巴瘤协会支持。研究者声明与多家药企存在联系。Mineishi博士声明与健赞公司存在联系。
相关英文论文摘要：
Long-term Outcomes Among Older Patients Following Nonmyeloablative Conditioning and Allogeneic Hematopoietic Cell Transplantation for Advanced Hematologic Malignancies
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/m2, 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 < .001 overall).
Conclusion Among patients aged 60 to 75 years treated with nonmyeloablative allogeneic HCT, 5-year overall and progression-free survivals were 35% and 32%, respectively.
英文论文链接：https://jama.ama-assn.org/content/306/17/1874.full?sid=39965a56-c47e-47db-819e-f549ca1fa3f1
