Princess Margaret Hospital, Toronto, Ontario, Canada.
Blood. 2013 Jan 10;121(2):339-50. doi: 10.1182/blood-2012-07-445098. Epub 2012 Nov 19.
Hematopoietic cell transplantation (HCT) and prolonged chemotherapy are standard postremission strategies for adult acute lymphoblastic leukemia in first complete remission, but the optimal strategy remains controversial. There are no randomized trials of allogeneic HCT. In the present study, updated individual patient data were collected and analyzed from studies with information on availability of matched sibling donor (used to mimic randomization) and from randomized trials of autograft versus chemotherapy. Data from 13 studies including 2962 patients, excluding Philadelphia chromosome-positive patients, showed a survival benefit for having a matched sibling donor for patients < 35 years of age (OR = 0.79; 95% CI, 0.70-0.90, P = .0003) but not for those ≥ 35 years of age (OR = 1.01; 95% CI, 0.85-1.19, P = .9; heterogeneity P = .03) because of the higher absolute risk of nonrelapse mortality for older patients. No differences were seen by risk group. There was a trend toward inferior survival for autograft versus chemotherapy (OR = 1.18; 95% CI, 0.99-1.41; P = .06). No beneficial effect of autografting was seen compared with chemotherapy in this analysis. We conclude that matched sibling donor myeloablative HCT improves survival only for younger patients, with an absolute benefit of approximately 10% at 5 years. Improved chemotherapy outcomes and reduced nonrelapse mortality associated with allogeneic HCT may change the relative effects of these treatments in the future.
造血细胞移植(HCT)和长期化疗是成人急性淋巴细胞白血病首次完全缓解后的标准缓解后策略,但最佳策略仍存在争议。目前尚无异基因 HCT 的随机试验。在本研究中,从有匹配同胞供体(用于模拟随机化)信息的研究和自体移植与化疗的随机试验中收集并分析了更新的个体患者数据。排除费城染色体阳性患者后,来自 13 项研究的 2962 例患者的数据显示,对于年龄<35 岁的患者,有匹配的同胞供体可带来生存获益(OR=0.79;95%CI,0.70-0.90,P=0.0003),但对于年龄≥35 岁的患者则没有获益(OR=1.01;95%CI,0.85-1.19,P=0.9;异质性 P=0.03),因为老年患者非复发死亡率的绝对风险较高。不同风险组之间没有差异。与化疗相比,自体移植的生存趋势较差(OR=1.18;95%CI,0.99-1.41;P=0.06)。在这项分析中,与化疗相比,自体移植没有带来生存获益。我们得出结论,对于年轻患者,匹配的同胞供体清髓性 HCT 仅能提高生存,5 年时的绝对获益约为 10%。随着异基因 HCT 相关化疗结果的改善和非复发死亡率的降低,这些治疗方法的相对效果可能会在未来发生变化。