Thomas X, Danaïla C, Le Q H, Sebban C, Troncy J, Charrin C, Lhéritier V, Michallet M, Magaud J P, Fiere D
Service d'Hématologie Clinique, Hôpital Edouard Herriot, Lyon, France.
Leukemia. 2001 Dec;15(12):1811-22. doi: 10.1038/sj.leu.2402289.
Although the prospect of long-term leukemia-free survival (LFS) after treatment for adult acute lymphoblastic leukemia (ALL) is widely accepted, few studies have reported long-term survival data. Three hundred and seventy-eight ALL patients, referred to our hospital from 1978 to 1999, were reviewed for long-term follow-up data. The analysis included data on 351 patients treated by standard chemotherapy according to 11 different successive and/or concomitant regimens. Complete remission (CR) was achieved in 299 patients (79%). Initial performance status, LDH level, immunophenotype, age, and risk group (defined according to Hoelzer's criteria) at diagnosis were of significant prognostic value for CR achievement. Median leukemia-free survival (LFS) was 14 months with a 3-year, a 5-year, and an 8-year LFS at 30%, 26%, and 24%, respectively. LFS was better in T cell lineage ALL than in B cell lineage ALL (P = 0.05). Younger age was also a favorable prognostic factor for LFS (P = 0.001). Philadelphia-positive (Ph+) ALL displayed a poor outcome since median LFS was 7 months with only 13% of survival at 3 years. Median overall survival (OS) of the entire cohort was 18 months with a 3-year, a 5-year, and an 8-year OS at 32%, 24%, and 22% respectively. Favorable prognostic factors for OS were younger age (P < 0.0001), and T cell lineage ALL (P = 0.001). Among non-T cell lineage ALL, standard-risk ALL confirmed a significant better outcome than high-risk ALL (P = 0.0003). It was apparent from this analysis that hazard rates for death and relapse were greatest in the first year, decreased substantially between years 1 and 2, then decrease further between years 2 and 3. Rates of death and relapse were quite low after 3-4 years. All patients relapsing after 3 years of CR were B or non-B non-T cell lineage ALL. Long-term survivors (LTS), defined as survival in CR > or =3 years, represented 23% of evaluable patients. Eighty-three patients remain alive in initial CR at >3 years, while only three were LTS after a second CR. Overall, no significant improvement was shown in terms of CR achievement and survival duration over the years. However, regarding survival, a significant improvement was demonstrated in T cell lineage ALL (P = 0.03). Furthermore, patients (aged less than 50 years) transplanted while in first CR did significantly better than those receiving only chemotherapy as post-remission therapy (P < 0.0001). The 3-year OS, after allogeneic transplantation in first CR, was 74% in T cell lineage ALL, while it was less than 50% in B cell lineage ALL. This single center study on a large cohort of ALL patients reflects the degree to which ALL treatment remains unsuccessful in adults. Only T cell lineage ALL outcomes have improved over the years. The results suggest a time (3 years) at which it becomes reasonable to speak of potential cure, provided the patient is in CR.
尽管成人急性淋巴细胞白血病(ALL)治疗后长期无白血病生存(LFS)的前景已被广泛认可,但很少有研究报告长期生存数据。对1978年至1999年转诊至我院的378例ALL患者进行了长期随访数据回顾。分析包括351例根据11种不同的连续和/或联合方案接受标准化疗的患者的数据。299例患者(79%)实现完全缓解(CR)。诊断时的初始体能状态、乳酸脱氢酶(LDH)水平、免疫表型、年龄和风险组(根据霍尔泽标准定义)对CR的实现具有显著的预后价值。中位无白血病生存期(LFS)为14个月,3年、5年和8年LFS分别为30%、26%和24%。T细胞系ALL的LFS优于B细胞系ALL(P = 0.05)。年龄较小也是LFS的有利预后因素(P = 0.001)。费城染色体阳性(Ph+)ALL预后较差,中位LFS为7个月,3年生存率仅为13%。整个队列的中位总生存期(OS)为18个月,3年、5年和8年OS分别为32%、24%和22%。OS的有利预后因素是年龄较小(P < 0.0001)和T细胞系ALL(P = 0.001)。在非T细胞系ALL中,标准风险ALL的预后明显优于高风险ALL(P = 0.0003)。从该分析中可以明显看出,死亡和复发的风险率在第一年最高,在第1年至第2年大幅下降,然后在第2年至第3年进一步下降。3 - 4年后死亡和复发率相当低。所有在CR 3年后复发的患者均为B或非B非T细胞系ALL。长期生存者(LTS)定义为CR生存≥3年,占可评估患者的23%。83例患者在初始CR状态下存活超过3年,而只有3例在第二次CR后成为LTS。总体而言,多年来在CR实现和生存持续时间方面未显示出显著改善。然而,就生存而言,T细胞系ALL有显著改善(P = 0.03)。此外,首次CR时接受移植的患者(年龄小于50岁)的表现明显优于仅接受化疗作为缓解后治疗的患者(P < 0.0001)。首次CR后接受异基因移植的患者,T细胞系ALL的3年OS为74%,而B细胞系ALL则低于50%。这项对大量ALL患者队列的单中心研究反映了ALL治疗在成人中仍未成功的程度。多年来只有T细胞系ALL的结局有所改善。结果表明,如果患者处于CR状态,3年时可以合理地认为有潜在治愈的可能。