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低度非霍奇金淋巴瘤自体造血干细胞移植后的长期随访

Long-term follow-up after autologous hematopoietic stem cell transplantation for low-grade non-Hodgkin lymphoma.

作者信息

Laudi Noel, Arora Mukta, Burns Linda J, Miller Jeffrey S, McGlave Philip B, Barker Juliet N, Ramsay Norma K C, Orchard Paul J, Macmillan Margaret L, Weisdorf Daniel J

机构信息

Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, MN 55455, USA.

出版信息

Biol Blood Marrow Transplant. 2005 Feb;11(2):129-35. doi: 10.1016/j.bbmt.2004.11.017.

Abstract

Autologous hematopoietic stem cell transplantation (AHSCT) in low-grade non-Hodgkin lymphoma (NHL) can result in a prolonged remission, although most patients eventually relapse and die of their disease. We report long-term outcomes of AHSCT for patients with relapsed low-grade NHL. Between May 1983 and 2001, 67 patients with relapsed or refractory stage III and IV low-grade NHL received an AHSCT at the University of Minnesota at a median of 2.3 years (range, 0.4-15.2 years) after diagnosis. At transplantation, 62 patients (92%) were in complete remission (CR) (6%) or partial remission (PR) (86%); 5 (8%) had resistant disease; and 9 (14%) had transformed to a higher-grade NHL. After AHSCT, 32 (49%) of 65 evaluable patients achieved CR, and 26 (40%) achieved PR. Overall survival (OS) was 50% (95% confidence interval [CI], 38%-62%) at 4 years and 33% (95% CI, 20%-46%) at both 10 and 18 years, whereas progression-free survival (PFS) was 28% (95% CI, 17%-39%) at 4 years, 18% (95% CI, 8%-28%) at 10 years, and 14% (95% CI, 4%-25%) at 18 years. Transplant-related mortality in the first 100 days was 3% (95% CI, 0%-7%). Relapse occurred in 62% (95% CI, 48%-75%) at 4 years and 72% (95% CI, 56%-87%) at 10 years. Eleven patients (16%) developed myelodysplastic syndrome/acute myeloid leukemia 1 to 8 years after AHSCT, and 3 (5%) developed solid tumors. In multiple regression analysis, the International Prognostic Index (IPI) score at transplantation was the most significant predictor for both OS and PFS. The median OS has not been reached in patients with an IPI score of 0 or 1 at transplantation (20 of 35 survive 2 to 18 years after AHSCT), whereas it was 2.3 and 1.6 years for IPI scores of 2 and 3, respectively ( P = .002). A good response (CR/PR) to AHSCT (relative risk [RR], 0.4; 95% CI, 0.2-0.9; P = .04) and age <50 years (RR, 0.5; 95% CI, 0.2-0.8; P = .01) were also independently significant predictors of good OS and PFS. We present mature follow-up data (median follow-up, 8 years; range, 2-18 years) of patients undergoing AHSCT for relapsed low-grade NHL and demonstrate extended OS and PFS. Very long-term remissions were seen in nearly 20% of patients. AHSCT remains promising, especially for patients with sensitive relapse and lower IPI scores. Recurrent lymphoma after AHSCT remains the major problem, and prolonged survival is further tempered by a significant risk of post-transplantation second malignancies, including myelodysplastic syndrome/acute myeloid leukemia and solid tumors.

摘要

自体造血干细胞移植(AHSCT)用于治疗低度非霍奇金淋巴瘤(NHL)可使缓解期延长,尽管大多数患者最终会复发并死于该疾病。我们报告了复发性低度NHL患者接受AHSCT的长期结果。1983年5月至2001年期间,67例复发或难治性III期和IV期低度NHL患者在明尼苏达大学接受了AHSCT,诊断后中位时间为2.3年(范围0.4 - 15.2年)。移植时,62例患者(92%)处于完全缓解(CR)(6%)或部分缓解(PR)(86%);5例(8%)为耐药疾病;9例(14%)已转化为高级别NHL。AHSCT后,65例可评估患者中有32例(49%)达到CR,26例(40%)达到PR。4年总生存率(OS)为50%(95%置信区间[CI],38% - 62%),10年和18年时均为33%(95% CI,20% - 46%),而无进展生存期(PFS)4年时为28%(95% CI,17% - 39%),10年时为18%(95% CI,8% - 28%),18年时为14%(95% CI,4% - 25%)。前100天的移植相关死亡率为3%(95% CI,0% - 7%)。4年时复发率为62%(95% CI,48% - 75%),10年时为72%(95% CI,56% - 87%)。11例患者(16%)在AHSCT后1至8年发生骨髓增生异常综合征/急性髓系白血病,3例(5%)发生实体瘤。在多因素回归分析中,移植时的国际预后指数(IPI)评分是OS和PFS的最显著预测因素。移植时IPI评分为0或1的患者中位OS尚未达到(35例中有20例在AHSCT后存活2至18年),而IPI评分为2和3的患者中位OS分别为2.3年和1.6年(P = 0.002)。对AHSCT有良好反应(CR/PR)(相对危险度[RR],0.4;95% CI,0.2 - 0.9;P = 0.04)以及年龄<50岁(RR,0.5;95% CI,0.2 - 0.8;P = 0.01)也是OS和PFS良好的独立显著预测因素。我们展示了复发性低度NHL患者接受AHSCT的成熟随访数据(中位随访时间8年;范围2 - 18年),并证明了OS和PFS的延长。近20%的患者出现了非常长期的缓解。AHSCT仍然很有前景,尤其是对于复发敏感且IPI评分较低的患者。AHSCT后复发性淋巴瘤仍然是主要问题,移植后发生包括骨髓增生异常综合征/急性髓系白血病和实体瘤在内的第二原发恶性肿瘤的显著风险进一步影响了长期生存。

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