供体淋巴细胞输注治疗成人急性髓系白血病异基因干细胞移植后首次血液学复发:EBMT急性白血病工作组的回顾性危险因素分析及与其他策略的比较

Donor lymphocyte infusion in the treatment of first hematological relapse after allogeneic stem-cell transplantation in adults with acute myeloid leukemia: a retrospective risk factors analysis and comparison with other strategies by the EBMT Acute Leukemia Working Party.

作者信息

Schmid Christoph, Labopin Myriam, Nagler Arnon, Bornhäuser Martin, Finke Jürgen, Fassas Athanasios, Volin Liisa, Gürman Günham, Maertens Johan, Bordigoni Pierre, Holler Ernst, Ehninger Gerhard, Polge Emmanuelle, Gorin Norbert-Claude, Kolb Hans-Jochem, Rocha Vanderson

机构信息

Department of Medicine II, Klinikum Augsburg, Ludwig Maximilians University of Munich, Augsburg, Germany.

出版信息

J Clin Oncol. 2007 Nov 1;25(31):4938-45. doi: 10.1200/JCO.2007.11.6053. Epub 2007 Oct 1.

Abstract

PURPOSE

To evaluate the role of donor lymphocyte infusion (DLI) in the treatment of relapsed acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (HSCT).

PATIENTS AND METHODS

We retrospectively analyzed the data of 399 patients with AML in first hematological relapse after HSCT whose treatment did (n = 171) or did not (n = 228) include DLI. After correction for imbalances and established risk factors, the two groups were compared with respect to overall survival. Further, a detailed analysis of risk factors for survival among DLI recipients was performed.

RESULTS

Median follow-up was 27 and 40 months, respectively. Estimated survival at 2 years (+/- standard deviation) was 21% +/- 3% for patients receiving DLI and 9% +/- 2% for patients not receiving DLI. After adjustment for differences between the groups, better outcome was associated with age younger than 37 years (P = .008), relapse occurring more than 5 months after HSCT (P < .0001), and use of DLI (P = .04). Among DLI recipients, a lower tumor burden at relapse (< 35% of bone marrow blasts; P = .006), female sex (P = .02), favorable cytogenetics (P = .004), and remission at time of DLI (P < .0001) were predictive for survival in a multivariate analysis. Two-year survival was 56% +/- 10%, if DLI was performed in remission or with favorable karyotype, and 15% +/- 3% if DLI was given in aplasia or with active disease.

CONCLUSION

Although further evidence for a graft-versus-leukemia effect by DLI is provided, our results confirm, that the clinical benefit is limited to a minority of patients. Strategies to reduce tumor burden before DLI, as well as alternative treatment options should be investigated in adults with relapsed AML after HSCT.

摘要

目的

评估供体淋巴细胞输注(DLI)在异基因造血干细胞移植(HSCT)后复发的急性髓系白血病(AML)治疗中的作用。

患者和方法

我们回顾性分析了399例HSCT后首次血液学复发的AML患者的数据,这些患者的治疗包括(n = 171)或不包括(n = 228)DLI。在对不平衡因素和既定风险因素进行校正后,比较两组的总生存期。此外,对接受DLI患者的生存风险因素进行了详细分析。

结果

中位随访时间分别为27个月和40个月。接受DLI的患者2年(±标准差)估计生存率为21%±3%,未接受DLI的患者为9%±2%。在对两组之间的差异进行调整后,较好的预后与年龄小于37岁(P = 0.008)、HSCT后5个月以上复发(P < 0.0001)以及使用DLI(P = 0.04)相关。在接受DLI的患者中,复发时较低的肿瘤负荷(骨髓原始细胞<35%;P = 0.006)、女性(P = 0.02)、良好的细胞遗传学(P = 0.004)以及DLI时处于缓解期(P < 0.0001)在多因素分析中可预测生存。如果在缓解期或核型良好时进行DLI,2年生存率为56%±10%,如果在再生障碍期或疾病活动期进行DLI,2年生存率为15%±3%。

结论

虽然DLI的移植物抗白血病作用有了进一步证据,但我们的结果证实,临床益处仅限于少数患者。对于HSCT后复发的成年AML患者,应研究在DLI前降低肿瘤负荷的策略以及替代治疗方案。

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