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欧洲急性白血病异基因骨髓移植的结果随时间推移有所改善——欧洲血液和骨髓移植组(EBMT)急性白血病工作组的报告。

Results of allogeneic bone marrow transplantation for acute leukemia have improved in Europe with time--a report of the acute leukemia working party of the European group for blood and marrow transplantation (EBMT).

作者信息

Frassoni F, Labopin M, Gluckman E, Prentice H G, Vernant J P, Zwaan F, Granena A, Gahrton G, De Witte T, Gratwohl A, Reiffers J, Gorin N C

出版信息

Bone Marrow Transplant. 1996 Jan;17(1):13-8.

PMID:8673048
Abstract

To evaluate whether the results of bone marrow transplantation have improved in Europe with time, we analyzed the outcome for 2195 patients with acute leukemia. 1405 had acute myeloid leukemia (AML) and 790 had acute lymphoblastic leukemia (ALL), and were allografted in first complete remission between September 1979 and December 1991 with marrow from an HLA-identical sibling donor. We found a continuing improvement more evident since 1987 for AML and since 1986 for ALL. A substantial reduction in the 3 years transplant related mortality (TRM): 26 vs 39% for AML (P = 10(-4)), and 25 vs 39% for ALL (P = 10(-4)), has resulted in an increase of the 5-year actuarial leukemia-free survival (LFS). 57 vs 45% for AML (P < 10(-4)) and 54 vs 45% (P = 10(-4)) for ALL. Four important changes have occurred. (1) Graft-versus-host disease (GVHD) prevention has involved an increased use of cyclosporin A (CsA) alone and subsequently its use in combination with methotrexate: this was associated with lower TRM both in AML and ALL; (2) Use of total body irradiation as pretransplant regimen has decreased; (3) a shorter interval from remission to BMT is more common; (4) an older population of patients has undergone BMT. Multivariate analyses were performed separately in AML and ALL. In AML four variables significantly influenced TRM favorably: year of BMT (P = 10(-4)), younger age at BMT (P = 10(-4)), prevention of GVHD including CsA (P = 0.008), sex match other than female donor to male recipient (P = 0.002). The relapse incidence (RI) was lower in patients with FAB M1-2-3 vs M4-5 (P = 0.0004). The LFS improved by year of BMT (P = 0.0004), younger age at BMT (P = 10(-4)), prevention of GVHD including CsA (P = 0.01), FAB M1-2-3 (P = 0.03). In ALL, three variables were associated with a lower TRM: year of BMT (P = 10(-4)), younger age at BMT (P = 10(-4)), sex combination other than female to male (P = 0.008). The LFS was better after 1986 (P = 0.0004) and in younger patients (P = 10(-4)). However a better outcome after 1986/87 was observed in patients receiving the same GVHD prophylaxis: therefore, other unidentified factors resulting in better patient care have also contributed to this. The improved results of allogeneic BMT are entirely related to a reduction in TRM without loss of the antileukemic effect since relapse incidence has not changed over the years.

摘要

为评估欧洲骨髓移植的结果是否随时间有所改善,我们分析了2195例急性白血病患者的治疗结果。其中1405例为急性髓系白血病(AML),790例为急性淋巴细胞白血病(ALL),他们均在1979年9月至1991年12月期间首次完全缓解时接受了来自 HLA 相同同胞供者的骨髓移植。我们发现自1987年以来AML以及自1986年以来ALL的情况持续改善更为明显。3年移植相关死亡率(TRM)大幅降低:AML为26% 对比39%(P = 10⁻⁴),ALL为25% 对比39%(P = 10⁻⁴),这使得5年无白血病生存(LFS)率有所提高。AML为57% 对比45%(P < 10⁻⁴),ALL为54% 对比45%(P = 10⁻⁴)。出现了四个重要变化。(1)移植物抗宿主病(GVHD)预防措施中,环孢素A(CsA)单独使用的频率增加,随后又与甲氨蝶呤联合使用:这与AML和ALL中较低的TRM相关;(2)作为移植前预处理方案的全身照射的使用减少;(3)从缓解到骨髓移植的间隔时间缩短更为常见;(4)接受骨髓移植的患者年龄更大。分别对AML和ALL进行了多因素分析。在AML中,四个变量对TRM有显著的有利影响:骨髓移植年份(P = 10⁻⁴)、骨髓移植时年龄较小(P = 10⁻⁴)、包括CsA在内的GVHD预防措施(P = 0.008)、除女性供者对男性受者之外的性别匹配(P = 0.002)。FAB M1 - 2 - 3型患者的复发率(RI)低于M4 - 5型患者(P = 0.0004)。LFS随骨髓移植年份改善(P = 0.0004)、骨髓移植时年龄较小(P = 10⁻⁴)、包括CsA在内的GVHD预防措施(P = 0.01)、FAB M1 - 2 - 3型(P = 0.03)。在ALL中,三个变量与较低的TRM相关:骨髓移植年份(P = 10⁻⁴)、骨髓移植时年龄较小(P = 10⁻⁴)、除女性对男性之外的性别组合(P = 0.008)。1986年之后(P = 0.0004)以及年轻患者中的LFS更好(P = 10⁻⁴)。然而,在接受相同GVHD预防措施的患者中,1986/87年之后观察到更好的结果:因此,其他导致更好患者护理的未明确因素也对此有所贡献。异基因骨髓移植结果的改善完全归因于TRM的降低,且由于多年来复发率未变,抗白血病效应并未丧失。

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