Lim Andrew B M, Curley Cameron, Fong Chun Y, Bilmon Ian, Beligaswatte Ashanka, Purtill Duncan, Getta Bartlomiej, Johnston Anne M, Armytage Tasman, Collins Marnie, Mason Kate, Fielding Katherine, Greenwood Matthew, Gibson John, Hertzberg Mark, Wright Matthew, Lewis Ian, Moore John, Curtis David, Szer Jeff, Kennedy Glen, Ritchie David
Department of Clinical Haematology and BMT Service, The Royal Melbourne Hospital, Melbourne, Victoria, Australia.
The University of Melbourne, Melbourne, Victoria, Australia.
Intern Med J. 2018 Mar;48(3):276-285. doi: 10.1111/imj.13522.
BACKGROUND/AIMS: We sought to determine factors associated with the overall survival from relapse (OSR) of acute myeloid leukaemia (AML) after allogeneic haemopoietic stem cell transplantation (alloHSCT) and the effect of first salvage therapy and subsequent graft-versus-host disease (GVHD) on OSR.
Data on 386 patients from nine Australian centres with relapsed AML post-alloHSCT were collected retrospectively. OSR was calculated using the Kaplan-Meier method. Univariate and multivariate analyses were conducted using the log-rank test and proportional hazards modelling, respectively and a prognostic index for OSR was derived from multivariate modelling.
On multivariate analysis, relapse within 6 months (hazard ratio (HR) 2.4, P < 0.001) and grade 3-4 acute GVHD preceding relapse (HR 2.0, P = 0.004), were associated with inferior OSR. Patients with 1-2 factors had inferior OSR compared to those with zero factors (all patients: HR 2.3, P < 0.001, patients given salvage: HR 1.8, P < 0.001). The first salvage therapy used post-relapse was donor cell therapy (DCT) (second alloHSCT or donor lymphocyte infusion) in 75, re-induction chemotherapy (CT) in 103, radiotherapy in 8 and interferon-α in 6. Although re-induction CT death rate was low (2%), survival after CT was inferior to DCT (HR 1.9, P < 0.001). No survival benefit was seen for patients who developed GVHD following salvage therapy (P = 0.405).
Patients with AML who relapse beyond 6 months from alloHSCT without prior grade 3-4 acute GVHD have a better outcome from salvage therapy. Salvage treatments employing DCT as the initial treatment of AML relapse confer a survival advantage over CT.
背景/目的:我们试图确定异基因造血干细胞移植(alloHSCT)后急性髓系白血病(AML)复发后的总生存(OSR)相关因素,以及首次挽救治疗和随后的移植物抗宿主病(GVHD)对OSR的影响。
回顾性收集来自澳大利亚九个中心的386例alloHSCT后复发AML患者的数据。采用Kaplan-Meier方法计算OSR。分别使用对数秩检验和比例风险模型进行单因素和多因素分析,并从多因素模型中得出OSR的预后指数。
多因素分析显示,6个月内复发(风险比[HR] 2.4,P < 0.001)和复发前3-4级急性GVHD(HR 2.0,P = 0.004)与较差的OSR相关。有1-2个因素的患者与无因素患者相比,OSR较差(所有患者:HR 2.3,P < 0.001,接受挽救治疗的患者:HR 1.8,P < 0.001)。复发后首次使用的挽救治疗为供体细胞治疗(DCT)(第二次alloHSCT或供体淋巴细胞输注)75例,再诱导化疗(CT)103例,放疗8例,干扰素-α 6例。虽然再诱导CT的死亡率较低(2%),但CT后的生存率低于DCT(HR 1.9,P < 0.001)。挽救治疗后发生GVHD的患者未观察到生存获益(P = 0.405)。
alloHSCT后6个月以上复发且无先前3-4级急性GVHD的AML患者,挽救治疗的预后较好。采用DCT作为AML复发初始治疗的挽救治疗比CT具有生存优势。