Boiron J M, Lerner D, Pigneux A, Fabères C, Bordessoule D, Turlure P, Cony-Makhoul P, Hau F, Dazey B, Agape P, Reiffers J, Marit G
Service des Maladies du Sang, CHU Bordeaux, Hôpital Haut-Lévêque, Avenue de Magellan, 33604 Pessac.
Leuk Lymphoma. 2001 Apr;41(3-4):285-96. doi: 10.3109/10428190109057983.
Allogeneic transplantation is a well recognized treatment strategy of leukemia. However, its use in advanced leukemia patients is a subject of some debate especially when donors are not HLA-identical siblings because of the toxicity and cost of the procedure. We reviewed retrospectively the outcome of patients (pts) who received allogeneic transplantation for advanced acute leukemia in our center between 09/86 and 11/97. Thirty-six pts (study group) who lacked a matched sibling donor received partially matched related donor (n=14: PMRD group) or matched unrelated donor transplantation (n=22: MUD group). Fifteen pts had AML and 21 ALL. Seventeen pts (47%) were in CR>1, 13 pts (36%) had refractory disease and six pts (17.7%) were in untreated relapse. The outcome was compared to that of 56 patients (AML: 45.5 %, ALL: 55.5 %, CR>1: 49.9 %, refractory disease: 37.5 %, untreated relapse 19.6 %) who received allogeneic transplantation from a matched sibling donor (control group). Various conditioning regimens and GVHD prophylaxis were used. The actuarial incidence of grade II to IV acute GVHD was significantly higher in the study group (57%) than in the control group (34%) (p=0.047). The actuarial risk of relapse at three years was 21% +/- 22% in the study group versus 65% +/- 16% in the control group (p= 0.04). The actuarial probability of transplant-related mortality at 3 years is 64 +/- 16% for the study group and 25 +/- 11% for the control group (p=0.001). The leading cause of death in the study group was infection (30%) followed by acute GVHD and relapse. Relapse was the major cause of death in the control group (54%), followed by infection, interstitial pneumonia, veno-occlusive disease and GVHD. The OS and probability of leukemia-free survival at 3 years were 28 % +/- 15% (95% CI) and 27% +/- 15% (95% CI) in the study group. The overall survival and probability of LFS at 3 years were respectively 28 +/- 12% (95% CI) and 23 +/- 12% (95% CI) in the control group (p = 0.08 and p=0.11 respectively). In multivariate analysis, transplant-related mortality was higher in the study group (p=0.04) and lower if both donor and recipient were seronegative for CMV (p=0.007). OS was significantly higher for seronegative couples (p=0.0001), and when CR was achieved before BMT (p=0.0022). These results suggest that all efforts in this field should be directed on lowering the transplant related mortality for non geno-identical transplants and the relapse rate in geno-identical transplants.
异基因移植是白血病一种公认的治疗策略。然而，其在晚期白血病患者中的应用存在一定争议，尤其是当供者不是 HLA 匹配的同胞时，因为该 procedure 存在毒性且成本较高。我们回顾性分析了 1986 年 9 月至 1997 年 11 月期间在我们中心接受异基因移植治疗晚期急性白血病的患者（pts）的结局。36 例患者（研究组）缺乏匹配的同胞供者，接受了部分匹配的相关供者（n = 14：PMRD 组）或匹配的无关供者移植（n = 22：MUD 组）。15 例为 AML，21 例为 ALL。17 例患者（47%）处于 CR>1 状态，13 例患者（36%）患有难治性疾病，6 例患者（17.7%）处于未治疗的复发状态。将结果与 56 例接受 HLA 匹配同胞供者异基因移植的患者（AML：45.5%，ALL：55.5%，CR>1：49.9%，难治性疾病：37.5%，未治疗的复发 19.6%）（对照组）进行比较。采用了各种预处理方案和移植物抗宿主病（GVHD）预防措施。研究组 II 至 IV 级急性 GVHD 的精算发生率（57%）显著高于对照组（34%）（p = 0.047）。研究组三年时的复发精算风险为 21%±22%，而对照组为 65%±16%（p = 0.04）。研究组三年时移植相关死亡率的精算概率为 64±16%，对照组为 25±11%（p = 0.001）。研究组的主要死亡原因是感染（30%），其次是急性 GVHD 和复发。复发是对照组的主要死亡原因（54%），其次是感染、间质性肺炎、静脉闭塞性疾病和 GVHD。研究组三年时的总生存率（OS）和无白血病生存率分别为 28%±15%（95%CI）和 27%±15%（95%CI）。对照组三年时的总生存率和 LFS 概率分别为 28±12%（95%CI）和 23±12%（95%CI）（分别为 p = 0.08 和 p = 0.11）。多因素分析显示，研究组的移植相关死亡率较高（p = 0.04），而供者和受者均为 CMV 血清学阴性时移植相关死亡率较低（p = 0.007）。血清学阴性的供受者对的 OS 显著较高（p = 0.0001），且在 BMT 前达到 CR 时 OS 也显著较高（p = 0.0022）。这些结果表明，该领域的所有努力都应致力于降低非基因相同移植的移植相关死亡率以及基因相同移植的复发率。
