Harrison C N, Gregory W, Hudson G V, Devereux S, Goldstone A H, Hancock B, Winfield D, MacMillan A K, Hoskin P, Newland A C, Milligan D, Linch D C
University College Medical School, London, UK.
Br J Cancer. 1999 Oct;81(3):476-83. doi: 10.1038/sj.bjc.6690718.
Hodgkin's disease is curable in the majority of patients, although a proportion of patients are resistant to or relapse after initial therapy. High-dose therapy with autologous stem cell support has become the standard salvage therapy for patients failing chemotherapy, but there have been reports of a high incidence of myelodysplasia/acute myeloid leukaemia (MDS/AML) following such treatment. Patients who receive such therapy form a selected group, however, who have already been subjected to other leukaemogenic factors, such as treatment with alkylating agents. In order to ascertain the true risk of MDS/AML, comparison must be made with other patients subjected to the same risks but not undergoing transplantation. We report a retrospective comparative study of 4576 patients with Hodgkin's disease from the BNLI and UCLH Hodgkin's databases, which includes 595 patients who have received a transplant. Statistical analysis including Cox's proportional hazards multivariate regression model with time-dependent covariates was employed. This analysis reveals that the risk of developing MDS/AML was dominated by three factors, namely quantity of prior therapy (relative risk [RR] 2.01, 95% confidence intervals [CI] 1.49-2.71, for each treatment block, P < 0.0001) and whether the patient had been exposed to MOPP (RR 3.61, 95% CI 1.64-7.95, P = 0.0009) or lomustine chemotherapy (RR 4.53, 95% CI 1.96-10.44, P = 0.001). Following adjustment for these factors in the multivariate model the relative risk associated with transplantation was 1.83 (95% CI 0.66-5.11, P = 0.25). This study provides no evidence of a significantly increased risk of MDS/AML associated with BEAM therapy and autologous transplantation in Hodgkin's disease. Concern over MDS/AML should not mitigate against the timely use of this treatment modality.
霍奇金淋巴瘤在大多数患者中是可治愈的,尽管一部分患者对初始治疗耐药或复发。大剂量治疗联合自体干细胞支持已成为化疗失败患者的标准挽救疗法,但有报道称,此类治疗后骨髓增生异常综合征/急性髓系白血病(MDS/AML)的发生率很高。然而,接受此类治疗的患者是经过挑选的,他们已经受到了其他致白血病因素的影响,比如烷化剂治疗。为了确定MDS/AML的真正风险,必须与其他面临相同风险但未接受移植的患者进行比较。我们对来自英国国家淋巴瘤调查组(BNLI)和伦敦大学学院医院(UCLH)霍奇金淋巴瘤数据库的4576例霍奇金淋巴瘤患者进行了一项回顾性比较研究,其中包括595例接受过移植的患者。采用了包括带有时间依存性协变量的Cox比例风险多变量回归模型在内的统计分析方法。该分析表明,发生MDS/AML的风险主要由三个因素决定,即既往治疗的疗程数(相对风险[RR]为2.01,95%置信区间[CI]为1.49 - 2.71,每增加一个治疗疗程,P < 0.0001)以及患者是否接受过MOPP方案治疗(RR为3.61,95% CI为1.64 - 7.95,P = 0.0009)或洛莫司汀化疗(RR为4.53,95% CI为1.96 - 10.44,P = 0.001)。在多变量模型中对这些因素进行调整后,与移植相关的相对风险为1.83(95% CI为0.66 - 5.11,P = 0.25)。这项研究没有提供证据表明霍奇金淋巴瘤患者接受BEAM方案治疗和自体移植后发生MDS/AML的风险会显著增加。对MDS/AML的担忧不应妨碍及时采用这种治疗方式。