Shimoyama M, Ota K, Kikuchi M, Yunoki K, Konda S, Takatsuki K, Ichimaru M, Ogawa M, Kimura I, Tominaga S
Hematology-Oncology Division, National Cancer Center Hospital, Tokyo, Japan.
J Clin Oncol. 1988 Jan;6(1):128-41. doi: 10.1200/JCO.1988.6.1.128.
One hundred sixty-three patients with advanced non-Hodgkin's lymphoma including adult T cell leukemia/lymphoma (ATL) were treated from 1981 to 1983 with VEPA (vincristine, cyclophosphamide, prednisolone, and doxorubicin) or VEPA-M (VEPA plus methotrexate) in randomized fashion after stratification by surface marker. The complete response (CR) rate and the 4-year survival rate of patients treated with VEPA-M was 62.2% and 36.9%, respectively, while for those treated with VEPA the rates were 51.9% and 26.6, respectively. The difference was not statistically significant, but pretreatment characteristics predictive for response and survival were interesting. Three factors, leukemic change, poor performance status (PS), and T cell marker, were negatively associated with both CR and survival rates, and high-grade pathology was adversely associated with survival rate in a multivariate analysis. These prognostic factors are somewhat different from those in Western lymphomas. This may be reflection of major differences in patients' characteristics between Japanese and Western lymphomas: in this study, there was a high incidence of T cell lymphoma/leukemia (50%) including ATL (33%), leukemic manifestation (34%), poor PS (34%), and a low incidence of follicular lymphoma (9%). The statistically significant three factors for both CR and survival rates were used to construct a model containing eight categories of patients at increasing risk for poor response and shortened survival. These categories were divided into four groups, with respective CR and 4-year survival rates of 91% and 73%, 67% and 35%, 27% and 7%, and 10% and 5%. Ninety-three patients in whom CR was induced by VEPA or VEPA-M therapy were evaluated for prognostic factors predictive for disease-free survival. A shorter period (less than 28 days) required to achieve CR, a clinical diagnosis of ATL, and a lower hemoglobin level were found to affect disease-free survival adversely. These results have important implications for both the design of prospective randomized therapeutic trials and the determination of optimal therapy for individual patients.
1981年至1983年期间,163例晚期非霍奇金淋巴瘤患者,包括成人T细胞白血病/淋巴瘤(ATL),在根据表面标志物分层后,以随机方式接受了VEPA(长春新碱、环磷酰胺、泼尼松龙和阿霉素)或VEPA-M(VEPA加甲氨蝶呤)治疗。接受VEPA-M治疗的患者的完全缓解(CR)率和4年生存率分别为62.2%和36.9%,而接受VEPA治疗的患者的相应比率分别为51.9%和26.6%。差异无统计学意义,但预测反应和生存的预处理特征很有意思。在多因素分析中,白血病改变、较差的体能状态(PS)和T细胞标志物这三个因素与CR率和生存率均呈负相关,高级别病理与生存率呈负相关。这些预后因素与西方淋巴瘤的预后因素有所不同。这可能反映了日本淋巴瘤和西方淋巴瘤患者特征的主要差异:在本研究中,T细胞淋巴瘤/白血病(50%)包括ATL(33%)、白血病表现(34%)、PS较差(34%)的发生率较高,而滤泡性淋巴瘤的发生率较低(9%)。用于构建一个包含八类患者的模型,这些患者对反应不佳和生存期缩短的风险逐渐增加,CR率和生存率在这八类患者中分别为91%和73%、67%和35%、27%和7%、10%和5%。对93例通过VEPA或VEPA-M治疗诱导CR的患者进行了预测无病生存的预后因素评估。发现达到CR所需的较短时间(少于28天)、ATL的临床诊断以及较低的血红蛋白水平对无病生存产生不利影响。这些结果对前瞻性随机治疗试验的设计和个体患者最佳治疗方案的确定都具有重要意义。