Kobayashi T, Tobinai K, Shimoyama M, Mikuni C, Konda S, Kozuru M, Araki K, Sai T, Fukuhara S, Matsumoto M, Aoki I, Deura K, Oyama A, Hotta T, Abe T, Toki H, Nagai M, Fukuda H, Niimi M, Yamaguchi N, Tajima K, Shirakawa S
Mie University School of Medicine, Tsu, Japan.
Jpn J Clin Oncol. 1999 Jul;29(7):340-8. doi: 10.1093/jjco/29.7.340.
Patients with acute lymphocytic leukemia (ALL) and those with lymphoblastic lymphoma (LBL) have overlapping clinical and immunophenotypic features and they have been treated with the same or very similar chemotherapy regimens. The goal of this multi-institutional phase II trial was to evaluate the therapeutic efficacy of a short-term, six-drug chemotherapy regimen for adult patients with untreated ALL or LBL.
Forty-six eligible patients, 41 with ALL and five with LBL, were treated with a short-term (planned total therapy duration; 36-38 weeks), simplified chemotherapy program; two courses of VEPA-L (vincristine, cyclophosphamide, prednisolone, doxorubicin, I-asparaginase plus intrathecal methotrexate and prednisolone) followed by four courses of M-VEPA (methotrexate plus VEPA), without the traditional maintenance therapy using daily 6-mercaptopurine and weekly methotrexate.
Thirty-six (78%; 95% confidence interval 64-89%) of the 46 eligible patients achieved complete remission (CR). Among the 36 patients who achieved CR, four (11%) died of treatment complications, 26 (72%) relapsed and six (17%) remain alive in continuous CR. The median survival for all 46 eligible patients is 14 months and the median disease-free survival (DFS) for the 36 patients who achieved CR is 11 months. The estimate of the proportion of survival at 7 years of all 46 eligible patients is 15% at a median follow-up time of 96 months and that of DFS of the 36 patients achieving CR is 17% at a median follow-up time of 93 months. Subgroup analysis showed that an elevated serum C-reactive protein (CRP) level, age of 30 years or older, the presence of B-symptom and T-cell phenotype were likely to be associated with shortened survival. Although the observed CR rate (78%) is within the range of satisfaction, the long-term survival rate (15%) is inferior to those of published programs incorporating maintenance therapy.
A fraction of adult patients with ALL or LBL are curable with a short-term, six-drug chemotherapy regimen. However, this simplified therapy of shorter duration cannot be recommended.
急性淋巴细胞白血病（ALL）患者和淋巴母细胞淋巴瘤（LBL）患者具有重叠的临床和免疫表型特征，并且一直采用相同或非常相似的化疗方案进行治疗。这项多机构II期试验的目的是评估一种短期六药化疗方案对未经治疗的成年ALL或LBL患者的治疗效果。
46例符合条件的患者，41例ALL患者和5例LBL患者，接受了短期（计划总治疗时长；36 - 38周）简化化疗方案；两个疗程的VEPA - L（长春新碱、环磷酰胺、泼尼松龙、阿霉素、L - 天冬酰胺酶加鞘内注射甲氨蝶呤和泼尼松龙），随后四个疗程的M - VEPA（甲氨蝶呤加VEPA），不使用传统的每日6 - 巯基嘌呤和每周甲氨蝶呤维持治疗。
46例符合条件的患者中有36例（78%；95%置信区间64 - 89%）实现完全缓解（CR）。在实现CR的36例患者中，4例（11%）死于治疗并发症，26例（72%）复发，6例（17%）持续CR存活。所有46例符合条件患者的中位生存期为14个月，实现CR的36例患者的中位无病生存期（DFS）为11个月。在中位随访时间96个月时，所有46例符合条件患者7年生存率估计为15%，在中位随访时间93个月时，实现CR的36例患者的DFS为17%。亚组分析表明，血清C反应蛋白（CRP）水平升高、30岁及以上年龄、存在B症状和T细胞表型可能与生存期缩短有关。虽然观察到的CR率（78%）在满意范围内，但长期生存率（15%）低于已发表的包含维持治疗方案的生存率。
一部分成年ALL或LBL患者可通过短期六药化疗方案治愈。然而，不推荐这种疗程较短的简化治疗。
