Takeuchi J, Kyo T, Naito K, Sao H, Takahashi M, Miyawaki S, Kuriyama K, Ohtake S, Yagasaki F, Murakami H, Asou N, Ino T, Okamoto T, Usui N, Nishimura M, Shinagawa K, Fukushima T, Taguchi H, Morii T, Mizuta S, Akiyama H, Nakamura Y, Ohshima T, Ohno R
First Department of Internal Medicine, Nihon University School of Medicine, Japan.
Leukemia. 2002 Jul;16(7):1259-66. doi: 10.1038/sj.leu.2402526.
In order to improve the disappointing prognosis of adult patients with acute lymphoblastic leukemia (ALL), we applied similar induction therapy as that used for acute myeloid leukemia (AML), ie frequent administration of doxorubicin (DOX). DOX 30 mg/m(2) was administered from days 1 to 3 and from days 8 to 10 together with vincristine, prednisolone, cyclophosphamide and L-asparaginase, followed by three courses of consolidation and four courses of intensification. From December 1993 to February 1997, 285 untreated adult patients with de novo ALL were entered. Of 263 evaluable patients (age 15 to 59; median 31), 205 (78%) obtained complete remission (CR). At a median follow-up period of 63 months, the predicted 6-year overall survival (OS) rate of all patients was 33%, and disease-free survival (DFS) rate of CR patients was 30%, respectively. By multivariate analysis, favorable prognostic factors for the achievement of CR were age <40 and WBC <50 000/microl; for longer OS were age <30 and WBC <30 000/microl; and for longer DFS of CR patients were FAB L1 and ALT <50 IU/l. Among 229 patients who had adequate cytogenetic data, 51 (22%) had Philadelphia (Ph) chromosome. Ph-negative chromosome was a common favorable prognostic factor for CR, longer OS and DFS. DFS was not different between early sequential intensification (n = 48) and intermittent intensification (n = 43) during the maintenance phase. Among CR patients under 40 years old, the 6-year survival was not different between the allocated related allo-BMT group (34 patients) and the allocated chemotherapy group (108 patients). However, among patients with Ph-positive ALL, the survival of patients who actually received allo-BMT was superior to that of patients who received chemotherapy (P = 0.046).
为改善成人急性淋巴细胞白血病（ALL）令人失望的预后，我们采用了与急性髓系白血病（AML）相似的诱导治疗方案，即频繁给予阿霉素（DOX）。在第1至3天以及第8至10天给予30mg/m²的DOX，同时联合长春新碱、泼尼松龙、环磷酰胺和L-天冬酰胺酶，随后进行三个疗程的巩固治疗和四个疗程的强化治疗。1993年12月至1997年2月，纳入了285例未经治疗的成人初发ALL患者。在263例可评估患者（年龄15至59岁；中位年龄31岁）中，205例（78%）获得完全缓解（CR）。在中位随访期63个月时，所有患者预计的6年总生存率（OS）为33%，CR患者的无病生存率（DFS）为30%。多因素分析显示，实现CR的有利预后因素为年龄<40岁且白细胞计数<50000/μl；OS较长的因素为年龄<30岁且白细胞计数<30000/μl；CR患者DFS较长的因素为FAB L1型且谷丙转氨酶（ALT）<50IU/l。在229例有足够细胞遗传学数据的患者中，51例（22%）有费城（Ph）染色体。Ph阴性染色体是CR、较长OS和DFS的常见有利预后因素。维持期早期序贯强化组（n = 48）和间歇强化组（n = 43）的DFS无差异。在40岁以下的CR患者中，分配至相关异基因骨髓移植组（34例患者）和分配至化疗组（108例患者）的6年生存率无差异。然而，在Ph阳性ALL患者中，实际接受异基因骨髓移植患者的生存率优于接受化疗的患者（P = 0.046）。
