Ueda T, Miyawaki S, Asou N, Kuraishi Y, Hiraoka A, Kuriyama K, Minami S, Ohshima T, Ino T, Tamura J, Kanamaru A, Nishikawa K, Tanimoto M, Oh H, Saito K, Nagata K, Naoe T, Yamada O, Urasaki Y, Sakura T, Ohno R
Department of Medicine, Fukui Medical University Hospital, Japan.
Int J Hematol. 1998 Oct;68(3):279-89. doi: 10.1016/s0925-5710(98)00075-9.
Adult patients with acute lymphoblastic leukemia (ALL) were treated according to the ALL90 study, the second prospective study for ALL of the Japan Adult Leukemia Study Group (JALSG). Its characteristics included response-oriented individualized induction therapy with six drugs (doxorubicin, mitoxantrone, vincristine, prednisolone, [corrected] cyclophosphamide and L-asparaginase), and a prospective comparison between allogeneic bone marrow transplantation (allo-BMT) and chemotherapy alone in patients below 45 years of age. The protocol consisted of one or two courses of induction, four courses of consolidation, and three courses of intensification including 12 month maintenance and six times of central nervous system (CNS) prophylaxis. Of 180 evaluable patients (median age, 43), 125 (69%) achieved complete remission (CR). Predicted overall survival (OAS), event-free survival and disease-free survival (DFS) were 15, 10 and 14%, respectively at the median follow-up period of 62 months. No specific toxicities were observed. Leukocytes < 30,000/microliter, normal karyotype, and blasts < 10% in bone marrow at day 15 of induction therapy were significantly favorable prognostic factors for the achievement of CR, DFS and OAS by univariate analysis. Multivariate analysis showed leukocytes < 30,000/microliter and blasts < 10% on day 15 was a significant factor for the achievement of CR, DFS and OAS. Ph-chromosome was found in 28% (36/130) of patients examined and was one of the worst prognostic factors. All Ph positive patients were predicted to die within 600 days. Allo-BMT was not significantly superior to chemotherapy with respect to DFS (P = 0.226). The overall results were inferior to those of the former ALL87 protocol. As reasons, the older median age of 43 years old (vs. 38 years old) and lower dose intensity, especially of l-asparaginase, etc. were suggested. However, patients with good prognostic factors (leukocyte < 30,000/microliter and age < 30 years old) showed better survival than others (P < 0.0001), and the result was similar to that of older children, the high risk group of childhood ALL, suggesting that ALL could be a disease of single entity, showing higher resistance to chemotherapy as patients become older.
成年急性淋巴细胞白血病（ALL）患者按照ALL90研究进行治疗，这是日本成人白血病研究组（JALSG）针对ALL的第二项前瞻性研究。其特点包括采用六种药物（阿霉素、米托蒽醌、长春新碱、泼尼松龙、[校正后]环磷酰胺和L-天冬酰胺酶）进行以反应为导向的个体化诱导治疗，以及对45岁以下患者进行异基因骨髓移植（allo-BMT）与单纯化疗的前瞻性比较。该方案包括一或两个诱导疗程、四个巩固疗程以及三个强化疗程，其中强化疗程包括12个月的维持治疗和六次中枢神经系统（CNS）预防。在180例可评估患者（中位年龄43岁）中，125例（69%）实现完全缓解（CR）。在中位随访期62个月时，预测的总生存率（OAS）、无事件生存率和无病生存率（DFS）分别为15%、10%和14%。未观察到特定毒性。诱导治疗第15天时白细胞<30,000/微升、核型正常以及骨髓中原始细胞<10%，经单因素分析，这些是实现CR、DFS和OAS的显著有利预后因素。多因素分析显示，诱导治疗第15天时白细胞<30,000/微升和原始细胞<10%是实现CR、DFS和OAS的显著因素。在接受检查的患者中，28%（36/130）发现有Ph染色体，这是最差的预后因素之一。所有Ph阳性患者预计在600天内死亡。就DFS而言，allo-BMT并不显著优于化疗（P = 0.226）。总体结果不如前一个ALL87方案。原因方面，提示中位年龄较大为43岁（对比38岁）以及剂量强度较低，尤其是L-天冬酰胺酶等。然而，具有良好预后因素（白细胞<30,000/微升且年龄<30岁）的患者生存率高于其他患者（P < 0.0001），结果与大龄儿童（儿童ALL高危组）相似，这表明ALL可能是一种单一实体疾病，随着患者年龄增长对化疗的耐药性更高。
