Preti A, Kantarjian H M
Department of Hematology, M.D. Anderson Cancer Center, Houston, TX 77030.
J Clin Oncol. 1994 Jun;12(6):1312-22. doi: 10.1200/JCO.1994.12.6.1312.
To discuss the controversies in current adult acute lymphocytic leukemia (ALL) management in relation to its different phases of therapy.
A review of treatments in adult ALL from the English literature.
Features signaling high risk for systemic relapse (older age, high WBC count at diagnosis, non-T-cell immunophenotype, Philadelphia chromosome (Ph)-positive karyotype, and longer time to achieve remission) are found in 60% to 70% of patients with adult ALL. These patients have a potential cure rate of 20% to 25%, compared with 60% to 70% for low-risk patients. Induction regimens with vincristine, anthracyclines, and corticosteroids appear to be optimal. Intensification-consolidation therapy increased cure rates modestly in adult ALL; higher-dose schedules of mercaptopurine (6-MP), methotrexate, and asparaginase may be beneficial. Maintenance therapy with 6-MP and methotrexate is suggested based on the worse outcome of patients in whom such maintenance was omitted. Allogeneic bone marrow transplantation (BMT) is indicated for patients in first remission with high-risk for relapse; autologous BMT for patients in first remission remains investigational. Patients with mature B-cell ALL require short-term, dose-intensive therapy that alternates hyperfractionated doses of cyclophosphamide with high-dose cytarabine (ara-C) and methotrexate. Patients with T-cell ALL may benefit from ara-C/cyclophosphamide combinations during maintenance therapy. CNS prophylaxis with intrathecal chemotherapy should be administered in patients at risk for CNS relapse.
Potential strategies to improve the prognosis of high-risk patients with ALL include increasing the dose-intensity of remission induction and consolidation-intensification therapies with growth factor support; discovering and using new anti-ALL drugs; improving autologous BMT results; translating biologic studies of leukemia cell characteristics, karyotype-related molecular aberrations, abnormal oncogenic expression, and minimal residual disease into clinically relevant therapies; and using investigational treatment strategies in high-risk patients.
探讨成人急性淋巴细胞白血病（ALL）当前治疗中与不同治疗阶段相关的争议。
对英文文献中成人ALL的治疗进行综述。
60%至70%的成人ALL患者具有提示全身复发高风险的特征（年龄较大、诊断时白细胞计数高、非T细胞免疫表型、费城染色体（Ph）阳性核型以及达到缓解的时间较长）。这些患者的潜在治愈率为20%至25%，而低风险患者为60%至70%。含长春新碱、蒽环类药物和皮质类固醇的诱导方案似乎是最佳的。强化巩固治疗使成人ALL的治愈率略有提高；较高剂量的巯嘌呤（6-MP）、甲氨蝶呤和天冬酰胺酶方案可能有益。基于未进行此类维持治疗的患者预后较差，建议使用6-MP和甲氨蝶呤进行维持治疗。对于首次缓解且复发风险高的患者，建议进行异基因骨髓移植（BMT）；首次缓解患者的自体BMT仍在研究中。成熟B细胞ALL患者需要短期、剂量密集的治疗，交替使用超分割剂量的环磷酰胺与高剂量阿糖胞苷（ara-C）和甲氨蝶呤。T细胞ALL患者在维持治疗期间可能从ara-C/环磷酰胺联合方案中获益。有中枢神经系统复发风险的患者应接受鞘内化疗进行中枢神经系统预防。
改善ALL高风险患者预后的潜在策略包括在生长因子支持下增加缓解诱导和巩固强化治疗的剂量强度；发现和使用新的抗ALL药物；改善自体BMT的效果；将白血病细胞特征、核型相关分子异常、异常致癌表达和微小残留病的生物学研究转化为临床相关治疗；以及在高风险患者中使用研究性治疗策略。
