Bassan R, Di Bona E, Lerede T, Pogliani E, Rossi G, D'Emilio A, Buelli M, Rambaldi A, Viero P, Rodeghiero F, Barbui T
Divisione/Servizio di Ematologia Ospedali Riuniti, Bergamo, Italy.
Leuk Lymphoma. 1996 Jul;22(3-4):295-301. doi: 10.3109/10428199609051761.
We report the results of a recent trial in elderly acute lymphoblastic leukemia (ALL) patients (> or = 60 years). Initial chemotherapy consisted of one 14-day course with single-dose idarubicin plus vincristine-prednisone-L-asparaginase. Idarubicin was preferred to other anthracyclines because of its shorter time to response. Sequential outpatient postremission therapy included single-dose idarubicin plus vincristine-cyclophosphamide-L-asparaginase pulses, cranial irradiation with intrathecal methotrexate-cytarabine, flexible weekly vincristine-cyclophosphamide alternating with cytarabine-teniposide, and two-year standard maintenance with mercaptopurine-methotrexate. Granulocyte colony-stimulating factor (G-CSF) was added to induction and early consolidation courses. Twenty-two patients mainly with high-risk features entered the study: median age was 64 years (60-73), 40% of cases were CD10- B-lineage and T-lineage ALL, 38% of CD10+ B-lineage ALL carried a BCR-ABL rearrangement, while 23% coexpressed myeloid antigen, 86% had L2 morphology, 50% had a blast count greater than 10 x 10(9)/1, 54% had hepato-splenomegaly and lymphadenopathy. The complete remission (CR) rate after induction therapy was 59%. A partial remission was obtained in two cases. There were four early deaths (18%) and three refractory ALL (14%). Median time to response was 21 days. With G-CSF, the median duration of absolute neutropenia was 10.5 days. Flexible postremission therapy was very well tolerated, causing no major toxicity. With a median follow-up of 2.6 years, 3 patients remain alive in first CR (23%), 2 of whom at 21.3 months and 39.6 months, respectively. Median survival of responders was 12 months compared to only 1.2 months for nonresponders (p < 0.001). This moderate-dose idarubicin-containing and G-CSF-supported regimen was associated with a high early remission rate in elderly ALL. Postremission therapy results were modest, though not appreciably different from the general experience in this patient population. Because further escalation of drug intensity appears unjustified, attempts to document and reverse drug resistance patterns and restore a dysregulated apoptosis must be considered.
我们报告了近期针对老年急性淋巴细胞白血病（ALL）患者（≥60岁）进行的一项试验结果。初始化疗包括一个为期14天的疗程，使用单剂量伊达比星加长春新碱 - 泼尼松 - L - 天冬酰胺酶。由于伊达比星达到缓解所需时间较短，所以相较于其他蒽环类药物更受青睐。序贯门诊缓解后治疗包括单剂量伊达比星加长春新碱 - 环磷酰胺 - L - 天冬酰胺酶脉冲治疗、联合鞘内注射甲氨蝶呤 - 阿糖胞苷的颅脑照射、灵活的每周长春新碱 - 环磷酰胺与阿糖胞苷 - 替尼泊苷交替治疗，以及为期两年的巯嘌呤 - 甲氨蝶呤标准维持治疗。在诱导和早期巩固疗程中加入了粒细胞集落刺激因子（G - CSF）。22例主要具有高危特征的患者进入该研究：中位年龄为64岁（60 - 73岁），40%的病例为CD10 - B系和T系ALL，38%的CD10 + B系ALL存在BCR - ABL重排，而23%共表达髓系抗原，86%具有L2形态，50%的原始细胞计数大于10×10⁹/L，54%有肝脾肿大和淋巴结病。诱导治疗后的完全缓解（CR）率为59%。2例患者获得部分缓解。有4例早期死亡（18%）和3例难治性ALL（14%）。中位缓解时间为21天。使用G - CSF后，绝对中性粒细胞减少的中位持续时间为10.5天。灵活的缓解后治疗耐受性良好，未引起重大毒性。中位随访2.6年，3例患者仍处于首次CR状态存活（23%），其中2例分别存活21.3个月和39.6个月。缓解者的中位生存期为12个月，而未缓解者仅为1.2个月（p < 0.001）。这种含中等剂量伊达比星并联合G - CSF支持的方案在老年ALL患者中具有较高的早期缓解率。缓解后治疗结果一般，不过与该患者群体的总体经验相比并无明显差异。由于进一步提高药物强度似乎不合理，所以必须考虑尝试记录和逆转耐药模式以及恢复失调的细胞凋亡。
