Fière D, Lepage E, Sebban C, Boucheix C, Gisselbrecht C, Vernant J P, Varet B, Broustet A, Cahn J Y, Rigal-Huguet F
Service d'Hématologie, Hôpital Edouard-Herriot, Lyon, France.
J Clin Oncol. 1993 Oct;11(10):1990-2001. doi: 10.1200/JCO.1993.11.10.1990.
In a prospective multicenter study, we analyzed the benefits of allogeneic bone marrow transplantation (BMT) in a nonselected group of adult patients with acute lymphoblastic leukemia (ALL) and, by a randomized trial, evaluated the effectiveness of autologous BMT over chemotherapy as postremission therapy in patients younger than 50 years who were not candidates for allogeneic BMT.
After induction therapy that randomized patients to receive one of two anthracycline-containing regimens, either daunorubicin (DNR) or zorubicin (ZRB), patients were assigned to postremission treatment according to age and results of HLA typing. Patients younger than 40 years with an HLA-identical sibling (group 1) were scheduled to receive cyclophosphamide 60 mg/kg on days 1 and 2, total-body irradiation (TBI), and allogeneic BMT. Patients older than 50 years (group 2) received the chemotherapy arm composed of three monthly consolidation courses (DNR or ZRB, cytarabine, and asparaginase) followed by maintenance chemotherapy (modified L10 regimen). The remaining population (group 3) was randomly assigned to receive, after the three 1-month consolidation courses, either the chemotherapy arm or autologous BMT following a conditioning regimen similar to that of group 1.
Of the 572 assessable patients, 436 achieved complete remission (78% +/- 2% for DNR v 74% +/- 3% for ZRB; P = .3). The estimated 3-year disease-free survival (DFS) rate for the 116 patients included in group 1 was 43% +/- 5%. Both autologous BMT (95 patients) and chemotherapy (96 patients) produced comparable 3-year DFS rates (39% +/- 5% v 32% +/- 5%) and survival durations (49% +/- 5% v 42% +/- 5%). However, late relapses after 36 months were mainly observed in the chemotherapy arm.
This first interim analysis did not demonstrate a benefit of this autologous BMT procedure over classical maintenance chemotherapy in patients with ALL who received consolidation chemotherapy.
在一项前瞻性多中心研究中，我们分析了异基因骨髓移植（BMT）在未经选择的成年急性淋巴细胞白血病（ALL）患者群体中的益处，并通过一项随机试验，评估了自体BMT相对于化疗作为缓解后治疗方案在年龄小于50岁且不适合进行异基因BMT的患者中的有效性。
在诱导治疗阶段，患者被随机分配接受两种含蒽环类药物方案中的一种，即柔红霉素（DNR）或表柔比星（ZRB），之后根据年龄和HLA分型结果分配缓解后治疗方案。年龄小于40岁且有HLA匹配同胞的患者（第1组）计划在第1天和第2天接受60mg/kg的环磷酰胺、全身照射（TBI）以及异基因BMT。年龄大于50岁的患者（第2组）接受由三个每月一次的巩固疗程（DNR或ZRB、阿糖胞苷和天冬酰胺酶）组成的化疗方案，随后进行维持化疗（改良L10方案）。其余患者群体（第3组）在三个为期1个月的巩固疗程后，被随机分配接受化疗方案或类似于第1组预处理方案的自体BMT。
在572例可评估患者中，436例实现完全缓解（DNR组为78%±2%，ZRB组为74%±3%；P = 0.3）。第1组纳入的116例患者的估计3年无病生存率（DFS）为43%±5%。自体BMT组（95例患者）和化疗组（96例患者）的3年DFS率（39%±5%对32%±5%）和生存时长（49%±5%对42%±5%）相当。然而，36个月后的晚期复发主要出现在化疗组。
这项首次中期分析未显示在接受巩固化疗的ALL患者中，这种自体BMT程序相对于传统维持化疗有任何益处。
