Bassan R, Lerede T, Di Bona E, Rambaldi A, Rossi G, Pogliani E, Oriani A, D'Emilio A, Izzi T, Lambertenghi-Deliliers G, Corneo G, Barbui T
Haematology/Bone Marrow Transplant Unit, Ospedali Riuniti, Bergamo, Italy.
Br J Haematol. 1999 Mar;104(4):755-62. doi: 10.1046/j.1365-2141.1999.01258.x.
Between 1991 and 1993 we conducted a collaborative trial in adult acute lymphoblastic leukaemia, introducing an idarubicin (IDA)-containing regimen for induction and early consolidation, and increasing consolidation intensity with an autologous bone marrow transplantation phase (ABMT, patients aged <51 years) followed by further chemotherapy for 12 weeks and low-dose maintenance for 6 months (ABMT patients) or 18 months. 96 patients were evaluable for antileukaemic response after induction with vincristine-prednisone-L-asparaginase plus cumulative IDA 36 or 20 mg/m2 (IVAP-1 and IVAP-2), and for disease-free survival (DFS) after a minimum follow-up >3.5 years with an off-therapy interval >1.5 years. The response rate was 44% (7/16) with IVAP-1 and 90% (72/80) with IVAP-2 (P=0.0001), due to regimen-related toxicities. Post-remission therapy was administered as planned to most cases but protocol violation was registered in some patients eligible to ABMT and post-graft chemotherapy. The 5-year disease-free survival (DFS) rate was 31%. Multivariate analysis indicated that DFS was improved in patients receiving a transplant (11 allogeneic, DFS 70%; 32 ABMT, 36%; 37 neither, 17%; P < 0.001) and was negatively affected by high-risk features such as blast cell count >25x10(9)/l, T-cell or mature B-cell immunophenotype, and t(9;22)/t(4;11) (all P values <0.05). The 5-year DFS rate was 54% for 26 patients with no high-risk factor, 26% for 35 patients with any one, and 6% for 18 patients with any two (P<0.005). IVAP-2 brought about a high complete response rate and post-remission treatment including ABMT was feasible and modestly toxic. In spite of the short post-graft chemotherapy phase, the long-term DFS rate was good in cases with no high-risk feature. However, because autografting may be redundant in the standard-risk category, its role requires further investigation for high-risk cases.
1991年至1993年期间，我们针对成人急性淋巴细胞白血病开展了一项合作试验，采用含去甲氧柔红霉素（IDA）的方案进行诱导和早期巩固治疗，并通过自体骨髓移植阶段（ABMT，年龄<51岁的患者）提高巩固强度，随后进行12周的进一步化疗以及6个月（ABMT患者）或18个月的低剂量维持治疗。96例患者在接受长春新碱-泼尼松-L-天冬酰胺酶联合累积剂量为36或20 mg/m²的IDA诱导治疗（IVAP-1和IVAP-2）后可评估抗白血病反应，并在至少随访>3.5年且无治疗间隔>1.5年后评估无病生存期（DFS）。由于方案相关毒性，IVAP-1的缓解率为44%（7/16），IVAP-2为90%（72/80）（P = 0.0001）。大多数病例按计划进行缓解后治疗，但在一些符合ABMT和移植后化疗条件的患者中出现了方案违规情况。5年无病生存率（DFS）为31%。多因素分析表明，接受移植的患者DFS有所改善（11例接受异基因移植，DFS为70%；32例接受ABMT，36%；37例均未接受移植，17%；P < 0.001），并受到高风险特征的负面影响，如原始细胞计数>25×10⁹/L、T细胞或成熟B细胞免疫表型以及t(9;22)/t(4;11)（所有P值<0.05）。26例无高风险因素的患者5年DFS率为54%，35例有任何一项高风险因素的患者为26%，18例有任何两项高风险因素的患者为6%（P<0.005）。IVAP-2带来了较高的完全缓解率，包括ABMT在内的缓解后治疗是可行的且毒性较小。尽管移植后化疗阶段较短，但无高风险特征的病例长期DFS率良好。然而，由于自体移植在标准风险类别中可能多余，其在高风险病例中的作用需要进一步研究。
