Fischer T, Reifenrath C, Hess G R, Corsetti M T, Kreil S, Beck J, Meinhardt P, Beltrami G, Schuch B, Gschaidmeier H, Hehlmann R, Hochhaus A, Carella A, Huber C
3 rd Medical Department, Johannes Gutenberg-University, Mainz, Germany.
Leukemia. 2002 Jul;16(7):1220-8. doi: 10.1038/sj.leu.2402565.
We examined safety and efficacy of STI-571 in 24 bcr/abl-positive patients with CML post PBSCT. At start of STI-571 therapy, nine patients presented in blast crisis (BC) or in accelerated phase (AP), and 15 in chronic phase (CP). Patients were evaluated for hematologic, cytogenetic and molecular response, survival and toxicity. In general, STI-571 was well tolerated in this heavily pretreated group of patients with a non-hematologic and hematologic toxicity profile similar to that observed in a previous phase I trial at comparable doses. Five of nine patients with CML in transformation (AP, BC) were evaluable for hematologic response. Two of five patients had transient reductions in WBC and blasts, and three patients achieved a sustained hematologic response (>4 weeks). Cytogenetic analysis in these patients revealed numerical and/or structural responses. In CML chronic phase, STI-571 induced complete hematologic responses in all patients and major cytogenetic responses in 61% of patients with a complete cytogenetic response rate of 46%. This report indicates that STI-571 is a safe and effective drug in heavily pretreated patients. No apparent additional side-effects were noted in this patient cohort. The high rate of complete hematologic and complete cytogenetic responses in CP patients is remarkable, as intensive treatment approaches plus IFN-alpha failed to be efficient in achieving long-term stabilization of CML in this patient cohort.
我们研究了STI-571对24例异基因外周血干细胞移植（PBSCT）后bcr/abl阳性慢性粒细胞白血病（CML）患者的安全性和有效性。在开始使用STI-571治疗时，9例患者处于急变期（BC）或加速期（AP），15例处于慢性期（CP）。对患者进行血液学、细胞遗传学和分子反应、生存率及毒性评估。总体而言，在这群经过大量预处理的患者中，STI-571耐受性良好，其非血液学和血液学毒性特征与先前在类似剂量下进行的I期试验中观察到的情况相似。9例处于转变期（AP、BC）的CML患者中有5例可评估血液学反应。5例患者中有2例白细胞和原始细胞短暂减少，3例患者获得持续血液学反应（>4周）。对这些患者的细胞遗传学分析显示有数量和/或结构反应。在CML慢性期，STI-571使所有患者获得完全血液学反应，61%的患者获得主要细胞遗传学反应，完全细胞遗传学反应率为46%。本报告表明，STI-571对经过大量预处理的患者是一种安全有效的药物。在该患者队列中未观察到明显的额外副作用。CP患者中完全血液学和完全细胞遗传学反应的高发生率引人注目，因为强化治疗方案加α干扰素未能有效实现该患者队列中CML的长期稳定。
