Yanada Masamitsu, Naoe Tomoki
Department of Hematology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan.
Leuk Lymphoma. 2006 Sep;47(9):1747-53. doi: 10.1080/10428190600634085.
The prognosis of Philadelphia chromosome-positive (Ph+) and/or BCR-ABL-positive acute lymphoblastic leukemia (ALL) is extremely poor, and for decades allogeneic hematopoietic stem cell transplantation (HSCT) has been considered the only option for a cure. However, the treatment for Ph+ ALL has been rapidly changing since imatinib, a selective inhibitor of the ABL tyrosine kinase, was introduced. Earlier clinical trials in which a moderate anti-leukemic effect of imatinib monotherapy was demonstrated have prompted investigators to explore the combination of imatinib and chemotherapy. The results of multiple studies indicate that chemotherapy combined with imatinib is well tolerated, induces complete hematological remission in almost every patient with newly diagnosed Ph+ ALL, and molecular remission in more than half of the cases. Future clinical studies need to focus on how imatinib can be incorporated into chemotherapy more effectively by determining the optimal dosage of imatinib, the optimal combinational schedule, and the role of allogeneic HSCT.
费城染色体阳性（Ph+）和/或BCR-ABL阳性急性淋巴细胞白血病（ALL）的预后极差，几十年来，异基因造血干细胞移植（HSCT）一直被认为是唯一的治愈选择。然而，自从引入ABL酪氨酸激酶的选择性抑制剂伊马替尼以来，Ph+ ALL的治疗方法一直在迅速变化。早期的临床试验证明了伊马替尼单药治疗具有适度的抗白血病作用，这促使研究人员探索伊马替尼与化疗的联合应用。多项研究结果表明，化疗联合伊马替尼耐受性良好，几乎能使每一位新诊断的Ph+ ALL患者实现完全血液学缓解，超过半数的病例实现分子学缓解。未来的临床研究需要通过确定伊马替尼的最佳剂量、最佳联合方案以及异基因HSCT的作用，来关注如何更有效地将伊马替尼纳入化疗方案。
