Aichi Cancer Center, Kanokoden, Chikusaku, Nagoya, Japan.
Curr Hematol Malig Rep. 2010 Oct;5(4):213-21. doi: 10.1007/s11899-010-0061-y.
In the pre-imatinib era, the treatment outcome of patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL) was dismal. Complete remission was generally achieved only in about 50% to 60% of patients, and allogeneic hematopoietic stem cell transplantation (allo-HSCT), when feasible in younger patients, was virtually the sole curative modality. Imatinib has changed the situation dramatically, however, in combination with conventional chemotherapy or with corticosteroid alone, producing about 95% complete remission and thus increasing the number of patients undergoing allo-HSCT. Currently, the overall survival of patients who have undergone allo-HSCT exceeds 50%, and a considerable proportion of patients for whom allo-HSCT is not feasible are predictably curable. The next question is how to prevent relapse, which is observed not only in more than half of patients for whom allo-HSCT is not feasible but also in a considerable number of patients after allo-HSCT. Thus, improvement of postremission therapy is crucial. Whether intensive chemotherapy with currently available cytotoxic drugs contributes to the prevention of relapse is questionable, because intensive chemotherapy alone in the pre-imatinib era nearly always failed to cure this disease. Promising partners to be combined with imatinib or with a second-generation tyrosine kinase inhibitor (TKI) will be corticosteroids and vincristine. New TKIs such as dasatinib should be incorporated into the early phase of postremission therapy. Recognizing the small number of patients with Ph(+) ALL, intergroup or international studies are necessary to develop the best postremission therapy. In the near future, it is hoped that Ph(+) ALL will become one of the leukemias for which allo-HSCT is offered only for relapsed or extremely high-risk patients.
在伊马替尼时代之前，费城染色体阳性急性淋巴细胞白血病 (Ph(+) ALL) 患者的治疗效果不佳。只有约 50%至 60%的患者能够达到完全缓解，而异基因造血干细胞移植（allo-HSCT）在年轻患者中可行时，几乎是唯一的治愈方式。然而，伊马替尼改变了这种情况，与常规化疗或单独使用皮质类固醇联合使用，产生了约 95%的完全缓解率，从而增加了接受 allo-HSCT 的患者数量。目前，接受 allo-HSCT 的患者的总生存率超过 50%，并且相当一部分无法进行 allo-HSCT 的患者可预测地得到治愈。下一个问题是如何预防复发，这种情况不仅在超过一半无法进行 allo-HSCT 的患者中观察到，而且在相当数量的 allo-HSCT 后患者中也观察到。因此，改善缓解后治疗至关重要。目前可用的细胞毒性药物强化化疗是否有助于预防复发是值得怀疑的，因为在伊马替尼时代之前，单纯强化化疗几乎总是无法治愈这种疾病。与伊马替尼或第二代酪氨酸激酶抑制剂 (TKI) 联合使用的有前途的药物将是皮质类固醇和长春新碱。新的 TKI 如达沙替尼应纳入缓解后治疗的早期阶段。鉴于 Ph(+) ALL 患者数量较少，需要进行组间或国际研究，以制定最佳缓解后治疗方案。在不久的将来，人们希望 Ph(+) ALL 将成为仅为复发或极高风险患者提供 allo-HSCT 的白血病之一。
