Oncology Frontier: Could you please talk about the application of the third-generation TKIs， ponatinib， in the management of adult Philadelphia-positive acute lymphoblastic leukemia (Ph⁺ ALL)?

　　《肿瘤瞭望》：请您谈谈第三代TKIs泊那替尼（ponatinib）在成人Ph⁺ ALL患者中的应用？

　　Prof. Kim: The use of ponatinib has been revised because it showed 40% vascular complications in the phase III prospective studies. We cannot use ponatinib anymore in the treatment of CML patients but it can still be used for Ph⁺ ALL. I have experience of ponatinib where the patient has had the ABL T315I mutation. All patients could achieve hematologic remission with the use of ponatinib and I think it is very effective especially for patients with Ph⁺ ALL when the ABL T315I mutation is present.

　　Kim教授：有关泊那替尼的III期前瞻性临床试验表明，其血管并发症发生率达40%，因此泊那替尼的临床应用已被修正。我们不再推荐泊那替尼用于慢性粒细胞白血病（CML）的治疗。然而，对于成人Ph⁺ALL患者泊那替尼仍然适用。在我所诊治的那些接受泊那替尼治疗的患者中，携带ABL T315I突变者均获得了血液学缓解。因此，泊那替尼对伴随ABL T315I突变的Ph⁺ALL患者尤为有效。

　　Oncology Frontier: TKIs are needed after alloHSCT. Under what circumstances and for how long should we use them?

　　《肿瘤瞭望》：异基因造血干细胞移植（alloHSCT）后， TKIs的应用仍有必要。您认为应该在什么情况下应用，需要用多长时间？

　　Prof. Kim: TKIs can be used for molecular relapse and even hematologic relapse. The best way to introduce TKIs after alloHSCT is where there is molecular relapse without hematologic relapse because it is very easy to control the disease in this situation. The important thing in this situation is the early detection of molecular relapse before the patient goes into overt hematologic relapse. But it is a difficult situation because overt hematologic relapse may be improved with the administration of other TKIs.If patients are treated with imatinib before transplantation， the patient can achieve a second remission after relapse with tyrosine kinase inhibitors from the next generation such as dasatinib or nilotinib.

　　We don’t know how we should use the TKIs in that situation. We have used a TKI for two years and when we have discontinued use， about 80% of patients relapse. So the use of TKIs should be much longer than two years and when we consider discontinuation of a TKI， we need to monitor for molecular relapse.

　　For the CML group， the French STIM trial showed that around 50% of patients could maintain their treatment-free remission status without imatinib. Such an approach is recommended but more clinical trials are required.

　　Kim教授：TKIs可以应用于已有分子生物学复发、甚至血液学复发的患者中。TKIs的最佳适应症是alloHSCT后仅有分子生物学复发、无血液学复发的患者，在这种情况下TKIs较易控制疾病进展。在患者发展到血液学复发之前，早期监测十分重要。一旦出现血液学复发，采用其他TKIs也仅能改善病情。例如，患者在alloHSCT前使用过伊马替尼，alloHSCT后使用二代TKIs，如达沙替尼、尼洛替尼，可以使复发患者再次获得缓解。

　　目前，二代TKIs在复发患者中的使用剂量及维持时间尚未有定论，我们曾在一些患者中使用TKIs两年，但停药后80%的患者出现再次复发。因此，我们认为这种情况下TKIs的使用应该在两年以上，而且停药前应检测是否存在分子生物学复发。

　　此外，法国的一项STIM临床研究显示，在CML患者中，伊马替尼停药后能维持无化疗缓解状态的约占50%。该项应用已被推荐，但仍需进行大规模的临床试验。

　　Oncology Frontier: Could antigen mismatch unrelated donor (MMUD)， haploidentical and umbilical cord blood (UCB) transplants be options for patients who are not candidates for standard HSCT?

　　《肿瘤瞭望》：对于没有全相合适供者的HSCT患者，无关不全和供者和脐血移植可以选择吗？

　　Prof. Kim: I think so. Because we are performing alloHSCT usingpartially mismatched unrelated donors and haploidentical family donors. I reported a meta-analysis of a prospective study looking at the feasibility of the donor for ALLs and I found that the relapse-free survival was similar between the different donor groups. Outcomes were similar if it was a matched sibling or well-matched unrelated donor compared to using partially mismatched or haploidentical transplant donors. For cord blood transplant patients， I have no experience as we don’t use UCB stem cell transplants. If the patient does not have a matched sibling or matched unrelated donor， we use haploidentical donors. This choice is the best available option.

　　Kim教授：我认为可以考虑。目前我们正在开展无关不全和、单倍体相合的alloHSCT。我近期发表了一篇荟萃分析，是关于ALL患者不同类型供者可行性的前瞻研究，结果发现不同类型供者的无复发生存时间并无统计学差异。同时，全相合同胞或者无关不全和供者与部分相合或者单倍体相合供者间的预后也非常相似。至于脐血移植，我们尚未开展脐血移植因此并没有多少经验。总之，对于没有全相合供者的患者，我们可考虑半相合供者，这是最好的替代选择。