泊那替尼挽救性治疗allo-HSCT后复发伴T315I突变CML 12例的疗效分析

Treatment efficacy of ponatinib as salvage therapy in relapse chronic myeloid leukemia with T315I mutation after allogeneic stem cell transplantation: report of 12 cases

目的分析泊那替尼挽救性治疗T315I突变慢性髓系白血病(CML-T315I)异基因造血干细胞移植(allo-HSCT)后复发的疗效。方法12例allo-HSCT后复发的CML-T315I患者(10例为移植前存在T315I突变,2例为移植后复发出现T315I突变)纳入该回顾性分析,泊那替尼应用包括泊那替尼单药或联合化学药物治疗和或供体淋巴细胞输注(DLI)。通过直接测序分析获得的用于RTQ-PCR样品的BCR/ABLKD突变。用Sanger测序法对BCR/ABLKD(氨基酸219-506)突变进行测序。复发标准包括血液学复发、细胞遗传学复发和分子生物学复发。结果12例移植后复发患者中,2例分子学复发患者给予单药泊那替尼治疗,10例血液学复发患者中1例患者给予单药泊那替尼治疗,3例患者给予泊那替尼联合供者淋巴细胞输注(DLI),剩余6例患者使用泊那替尼联合化学药物治疗序贯DLI。泊那替尼治疗后,11例患者获得有效,其中血液学反应为10例患者获得血液学完全缓解(CHR),1例血液学部分缓解(PHR)和1例无效(NR);细胞遗传学反应为10例完全细胞遗传学反应(CCyR)、1例部分细胞遗传学反应(PCyR)和1例无细胞遗传学反应;分子生物学反应为9例患者获得完全分子学反应(CMR),1例主要分子生物学反应MMR和2例无分子生物学反应。获得CHR的时间中位数为36d(29~96)d,获得CCyR的时间中位数为63d(32~127)d,获得CMR的时间中位数为89d(27~152)d。泊那替尼治疗后中位随访时间598d(93~1470)d,9例患者存活,3例死亡,死亡原因包括2例复发,1例治疗无效。12例复发患者使用泊那替尼治疗后2年总存活率和无复发存活率分别为(75.0±12.5)%和(31.7±14.9)%,治疗后生存时间中位数为621d(93~1470)d。结论小样本回顾性研究提示,泊那替尼挽救性治疗allo-HSCT后复发CML-T315I患者有较好的疗效。

Objective To analyze the efficacy of ponatinib as salvage therapy in relapse chronic myeloid leukemia with T315I mutation (CML-T315I) after allogeneic stem cell transplantation (allo-HSCT).Methods Twelve patients with CML-T315I (10 cases of T315I mutation before transplantation and 2 cases of T315I mutation at the time of relapse after transplantation) were included in this retrospective analysis.Ponatinib was used as single agent or combined with chemotherapy and/or donor lymphocyte infusion.The samples obtained for RTQ-PCR were also analyzed for the BCR ABL1 mutation by direct sequencing.Scanning of the ABL KD (amino acids 219-506) for the presence of mutations was sequenced by Sanger.Results In 12 patients with relapse after transplantation,2 patients with molecular relapse were treated with only single-agent ponatinib,and among 10 patients with hematologic relapse,1 patient was treated with single-agent ponatinib and 3 patients were given ponatinib combined with donor lymphocyte infusion (DLI),the remaining 6 patients were treated with ponatinib combined with chemotherapy and DLI.After the treatment with ponatinib,11 patients had a good response,10 patients obtained complete hematologic remission (CHR),1 patient obtained partial hematologic remission (PHR) and 1 patient had no response (NR).For cytogenetic response,10 patients obtained complete cytogenetic response (CCyR),1 patient obtained partial cytogenetic response (PCyR) and one patient had no cytogenetic response.For the molecular biological response,9 patients obtained complete molecular response (CMR),1 patient obtained majore molecular response (MMR) and 2 patients had no molecular biological response.The median time to obtain CHR was 36 days (29-96 days),the median time to obtain CCyR was 63 days (32-127 days),and the median time to obtain CMR was 89 days (27-152 days).The median follow-up time after treatment with ponatinib was 598 (range,93-1470) days,9 patients survived and 3 died.Causes of deaths included leukemia relapse (n=2)and ineffective treatment (n=1).The 2-year overall and disease-free survival rate after relapse in 12 patients was 75.0%±12.5% and 31.7%±14.9%,respectively.Conclusion This small sample data suggested that ponatinib as salvage therapy had a good response to the relapse CML-T315I after allo-HSCT.