帕纳替尼及联合化疗治疗伴T315I突变的Ph染色体阳性急性淋巴细胞白血病4例

Ponatinib combined with chemotherapy in the treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia with T315I mutation in 4 cases

目的探讨帕纳替尼及联合化疗治疗伴T315I突变的Ph染色体阳性急性淋巴细胞白血病(Philadelphia chromosome-positive acute lymphoblastic leukemia, Ph^+ALL)患者的临床疗效及不良反应。方法伊马替尼或达沙替尼联合化疗治疗后复发,且治疗期间发生T315I突变Ph^+ALL患者4例,均给予帕纳替尼30 mg/d或45 mg/d,口服,视治疗情况给予联合化疗,随访观察治疗效果,记录总生存期及并发症发生情况。结果 1例应用帕纳替尼45 mg/d治疗1个月达分子生物学完全缓解,后BCR-ABL基因转阳但处于完全缓解状态;1例应用帕纳替尼30 mg/d治疗25 d后达完全缓解,复发后联合鞘内注射甲氨蝶呤+阿糖胞苷+地塞米松治疗再次达完全缓解;2例应用帕纳替尼45 mg/d治疗1个月后达完全缓解,其中1例3个月后复发,帕纳替尼联合Hyper-CVAD(环磷酰胺+表阿霉素+长春地辛+地塞米松)治疗后仍为部分缓解,后失访;末次随访时3例未失访者中位总生存期为16.4个月;4例患者均出现Ⅳ级骨髓抑制,2例出现肺部感染,1例出现心功能不全,经对症治疗后缓解,无治疗相关死亡。结论帕纳替尼及联合化疗治疗伴T315I突变的Ph^+ALL疗效确切,不良反应可耐受。

Objective To explore the efficacy and adverse reactions of ponatinib combined with chemotherapy in the treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia(Ph+ALL)with T315Imutation.Methods Four patients with relapsed ALL after treatment with imatinib or dasatinib and Ph+ALL with T315Imutation during treatment,were given oral administration of ponatinib 30 mg/d or 45 mg/d,and chemotherapy if necessary.The therapeutic effect was followed up.The median overall survival and adverse reactions were recorded.Results Complete molecular remission was achieved in 1patient after oral administration of 45mg/d ponatinib for 1month,and complete remission was achieved when BCR-ABL gene turned positive.Complete remission was achieved in 1patient after oral administration of 30 mg/d ponatinib for 25d,and was achieved again after intrathecal injection of methotrexate, cytarabine and dexamethasone when relapse.Complete remission was achieved after one-month treatment with 45mg/d ponatinib in 2patients,in which partial remission was achieved in 1patient after treatment with ponatinib combined with hyper-CVAD(cyclophosphamide+epirubicin+vinpodiacin+dexamethasone)when relapse 3 months later,and this patient was lost follow-up.Till the final follow-up,the median overall survival time was 16.4 months.Grade Ⅳ myelosuppression occurred in all 4patients,pulmonary infection occurred in 2,and cardiac dysfunction occurred in 1, which were relieved after symptomatic treatment and no deaths occurred during treatment.Conclusion Ponatinib combined with chemotherapy is effective for Ph+ALL with T315Imutation.