Central nervous system leukemia (CNSL) relapse is relatively common among Philadelphia chromosome‐positive (Ph+) leukemia patients who undergo allogeneic hematopoietic stem cell transplantation (allo‐HSCT). The prognosis of patients is dismal for those with a BCR‐ABL T315I mutation, which is resistant to TKIs including second‐generation drugs. We assessed ponatinib for nine patients with recurrent Ph+ CNSL and a T315I mutation after allo‐HSCT, including five patients with Ph+ acute lymphoblastic leukemia and four with chronic myelogenous leukemia. Five patients experienced isolated CNSL relapse, and four experienced CNSL with hematologic relapse. All patients received ponatinib combined with intrathecal chemotherapy, and four patients with hematologic relapse received systemic chemotherapy and/or donor lymphocyte infusion. All patients achieved a deep molecular response and central nervous system remission (CNSR) at a median time of 1.5 (range: 0.7–3) months after ponatinib treatment. Two patients experienced a second CNSL relapse due to ponatinib reduction, but they achieved CNSR again after an increase to the standard dosage. Six patients developed graft versus host disease. By April 1, 2019, eight patients were alive, and one died of pneumonia. The median time of survival after the first CNSL relapse posttransplantation was 18 (range: 11.2–48.5) months. Our data from a small number of samples suggests that ponatinib is effective for recurrent Ph+ CNSL patients with a BCR‐ABL T315I mutation after allo‐HSCT and warrants broader clinical evaluation.

中文翻译：

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Ponatinib治疗Allo-HSCT后复发性T315I突变的费城染色体阳性中枢神经系统白血病。

在接受异基因造血干细胞移植（allo-HSCT）的费城染色体阳性（Ph +）白血病患者中，中枢神经系统白血病（CNSL）复发相对常见。对于具有BCR-ABL T315I突变的患者，其预后令人沮丧，该突变对包括第二代药物在内的TKI耐药。我们评估了ponatinib用于9例在同种异体造血干细胞移植后复发的Ph + CNSL和T315I突变的患者，包括5例Ph +急性淋巴细胞性白血病和4例慢性粒细胞性白血病。五名患者经历了孤立的CNSL复发，四名经历了血液学复发的CNSL。所有患者均接受ponatinib联合鞘内化疗，四名血液学复发患者接受全身化疗和/或供体淋巴细胞输注。所有患者在接受ponatinib治疗后的中位时间为1.5（范围：0.7-3）个月，均达到了深层分子反应和中枢神经系统缓解（CNSR）。两名患者由于ponatinib减少而经历了第二次CNSL复发，但在增加至标准剂量后又再次获得了CNSR。六例患者发生了移植与宿主疾病。到2019年4月1日，有8位患者还活着，其中1位死于肺炎。移植后首次CNSL复发后的中位生存时间为18（范围：11.2–48.5）个月。我们从少量样本中获得的数据表明，ponatinib对同种异体造血干细胞移植术后复发性BCR-ABL T315I突变的Ph + CNSL复发患者有效，值得进行更广泛的临床评估。