Gene

Biology

Dasatinib

Transplantation

Mutation

Biochemistry

Leukemia

Philadelphia chromosome

Hematopoietic stem cell transplantation

Ponatinib

Immunology

Myeloid leukemia

Genetics

Pediatrics

Chromosomal translocation

Imatinib

Internal medicine

Chemotherapy

Oncology

Medicine

International Journal of Cancer

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.

Ponatinib therapy in recurrent Philadelphia chromosome‐positive central nervous system leukemia with T315I mutation after Allo‐HSCT