Ponatinib Induces a Persistent Molecular Response and Graft-versus-Host Disease/Graft-versus-Leukemia Effect in a Patient with Philadelphia-Positive Acute Lymphoblastic Leukemia with a T315I Mutation following Early Relapse after Allogeneic Transplant

Chemotherapy. 2017;62(1):58-61. doi: 10.1159/000448750. Epub 2016 Sep 10.

Abstract

We describe the case of a patient with a Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL) treated with dasatinib plus steroids as the first-line therapy who achieved a molecular complete remission and then underwent a matched, unrelated donor allogeneic transplant. Five months after the transplant, he experienced a disease relapse with an T315I mutation, which was resistant to salvage chemotherapy. Once the details of the T315I mutation were acquired, we initiated ponatinib treatment at a standard dosage and observed a rapid decrease of minimal residual disease (MRD) at molecular assessment. The bone marrow evaluation after 2, 3, 6, 10 and 13 months was negative for MRD. After starting ponatinib, the patient experienced a skin graft-versus-host disease (GVHD), whereas no occurrence of GVHD was observed after transplant, suggesting that the efficacy of ponatinib could be related not only to the direct antileukemic effect, but also to its ability to promote an indirect graft-versus-leukemia effect. Ponatinib was well tolerated but a thyroid dysfunction mimicking a cardiovascular toxicity was observed and solved with hormonal substitutive treatment.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Antineoplastic Agents / therapeutic use*
  • Bone Marrow / pathology
  • Fusion Proteins, bcr-abl / genetics
  • Graft vs Host Disease / etiology*
  • Graft vs Host Disease / prevention & control
  • Hematopoietic Stem Cell Transplantation / adverse effects*
  • Humans
  • Imidazoles / therapeutic use*
  • Male
  • Mutation
  • Neoplasm, Residual
  • Philadelphia Chromosome
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • Pyridazines / therapeutic use*
  • Recurrence
  • Skin Diseases / etiology
  • Transplantation, Homologous

Substances

  • Antineoplastic Agents
  • Imidazoles
  • Pyridazines
  • ponatinib
  • Fusion Proteins, bcr-abl