Ponatinib-Induced Graft-versus-Host Disease/Graft-versus-Leukemia Effect in a Patient with Philadelphia-Positive Acute Lymphoblastic Leukemia without the T315I Mutation Relapsing after Allogeneic Transplant

Chemotherapy. 2017;62(6):353-356. doi: 10.1159/000477714. Epub 2017 Aug 16.

Abstract

We describe the case of a patient with Philadelphia-positive acute lymphoblastic leukemia treated with dasatinib plus steroids as first-line therapy, who achieved a major molecular response (MMR) before undergoing matched, unrelated donor allogeneic stem cell transplant. Eleven months after the transplant, she experienced molecular relapse. Mutational screening showed negativity for the T315I mutation, The patient underwent a salvage chemotherapy regimen with clofarabine + cyclophosphamide + steroids and ponatinib (clofarabine 70 mg i.v., days 1-5, cyclophosphamide 700 mg i.v., days 1-5, and ponatinib 45 mg p.o., daily starting at day 15). We observed a rapid decrease in minimal residual disease on molecular assessment with an MMR of P190-BCR-ABL/ABL = 0.01% confirmed by bone marrow revaluations at days +23, +59, +108, and +191 after the first day of salvage chemotherapy. After starting ponatinib, the patient experienced skin graft-versus-host disease, 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 treatment was well tolerated and considered safe with easily manageable side effects.

Keywords: Acute lymphoblastic leukemia; Philadelphia-positive chromosome; Ponatinib.

MeSH terms

  • Adenine Nucleotides / administration & dosage
  • Adult
  • Arabinonucleosides / administration & dosage
  • Bone Marrow / pathology
  • Clofarabine
  • Cyclophosphamide / administration & dosage
  • Disease-Free Survival
  • Female
  • Fusion Proteins, bcr-abl / genetics
  • Graft vs Host Disease / etiology*
  • Humans
  • Imidazoles / adverse effects
  • Imidazoles / therapeutic use*
  • Immunophenotyping
  • Mutation
  • Neoplasm, Residual
  • Philadelphia Chromosome
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / mortality
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy*
  • Prednisone / administration & dosage
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use*
  • Pyridazines / adverse effects
  • Pyridazines / therapeutic use*
  • Recurrence
  • Salvage Therapy
  • Transplantation, Homologous

Substances

  • Adenine Nucleotides
  • Arabinonucleosides
  • Imidazoles
  • Protein Kinase Inhibitors
  • Pyridazines
  • ponatinib
  • Clofarabine
  • Cyclophosphamide
  • Fusion Proteins, bcr-abl
  • Prednisone