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

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 tran...

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Veröffentlicht in:Chemotherapy (Basel) 2017-01, Vol.62 (6), p.353-356
Hauptverfasser: Petrungaro, Annamaria, Gentile, Massimo, Mazzone, Carla, Greco, Rosa, Uccello, Giuseppina, Recchia, Anna Grazia, De Stefano, Laura, Bossio, Sabrina, Palummo, Angela, Morelli, Rosellina, Musolino, Caterina, Morabito, Fortunato, Vigna, Ernesto
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container_end_page 356
container_issue 6
container_start_page 353
container_title Chemotherapy (Basel)
container_volume 62
creator Petrungaro, Annamaria
Gentile, Massimo
Mazzone, Carla
Greco, Rosa
Uccello, Giuseppina
Recchia, Anna Grazia
De Stefano, Laura
Bossio, Sabrina
Palummo, Angela
Morelli, Rosellina
Musolino, Caterina
Morabito, Fortunato
Vigna, Ernesto
description 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.
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subjects Adenine Nucleotides - administration & dosage
Adult
Anticancer Section / Novel Insights from Clinical Practice
Arabinonucleosides - administration & dosage
Bone Marrow - pathology
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
title 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
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