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 |
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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. |
doi_str_mv | 10.1159/000477714 |
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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.</description><identifier>ISSN: 0009-3157</identifier><identifier>EISSN: 1421-9794</identifier><identifier>DOI: 10.1159/000477714</identifier><identifier>PMID: 28810255</identifier><language>eng</language><publisher>Basel, Switzerland</publisher><subject>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</subject><ispartof>Chemotherapy (Basel), 2017-01, Vol.62 (6), p.353-356</ispartof><rights>2017 S. 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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.</description><subject>Adenine Nucleotides - administration & dosage</subject><subject>Adult</subject><subject>Anticancer Section / Novel Insights from Clinical Practice</subject><subject>Arabinonucleosides - administration & dosage</subject><subject>Bone Marrow - pathology</subject><subject>Cyclophosphamide - administration & dosage</subject><subject>Disease-Free Survival</subject><subject>Female</subject><subject>Fusion Proteins, bcr-abl - genetics</subject><subject>Graft vs Host Disease - etiology</subject><subject>Humans</subject><subject>Imidazoles - adverse effects</subject><subject>Imidazoles - therapeutic use</subject><subject>Immunophenotyping</subject><subject>Mutation</subject><subject>Neoplasm, Residual</subject><subject>Philadelphia Chromosome</subject><subject>Precursor Cell Lymphoblastic Leukemia-Lymphoma - mortality</subject><subject>Precursor Cell Lymphoblastic Leukemia-Lymphoma - therapy</subject><subject>Prednisone - administration & dosage</subject><subject>Protein Kinase Inhibitors - adverse effects</subject><subject>Protein Kinase Inhibitors - therapeutic use</subject><subject>Pyridazines - adverse effects</subject><subject>Pyridazines - therapeutic use</subject><subject>Recurrence</subject><subject>Salvage Therapy</subject><subject>Transplantation, Homologous</subject><issn>0009-3157</issn><issn>1421-9794</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkUtvEzEYRS0EoqGwYI-Ql7Awtefl8TIqpY0URITCeuTxfM6YztiDH0X9k_wmXCVEYmXZPvfoSheht4x-YqwWV5TSinPOqmdoxaqCEcFF9Ryt8rsgJav5BXoVws98LZuSvUQXRdsyWtT1Cv3ZOSujsaYnGzskBQO-9VJH8gA-pEDuXIj4swkgA1z997OFdA-zkfhGa1ARG4sl3mUX2Ih_mzji3WgmOcC0jEaSnQsmmgfAa5Ui4O3jvIyun2SIRuGz6ynnUsRxBLzPzTf4a4rZ6Sz-DpNcgrEHnEuAx-tpcgewkON7L21YJmnja_RCyynAm9N5iX58udlf35Htt9vN9XpLVFmxSIaag6RaN0MjJdeatorzslG1AlEqpjgVSnMYRF31UAy05UAFZLYGPpS9Li_Rh6N38e5XghC72QQFU-4ALoWOiUK0QvC2yejHI6q8C8GD7hZvZukfO0a7p_m683yZfX_Spn6G4Uz-2ysD747AvfQH8GfglP8LOAmjgg</recordid><startdate>20170101</startdate><enddate>20170101</enddate><creator>Petrungaro, Annamaria</creator><creator>Gentile, Massimo</creator><creator>Mazzone, Carla</creator><creator>Greco, Rosa</creator><creator>Uccello, Giuseppina</creator><creator>Recchia, Anna Grazia</creator><creator>De Stefano, Laura</creator><creator>Bossio, Sabrina</creator><creator>Palummo, Angela</creator><creator>Morelli, Rosellina</creator><creator>Musolino, Caterina</creator><creator>Morabito, Fortunato</creator><creator>Vigna, Ernesto</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20170101</creationdate><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</title><author>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</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c341t-d57ea0ff6d6aa7ff08c7736c5ce93c1c709cf7ed954be2d087e09e6aa5e7d3bf3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adenine Nucleotides - administration & dosage</topic><topic>Adult</topic><topic>Anticancer Section / Novel Insights from Clinical Practice</topic><topic>Arabinonucleosides - administration & dosage</topic><topic>Bone Marrow - pathology</topic><topic>Cyclophosphamide - administration & dosage</topic><topic>Disease-Free Survival</topic><topic>Female</topic><topic>Fusion Proteins, bcr-abl - genetics</topic><topic>Graft vs Host Disease - etiology</topic><topic>Humans</topic><topic>Imidazoles - adverse effects</topic><topic>Imidazoles - therapeutic use</topic><topic>Immunophenotyping</topic><topic>Mutation</topic><topic>Neoplasm, Residual</topic><topic>Philadelphia Chromosome</topic><topic>Precursor Cell Lymphoblastic Leukemia-Lymphoma - mortality</topic><topic>Precursor Cell Lymphoblastic Leukemia-Lymphoma - therapy</topic><topic>Prednisone - administration & dosage</topic><topic>Protein Kinase Inhibitors - adverse effects</topic><topic>Protein Kinase Inhibitors - therapeutic use</topic><topic>Pyridazines - adverse effects</topic><topic>Pyridazines - therapeutic use</topic><topic>Recurrence</topic><topic>Salvage Therapy</topic><topic>Transplantation, Homologous</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Petrungaro, Annamaria</creatorcontrib><creatorcontrib>Gentile, Massimo</creatorcontrib><creatorcontrib>Mazzone, Carla</creatorcontrib><creatorcontrib>Greco, Rosa</creatorcontrib><creatorcontrib>Uccello, Giuseppina</creatorcontrib><creatorcontrib>Recchia, Anna Grazia</creatorcontrib><creatorcontrib>De Stefano, Laura</creatorcontrib><creatorcontrib>Bossio, Sabrina</creatorcontrib><creatorcontrib>Palummo, Angela</creatorcontrib><creatorcontrib>Morelli, Rosellina</creatorcontrib><creatorcontrib>Musolino, Caterina</creatorcontrib><creatorcontrib>Morabito, Fortunato</creatorcontrib><creatorcontrib>Vigna, Ernesto</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Chemotherapy (Basel)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Petrungaro, Annamaria</au><au>Gentile, Massimo</au><au>Mazzone, Carla</au><au>Greco, Rosa</au><au>Uccello, Giuseppina</au><au>Recchia, Anna Grazia</au><au>De Stefano, Laura</au><au>Bossio, Sabrina</au><au>Palummo, Angela</au><au>Morelli, Rosellina</au><au>Musolino, Caterina</au><au>Morabito, Fortunato</au><au>Vigna, Ernesto</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>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</atitle><jtitle>Chemotherapy (Basel)</jtitle><addtitle>Chemotherapy</addtitle><date>2017-01-01</date><risdate>2017</risdate><volume>62</volume><issue>6</issue><spage>353</spage><epage>356</epage><pages>353-356</pages><issn>0009-3157</issn><eissn>1421-9794</eissn><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.</abstract><cop>Basel, Switzerland</cop><pmid>28810255</pmid><doi>10.1159/000477714</doi><tpages>4</tpages><oa>free_for_read</oa></addata></record> |
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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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