Clinical Outcome in Pediatric Patients with Philadelphia Chromosome Positive ALL Treated with Tyrosine Kinase Inhibitors Plus Chemotherapy-The Experience of a Polish Pediatric Leukemia and Lymphoma Study Group
The treatment of children with Philadelphia chromosome positive acute lymphoblastic leukemia (ALL Ph+) is currently unsuccessful. The use of tyrosine kinase inhibitors (TKIs) combined with chemotherapy has modernized ALL Ph+ therapy and appears to improve clinical outcome. We report herein the toxic...
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| Veröffentlicht in: | Cancers 2020-12, Vol.12 (12), p.3751 |
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| creator | Zawitkowska, Joanna Lejman, Monika Płonowski, Marcin Bulsa, Joanna Szczepański, Tomasz Romiszewski, Michał Mizia-Malarz, Agnieszka Derwich, Katarzyna Karolczyk, Grażyna Ociepa, Tomasz Ćwiklińska, Magdalena Trelińska, Joanna Owoc-Lempach, Joanna Irga-Jaworska, Ninela Małecka, Anna Machnik, Katarzyna Urbańska-Rakus, Justyna Chaber, Radosław Kowalczyk, Jerzy Młynarski, Wojciech |
| description | The treatment of children with Philadelphia chromosome positive acute lymphoblastic leukemia (ALL Ph+) is currently unsuccessful. The use of tyrosine kinase inhibitors (TKIs) combined with chemotherapy has modernized ALL Ph+ therapy and appears to improve clinical outcome. We report herein the toxicity events and results of children with ALL Ph+ treated according to the EsPhALL2010 protocol (the European intergroup study of post-induction treatment of Philadelphia chromosome positive ALL) in 15 hemato-oncological centers in Poland between the years 2012 and 2019. The study group included 31 patients, aged 1-18 years, with newly diagnosed ALL Ph+. All patients received TKIs. Imatinib was used in 30 patients, and ponatinib was applied in one child due to T315I and M244V mutation. During therapy, imatinib was replaced with dasatinib in three children. The overall survival of children with ALL Ph+ treated according to the EsPhALL2010 protocol was 74.1% and event-free survival was 54.2% after five years. The cumulative death risk of the study group at five years was estimated at 25.9%, and its cumulative relapse risk was 30%. Our treatment outcomes are still disappointing compared to other reports. Improvements in supportive care and emphasis placed on the determination of minimal residual disease at successive time points, which will impact decisions on therapy, may be required. |
| doi_str_mv | 10.3390/cancers12123751 |
| format | Article |
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The use of tyrosine kinase inhibitors (TKIs) combined with chemotherapy has modernized ALL Ph+ therapy and appears to improve clinical outcome. We report herein the toxicity events and results of children with ALL Ph+ treated according to the EsPhALL2010 protocol (the European intergroup study of post-induction treatment of Philadelphia chromosome positive ALL) in 15 hemato-oncological centers in Poland between the years 2012 and 2019. The study group included 31 patients, aged 1-18 years, with newly diagnosed ALL Ph+. All patients received TKIs. Imatinib was used in 30 patients, and ponatinib was applied in one child due to T315I and M244V mutation. During therapy, imatinib was replaced with dasatinib in three children. The overall survival of children with ALL Ph+ treated according to the EsPhALL2010 protocol was 74.1% and event-free survival was 54.2% after five years. The cumulative death risk of the study group at five years was estimated at 25.9%, and its cumulative relapse risk was 30%. Our treatment outcomes are still disappointing compared to other reports. Improvements in supportive care and emphasis placed on the determination of minimal residual disease at successive time points, which will impact decisions on therapy, may be required.</description><identifier>ISSN: 2072-6694</identifier><identifier>EISSN: 2072-6694</identifier><identifier>DOI: 10.3390/cancers12123751</identifier><identifier>PMID: 33322172</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Acute lymphoblastic leukemia ; Bone marrow ; Chemotherapy ; Children ; Children & youth ; Chromosomes ; Dermatitis ; Imatinib ; Infections ; Kinases ; Leukemia ; Lymphatic leukemia ; Lymphoma ; Minimal residual disease ; Patients ; Pediatrics ; Philadelphia chromosome ; Stem cells ; Survival ; Toxicity ; Transplants & implants ; Tyrosine kinase inhibitors</subject><ispartof>Cancers, 2020-12, Vol.12 (12), p.3751</ispartof><rights>2020. This work is licensed under http://creativecommons.org/licenses/by/3.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2020 by the authors. 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c421t-309d025752766e0219ca5105d568346b7ae4a07304995a0bf20c3f89f17c84643</citedby><cites>FETCH-LOGICAL-c421t-309d025752766e0219ca5105d568346b7ae4a07304995a0bf20c3f89f17c84643</cites><orcidid>0000-0003-2714-5851 ; 0000-0001-7239-4035 ; 0000-0002-8760-0775 ; 0000-0002-6862-9142 ; 0000-0001-7207-156X ; 0000-0001-5336-261X ; 0000-0003-3080-0845</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763070/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763070/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33322172$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zawitkowska, Joanna</creatorcontrib><creatorcontrib>Lejman, Monika</creatorcontrib><creatorcontrib>Płonowski, Marcin</creatorcontrib><creatorcontrib>Bulsa, Joanna</creatorcontrib><creatorcontrib>Szczepański, Tomasz</creatorcontrib><creatorcontrib>Romiszewski, Michał</creatorcontrib><creatorcontrib>Mizia-Malarz, Agnieszka</creatorcontrib><creatorcontrib>Derwich, Katarzyna</creatorcontrib><creatorcontrib>Karolczyk, Grażyna</creatorcontrib><creatorcontrib>Ociepa, Tomasz</creatorcontrib><creatorcontrib>Ćwiklińska, Magdalena</creatorcontrib><creatorcontrib>Trelińska, Joanna</creatorcontrib><creatorcontrib>Owoc-Lempach, Joanna</creatorcontrib><creatorcontrib>Irga-Jaworska, Ninela</creatorcontrib><creatorcontrib>Małecka, Anna</creatorcontrib><creatorcontrib>Machnik, Katarzyna</creatorcontrib><creatorcontrib>Urbańska-Rakus, Justyna</creatorcontrib><creatorcontrib>Chaber, Radosław</creatorcontrib><creatorcontrib>Kowalczyk, Jerzy</creatorcontrib><creatorcontrib>Młynarski, Wojciech</creatorcontrib><title>Clinical Outcome in Pediatric Patients with Philadelphia Chromosome Positive ALL Treated with Tyrosine Kinase Inhibitors Plus Chemotherapy-The Experience of a Polish Pediatric Leukemia and Lymphoma Study Group</title><title>Cancers</title><addtitle>Cancers (Basel)</addtitle><description>The treatment of children with Philadelphia chromosome positive acute lymphoblastic leukemia (ALL Ph+) is currently unsuccessful. The use of tyrosine kinase inhibitors (TKIs) combined with chemotherapy has modernized ALL Ph+ therapy and appears to improve clinical outcome. We report herein the toxicity events and results of children with ALL Ph+ treated according to the EsPhALL2010 protocol (the European intergroup study of post-induction treatment of Philadelphia chromosome positive ALL) in 15 hemato-oncological centers in Poland between the years 2012 and 2019. The study group included 31 patients, aged 1-18 years, with newly diagnosed ALL Ph+. All patients received TKIs. Imatinib was used in 30 patients, and ponatinib was applied in one child due to T315I and M244V mutation. During therapy, imatinib was replaced with dasatinib in three children. The overall survival of children with ALL Ph+ treated according to the EsPhALL2010 protocol was 74.1% and event-free survival was 54.2% after five years. The cumulative death risk of the study group at five years was estimated at 25.9%, and its cumulative relapse risk was 30%. Our treatment outcomes are still disappointing compared to other reports. 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Outcome in Pediatric Patients with Philadelphia Chromosome Positive ALL Treated with Tyrosine Kinase Inhibitors Plus Chemotherapy-The Experience of a Polish Pediatric Leukemia and Lymphoma Study Group</title><author>Zawitkowska, Joanna ; Lejman, Monika ; Płonowski, Marcin ; Bulsa, Joanna ; Szczepański, Tomasz ; Romiszewski, Michał ; Mizia-Malarz, Agnieszka ; Derwich, Katarzyna ; Karolczyk, Grażyna ; Ociepa, Tomasz ; Ćwiklińska, Magdalena ; Trelińska, Joanna ; Owoc-Lempach, Joanna ; Irga-Jaworska, Ninela ; Małecka, Anna ; Machnik, Katarzyna ; Urbańska-Rakus, Justyna ; Chaber, Radosław ; Kowalczyk, Jerzy ; Młynarski, Wojciech</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c421t-309d025752766e0219ca5105d568346b7ae4a07304995a0bf20c3f89f17c84643</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Acute lymphoblastic leukemia</topic><topic>Bone 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| ispartof | Cancers, 2020-12, Vol.12 (12), p.3751 |
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| source | MDPI - Multidisciplinary Digital Publishing Institute; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; PubMed Central Open Access |
| subjects | Acute lymphoblastic leukemia Bone marrow Chemotherapy Children Children & youth Chromosomes Dermatitis Imatinib Infections Kinases Leukemia Lymphatic leukemia Lymphoma Minimal residual disease Patients Pediatrics Philadelphia chromosome Stem cells Survival Toxicity Transplants & implants Tyrosine kinase inhibitors |
| title | Clinical Outcome in Pediatric Patients with Philadelphia Chromosome Positive ALL Treated with Tyrosine Kinase Inhibitors Plus Chemotherapy-The Experience of a Polish Pediatric Leukemia and Lymphoma Study Group |
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