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Comparing osteonecrosis clinical phenotype, timing, and risk factors in children and young adults treated for acute lymphoblastic leukemia
Background Treatment‐related osteonecrosis (ON) is a serious complication of treatment of acute lymphoblastic leukemia (ALL). Procedure This study included 1,489 patients with ALL, aged 1–45 years, treated according to the Nordic Society of Paediatric Haematology and Oncology ALL2008 protocol, using...
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Published in: | Pediatric blood & cancer 2018-10, Vol.65 (10), p.e27300-n/a |
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creator | Mogensen, Signe Sloth Harila‐Saari, Arja Mäkitie, Outi Myrberg, Ida Hed Niinimäki, Riitta Vestli, Anne Hafsteinsdottir, Solveig Griškevicius, Laimonas Saks, Kadri Hallböök, Helene Retpen, Jens Helt, Louise Rold Toft, Nina Schmiegelow, Kjeld Frandsen, Thomas Leth |
description | Background
Treatment‐related osteonecrosis (ON) is a serious complication of treatment of acute lymphoblastic leukemia (ALL).
Procedure
This study included 1,489 patients with ALL, aged 1–45 years, treated according to the Nordic Society of Paediatric Haematology and Oncology ALL2008 protocol, using alternate‐week dexamethasone during delayed intensification, with prospective registration of symptomatic ON. We aimed at comparing risk factors, timing, and clinical characteristics of ON in children and young adults.
Results
ON was diagnosed in 67 patients, yielding a 5‐year cumulative incidence of 6.3%, but 28% in female adolescents. Median age at ALL diagnosis was 12.1 years and 14.9 years for females and males, respectively. At ON diagnosis, 59 patients had bone pain (91%) and 30 (46%) had multiple‐joint involvement. The median interval between ALL and ON diagnosis was significantly shorter in children aged 1.0–9.9 years (0.7 years [range: 0.2–2.1]) compared with adolescents (1.8 years [range: 0.3–3.7, P |
doi_str_mv | 10.1002/pbc.27300 |
format | article |
fullrecord | <record><control><sourceid>proquest_swepu</sourceid><recordid>TN_cdi_swepub_primary_oai_swepub_ki_se_487388</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2091878277</sourcerecordid><originalsourceid>FETCH-LOGICAL-c5790-a1d831501b731272ba575030e29f765de5fc6a582f49e6b2e92a3ece9e8c18023</originalsourceid><addsrcrecordid>eNp1ks1u1DAUhSMEomVgwQsgS2xAmmltJ47tZRl-pUqwALaW49x03HHi1I5VzSvw1Hia6SAhzcpX9neO7r0-RfGa4AuCMb0cG3NBeYnxk-KcsIqtGCb86bHG8qx4EeNtRmvMxPPijEpZlRKz8-LP2vejDna4QT5O4AcwwUcbkXF2sEY7NG5g8NNuhCWabJ_BJdJDi4KNW9RpM_kQkR2Q2VjXBhgeHnc-ZUPdJjdFNAXQE7So8wFpkyZAbtePG984HSdrkIO0hd7ql8WzTrsIrw7novj1-dPP9dfV9fcv39ZX1yvDuMQrTVpRkjxhw0tCOW004wyXGKjseM1aYJ2pNRO0qyTUDQVJdQkGJAhDBKbloljNvvEextSoMdheh53y2qrD1TZXoCrBSyEyL0_yY_DtP9GjkOTdlkTUJGuXJ7Uf7e8r5cONSkmVNcVZsyjezXj2vUsQJ9XbaMA5PYBPUVHMZJ62qvddvf0PvfUpDHlxmZJEcEE5z9T7mdr_agzQHTsgWO2zo3J21EN2Mvvm4JiaHtoj-RiWDFzOwL11sDvtpH58WM-WfwERC9Cx</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2091878277</pqid></control><display><type>article</type><title>Comparing osteonecrosis clinical phenotype, timing, and risk factors in children and young adults treated for acute lymphoblastic leukemia</title><source>Wiley</source><creator>Mogensen, Signe Sloth ; Harila‐Saari, Arja ; Mäkitie, Outi ; Myrberg, Ida Hed ; Niinimäki, Riitta ; Vestli, Anne ; Hafsteinsdottir, Solveig ; Griškevicius, Laimonas ; Saks, Kadri ; Hallböök, Helene ; Retpen, Jens ; Helt, Louise Rold ; Toft, Nina ; Schmiegelow, Kjeld ; Frandsen, Thomas Leth</creator><creatorcontrib>Mogensen, Signe Sloth ; Harila‐Saari, Arja ; Mäkitie, Outi ; Myrberg, Ida Hed ; Niinimäki, Riitta ; Vestli, Anne ; Hafsteinsdottir, Solveig ; Griškevicius, Laimonas ; Saks, Kadri ; Hallböök, Helene ; Retpen, Jens ; Helt, Louise Rold ; Toft, Nina ; Schmiegelow, Kjeld ; Frandsen, Thomas Leth ; Nordic Society of Paediatric Haematology and Oncology (NOPHO) group ; Nordic Society of Paediatric Haematology and Oncology (NOPHO) group</creatorcontrib><description>Background
Treatment‐related osteonecrosis (ON) is a serious complication of treatment of acute lymphoblastic leukemia (ALL).
Procedure
This study included 1,489 patients with ALL, aged 1–45 years, treated according to the Nordic Society of Paediatric Haematology and Oncology ALL2008 protocol, using alternate‐week dexamethasone during delayed intensification, with prospective registration of symptomatic ON. We aimed at comparing risk factors, timing, and clinical characteristics of ON in children and young adults.
Results
ON was diagnosed in 67 patients, yielding a 5‐year cumulative incidence of 6.3%, but 28% in female adolescents. Median age at ALL diagnosis was 12.1 years and 14.9 years for females and males, respectively. At ON diagnosis, 59 patients had bone pain (91%) and 30 (46%) had multiple‐joint involvement. The median interval between ALL and ON diagnosis was significantly shorter in children aged 1.0–9.9 years (0.7 years [range: 0.2–2.1]) compared with adolescents (1.8 years [range: 0.3–3.7, P < 0.001]) and adults (2.1 years [range: 0.4–5.3, P = 0.001]). Female sex was a risk factor in adolescent patients (hazard ratio [HR] = 2.1, 95% confidence interval [CI]: 1.1–4.2) but not in children aged 1.1–9.9 years (HR = 2.4, 95% CI: 0.9–6.2, P = 0.08) or adults aged 19–45 years (HR = 1.1, 95% CI: 0.3–4.0). Age above 10 years at ALL diagnosis (odds ratio [OR] = 3.7, P = 0.026) and multiple joints affected at ON diagnosis (OR = 3.4, P = 0.027) were risk factors for developing severe ON.
Conclusion
We provide a detailed phenotype of patients with ALL with symptomatic ON, including description of risk factors and timing of ON across age groups. This awareness is essential in exploring measures to prevent development of ON.</description><identifier>ISSN: 1545-5009</identifier><identifier>ISSN: 1545-5017</identifier><identifier>EISSN: 1545-5017</identifier><identifier>DOI: 10.1002/pbc.27300</identifier><identifier>PMID: 29943905</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Acute lymphoblastic leukemia ; Adolescents ; Age ; Children ; Dexamethasone ; Diagnosis ; Females ; Hematology ; Leukemia ; Lymphatic leukemia ; Males ; Medicin och hälsovetenskap ; Oncology ; Osteonecrosis ; Pain ; Patients ; Pediatrics ; phenotype ; Phenotypes ; Risk factors ; Teenagers ; Young adults</subject><ispartof>Pediatric blood & cancer, 2018-10, Vol.65 (10), p.e27300-n/a</ispartof><rights>2018 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5790-a1d831501b731272ba575030e29f765de5fc6a582f49e6b2e92a3ece9e8c18023</citedby><cites>FETCH-LOGICAL-c5790-a1d831501b731272ba575030e29f765de5fc6a582f49e6b2e92a3ece9e8c18023</cites><orcidid>0000-0003-0190-5664 ; 0000-0001-8495-5274 ; 0000-0002-0829-4993 ; 0000-0002-3758-3807 ; 0000-0003-2767-5828</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29943905$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-362090$$DView record from Swedish Publication Index$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:139031861$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Mogensen, Signe Sloth</creatorcontrib><creatorcontrib>Harila‐Saari, Arja</creatorcontrib><creatorcontrib>Mäkitie, Outi</creatorcontrib><creatorcontrib>Myrberg, Ida Hed</creatorcontrib><creatorcontrib>Niinimäki, Riitta</creatorcontrib><creatorcontrib>Vestli, Anne</creatorcontrib><creatorcontrib>Hafsteinsdottir, Solveig</creatorcontrib><creatorcontrib>Griškevicius, Laimonas</creatorcontrib><creatorcontrib>Saks, Kadri</creatorcontrib><creatorcontrib>Hallböök, Helene</creatorcontrib><creatorcontrib>Retpen, Jens</creatorcontrib><creatorcontrib>Helt, Louise Rold</creatorcontrib><creatorcontrib>Toft, Nina</creatorcontrib><creatorcontrib>Schmiegelow, Kjeld</creatorcontrib><creatorcontrib>Frandsen, Thomas Leth</creatorcontrib><creatorcontrib>Nordic Society of Paediatric Haematology and Oncology (NOPHO) group</creatorcontrib><creatorcontrib>Nordic Society of Paediatric Haematology and Oncology (NOPHO) group</creatorcontrib><title>Comparing osteonecrosis clinical phenotype, timing, and risk factors in children and young adults treated for acute lymphoblastic leukemia</title><title>Pediatric blood & cancer</title><addtitle>Pediatr Blood Cancer</addtitle><description>Background
Treatment‐related osteonecrosis (ON) is a serious complication of treatment of acute lymphoblastic leukemia (ALL).
Procedure
This study included 1,489 patients with ALL, aged 1–45 years, treated according to the Nordic Society of Paediatric Haematology and Oncology ALL2008 protocol, using alternate‐week dexamethasone during delayed intensification, with prospective registration of symptomatic ON. We aimed at comparing risk factors, timing, and clinical characteristics of ON in children and young adults.
Results
ON was diagnosed in 67 patients, yielding a 5‐year cumulative incidence of 6.3%, but 28% in female adolescents. Median age at ALL diagnosis was 12.1 years and 14.9 years for females and males, respectively. At ON diagnosis, 59 patients had bone pain (91%) and 30 (46%) had multiple‐joint involvement. The median interval between ALL and ON diagnosis was significantly shorter in children aged 1.0–9.9 years (0.7 years [range: 0.2–2.1]) compared with adolescents (1.8 years [range: 0.3–3.7, P < 0.001]) and adults (2.1 years [range: 0.4–5.3, P = 0.001]). Female sex was a risk factor in adolescent patients (hazard ratio [HR] = 2.1, 95% confidence interval [CI]: 1.1–4.2) but not in children aged 1.1–9.9 years (HR = 2.4, 95% CI: 0.9–6.2, P = 0.08) or adults aged 19–45 years (HR = 1.1, 95% CI: 0.3–4.0). Age above 10 years at ALL diagnosis (odds ratio [OR] = 3.7, P = 0.026) and multiple joints affected at ON diagnosis (OR = 3.4, P = 0.027) were risk factors for developing severe ON.
Conclusion
We provide a detailed phenotype of patients with ALL with symptomatic ON, including description of risk factors and timing of ON across age groups. This awareness is essential in exploring measures to prevent development of ON.</description><subject>Acute lymphoblastic leukemia</subject><subject>Adolescents</subject><subject>Age</subject><subject>Children</subject><subject>Dexamethasone</subject><subject>Diagnosis</subject><subject>Females</subject><subject>Hematology</subject><subject>Leukemia</subject><subject>Lymphatic leukemia</subject><subject>Males</subject><subject>Medicin och hälsovetenskap</subject><subject>Oncology</subject><subject>Osteonecrosis</subject><subject>Pain</subject><subject>Patients</subject><subject>Pediatrics</subject><subject>phenotype</subject><subject>Phenotypes</subject><subject>Risk factors</subject><subject>Teenagers</subject><subject>Young adults</subject><issn>1545-5009</issn><issn>1545-5017</issn><issn>1545-5017</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><recordid>eNp1ks1u1DAUhSMEomVgwQsgS2xAmmltJ47tZRl-pUqwALaW49x03HHi1I5VzSvw1Hia6SAhzcpX9neO7r0-RfGa4AuCMb0cG3NBeYnxk-KcsIqtGCb86bHG8qx4EeNtRmvMxPPijEpZlRKz8-LP2vejDna4QT5O4AcwwUcbkXF2sEY7NG5g8NNuhCWabJ_BJdJDi4KNW9RpM_kQkR2Q2VjXBhgeHnc-ZUPdJjdFNAXQE7So8wFpkyZAbtePG984HSdrkIO0hd7ql8WzTrsIrw7novj1-dPP9dfV9fcv39ZX1yvDuMQrTVpRkjxhw0tCOW004wyXGKjseM1aYJ2pNRO0qyTUDQVJdQkGJAhDBKbloljNvvEextSoMdheh53y2qrD1TZXoCrBSyEyL0_yY_DtP9GjkOTdlkTUJGuXJ7Uf7e8r5cONSkmVNcVZsyjezXj2vUsQJ9XbaMA5PYBPUVHMZJ62qvddvf0PvfUpDHlxmZJEcEE5z9T7mdr_agzQHTsgWO2zo3J21EN2Mvvm4JiaHtoj-RiWDFzOwL11sDvtpH58WM-WfwERC9Cx</recordid><startdate>201810</startdate><enddate>201810</enddate><creator>Mogensen, Signe Sloth</creator><creator>Harila‐Saari, Arja</creator><creator>Mäkitie, Outi</creator><creator>Myrberg, Ida Hed</creator><creator>Niinimäki, Riitta</creator><creator>Vestli, Anne</creator><creator>Hafsteinsdottir, Solveig</creator><creator>Griškevicius, Laimonas</creator><creator>Saks, Kadri</creator><creator>Hallböök, Helene</creator><creator>Retpen, Jens</creator><creator>Helt, Louise Rold</creator><creator>Toft, Nina</creator><creator>Schmiegelow, Kjeld</creator><creator>Frandsen, Thomas Leth</creator><general>Wiley Subscription Services, Inc</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>7TK</scope><scope>7TO</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>DF2</scope><orcidid>https://orcid.org/0000-0003-0190-5664</orcidid><orcidid>https://orcid.org/0000-0001-8495-5274</orcidid><orcidid>https://orcid.org/0000-0002-0829-4993</orcidid><orcidid>https://orcid.org/0000-0002-3758-3807</orcidid><orcidid>https://orcid.org/0000-0003-2767-5828</orcidid></search><sort><creationdate>201810</creationdate><title>Comparing osteonecrosis clinical phenotype, timing, and risk factors in children and young adults treated for acute lymphoblastic leukemia</title><author>Mogensen, Signe Sloth ; Harila‐Saari, Arja ; Mäkitie, Outi ; Myrberg, Ida Hed ; Niinimäki, Riitta ; Vestli, Anne ; Hafsteinsdottir, Solveig ; Griškevicius, Laimonas ; Saks, Kadri ; Hallböök, Helene ; Retpen, Jens ; Helt, Louise Rold ; Toft, Nina ; Schmiegelow, Kjeld ; Frandsen, Thomas Leth</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5790-a1d831501b731272ba575030e29f765de5fc6a582f49e6b2e92a3ece9e8c18023</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Acute lymphoblastic leukemia</topic><topic>Adolescents</topic><topic>Age</topic><topic>Children</topic><topic>Dexamethasone</topic><topic>Diagnosis</topic><topic>Females</topic><topic>Hematology</topic><topic>Leukemia</topic><topic>Lymphatic leukemia</topic><topic>Males</topic><topic>Medicin och hälsovetenskap</topic><topic>Oncology</topic><topic>Osteonecrosis</topic><topic>Pain</topic><topic>Patients</topic><topic>Pediatrics</topic><topic>phenotype</topic><topic>Phenotypes</topic><topic>Risk factors</topic><topic>Teenagers</topic><topic>Young adults</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mogensen, Signe Sloth</creatorcontrib><creatorcontrib>Harila‐Saari, Arja</creatorcontrib><creatorcontrib>Mäkitie, Outi</creatorcontrib><creatorcontrib>Myrberg, Ida Hed</creatorcontrib><creatorcontrib>Niinimäki, Riitta</creatorcontrib><creatorcontrib>Vestli, Anne</creatorcontrib><creatorcontrib>Hafsteinsdottir, Solveig</creatorcontrib><creatorcontrib>Griškevicius, Laimonas</creatorcontrib><creatorcontrib>Saks, Kadri</creatorcontrib><creatorcontrib>Hallböök, Helene</creatorcontrib><creatorcontrib>Retpen, Jens</creatorcontrib><creatorcontrib>Helt, Louise Rold</creatorcontrib><creatorcontrib>Toft, Nina</creatorcontrib><creatorcontrib>Schmiegelow, Kjeld</creatorcontrib><creatorcontrib>Frandsen, Thomas Leth</creatorcontrib><creatorcontrib>Nordic Society of Paediatric Haematology and Oncology (NOPHO) group</creatorcontrib><creatorcontrib>Nordic Society of Paediatric Haematology and Oncology (NOPHO) group</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Uppsala universitet</collection><jtitle>Pediatric blood & cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mogensen, Signe Sloth</au><au>Harila‐Saari, Arja</au><au>Mäkitie, Outi</au><au>Myrberg, Ida Hed</au><au>Niinimäki, Riitta</au><au>Vestli, Anne</au><au>Hafsteinsdottir, Solveig</au><au>Griškevicius, Laimonas</au><au>Saks, Kadri</au><au>Hallböök, Helene</au><au>Retpen, Jens</au><au>Helt, Louise Rold</au><au>Toft, Nina</au><au>Schmiegelow, Kjeld</au><au>Frandsen, Thomas Leth</au><aucorp>Nordic Society of Paediatric Haematology and Oncology (NOPHO) group</aucorp><aucorp>Nordic Society of Paediatric Haematology and Oncology (NOPHO) group</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Comparing osteonecrosis clinical phenotype, timing, and risk factors in children and young adults treated for acute lymphoblastic leukemia</atitle><jtitle>Pediatric blood & cancer</jtitle><addtitle>Pediatr Blood Cancer</addtitle><date>2018-10</date><risdate>2018</risdate><volume>65</volume><issue>10</issue><spage>e27300</spage><epage>n/a</epage><pages>e27300-n/a</pages><issn>1545-5009</issn><issn>1545-5017</issn><eissn>1545-5017</eissn><abstract>Background
Treatment‐related osteonecrosis (ON) is a serious complication of treatment of acute lymphoblastic leukemia (ALL).
Procedure
This study included 1,489 patients with ALL, aged 1–45 years, treated according to the Nordic Society of Paediatric Haematology and Oncology ALL2008 protocol, using alternate‐week dexamethasone during delayed intensification, with prospective registration of symptomatic ON. We aimed at comparing risk factors, timing, and clinical characteristics of ON in children and young adults.
Results
ON was diagnosed in 67 patients, yielding a 5‐year cumulative incidence of 6.3%, but 28% in female adolescents. Median age at ALL diagnosis was 12.1 years and 14.9 years for females and males, respectively. At ON diagnosis, 59 patients had bone pain (91%) and 30 (46%) had multiple‐joint involvement. The median interval between ALL and ON diagnosis was significantly shorter in children aged 1.0–9.9 years (0.7 years [range: 0.2–2.1]) compared with adolescents (1.8 years [range: 0.3–3.7, P < 0.001]) and adults (2.1 years [range: 0.4–5.3, P = 0.001]). Female sex was a risk factor in adolescent patients (hazard ratio [HR] = 2.1, 95% confidence interval [CI]: 1.1–4.2) but not in children aged 1.1–9.9 years (HR = 2.4, 95% CI: 0.9–6.2, P = 0.08) or adults aged 19–45 years (HR = 1.1, 95% CI: 0.3–4.0). Age above 10 years at ALL diagnosis (odds ratio [OR] = 3.7, P = 0.026) and multiple joints affected at ON diagnosis (OR = 3.4, P = 0.027) were risk factors for developing severe ON.
Conclusion
We provide a detailed phenotype of patients with ALL with symptomatic ON, including description of risk factors and timing of ON across age groups. This awareness is essential in exploring measures to prevent development of ON.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>29943905</pmid><doi>10.1002/pbc.27300</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0003-0190-5664</orcidid><orcidid>https://orcid.org/0000-0001-8495-5274</orcidid><orcidid>https://orcid.org/0000-0002-0829-4993</orcidid><orcidid>https://orcid.org/0000-0002-3758-3807</orcidid><orcidid>https://orcid.org/0000-0003-2767-5828</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Acute lymphoblastic leukemia Adolescents Age Children Dexamethasone Diagnosis Females Hematology Leukemia Lymphatic leukemia Males Medicin och hälsovetenskap Oncology Osteonecrosis Pain Patients Pediatrics phenotype Phenotypes Risk factors Teenagers Young adults |
title | Comparing osteonecrosis clinical phenotype, timing, and risk factors in children and young adults treated for acute lymphoblastic leukemia |
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