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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
Main Authors: 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
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container_title Pediatric blood & cancer
container_volume 65
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
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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 &lt; 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 &amp; 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 &amp; 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 &lt; 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. 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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 &amp; 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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 &lt; 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. 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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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