Comparing osteonecrosis clinical phenotype, timing, and risk factors in children and young adults treated for acute lymphoblastic leukemia

Signe Sloth Mogensen; Arja Harila-Saari; Outi Mäkitie; Ida Hed Myrberg; Riitta Niinimäki; Anne Vestli; Solveig Hafsteinsdottir; Laimonas Griškevicius; Kadri Saks; Helene Hallböök; Jens Retpen; Louise Rold Helt; Nina Toft; Kjeld Schmiegelow; Thomas Leth Frandsen; Nordic Society of Paediatric Haematology and Oncology (NOPHO) group

doi:10.1002/pbc.27300

Comparing osteonecrosis clinical phenotype, timing, and risk factors in children and young adults treated for acute lymphoblastic leukemia

Signe Sloth Mogensen, Arja Harila-Saari, Outi Mäkitie, Ida Hed Myrberg, Riitta Niinimäki, Anne Vestli, Solveig Hafsteinsdottir, Laimonas Griškevicius, Kadri Saks, Helene Hallböök, Jens Retpen, Louise Rold Helt, Nina Toft, Kjeld Schmiegelow, Thomas Leth Frandsen, Nordic Society of Paediatric Haematology and Oncology (NOPHO) group

Department of Clinical Medicine

13 Citations (Scopus)

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.

Original language	English
Article number	e27300
Journal	Pediatric Blood & Cancer
Volume	65
Issue number	10
Number of pages	10
ISSN	1545-5009
DOIs	https://doi.org/10.1002/pbc.27300
Publication status	Published - Oct 2018

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Mogensen, S. S., Harila-Saari, A., Mäkitie, O., Myrberg, I. H., Niinimäki, R., Vestli, A., Hafsteinsdottir, S., Griškevicius, L., Saks, K., Hallböök, H., Retpen, J., Helt, L. R., Toft, N., Schmiegelow, K., Frandsen, T. L., & Nordic Society of Paediatric Haematology and Oncology (NOPHO) group (2018). Comparing osteonecrosis clinical phenotype, timing, and risk factors in children and young adults treated for acute lymphoblastic leukemia. Pediatric Blood & Cancer, 65(10), Article e27300. https://doi.org/10.1002/pbc.27300

Mogensen, SS, Harila-Saari, A, Mäkitie, O, Myrberg, IH, Niinimäki, R, Vestli, A, Hafsteinsdottir, S, Griškevicius, L, Saks, K, Hallböök, H, Retpen, J, Helt, LR, Toft, N, Schmiegelow, K, Frandsen, TL & Nordic Society of Paediatric Haematology and Oncology (NOPHO) group 2018, 'Comparing osteonecrosis clinical phenotype, timing, and risk factors in children and young adults treated for acute lymphoblastic leukemia', Pediatric Blood & Cancer, vol. 65, no. 10, e27300. https://doi.org/10.1002/pbc.27300

@article{9118a0f9b18a498bacf126bcc9bfe0ef,

title = "Comparing osteonecrosis clinical phenotype, timing, and risk factors in children and young adults treated for acute lymphoblastic leukemia",

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.",

author = "Mogensen, {Signe Sloth} and Arja Harila-Saari and Outi M{\"a}kitie and Myrberg, {Ida Hed} and Riitta Niinim{\"a}ki and Anne Vestli and Solveig Hafsteinsdottir and Laimonas Gri{\v s}kevicius and Kadri Saks and Helene Hallb{\"o}{\"o}k and Jens Retpen and Helt, {Louise Rold} and Nina Toft and Kjeld Schmiegelow and Frandsen, {Thomas Leth} and {Nordic Society of Paediatric Haematology and Oncology (NOPHO) group}",

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year = "2018",

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doi = "10.1002/pbc.27300",

language = "English",

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TY - JOUR

T1 - Comparing osteonecrosis clinical phenotype, timing, and risk factors in children and young adults treated for acute lymphoblastic leukemia

AU - Mogensen, Signe Sloth

AU - Harila-Saari, Arja

AU - Mäkitie, Outi

AU - Myrberg, Ida Hed

AU - Niinimäki, Riitta

AU - Vestli, Anne

AU - Hafsteinsdottir, Solveig

AU - Griškevicius, Laimonas

AU - Saks, Kadri

AU - Hallböök, Helene

AU - Retpen, Jens

AU - Helt, Louise Rold

AU - Toft, Nina

AU - Schmiegelow, Kjeld

AU - Frandsen, Thomas Leth

AU - Nordic Society of Paediatric Haematology and Oncology (NOPHO) group

PY - 2018/10

Y1 - 2018/10

N2 - 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.

AB - 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.

U2 - 10.1002/pbc.27300

DO - 10.1002/pbc.27300

M3 - Journal article

C2 - 29943905

SN - 1545-5009

VL - 65

JO - Pediatric Blood & Cancer

JF - Pediatric Blood & Cancer

IS - 10

M1 - e27300

ER -

Comparing osteonecrosis clinical phenotype, timing, and risk factors in children and young adults treated for acute lymphoblastic leukemia

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