Signe Sloth Mogensen1, Arja Harila-Saari2, Outi Mäkitie3,4, Ida Hed Myrberg2, Riitta Niinimäki5,6, Anne Vestli7, Solveig Hafsteinsdottir8, Laimonas Griškevicius9,10, Kadri Saks11, Helene Hallböök12, Jens Retpen13, Louise Rold Helt1, Nina Toft14, Kjeld Schmiegelow1,15, Thomas Leth Frandsen1. 1. Department of Pediatrics and Adolescent Medicine, the Juliane Marie Center, University Hospital Rigshospitalet, Copenhagen, Denmark. 2. Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden. 3. Department of Molecular Medicine and Surgery and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden. 4. Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden. 5. Department of Children and Adolescents, Oulu University Hospital, Oulu, Finland. 6. PEDEGO Research Unit, University of Oulu, Oulu, Finland. 7. Department of Pediatric Oncology and Hematology, Division of Pediatric and Adolescent Medicine, Oslo University Hospital, Oslo, Norway. 8. Children's Hospital, Landspitali University Hospital, Reykjavik, Iceland. 9. Department of Hematology, Oncology, and Transfusion Medicine Center, Vilnius University Hospital Santariskiu Klinikos, Vilnius, Lithuania. 10. Faculty of Medicine, Vilnius University, Vilnius, Lithuania. 11. Department of Hematology Oncology, Tallinn Children´s Hospital, Tallinn, Estonia. 12. Department of Medical Sciences, Uppsala University, Uppsala, Sweden. 13. Department of Orthopedic Surgery, University Hospital Herlev Gentofte, Copenhagen, Denmark. 14. Department of Hematology, University Hospital Rigshospitalet, Copenhagen, Denmark. 15. Institute of Clinical Medicine, Faculty of Medicine, University of Copenhagen, Copenhagen, Denmark.
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.
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.
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