Subject(s)
Antineoplastic Combined Chemotherapy Protocols/metabolism , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Down Syndrome/mortality , Maintenance Chemotherapy/mortality , Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality , Adolescent , Case-Control Studies , Child , Child, Preschool , Down Syndrome/drug therapy , Down Syndrome/metabolism , Down Syndrome/pathology , Female , Follow-Up Studies , Humans , Infant , Male , Mercaptopurine/administration & dosage , Methotrexate/administration & dosage , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/metabolism , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology , Prognosis , Survival RateABSTRACT
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.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , Osteonecrosis/chemically induced , Osteonecrosis/epidemiology , Osteonecrosis/pathology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Adolescent , Adult , Case-Control Studies , Child , Child, Preschool , Female , Humans , Incidence , Infant , Male , Middle Aged , Phenotype , Risk Factors , Young AdultABSTRACT
AIM: The aim of our study was to get epidemiological information on bacterial infections in children treated for ALL and to analyse which patients have an enhanced infection risk. METHODS: Episodes of suspected or confirmed infections were evaluated during the first 12 months of treatment for childhood acute lymphoblastic leukaemia (ALL). RESULTS: The number of patients was 73 (43 boys). The median age was 4.6 years. A total of 179 episodes occurred, varying from none in six patients to eight in one. Bacteria were cultured in 57 episodes (31.8%), the most common being coagulase-negative staphylococci. The number of episodes fell significantly with increasing age for suspected and confirmed infections (p < 0.001 and p = 0.03). The proportion of confirmed infections was significantly higher (p < 0.001) in the first episodes. The average number of suspected infections was higher in girls than in boys (p = 0.03), but confirmed infections were not. CONCLUSION: Most of the serious infections occur early in the treatment and the number of suspected and confirmed infections falls with age. Suspicion of infection is more likely in girls, but the number of confirmed infections is equal in both sexes. Coagulase-negative staphylococcus was most commonly isolated, highlighting the importance of careful handling of central venous devices.
