Temporal changes in incidence of relapse and outcome after relapse of childhood acute lymphoblastic leukemia over three decades; a Nordic population-based cohort study.

Relapse remains the main obstacle to curing childhood acute lymphoblastic leukemia (ALL). The aims of this study were to compare incidence of relapse, prognostic factors, and survival after relapse between three consecutive Nordic Society of Pediatric Hematology and Oncology trials. Relapse occurred as a primary event in 638 of 4 458 children (1.0-14.9 years) diagnosed with Ph-negative ALL between 1992 and 2018. The 5-year cumulative incidence of relapse was 17.3% (95% CI 15.4-19.2%) and 16.5% (95% CI 14.3-18.8%) for patients in the ALL1992 and ALL2000 trials, respectively, but decreased to 8.4% (95% CI 7.0-10.1%) for patients in the ALL2008 trial. No changes in duration of first complete remission and site of relapse were observed over time; however, high hyperdiploidy, and t(12;21) decreased in the ALL2008 trial. The 4-year overall survival after relapse was 56.6% (95% CI 52.5-60.5%) and no statistically significant temporal improvements were observed. Age ≥10 years, T-cell immunophenotype, bone-marrow involvement, early and very early relapse, hypodiploidy, and Down syndrome all independently predicted worse outcome after relapse. Improvements in the primary treatment of childhood ALL has resulted in fewer relapses. However, failure to improve outcome of remaining relapses suggests a selection of harder-to-cure relapses and calls for new therapeutic strategies.

Health care utilisation preceding relapse or second malignant neoplasm after childhood acute lymphoblastic leukaemia: a population-based matched cohort study.

OBJECTIVES: To investigate health care utilisation including both primary and secondary health care 6 months before the diagnosis of a relapse or a second malignant neoplasm (SMN) in survivors of childhood acute lymphoblastic leukaemia (ALL). DESIGN AND SETTING: A Danish population-based matched cohort study linking multiple nationwide registries. PARTICIPANTS: Participants were recruited from a total of 622 childhood ALL 2.5-year event-free survivors diagnosed between 1994 and 2015. Cases were survivors developing a relapse or an SMN and references were survivors still in first remission. Each case was matched with five references on age, sex, treatment protocol and risk group. PRIMARY OUTCOME MEASURES: Consultations in general practice and hospital the last 6 months before relapse or SMN. Cases and references were compared with monthly incidence rate ratios (IRRs) from negative binomial regression models. RESULTS: Of the 622 childhood ALL survivors, 60 (9.6%) developed a relapse (49) or an SMN (11) and 295 matched references were identified. Health care utilisation in general practice increased among cases the last month before the event compared with references with an IRR of 2.71 (95% CI 1.71 to 4.28). Data showed a bimodal structure with a significantly increased number of visits 4, 5 and 6 months before the event. Hospital health care utilisation increased 2 months before the event in cases with an IRR of 5.01 (3.78 to 6.63) the last month before the event and an IRR of 1.94 (1.32 to 2.85) the second-last month comparing cases and references. CONCLUSIONS: Survivors of childhood ALL developing a relapse or an SMN have a short period of increased health care utilisation before diagnosis. At hospital, this might be explained by pre-diagnostic examinations. In general practice, data suggest a bimodal structure with children later developing a relapse having more contacts also half a year before the relapse, suggesting that there could be early warnings.

Health care utilisation following childhood acute lymphoblastic leukaemia: a population-based matched cohort study.

OBJECTIVES: Survival among children diagnosed with acute lymphoblastic leukaemia (ALL) has increased considerably. However, morbidity in survivors constitutes a potential increasing burden not limited to secondary health care. Our objectives were to compare health care utilisation, including both primary and secondary health care, between childhood ALL survivors and matched references up to 15 years after curative treatment. Moreover, to increase knowledge on survivors' health service seeking behaviour as time from treatment elapsed. DESIGN AND SETTING: A Danish population-based matched cohort study linking multiple nationwide registries. PARTICIPANTS: 675 cases, diagnosed with childhood (1.0-17.9 years) ALL between 1994 and 2015, and 6750 matched references sampled randomly from the source population (matched on age, gender and geographical region). PRIMARY OUTCOME MEASURES: Repeated consultations in general practice and hospital (outpatient and inpatient) estimated as yearly rates from 2.5 years after diagnosis and onwards. We compared cases and references with yearly incidence rate ratios (IRRs) from negative binomial regression models. RESULTS: Survivors of childhood ALL had a mean number of yearly daytime contacts in general practice of 4.75 (95% CI 4.41 to 5.11) the first year, corresponding to an IRR of 1.85 (95% CI 1.71 to 2.00); decreasing to 1.16 (1.01 to 1.34) after 15 years, and without significant impact of gender (p=0.894) or age (p=0.399). For hospital contacts, ALL survivors had a mean number of yearly contacts of 14.21 (13.38-15.08) the first year, corresponding to an IRR of 31.50 (28.29-35.07); decreasing to 2.42 (1.59-3.68) after 15 years. No differences were found across calendar time. CONCLUSIONS: ALL survivors used significantly more health care services across sectors than the reference population. Decreasing use over 15 years illustrated the dynamics of health care needs; this knowledge may inform the future organisation of integrated follow-up programmes. TRIAL REGISTRATION NUMBER: NCT03985826.

[Lethal course following overlooked foreign body in the airway]. / Letalt forløb efter overset fremmedlegeme i luftvejen.

A 52-year-old previously healthy woman suffered death from choking. Asphyxia after aspiration of a foreign body is a well-known, but frequently overlooked cause of sudden death. We describe a case in which a foreign body in the airway was initially overlooked. Early recognition and treatment might have altered the outcome.