Objective
As survival rates increase, growing numbers of childhood acute lymphoblastic leukemia (ALL) survivors are at risk for somatic and psychosocial late effects. Adolescent and young adult (AYA) ...survivors represent a distinct and vulnerable group. This study aimed to explore how AYA survivors of childhood ALL experience everyday life after cancer while adjusting to the potential impact of prior disease and treatment.
Methods
Semi‐structured interviews were performed with survivors aged 15‐22 years. Criterion‐based homogenous purposive sampling was used to identify similarities within the group. Data were analyzed using an inductive, thematic approach.
Results
Data saturation occurred after 18 interviews. Identified themes included the post‐chemo body, negotiating identities, and disruption. More than 80% reported physical or cognitive late effects, but survivors adapted to these and had a positive view on own health. However, a co‐existing experience of frailty persisted. Social disruption during treatment had a negative impact on social relations even years following cure. Identity issues revolved around the paradox of seeking recognition for their cancer‐related experiences, while also wanting to be treated like everyone else. Some participants aged 18‐22 years experienced delayed reactions and a new, but unmet, need to process the past.
Conclusions
AYA survivors of childhood ALL adapt well to their new life situations, but many experience ongoing cancer‐related disruptions and experience not being fully understood. We suggest exploration and verbalization of these issues alongside somatic follow‐up around the age of 16‐18 years to support the AYA survivors during their transition into adulthood.
Pancreatitis is a common and severe toxicity that occurs during asparaginase treatment for acute lymphoblastic leukemia, and has received increasing attention during the last decades. However, no ...consensus regarding follow‐up exists. In this commentary, we highlight potential long‐term health‐related effects following asparaginase‐associated pancreatitis, thereby providing clinicians with a framework when following these patients during and after cessation of therapy.
Abstract
Background
The established association between acute lymphoblastic leukemia (ALL) and hyperlipidemia has, in some studies, been linked to toxicities such as pancreatitis, thrombosis, and ...osteonecrosis. However, a systematic review investigating the incidence, management, and clinical implications of hyperlipidemia during childhood ALL treatment is lacking.
Objectives
Systematically assess the incidence of hyperlipidemia during ALL treatment, explore associations with risk factors and severe toxicities (osteonecrosis, thrombosis, and pancreatitis), and review prevalent management strategies.
Methods
A systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) statement. Data synthesis was descriptive, and a meta‐analysis of hypertriglyceridemia and risk of severe toxicities was performed.
Results
We included 13 studies with 3,425 patients. Hyperlipidemia incidence varied widely (6.7%‐85%) but with inconsistent definitions and screening strategies across studies. Evidence regarding risk factors was conflicting, but age (> 10 years) and treatment with asparaginase and glucocorticosteroids seem to be associated with hyperlipidemia. Hypertriglyceridemia (grade 3/4) increased the risk for osteonecrosis (odds ratio (OR): 4.27, 95% confidence interval (CI): 2.77‐6.61). No association could be established for pancreatitis (OR: 1.60, 95% CI: 0.53‐4.82) or thrombosis (OR: 2.45, 95% CI: 0.86‐7.01), but larger studies are needed to confirm this.
Conclusion
The overall evidence of this systematic review is limited by the small number of studies and risk of bias. Our review suggests that hypertriglyceridemia increases the risk for osteonecrosis. However, larger studies are needed to explore the clinical implications of hyperlipidemia and randomized trials investigating hyperlipidemia management and its impact on severe toxicities.
Objectives
Asparaginase‐associated pancreatitis (AAP) occurs in up to 18% of patients treated for acute lymphoblastic leukemia (ALL); however, long‐term sequelae are largely unexplored. We aimed to ...explore pancreatic sequelae among ALL survivors with and without AAP.
Methods
We investigated pancreatic sequelae in a national cohort of ALL survivors, aged 1–45 years at ALL diagnosis treated according to the NOPHO‐ALL2008 protocol and included sex‐ and age‐matched community controls.
Results
We included 368 survivors (median follow‐up 6.9 years), including 47 survivors with AAP and 369 controls. The p‐lipase and p‐pancreas‐type amylase levels were lower in AAP survivors compared with both non‐AAP survivors (Medians: 23 U/L IQR 14–32 and 18 U/L IQR 10–25 versus 29 IQR 24–35 and 22 17–28, p < .001 and p = .002) and community controls (28 U/L IQR 22–33 and 21 U/L IQR 17–26, both p < .006). Fecal‐elastase was more frequently reduced in AAP survivors compared with non‐AAP survivors (7/31 vs. 4/144, p = .001). Persisting pancreatic sequelae were found in 15/47 of AAP survivors and 20/323 of non‐AAP survivors (p < .001), including diabetes mellitus in 2/39 of AAP survivors and 2/273 of non‐AAP survivors.
Conclusions
ALL survivors with AAP are at increased risk of persisting pancreatic dysfunction and require special attention during follow‐up.
The treatment of acute lymphoblastic leukemia (ALL) is frequently complicated by toxicity, including venous thromboembolism (VTE) affecting roughly 8% of patients. VTE can lead to post‐thrombotic ...syndrome (PTS), a group of signs and symptoms developed as a complication to deep venous thrombosis (DVT), imposing risk of permanent disability and reduced quality of life (QoL). PTS prevalence ranges from 0% to 70%, reflecting very heterogenous cohorts and assessment tools. We aimed to estimate sequelae, including PTS and QoL in children and adults (<45 years old) who had a DVT during ALL treatment. PTS and QoL scores were obtained through use of Villalta and Modified Villalta Scale, PedsQL, and Short Form‐36 questionnaires. The cohort comprised 20 children (<18 years) and seven adults (median age: 12.9 years, range: 2–44 years) at the time of DVT diagnosis. In total, 25 ALL survivors underwent PTS examination. The examination took place when survivors were 7–48 years (median age: 20.3 years, median follow‐up time 6.8 years). QoL was assessed correlating cases with three matching ALL survivors without VTE. Two adults (15.4%) showed mild or moderate PTS. Eight children (66.7%) were diagnosed with mild PTS, while three cases had collaterals as sole symptoms. Pain or symptoms affecting daily life were reported by 16%. No difference in QoL was found (p = .9). This study underscores the need for comprehensive population‐based investigations with validation of PTS instruments in ALL survivors.
Based on developing, implementing, and evaluating postgraduate interprofessional case-based learning, we have written these twelve tips for health education planners who wish to apply case-based ...learning in the clinical setting. Interprofessional case-based learning engages participants in a structured manner towards uncovering decisions processes and patterns of action that resemble the clinical reality in which various healthcare professionals handle multifaceted tasks related to the optimal patient treatment. Postgraduate interprofessional case-based learning has the potential to break down traditional hierarchical structures as interactions generate respectful behaviour. We present two models of case-based learning to assist in standardising, structuring, and systematising postgraduate interprofessional case-based learning. We have created 12 practical tips for the design, implementation, and evaluation of successful postgraduate interprofessional case-based learning integrated into the existing clinical setting.
Antenatal ultrasound diagnosed anomalies of the kidney and urinary tract (AUDAKUT) are reported in 0.3%-5% on prenatal ultrasound (US) and 0.3%-4.5% on postnatal US. The anterior-posterior diameter ...of the renal pelvis (APD) is an essential measurement. Series with low threshold values of APD prenatally and postnatally will include healthy infants. It is important to avoid follow-up of such infants.
In 2006, new Danish guidelines for AUDAKUT were introduced.
Investigations of incidences and type of AUDAKUT based on Danish guidelines, including long-term follow-up.
Cohort study.
Copenhagen University Hospital Hvidovre and Copenhagen University Hospital Rigshospitalet, Denmark.
Consecutive cases with AUDAKUT in the second and third trimesters, which were either terminated before 22 completed weeks of gestation or born in the 8-year period January 2006-December 2013. Patients were followed until June 2014.
50 193 live born children and 24 terminated fetuses (0.05%) were included. The prevalence of AUDAKUT was only 0.39% prenatally, 0.29% at first postnatal US and 0.22% at the end of follow-up, including terminated cases. The greater the prenatal and postnatal APD, the higher risk of febrile urinary tract infection (fUTI) and surgical intervention, and lower probability of resolution. 25% of the identified patients had fUTI and/or surgery.
We recommend threshold values of APD at least 10 mm in the third trimester and in general at least 12 mm at first postnatal US for intensive follow-up. In this largest to date unselected birth cohort of AUDAKUT, the incidences of clinically significant AUDAKUT were in the lowest range of those previously published.
Abstract
Purpose
We aimed to determine the effects of a classmate-supported, supervised, in-hospital physical activity program during treatment primarily on cardiorespiratory fitness and secondarily ...on physical function.
Methods
A multicenter non-randomized controlled intervention study including children diagnosed with cancer, 6–18 years at diagnosis treated with chemo-/radiotherapy. The intervention comprised (i) an educational session on cancer in the child’s school class; (ii) selection of two “ambassadors”—classmates who were co-admitted, supporting the child’s everyday hospital life; and (iii) supervised in-hospital physical activity from diagnosis and throughout intensive treatment. One-year post-treatment, physical testing included cardiorespiratory fitness (primary outcome), Sit-to-Stand test, Timed-Up-and-Go, and Handgrip Strength.
Results
The intervention group included 75 of 120 children (61% boys, 13.4 ± 3.1 years); the control groups included 33 of 58 children with cancer (58% boys, 13.5 ± 2.5 years), and 94 age- and sex-matched children without a cancer history. One-year post-treatment, cardiorespiratory fitness tended to be higher in the intervention group (37.0 ± 6.0 mL/kg/min) than in the patient control group with cancer (32.3 ± 9.7 mL/kg/min) (mean difference 4.7 0.4 to 9.1,
p
= 0.034). The intervention group performed better in the secondary outcomes. Compared with community controls, both patient groups had lower cardiorespiratory fitness. The patient control group had lower Sit-to-Stand, Timed Up and Go, and Handgrip Strength, while the intervention group had strength comparable to that of the community controls.
Conclusions
Peer-supported, supervised, in-hospital physical activity during treatment may improve cardiorespiratory fitness and muscle strength 1-year post-treatment in children with cancer; however, survivors continue to have lower cardiorespiratory fitness than community controls.
Implications for Cancer Survivors
Children with cancer may benefit from in-hospital physical activity in improving long-term cardiorespiratory fitness and muscle strength.
Cardiovascular diseases manifest differently in males and females, potentially influenced by inherent sex- and age-related differences in myocardial tissue composition. Such inherent differences are ...not well-established in the literature. With this study using cardiac magnetic resonance (CMR) native T1 mapping, we aim to determine the effect of sex and age on myocardial tissue composition in healthy individuals.
CMR native T1 mapping was performed in 276 healthy individuals (55% male, age 8---84 years) on a 1.5 Tesla scanner using a MOLLI 5(3)3 acquisition scheme. Additionally, 30 healthy participants (47% male, age 24-68 years) underwent a 1-year follow-up CMR to assess the longitudinal changes of native T1. Mean native T1 values were 1000±22 ms in males and 1022±23 ms in females (mean difference MD=22 ms, 95% CI 17, 27). Female sex was associated with higher native T1 in multivariable linear regression adjusting for age, heart rate, left ventricular mass index, and blood T1 (β=10 ms, 95% CI 3.4, 15.8). There was no significant interaction between sex and age (p=0.27). Further, age was not associated with native T1 (β=0.1 ms, 95% CI -0.02, 0.2), and native T1 did not change during a 1-year period (MD -4 ms, 95% CI -11, 3).
Female sex was associated with higher native T1; however, there was no association between age and native T1. Additionally, there was no evidence of an interaction between sex and age. Our findings indicate intrinsic sex-based disparities in myocardial tissue composition.
Endothelial dysfunction has not previously been investigated as a thrombogenic risk factor among patients with acute lymphoblastic leukemia (ALL), known to be at high risk of thromboembolism. We ...retrospectively explored the association between three circulating biomarkers of endothelial dysfunction (thrombomodulin, syndecan-1, VEGFR-1) measured in prospectively collected blood samples and risk of thromboembolism in 55 cases and 165 time-matched controls, treated according to the NOPHO ALL2008 protocol. In age-, sex-, and risk group-adjusted analysis, increasing levels of thrombomodulin and VEGFR-1 were independently associated with increased odds of developing thromboembolism (OR 1.37 per 1 ng/mL 95% CI 1.20‒1.56, P < 0.0001 and OR 1.21 per 100 pg/mL 95% CI 1.02‒1.21, P = 0.005, respectively). These associations remained significant when including only samples drawn >30 days before thromboembolic diagnosis. Thrombomodulin levels were on average 3.2 ng/mL (95% CI 2.6-8.2 ng/mL) higher in samples with measurable asparaginase activity (P < 0.0001). Among single nucleotide variants located in or neighboring coding genes for the three biomarkers, none were significantly associated with odds of thromboembolism. If results are validated in another cohort, thrombomodulin and VEGFR-1 could serve as predictive biomarkers, identifying patients in need of preemptive antithrombotic prophylaxis.
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