Impact of body mass index on outcome and treatment-related toxicity in young adults with acute lymphoblastic leukemia.

BACKGROUND: Data on outcome for patients in different body mass index (BMI) categories in young adults with acute lymphoblastic leukemia (ALL) are scarce. We explored survival and toxicities in different BMI categories in young adults with ALL. MATERIAL AND METHODS: Patients aged 18-45 years, diagnosed with ALL between July 2008 and June 2022 in the Nordic countries, Estonia, or Lithuania, and treated according to the NOPHO ALL2008 protocol, were retrospectively enrolled and classified into different BMI categories. Endpoints were overall survival (OS), event-free survival (EFS) and cumulative incidence of relapse as well as incidence rate ratio (IRR) of severe predefined toxic events, and treatment delays. RESULTS: The group comprised 416 patients, of whom 234 (56%) were stratified to non-high-risk (non-HR) treatment. In the non-HR group, patients with severe obesity, BMI ≥35 kg/m2 had worse EFS due to relapses but there was no effect on toxicity or treatment delays compared with the healthy-weight patients. There was no association between BMI category and OS, overall toxicity, or treatment delays in the patients with high-risk treatment. CONCLUSION: Severe obesity is associated with worse EFS in young adults treated according to the non-HR arms of the NOPHO ALL2008 protocol. Poorer outcome is explained with a higher risk of relapse, possibly due to under treatment, and not caused by excess therapy-related mortality.

Changes in body mass index during treatment of childhood acute lymphoblastic leukemia with the Nordic ALL2008 protocol.

OBJECTIVES: Children with acute lymphoblastic leukemia (ALL) have a tendency to gain weight during treatment. As overweight and obesity associate with health problems, prophylactic interventions are warranted. Therefore, it is important to identify the children most prone to gain weight. METHODS: Patients aged 2.0-17.9 years at ALL diagnosis were identified from the NOPHO ALL2008 registry. Registry data was complemented with height and weight at the end of therapy from questionnaires. Body mass index (BMI) was classified according to international age- and sex-adjusted International Obesity Task Force BMI cut-offs. BMI values were transformed into standard deviation scores (SDS) to calculate the difference in BMISDS during treatment. RESULTS: Data on BMI change were available for 765 children. Overweight and obesity doubled during treatment: 9.7% were overweight and 2.1% obese at diagnosis and 21.8% and 5.4% at the end of therapy, respectively. The mean BMISDS change was +0.64. Younger (2.0-5.9 years) and healthy weight children were most prone to become overweight (mean change in BMI SDS +0.85 and + 0.65, respectively). CONCLUSIONS: Younger children (2.0-5.9 years) with healthy weight at diagnosis were most prone to becoming overweight and therefore are an important group to target while considering interventions.

Obesity as a predictor of treatment-related toxicity in children with acute lymphoblastic leukaemia.

Obesity is associated with poor outcomes in childhood acute lymphoblastic leukaemia (ALL). We explored whether severe treatment-related toxicity and treatment delays could explain this observation. This study included 1 443 children aged 2·0-17·9 years with ALL treated with the Nordic Society of Pediatric Haematology and Oncology (NOPHO) ALL2008 non-high-risk protocol. Prospective treatment-related toxicities registered every three-month interval were used. Patients were classified according to sex- and age-adjusted international childhood cut-off values, corresponding to adult body mass index: underweight, <17 kg/m2 ; healthy weight, 17 to <25 kg/m2 ; overweight, 25 to <30 kg/m2 ; and obese, ≥30 kg/m2 . Obese children had a higher incidence rate ratio (IRR) for severe toxic events {IRR: 1·55 [95% confidence interval (CI) 1·07-2·50]}, liver and kidney failures, bleeding, abdominal complication, suspected unexpected severe adverse reactions and hyperlipidaemia compared with healthy-weight children. Obese children aged ≥10 years had increased IRRs for asparaginase-related toxicities compared with healthy-weight older children: thromboses [IRR 2·87 (95% CI 1·00-8·21)] and anaphylactic reactions [IRR 7·95 (95% CI 2·15-29·37)] as well as higher risk for truncation of asparaginase [IRR 3·54 (95% CI 1·67-7·50)]. The high prevalence of toxicity and a higher risk of truncation of asparaginase may play a role in the poor prognosis of obese children aged ≥10 years with ALL.

Impact of body mass index on relapse in children with acute lymphoblastic leukemia treated according to Nordic treatment protocols.

OBJECTIVES: High body mass index (BMI) is associated with poorer survival in childhood acute lymphoblastic leukemia (ALL), but the actual impact on the risk of relapse still needs to be clarified. We evaluated the impact of BMI at diagnosis on the risk of relapse in children with ALL treated according to Nordic Society of Paediatric Haematology and Oncology (NOPHO) protocols. METHOD: In a multicenter study, we collected data on BMI at diagnosis and outcome of 2558 children aged 2.0-17.9 years diagnosed between 1992 and 2016. Patients were divided into four groups according to International Obesity Task Force (IOTF) childhood BMI cut-offs: underweight, <17; healthy weight, 17-25; overweight, 25-30; and obese, ≥30 kg/m2 . RESULTS: In Cox multivariate regression analyses, an increased risk of relapse was observed in children aged 10-17.9 years with unhealthy BMI at diagnosis (underweight hazard ratio HR: 2.90 [95% confidence interval: 1.24-6.78], P = .01; overweight, HR: 1.95 [1.11-3.43], P = .02, and obese HR: 4.32 [95% 2.08-8.97], P < .001), compared to children with healthy weight. BMI had no impact on relapse in children under 10 years of age. CONCLUSION: High BMI, and especially obesity at diagnosis, is an independent adverse prognostic factor for relapse in older children with ALL.

Jejunostomy enteral feeding in children: outcome and safety.

BACKGROUND: The aim of this study was to report on the clinical outcome and safety of jejunostomy tube feeding used in our clinical setting for more than 14 years. MATERIAL AND METHODS: A retrospective study of all children who underwent a surgical catheter jejunostomy placement between July 1996 and March 2010 was conducted. Data were collected regarding the outcome and complications. RESULTS: Thirty-three children (14 girls) were included. The median age at the time of primary surgery was 1.43 years (range, 0.15-17.7 years), and the median time of follow-up was 2.34 years (range, 0.27-12.6 years). Seventeen children were severely neurologically impaired (NI). Surgical insertion of a jejunostomy tube was performed due to 1 or more of the following indications: gastroesophageal reflux disease (GERD), failure to thrive, recurrent pneumonia, esophageal disease, or oral feeding difficulties. The effect of the indications showed a reduction in GERD and pneumonia. Feeding difficulties also decreased. Weaning was possible in 12 of 16 children without NI but in only 2 of 17 with NI. Major complications requiring surgical reoperation affected 8 children. No mortality was related to the jejunostomy feeding catheter. CONCLUSION: In selected cases, surgically placed jejunostomy tubes for feeding in children is an effective and safe method to overcome GERD, feeding difficulties, or recurrent pneumonia without major surgery.

Long-term prognostic value of dobutamine stress CMR.

OBJECTIVES: The aim of this study was to assess the long-term value of high-dose dobutamine cardiac magnetic resonance (DCMR) for the prediction of cardiac events in a large cohort of patients with known or suspected coronary artery disease. BACKGROUND: High-dose DCMR has been shown to be a useful technique for diagnosis and intermediate-term prognostic stratification. METHODS: Clinical data and DCMR results were analyzed in 1,463 consecutive patients undergoing DCMR between 2000 and 2004. Ninety-four patients were lost to follow-up. The remaining 1,369 patients were followed up for a mean of 44 ± 24 months. Cardiac events, defined as cardiac death and nonfatal myocardial infarction, were related to clinical and DCMR results. RESULTS: Three-hundred fifty-two patients underwent early revascularization (≤ 3 months of DCMR) and were excluded from analysis. Of the remaining 1,017 patients, 301 patients (29.6%) experienced inducible wall motion abnormalities (WMA). Forty-six cardiac events were reported. In those with and without inducible WMA, the proportion of patients with cardiac events was 8.0% versus 3.1%, respectively, p = 0.001 (hazard ratio: 3.3; 95% confidence interval: 1.8 to 5.9 for the presence of inducible WMA; p < 0.001). A DCMR without inducible WMA carried an excellent prognosis, with a 6-year cardiac event-free survival of 96.8%. In all 1,369 patients in the patient group with stress-inducible WMA, those patients with medical therapy demonstrated a trend to a higher cardiac event rate (8.0%) than those with early revascularization (5.4%) (p = 0.234). Patients with normal DCMR and medical therapy or early revascularization demonstrated similar cumulative cardiac event rates (3.1% vs. 3.2%, p = 0.964). CONCLUSIONS: In a large cohort of patients, DCMR has an added value for predicting cardiac events during long-term follow-up, improving the differentiation between high-risk and low-risk patients. Patients with inducible WMA and following early revascularization, demonstrate lower cardiac event rates than patients with medical therapy alone.

Prognostic value of negative dobutamine-stress cardiac magnetic resonance imaging.

BACKGROUND: Assessment of left ventricular wall motion during dobutamine-stress magnetic resonance (DSMR) is well established for the identification of myocardial ischemia. However, the integration of DSMR into the process of clinical decision-making in patients with suspected CAD is not well established. The aim of this study was to assess the value of DSMR used for clinical decision-making and to stratify the prognosis following this strategy. MATERIAL/METHODS: Medical records of 123 consecutive patients suspected of having CAD who underwent high-dose DSMR were reviewed and followed for a median of 23+/-12 months. DSMR results were used for decision-making, for example in favor of catheterization by the referring physician. RESULTS: Thirty-four (27.6%) patients had inducible ischemia, of whom 31 (91.2%) underwent invasive angiography, 25 (80.6%) having stenoses of >50% in a vessel of > or =2 mm in diameter. Fifteen of these patients received vascularization (PCI/CABG); only two events (myocardial infarction) were observed during follow-up in this group. Eighty-nine (72.4%) patients had no inducible ischemia; 21 of them (23.6%) had invasive angiography resulting in 0 (0%) significant findings. In the remaining 68 (76.4%) patients with negative DSMR and who were not catheterized, an annual event rate of 0% was observed. CONCLUSIONS: DSMR can be used for clinical decision-making in patients suspected of having CAD. This strategy results in a high prevalence of CAD in patients referred for invasive angiography due to a positive DSMR and an excellent prognosis in all patients with a negative DSMR.