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

ABSTRACT: 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.

SUBMITTER: Egnell C

PROVIDER: S-EPMC7693088 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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

Egnell Christina C Ranta Susanna S Banerjee Joanna J Merker Andrea A Niinimäki Riitta R Lund Bendik B Mogensen Pernille Rudebeck PR Jonsson Ólafur G ÓG Vaitkeviciene Goda G Lepik Kristi K Forslund Anders A Heyman Mats M Harila-Saari Arja A

European journal of haematology 20200920 6

<h4>Objectives</h4>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.<h4>Method</h4>In a multicenter study, we collected data on BMI at diagnosis and outcome of 2558 children aged 2.0- ...[more]

PMID: 32909636

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Project description:BACKGROUND:Children with acute lymphoblastic leukemia (ALL) have an increased risk of obesity and short stature. To the authors' knowledge, data regarding patients treated on contemporary protocols without cranial irradiation are limited. METHODS:Changes in z scores for body mass index (BMI), height, and weight from the time of diagnosis to 5 years off therapy were evaluated using multivariable analysis in 372 children with ALL who were aged 2 to 18 years at the time of diagnosis and were enrolled on the St. Jude Children's Research Hospital Total XV protocol from 2000 through 2007. RESULTS:The percentage of overweight/obese patients increased from 25.5% at the time of diagnosis to approximately 50% during the off-therapy period. Median BMI z scores increased significantly during glucocorticoid therapy (induction: ?0.56; 95% confidence interval [95% CI], 0.29-0.64 [P<.001]; and reinduction II: ?0.22; 95% CI, 0.13-0.49 [P=.001]) and during the first year after therapy (?0.18; 95% CI, 0.08-0.46 [P=.006]). Among patients who were of healthy weight/underweight at the time of diagnosis, those aged 2 to <10 years at diagnosis had a significantly higher risk of becoming overweight/obese during or after therapy compared with those aged ?10 years (P=.001). Height z scores declined during treatment and improved after therapy. Being aged 2 to <10 years at the time of diagnosis, being of low-risk status, having a white blood cell count?<?50×109 /L at the time of diagnosis, and having negative central nervous system disease were associated with significantly better improvements in z scores for height during the off-therapy period compared with being aged ?10 years, being of standard-risk/high-risk status, having a white blood cell count ???50×109 /L, and having positive central nervous system disease, respectively. CONCLUSIONS:The results of the current study demonstrate that obesity is prevalent, and height growth, especially in patients with identified risk factors, appears compromised. Multidisciplinary intervention should begin during induction therapy and continue during the off-therapy period.

Project description:ImportanceOptimal chemotherapy dosing in obese patients remains uncertain, with variation in practice. Dose reduction strategies are often used to avoid chemotoxicity, but recent American Society of Clinical Oncology guidelines recommend full dose.ObjectiveTo evaluate the impact of body mass index (BMI) on chemotherapy dosing and of dose reduction on ovarian cancer survival.Design, setting, and participantsCohort study in Kaiser Permanente Northern California (KPNC) health care setting of patients with primary invasive epithelial ovarian cancers diagnosed from January 2000 through March 2013. Analyses focused on 806 patients receiving adjuvant first-line therapy of carboplatin and paclitaxel with curative intent.Main outcomes and measuresOverall and ovarian cancer-specific mortality. Deaths were identified through the KPNC Mortality Linkage System, with median follow-up of 52.5 months. Hazard ratios (HRs) and 95% CIs were estimated from proportional hazards regression, accounting for prognostic variables including age at diagnosis, race, stage, grade, histologic type, chemotoxic effects, comorbidities, cancer antigen 125 levels, and BMI at diagnosis.ResultsThe strongest predictor of dose reduction was a high BMI. Compared with normal-weight women, obese class III women received 38% and 45% lower doses in milligrams per kilogram of body weight of paclitaxel and carboplatin, respectively (P < .001 for each agent). They also received lower relative dose intensity (RDI) for each agent and the combined regimen, calculated as average RDI (ARDI). Mean ARDI was 73.7% for obese class III women and 88.2% for normal-weight women (P < .001). Lower ARDI (<70%) was associated with worse overall (HR, 1.62 [95% CI, 1.10-2.37]) and ovarian cancer-specific survival (HR, 1.69 [95% CI, 1.12-2.55]). Women who were obese at diagnosis appeared to have better survival. In multivariable-adjusted analyses considering joint effects by BMI and ARDI, compared with women with normal weight and no dose reduction, normal-weight women with dose reduction (ARDI < 85%) experienced worse survival (HR, 1.50 [95% CI, 1.02-2.21]). For each BMI category, those with ARDI less than 85% had worse survival than those without dose reduction. The improved survival among obese women was no longer apparent with dose reduction.Conclusions and relevanceLower RDI was an independent predictor of ovarian cancer mortality. This finding was strongest among normal-weight women but seen at all levels of BMI. Our results suggest that body size should not be a major factor influencing dose reduction decisions in women with ovarian cancer.

Project description:Further improvement of outcome in childhood acute lymphoblastic leukemia could be achieved by identifying additional high-risk patients who may benefit from intensified treatment. We earlier identified PTPRC (CD45) gene expression as a potential new stratification marker and now analyzed the prognostic relevance of CD45 protein expression. CD45 was measured by flow cytometry in 1065 patients treated according to the ALL-BFM-2000 protocol. The 75(th) percentile was used as cut-off to distinguish a CD45-high from a CD45-low group. As mean CD45 expression was significantly higher in T-cell acute lymphoblastic leukemia than in B-cell-precursor acute lymphoblastic leukemia (P<0.0001), the analysis was performed separately in both groups. In B-cell-precursor acute lymphoblastic leukemia we observed a significant association of a high CD45 expression with older age, high initial white blood cell count, ETV6/RUNX1 negativity, absence of high hyperdiploidy (P<0.0001), MLL/AF4 positivity (P=0.002), BCR/ABL1 positivity (P=0.007), prednisone poor response (P=0.002) and minimal residual disease (P<0.0001). In T-cell acute lymphoblastic leukemia we observed a significant association with initial white blood cell count (P=0.0003), prednisone poor response (P=0.01), and minimal residual disease (P=0.02). Compared to CD45-low patients, CD45-high patients had a lower event-free survival rate (B-cell-precursor acute lymphoblastic leukemia: 72 ± 3% versus 86 ± 1%, P<0.0001; T-cell acute lymphoblastic leukemia: 60 ± 8% versus 78 ± 4%, P=0.02), which was mainly attributable to a higher cumulative relapse incidence (B-cell-precursor acute lymphoblastic leukemia: 22 ± 3% versus 11 ± 1%, P<0.0001; T-cell acute lymphoblastic leukemia: 31 ± 8% versus 11 ± 3%, P=0.003) and kept its significance in multivariate analysis considering sex, age, initial white blood cell count, and minimal residual disease in B-cell-precursor- and T-cell acute lymphoblastic leukemia, and additionally presence of ETV6/RUNX1, MLL/AF4 and BCR/ABL1 rearrangements in B-cell-precursor acute lymphoblastic leukemia (P=0.002 and P=0.025, respectively). Consideration of CD45 expression may serve as an additional stratification tool in BFM-based protocols. (ClinicalTrials.gov identifier: NCT00430118).

Dataset Information

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

Publications

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

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