| 1. |
- Anastasopoulou, Stavroula, et al.
(författare)
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Acute central nervous system toxicity during treatment of pediatric acute lymphoblastic leukemia : phenotypes, risk factors and genotypes
- 2020
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Ingår i: Haematologica. - : Ferrata Storti Foundation. - 0390-6078 .- 1592-8721. ; 107:10, s. 2318-2328
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Tidskriftsartikel (refereegranskat)abstract
- Central nervous system (CNS) toxicity is common at diagnosis and during treatment of pediatric acute lymphoblastic leukemia (ALL). We studied CNS toxicity in 1,464 children aged 1.0-17.9 years, diagnosed with ALL and treated according to the Nordic Society of Pediatric Hematology and Oncology ALL2008 protocol. Genome-wide association studies, and a candidate single-nucleotide polymorphism (SNP; n=19) study were performed in 1,166 patients. Findings were validated in an independent Australian cohort of children with ALL (n=797) in whom two phenotypes were evaluated: diverse CNS toxicities (n=103) and methotrexate-related CNS toxicity (n=48). In total, 135/1,464 (9.2%) patients experienced CNS toxicity for a cumulative incidence of 8.7% (95% confidence interval: 7.31-10.20) at 12 months from diagnosis. Patients aged >= 10 years had a higher risk of CNS toxicity than had younger patients (16.3% vs. 7.4%; P < 0.001). The most common CNS toxicities were posterior reversible encephalopathy syndrome (n=52, 43 with seizures), sinus venous thrombosis (n=28, 9 with seizures), and isolated seizures (n=16). The most significant SNP identified by the genome-wide association studies did not reach genomic significance (lowest P-value: 1.11x10(-6)), but several were annotated in genes regulating neuronal functions. In candidate SNP analysis, ATXN1 rs68082256, related to epilepsy, was associated with seizures in patients < 10 years (P=0.01). ATXN1 rs68082256 was validated in the Australian cohort with diverse CNS toxicities (P=0.04). The role of ATXN1 as well as the novel SNP in neurotoxicity in pediatric ALL should be further explored.
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| 2. |
- Banerjee, Joanna, et al.
(författare)
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The spectrum of acute central nervous system symptoms during the treatment of childhood acute lymphoblastic leukaemia
- 2020
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Ingår i: Pediatric Blood & Cancer. - : WILEY. - 1545-5009 .- 1545-5017. ; 67:2
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Tidskriftsartikel (refereegranskat)abstract
- Background: Children with central nervous system (CNS) toxicity during therapy for acute lymphoblastic leukaemia (ALL) are at risk for treatment modifications, long-term sequelae and even higher mortality. A better understanding of CNS symptoms and their complications improves the potential to prevent and treat them.Methods: Patient files from 649 children treated with Nordic Society of Pediatric Hematology and Oncology ALL92 and ALL2000 protocols in Finland were reviewed retrospectively for any acute CNS symptom. Detailed data on symptoms, examinations and treatment of the underlying CNS complications were collected from the medical records. Disease-related and outcome data were retrieved from the Nordic leukaemia registry.Results: Altogether, 13% (86) of patients with ALL had acute CNS symptoms. Most symptoms (64%) occurred during the first 2 months of therapy. Posterior reversible encephalopathy syndrome was the most frequent complication (4.5%). Cerebrovascular events were diagnosed in 10 cases (1.6%), while methotrexate-related stroke-like syndrome (SLS) was observed in only one patient (0.2%). CNS symptoms due to systemic or unclear conditions, especially sepsis, were important for differential diagnosis. CNS leukaemia was associated with CNS symptoms (hazard ratio [HR] = 4.03; P = .003), and epilepsy was a common sequel of CNS complications (19%).Conclusions: Acute CNS symptoms are common during ALL therapy, occurring mainly during the first 2 months of treatment. Patients with CNS leukaemia at diagnosis are at a higher risk for CNS toxicity. Despite intensive CNS-directed methotrexate treatment, SLS was diagnosed extremely rarely in our series.
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| 3. |
- Egnell, Christina, et al.
(författare)
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Impact of body mass index on relapse in children with acute lymphoblastic leukemia treated according to Nordic treatment protocols
- 2020
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Ingår i: European Journal of Haematology. - : WILEY. - 0902-4441 .- 1600-0609. ; 105:6, s. 797-807
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Tidskriftsartikel (refereegranskat)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/m(2). 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.
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| 4. |
- Nava, Tiago, et al.
(författare)
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Supportive care during pediatric hematopoietic stem cell transplantation : beyond infectious diseases. A report from workshops on supportive care of the Pediatric Diseases Working Party (PDWP) of the European Society for Blood and Marrow Transplantation (EBMT)
- 2020
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Ingår i: Bone Marrow Transplantation. - : Springer Science and Business Media LLC. - 0268-3369 .- 1476-5365. ; 55:6, s. 1126-1136
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Tidskriftsartikel (refereegranskat)abstract
- Hematopoietic stem cell transplantation (HSCT) is currently the standard of care for many malignant and nonmalignant blood diseases. As several treatment-emerging acute toxicities are expected, optimal supportive measurements critically affect HSCT outcomes. The paucity of good clinical studies in supportive practices gives rise to the establishment of heterogeneous guidelines across the different centers, which hampers direct clinical comparison in multicentric studies. Aiming to harmonize the supportive care provided during the pediatric HSCT in Europe, the Pediatric Diseases Working Party (PDWP) of the European Society for Blood and Marrow Transplantation (EBMT) promoted dedicated workshops during the years 2017 and 2018. The present paper describes the resulting consensus on the management of sinusoidal obstructive syndrome, mucositis, enteral and parenteral nutrition, iron overload, and emesis during HSCT.
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| 5. |
- Thastrup, Maria, et al.
(författare)
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Flow cytometric detection of leukemic blasts in cerebrospinal fluid predicts risk of relapse in childhood acute lymphoblastic leukemia : a Nordic Society of Pediatric Hematology and Oncology study
- 2020
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Ingår i: Leukemia. - : Springer Nature. - 0887-6924 .- 1476-5551. ; 34:2, s. 336-346
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Tidskriftsartikel (refereegranskat)abstract
- Central nervous system (CNS) involvement by cytospin is associated with increased risk of relapse in childhood acute lymphoblastic leukemia. We investigated if flow cytometric analysis of cerebrospinal fluid (CSF) at diagnosis improves the prediction of relapse. This prospective cohort study included patients (1.0-17.9 years) treated according to the Nordic Society of Pediatric Hematology and Oncology ALL2008 protocol. CSF flow cytometry samples were obtained at 17 centers, preserved with Transfix (R), and analyzed at a central laboratory. One-hundred and seventy-one (25.4%) of 673 patients were positive by flow cytometry (CNSflow+). The 4-year cumulative incidence of relapse was higher for patients with cytospin positivity (CNScyto+) (17.1% vs. 7.5%), CNSflow+ (16.5% vs. 5.6%), and cytospin and/or flow positivity (CNScomb+) (16.7% vs. 5.1%). In Cox regression analysis stratified by immunophenotype and minimal residual disease day 29 and adjusted by sex, predictors of relapse were age (hazard ratio [HR] 1.1, 95% CI 1.1-1.2, P < 0.001), white blood cell count at diagnosis (HR 1.4, 95% CI 1.1-1.6, P < 0.001), and CNScomb+ (HR 2.2, 95% CI 1.0-4.7, P = 0.042). Flow cytometric analysis of CSF improves detection of CNS leukemia, distinguishes patients with high and low risk of relapse, and may improve future risk stratification and CNS-directed therapy.
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