| 1. |
- Aarnivala, Henri, et al.
(författare)
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Trends in age- and sex-adjusted body mass index and the prevalence of malnutrition in children with cancer over 42 months after diagnosis : a single-center cohort study
- 2020
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Ingår i: European Journal of Pediatrics. - : SPRINGER. - 0340-6199 .- 1432-1076. ; 179:1, s. 91-98
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Tidskriftsartikel (refereegranskat)abstract
- The adequate nutritional status of pediatric cancer patients is particularly important to enable them to cope with the demands of the disease and its treatment and to maintain normal growth. Malnutrition and obesity have both been associated with reduced survival and increased drug toxicity. We investigated trends in the age- and sex-adjusted body mass index (ISO-BMI) and the prevalence of malnutrition in a Finnish cohort of 139 consecutive children receiving chemotherapy for cancer, with a follow-up period of 42 months after diagnosis. In total, 28% (39/139) of the patients experienced malnutrition (ISO-BMI < 17 or > 10% weight loss), and 12% (16/139) had a nasogastric tube or underwent gastrostomy. Patients with acute or chronic myeloid leukemia (5/10), central nervous system (CNS) tumors (5/13), or solid tumors (13/31) most frequently suffered from malnutrition. There was a significant increase in the ISO-BMI of patients with acute lymphoblastic leukemia (ALL) (+ 2.1 kg/m(2)) and lymphomas (+ 2.4 kg/m(2)) during the first 6 months, and the ISO-BMI of patients with ALL remained higher at 42 months compared to baseline (+ 1.9 kg/m(2)). Conclusion: The cumulative incidence of malnutrition in Finnish pediatric cancer patients is comparable to that reported in other populations. The nutritional status of patients with acute myeloid leukemia, CNS tumors, or solid tumors should be monitored with extra care to facilitate early intervention in the case of impending malnutrition.
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| 2. |
- Albertsen, Birgitte Klug, et al.
(författare)
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Asparaginase treatment in infants with acute lymphoblastic leukemia; pharmacokinetics and asparaginase hypersensitivity in Interfant-06
- 2019
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Ingår i: Leukemia and Lymphoma. - : TAYLOR & FRANCIS LTD. - 1042-8194 .- 1029-2403. ; 60:6, s. 1469-1475
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Tidskriftsartikel (refereegranskat)abstract
- Acute lymphoblastic leukemia (ALL) is a rare disease in infants. Asparaginase is an essential part of the treatment, and there Acute is a need to evaluate the efficiency and safety of this drug in this age group. We evaluated the pharmacokinetics of intramuscularly administered native E. coli asparaginase (Asparaginase Medac((R))) and PEG-asparaginase (Oncaspar((R))) as well as hypersensitivity reactions during treatment in Interfant-06 (www.clinicaltrials.gov: NCT01025804). All patients without hypersensitivity had sufficiently high enzyme activity levels during treatment with both preparations. Patients with hypersensitivity reactions during treatment, characterized by the presence of either or not of clinical symptoms and no measurable enzyme activity, received ineffective therapy. For optimization of the bad prognosis in infant ALL, therapeutic drug monitoring should be performed for identification of patients who should be switched to a different asparaginase preparation because of inactivation of the drug.
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| 3. |
- Jarviaho, Tekla, et al.
(författare)
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Predisposition to childhood acute lymphoblastic leukemia caused by a constitutional translocation disrupting ETV6
- 2019
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Ingår i: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 3:18, s. 2722-2731
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Tidskriftsartikel (refereegranskat)abstract
- Pathogenic germline variants in ETV6 have been associated with familial predisposition to thrombocytopenia and hematological malignancies, predominantly childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL). In addition, overrepresentation of a high hyperdiploid subtype and older age at diagnosis have been reported among sporadic BCP-ALL cases with germline variants in ETV6. We studied a family with 2 second-degree relatives who developed childhood high hyperdiploid BCP-ALL at ages 8 and 12 years, respectively. A constitutional balanced reciprocal translocation t(12;14)(p13.2;q23.1) was discovered in both patients by routine karyotyping at diagnosis and, subsequently, in 7 healthy family members who had not experienced hematological malignancies. No carriers had thrombocytopenia. Whole-genome sequencing confirmed the translocation, resulting in 2 actively transcribed but nonfunctional fusion genes, causing heterozygous loss and consequently monoallelic expression of ETV6. Whole-genome sequencing analysis of the affected female subjects' leukemia excluded additional somatic aberrations in ETV6 and RTN1 as well as shared somatic variants in other genes. Expression studies, performed to confirm decreased expression of ETV6, were not conclusive. We suggest that germline aberrations resulting in monoallelic expression of ETV6 contribute to leukemia susceptibility, whereas more severe functional deficiency of ETV6 is required for developing THC5. To our knowledge, this report is the first of a constitutional translocation disrupting ETV6 causing predisposition to childhood ALL.
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| 4. |
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| 5. |
- Tesi, Bianca, et al.
(författare)
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Gain-of-function SAMD9L mutations cause a syndrome of cytopenia, immunodeficiency, MDS, and neurological symptoms
- 2017
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Ingår i: Blood. - : AMER SOC HEMATOLOGY. - 0006-4971 .- 1528-0020. ; 129:16, s. 2266-2279
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Tidskriftsartikel (refereegranskat)abstract
- Several monogenic causes of familial myelodysplastic syndrome (MDS) have recently been identified. We studied 2 families with cytopenia, predisposition to MDS with chromosome 7 aberrations, immunodeficiency, and progressive cerebellar dysfunction. Genetic studies uncovered heterozygous missense mutations in SAMD9L, a tumor suppressor gene located on chromosome arm 7q. Consistent with a gain-of-function effect, ectopic expression of the 2 identified SAMD9L mutants decreased cell proliferation relative to wild-type protein. Of the 10 individuals identified who were heterozygous for either SAMD9L mutation, 3 developed MDS upon loss of the mutated SAMD9L allele following intracellular infections associated with myeloid, B-, and natural killer (NK)-cell deficiency. Five other individuals, 3 with spontaneously resolved cytopenic episodes in infancy, harbored hematopoietic revertant mosaicism by uniparental disomy of 7q, with loss of the mutated allele or additional in cis SAMD9L truncating mutations. Examination of 1 individual indicated that somatic reversions were postnatally selected. Somatic mutations were tracked to CD34 1 hematopoietic progenitor cell populations, being further enriched in B and NK cells. Stimulation of these cell types with interferon (IFN)-alpha or IFN-gamma induced SAMD9L expression. Clinically, revertant mosaicism was associated with milder disease, yet neurological manifestations persisted in 3 individuals. Two carriers also harbored a rare, in trans germ line SAMD9L missense loss-of-function variant, potentially counteracting the SAMD9L mutation. Our results demonstrate that gain-of-function mutations in the tumor suppressor SAMD9L cause cytopenia, immunodeficiency, variable neurological presentation, and predisposition to MDS with 27/del(7q), whereas hematopoietic revertant mosaicism commonly ameliorated clinical manifestations. The findings suggest a role for SAMD9L in regulating IFN-driven, demand-adapted hematopoiesis.
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