Publications by authors named "Hasle H"

Purpose: The aim was to assess the feasibility of a randomized controlled exercise intervention, including physical assessments, in children and adolescents during the first 6 months of cancer treatment.

Materials And Methods: A sample of children and adolescents (n = 84, 6‒17.9 years) from an ongoing trial (INTERACT: NCT04706676) was randomly assigned to an integrative neuromuscular training (INT) intervention or active control intervention during treatment.

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  • Several genomic subsets of mutations in acute myeloid leukemia (AML) patients were studied to understand their impact on outcomes and the underlying biology, revealing that type D mutations correlated with poorer survival rates compared to other types.
  • In a cohort of over 4,000 patients, a study found that those with type A, B, and rare variants had more favorable overall survival rates, while type D patients exhibited significantly worse outcomes.
  • The research highlighted that codon optimality in type D mutations affects gene expression and translation efficiency, leading to poorer prognostic implications and indicating the need for a potential reclassification of type D patients to higher-risk groups.
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Delayed neutrophil recovery during acute lymphoblastic leukemia (ALL) treatment increases risk of infection and causes delay in chemotherapy. Emerging evidence implicates the gut microbiota in neutrophil reconstitution after chemotherapy. We explored the interplay between the gut microbiota and neutrophil dynamics, including neutrophil chemoattractants, in 51 children with newly-diagnosed ALL.

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  • Acute myeloid leukemia (AML) with the t(7;12) translocation is common in infants and has been recognized by the WHO, although the exact mechanism behind its development is unclear.
  • A study of 12 pediatric AML cases with this translocation found no significant difference in survival rates compared to other AML types, but noted a consistent high expression of MNX1 across all cases.
  • Whole transcriptome and genome sequencing revealed various fusion transcripts, primarily involving NOM1, but emphasized the importance of MNX1's overexpression as the key driving factor in this AML subtype.
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  • Researchers studied how surviving childhood leukemia (ALL) might affect mental health as kids grow up.
  • They looked at almost 2,000 survivors and compared them to their siblings and other kids to see who had more psychiatric problems by age 30.
  • They found that survivors had a slightly higher chance of mental health issues, especially those who had serious treatments, but overall, the risks were similar to their siblings and friends.
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Objectives: Childhood cancer often presents with non-specific signs and symptoms that might mimic non-malignant disorders including musculoskeletal diseases, potentially leading to rheumatic and orthopaedic misdiagnoses. We aimed to compare clinical presentation, diagnostic interval and survival in paediatric acute myeloid leukaemia (AML) with and without initial musculoskeletal symptoms.

Methods: This nationwide retrospective, cohort study reviewed medical records of 144 children below 15 years diagnosed with AML in Denmark from 1996 to 2018.

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The treatment of childhood cancer is challenged by toxic side effects mainly due to chemotherapy-induced organ damage and infections, which are accompanied by severe systemic inflammation. Insulin-like growth factor I (IGF-I) is a key regulating factor in tissue repair. This study investigated associations between the circulating IGF-I levels and chemotherapy-related toxicity in pediatric acute lymphoblastic leukemia (ALL).

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Because of the low mutational burden and consequently, fewer potential neoantigens, children with acute myeloid leukemia (AML) are thought to have a T cell-depleted or 'cold' tumor microenvironment and may have a low likelihood of response to T cell-directed immunotherapies. Understanding the composition, phenotype, and spatial organization of T cells and other microenvironmental populations in the pediatric AML bone marrow (BM) is essential for informing future immunotherapeutic trials about targetable immune-evasion mechanisms specific to pediatric AML. Here, we conducted a multidimensional analysis of the tumor immune microenvironment in pediatric AML and non-leukemic controls.

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Cisplatin and amphotericin B are both known to be potentially nephrotoxic. We describe acute kidney injury due to the combination of Liposomal amphotericin B and cisplatin in an adolescent with osteosarcoma. Acute kidney injury (peak creatinine 431 µmol/L) consistent with drug-induced acute tubulointerstitial nephritis was observed a few days after concomitant administration of cisplatin and amphotericin B.

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Background: Hereditary anemias are a group of genetic diseases prevalent worldwide and pose a significant health burden on patients and societies. The clinical phenotype of hereditary anemias varies from compensated hemolysis to life-threatening anemia. They can be roughly categorized into three broad categories: hemoglobinopathies, membranopathies, and enzymopathies.

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Background: Childhood tumors in the central nervous system (CNS) have longer diagnostic delays than other pediatric tumors. Vague presenting symptoms pose a challenge in the diagnostic process; it has been indicated that patients and parents may be hesitant to seek help, and health care professionals (HCPs) may lack awareness and knowledge about clinical presentation. To raise awareness among HCPs, the Danish CNS tumor awareness initiative hjernetegn.

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Therapy-related myeloid neoplasms (t-MN) arise as a complication of chemo- and/or radiotherapy. Although t-MN can occur both in adult and childhood cancer survivors, the mechanisms driving therapy-related leukemogenesis likely vary across different ages. Chemotherapy is thought to induce driver mutations in children, whereas in adults pre-existing mutant clones are selected by the exposure.

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Treatment of relapsed and refractory myeloid leukemia in Down syndrome (r/r ML-DS) poses significant challenges, as prognosis is dire and there is no established standard treatment. This guideline provides treatment recommendations based on a literature review and collection of expert opinions, aiming to improve overall and event-free survival of patients. Treatment options include fludarabine and cytarabine (FLA) ± gemtuzumab ozogamicin (GO), azacytidine (AZA) ± panobinostat, and hematopoietic stem cell transplantation (HSCT).

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Ataxia-telangiectasia (A-T) is an autosomal-recessive disorder caused by pathogenic variants (PVs) of the ATM gene, predisposing children to hematological malignancies. We investigated their characteristics and outcomes to generate data-based treatment recommendations. In this multinational, observational study we report 202 patients aged ≤25 years with A-T and hematological malignancies from 25 countries.

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Background: Diagnostic delays in childhood tumors of the central nervous system (CNS) pose a significant challenge. The aim of this study was to map diagnostic delay and presenting symptoms in Denmark.

Methods: The study was a retrospective questionnaire study, mapping delay and symptoms in pediatric patients (0-17 years), diagnosed with a CNS tumor from 2015 to 2019.

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Autoimmune neutropenia (AIN) in early childhood is characterized by chronic neutropenia and positivity for human neutrophil antibodies (HNA), resulting in the excessive destruction of neutrophils. The association between regulatory T cells (Tregs) and AIN has been described, and in this study, we investigated three Treg-associated genes, IL-2, IL-10 and FOXP3. The frequencies of three single nucleotide polymorphisms (SNPs) in IL-2 -330T>G (rs2069762), +114G>T (rs2069763) and IVS3-116 A>G (rs2069772), four SNPs in IL-10 -3575T>A (rs1800890), -1082G>A (rs1800896), -819 C>T (rs1800871) and -592 C>A (rs1800872) and three SNPs in FOXP3 -3499 A>G (rs3761547), -3279 C>A (rs3761548) and -924 A>G (rs2232365) were compared between 166 Danish AIN patients and 358 healthy controls.

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Hyperleukocytosis in pediatric acute myeloid leukemia (AML) is associated with severe complications and an inferior outcome. We report results on patients with hyperleukocytosis included in the NOPHO-DBH AML 2012 study. We recommended immediate initiation of full-dose chemotherapy (etoposide monotherapy for 5 days as part of the first course), avoiding leukapheresis and prephase chemotherapy.

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Objective: Childhood spinal tumors often present with musculoskeletal symptoms, potentially causing a misdiagnosis and delays in diagnosis and treatment. This study aims to identify, characterize, and compare children with spinal tumors who had prior musculoskeletal misdiagnoses to those without, analyzing clinical presentation, diagnostic interval, and outcome.

Study Design: This retrospective cohort study evaluated all children aged 0-14 years diagnosed with a spinal tumor in Denmark from 1996 to 2018.

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  • A phase 3 trial was conducted to evaluate the efficacy and safety of mavorixafor, an oral medication, in individuals with WHIM syndrome, a rare immunodeficiency disorder caused by genetic mutations.
  • Participants were randomly assigned to receive either mavorixafor or a placebo for 52 weeks, with the study focusing on the time above certain white blood cell counts as the primary endpoint.
  • Results showed mavorixafor significantly increased white blood cell counts, reduced infection rates and severity, and was well tolerated without serious adverse events occurring during the study.
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  • * Three new recurring KMT2A-rearranged groups were identified, and a significant variation in 5-year event-free survival rates was observed across 13 different groups, highlighting the impact of genetic factors on patient outcomes.
  • * The research suggests incorporating five specific adverse-risk KMT2A fusions into current risk stratification models and calls for further studies to confirm the associations
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Purpose: Measurable residual disease (MRD) by using flow cytometry after induction therapy is strongly prognostic in pediatric AML, and hematopoietic stem-cell transplant (hSCT) may counteract a poor response. We designed a phase III study with intensified response-guided induction and MRD-based risk stratification and treated poor induction response with hSCT. The efficacy of liposomal daunorubicin (DNX) in induction was compared with mitoxantrone.

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Importance: There is some evidence that tooth agenesis (congenital absence of 1 or more teeth) is associated with cancer risk, especially carcinomas of the colon and ovaries, but results of previous studies are conflicting, and associations have not yet been evaluated in a population-based setting.

Objective: To examine the association between tooth agenesis and specific cancer types before 40 years of age.

Design, Setting, And Participants: This population-based cohort study used linking data from nationwide registries in Denmark to assess all Danish live-born singletons born from January 1, 1977, to December 31, 2018, and followed up for up to 40 years.

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HLA studies in patients with autoimmune neutropenia (AIN) have shown very consistent results for the association with HLA class II alleles at low resolution. This study aimed to examine the association of both HLA class I and class II at high resolution to clarify the contribution of risk alleles to the disease. A total of 107 AIN patients were genotyped for six loci of HLA class I (HLA-A, -B and -C) and class II (HLA-DRB1, -DQB1, and -DPB1) genes by a high-resolution (3-field, 6-digit) analysis and compared with HLA typing of 1000 healthy controls.

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Primary bone tumors in children and adolescents, while rare, pose significant challenges in diagnosis and management. Children treated for Ewing sarcoma and osteosarcoma are offered a 5-year follow-up program after end of treatment, including radiological surveillance of primary location of tumor and the lungs. There is no consensus regarding how often and how the children should be followed with radiological imaging.

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