Hyperglycaemia In Childhood Hematologic Malignancies
Condition: Diabetes Mellitus Risk
MeSH terms: Hyperglycemia
Study type: Observational

Summary: 
      BACKGROUND/AIM: Secondary forms of diabetes are often understudied and underdiagnosed in
      children and adolescents with cancer. The objectives of this cohort study were to study the
      incidence and risk factors for hyperglycaemia in leukaemia and lymphoma patients.

      METHODS: The investigators retrospectively collected 15 years of data from paediatric
      patients treated for acute lymphoblastic leukaemia (ALL), Hodgkin's lymphoma (HL), and
      non-Hodgkin's lymphoma (NHL) immediately at cancer diagnosis. They studied risk factors for
      hyperglycaemia in univariate and multivariate analyses.
    

Detailed description: 
      BACKGROUND:

      Children and adolescents diagnosed with acute lymphoblastic leukaemia (ALL), Hodgkin's
      lymphoma (HL), and non-Hodgkin's lymphoma (NHL) are treated with specific and individual
      chemotherapy protocols sometimes combined with radiotherapy and/or hematopoietic stem cell
      transplant (HSCT). Thanks to research initiatives allowing constant re-evaluation of these
      protocols, survival rate of childhood cancer exceeds 83%. However, the effectiveness of these
      treatments is not without consequences: 50% of childhood cancer survivors (CCS) develop
      endocrine sequelae including metabolic syndrome and glucose metabolism disorders such as
      diabetes, insulin resistance and impaired glucose tolerance (IGT). In the general population,
      diabetes confers a 2 to 3 times increased risk of cardiovascular disease and corresponds to
      12-55% of cases of end-stage renal disease worldwide, being as such the 7th expected leading
      cause of death by 2030.

      In CCS, the incidence of hyperglycaemia is still ill-defined and might range between 11 and
      35% of cases. Moreover, despite the whole body of evidence that asparaginase, steroids and
      total body irradiation increase the risk of developing hyperglycaemia and diabetes, risk
      factors are missing and - asides from treatments - understudied (e.g., pre-existing obesity,
      sex, age, ethnicity, family history of diabetes, etc.).

      AIM:

      DIAB-ONCO. The purpose of this study was to assess the incidence and associated risk factors
      of developing hyperglycaemia in children and adolescents diagnosed with ALL, HL and NHL.
      Deciphering the factors associated with the onset of hyperglycaemia in paediatric patients
      treated for cancer will provide leverage for lifestyle or therapeutic intervention from a
      prevention perspective in newly diagnosed patients.

      INTERVENTION:

      The DIABONCO retrospective study is being carried out in collaboration with the Paediatric
      Haematology and Oncology (Institut Roi Albert II) of Cliniques universitaires Saint-Luc in
      Belgium (Brussels). The local ethical committee (Saint-Luc and UCL Hospital-Faculty Ethics
      Committee) approved this study protocol (approval number 2018/20MAR/122) and the study was
      conducted in accordance with the Declaration of Helsinki.

      This investigation included patients receiving treatment protocols conferring a diabetogenic
      risk. This included total body, cranial and abdominal irradiation (respectively TBI, CI and
      AI), steroids and L-asparaginase. Our cohort was therefore composed of patients treated for
      acute lymphoblastic leukaemia (ALL), Hodgkin's lymphoma (HL) and non-Hodgkin's lymphoma
      (NHL). The patients were stratified according to the presence or absence of hyperglycaemia
      during the treatment protocol and during clinical follow-up, which ended in August 2020. The
      groups were called the " hyperglycaemia-positive ALL, NHL or HL " and the
      "hyperglycaemia-free ALL, NHL or HL".

      INCLUSION and EXCLUSION CRITERIA:

      All children and adolescents aged 0 to 18 years treated with the aforementioned diabetogenic
      treatment protocols and diagnosed at Cliniques universitaires Saint-Luc with ALL, NHL or HL
      between January 2004 and December 2019 were included. Patients with an incomplete file or a
      history of the following conditions were excluded: previous diabetes (i.e., type 1, type 2,
      neonatal or monogenic diabetes), pancreatitis, steatosis, Down syndrome, pancreas and liver
      surgery, kidney disease and previous cancer other than leukaemia and lymphoma.
    

Observational model: Cohort
Time perspective: Retrospective
Sampling method: Probability Sample
Study population: 
        Our cohort was composed of patients treated for acute lymphoblastic leukaemia (ALL),
        Hodgkin's lymphoma (HL) and non-Hodgkin's lymphoma (NHL).