Ada Zaccaron

Unlicensed and off‐label uses of drugs in paediatrics: a review of the literature

The off‐label and unlicensed use of drugs to treat children is a common practice that occurs either in hospital or in the community. This derives from the fact that research for establishing drug efficacy and safety in children has not been carried out due to ethical problems, logistical difficulties, financial and legal concerns. In this work we report the studies available in literature documenting the extent of drug use in the paediatric field outside the recommendations of the license. From our analysis, a widespread attitude to prescribe medicines to children outside their product license either in the hospitals or in the community is confirmed. This suggests an immediate action for a more rationale use of drugs in paediatrics, to avoid exposing children and infants to unnecessary risks, but also to avoid depriving them of potentially effective and sometimes life‐saving therapies.

Vincristine-Related Neuropathy Versus Acute Inflammatory Demyelinating Polyradiculoneuropathy in Children With Acute Lymphoblastic Leukemia

The objective of this study was to evaluate whether electroneurography could help in differentiating between vincristine-induced neuropathy and acute inflammatory demyelinating polyradiculoneuropathy. We performed electroneurography in 7 children from September 2006 to March 2009 admitted to receive chemotherapy including vincristine for acute lymphoblastic leukemia, in whom severe acute limb weakness developed, suggesting vincristine-induced neuropathy. Three of 7 patients had electroneurography, suggesting acute inflammatory demyelinating polyradiculoneuropathy. They received intravenous immunoglobulins without discontinuing chemotherapy, and within 10 days their electroclinical conditions improved. Although electroneurography showed only absent F waves, preventing us from reaching a definitive neurophysiological diagnosis of acute inflammatory demyelinating polyradiculoneuropathy, children’s presenting clinical manifestations, their disease course, and rapid and complete recovery after intravenous immunoglobulins argued strongly in its favor. A prompt, correct differential diagnosis of vincristine neuropathy and acute inflammatory demyelinating polyradiculoneuropathy in patients with acute lymphoblastic leukemia receiving vincristine is essential to improve disease outcome and prolong life expectancy.

The prognostic value of biological markers in paediatric Hodgkin lymphoma

BACKGROUND Many biological and inflammatory markers have been proposed as having a prognostic value at diagnosis of Hodgkin lymphoma (HL), but very few have been validated in paediatric patients. We explored the significance of these markers in a large population of 769 affected children. PATIENTS AND METHODS By using the database of patients enrolled in A.I.E.O.P. (Associazione Italiana di Emato-Oncologia Pediatrica) trial LH2004 for paediatric HL, we identified 769 consecutive patients treated with curative intent from 1st June 2004 to 1st April 2014 with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine), or hybrid COPP/ABV (cyclophosphamide, vincristine, prednisone, procarbazine, doxorubicin, bleomycin and vinblastine) regimens. RESULTS On multivariate analysis with categorical forms, the 5-year freedom from progression survival was significantly lower in patients with stage IV or elevated value of platelets, eosinophils and ferritin at diagnosis. Furthermore, stage IV and eosinophils seem to maintain their predictive value independently of interim (after IV cycles of chemotherapy) positron emission tomography. CONCLUSION Using the combination of four simple markers such as stage IV and elevated levels of platelets, ferritin and eosinophils, it is possible to classify the patients into subgroups with very different outcomes.

Immunophenotypic analysis of hematopoiesis in patients suffering from Shwachman-Bodian-Diamond Syndrome.

Shwachman–Diamond syndrome is a rare disorder characterized by exocrine pancreatic insufficiency, skeletal abnormalities, and bone marrow failure, with high risk of leukemic evolution. The aim of the study was the immunophenotypic characterization of bone marrow cells from patients with Shwachman–Diamond syndrome to assess the maturation pathway of blood progenitor cells and to identify the presence of recurrent abnormalities.

Venoocclusive disease due to chemotherapy for pediatric acute lymphoblastic leukemia is associated with increased levels of plasminogen-activator inhibitor-1

We describe three cases of sinusoidal obstruction syndrome/venoocclusive disease (SOS) in pediatric patients with acute lymphoblastic leukemia (ALL). All three episodes occurred during or just after the induction or reinduction phase of treatment based on prednisone/dexamethasone, vincristine, daunorubicin, and pegylated‐l‐asparaginase. SOS episodes were categorized as mild/moderate and resolved in 7, 10, and 16 days using supportive measures or defibrotide therapy. In all three episodes, the clinical diagnosis of SOS was associated with a significant increase in plasminogen‐activator inhibitor‐1 (PAI‐1) that reduced with patient clinical improvement. PAI‐1 warrants study as a diagnostic marker for SOS in ALL.