By phenotypic analysis of affected relatives and carriers of the same ELA2 mutations, we showed that the expression of neutropenia in CN and SCN may be either homogeneous or variable according to the type of mutations, suggesting different pathogenetic mechanisms.
We therefore screened GFI1 as a candidate for association with neutropenia in affected individuals without mutations in ELA2 (encoding neutrophil elastase), the most common cause of severe congenital neutropenia (SCN; ref.3).
All cases of cyclic neutropenia and most cases of severe congenital neutropenia result from heterozygous germline mutations in the gene encoding neutrophil elastase, ela2.
These data demonstrate that impaired survival of bone marrow myeloid progenitor cells, probably driven by expression of mutant NE, is the cellular mechanism responsible for neutropenia in SCN.
The patient extends the clinical variability associated to JAGN1 mutations, and this case highlights the importance of genetic investigations in patients with suspected neutropenia.
We evaluated a retrospective cohort of 228 adult lung transplant recipients between 2008 and 2013 to assess the association of neutropenia and granulocyte colony-stimulating factor (GCSF) treatment with outcomes.
The review concludes with the roles that the UGT1A1*28 and UGT1A1*6 alleles play in adverse drug reactions (decreased glucuronidation of irinotecan, belinostat, atazanavir, pegvisomant) leading to increased exposure, reduced clearance and neutropenia (irinotecan, belinostat), increased risk for jaundice and hyperbilirubinaemia (atazanavir) and liver toxicity (pegvisomant) before discussing the future role of UGT1A1 in personalised medicine.
Chemotherapy delays due to neutropenia and leukopenia were significantly decreased among patients that received G-CSF (OR 0.098, 95% CI 0.06-0.15 and OR 0.32, 95% CI 0.18-0.58, respectively).<b>Discussion:</b> In conclusion, G-CSF support reduces neutropenic events and permits increased relative dose intensity, which is essential for improved survival outcomes.
Granulocyte colony-stimulating factor (G-CSF) is widely used for prophylaxis and treatment of neutropenia in cancer patients and also for peripheral blood stem cells (PBSC) mobilization.
Patients with WHIM syndrome are often treated with granulocyte colony-stimulating factor (G-CSF), which can increase neutrophil counts but does not affect cytopenias other than neutropenia.
CYP2C8*3 was significantly associated with increased risks of severe (grades 3-4) neutropenia (OR<sub>adjusted</sub> 2.11; 95% CI 1.24-3.6; dominant model) and severe thrombocytopenia (OR<sub>adjusted</sub> 4.93; 95% CI 1.69-14.35; recessive model), whereas ABCB1 variant genotypes (OR<sub>adjusted</sub> 2.13; 95% CI 1.32-3.42), in association with CYP2C8*3 wild type (GG) (OR<sub>adjusted</sub> 1.93; 95% CI 1.17-3.19), were predictive of severe fatigue.
Treatment with recombinant human granulocyte-colony stimulating factor (G-CSF) is accepted standard for prevention of chemotherapy-induced neutropenia.
Current guidelines (GL) recommend neutropenia prophylaxis with G-CSF after chemotherapy (CTX) for patients with high (≥ 20%), or, if additional risk factors are present, intermediate (≥ 10-20%) risk of febrile neutropenia.