Disease relevance of Neutropenia

• In the 1500-mg zidovudine group, severe hematologic toxicity (anemia or neutropenia) was more frequent than in the other groups (P less than 0.0001) [1].
• Amphotericin B is used increasingly in high-risk patients with profound neutropenia and suspected sepsis [2].
• Grade 3 or 4 mucositis, grade 4 neutropenia, and neutropenic fever were less frequent during treatment with irinotecan, fluorouracil, and leucovorin [3].
• Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been shown to shorten the duration of neutropenia and decrease infectious complications when administered after chemotherapy to patients with lymphomas and solid tumors [4].
• Liposomal amphotericin B for empirical therapy in patients with persistent fever and neutropenia. National Institute of Allergy and Infectious Diseases Mycoses Study Group [5].

Psychiatry related information on Neutropenia

• Cohen syndrome is a rare autosomal recessive disorder with a variable clinical picture mainly characterized by developmental delay, mental retardation, microcephaly, typical facial dysmorphism, progressive pigmentary retinopathy, severe myopia, and intermittent neutropenia [6].
• Trial results demonstrated amifostine had no significant effect on oncolytic efficacy, but side effect profiles improved for febrile neutropenia (absolute risk reduction [ARR] 11%), neurotoxicity (ARR 11%), and nephrotoxicity (ARR 26%) [7].
• We report a 2-year experience with olanzapine treatment (20 mg daily) in a 65-year-old male patient with treatment-resistant paranoid schizophrenia, who had previously developed leucopenia and neutropenia first on clozapine and, subsequently, also on risperidone [8].
• Investigation of patients with GSD I shows that those with GSD Ia are mutated in the glucose-6-phosphate hydrolase gene, whereas those diagnosed as GSD Ib, GSD Ic or GSD Id are mutated in the glucose-6-phosphate translocase gene, and are therefore GSD Ib patients, in agreement with the fact that they all have neutropenia or neutrophil dysfunction [9].
• Toxicity associated with raltitrexed comprised grade 1/2 diarrhoea (31.6% of treatment cycles), nausea (12.4%) and vomiting (8.4%), with no grade 3/4 events; grade 1/2 alopecia (17.9%); grade 1 (only) stomatitis (2.3%) and grade 1/2/3 lethargy (70.3%, only 2.3% grade 3), anaemia (14.3%, only 0.3% grade 3) and neutropenia (3.3%, only 0.3% grade 3) [10].

High impact information on Neutropenia

• Mutations in proto-oncogene GFI1 cause human neutropenia and target ELA2 [11].
• Inflammatory reactions and severe neutropenia in mice lacking the transcriptional repressor Gfi1 [12].
• Severe infections and neutropenia were more frequent with fludarabine than with chlorambucil (P=0.08), although, overall, toxic effects were tolerable with the two single-drug regimens [13].
• BACKGROUND: In patients with persistent fever and neutropenia, amphotericin B is administered empirically for the early treatment and prevention of clinically occult invasive fungal infections [5].
• Liposomal amphotericin B for fever and neutropenia [14].

Chemical compound and disease context of Neutropenia

• Of 550 evaluable episodes of fever and neutropenia, 282 were treated with ceftazidime alone and 268 with the combination [15].
• Treatment was discontinued in 11 ganciclovir recipients and 1 placebo recipient because of neutropenia (P = 0.003) [16].
• Lithium carbonate in chemotherapy-induced neutropenia [17].
• When the patients who actually received the escalated doses of doxorubicin were compared with the patients in the s-BACOP group in whom neutropenia did not develop during the first treatment cycle, no difference between their outcomes was observed [18].
• The reduced daily dose of zidovudine used in this study was at least as effective as the standard dose and was less toxic; however, with the use of a four-week induction period with a high dose followed by low-dose treatment, severe anemia and neutropenia were common complications of treatment with zidovudine [19].
• The UGT1A1*28/*28 genotype was associated with an increased risk of neutropenia not only at medium or high doses of irinotecan but also at low doses [20].

Biological context of Neutropenia

• Autosomal dominant mutations of ELA2, encoding the protease neutrophil elastase, found in lysosome-like granules, cause cyclic hematopoiesis and most cases of the pre-leukemic disorder severe congenital neutropenia (SCN; ref. 3) in humans [21].
• However, rhG-CSF caused neutrophilia, prevented the recurrent neutropenia and, in the two animals not developing antibodies to rhG-CSF, obliterated periodic fluctuation of monocyte, eosinophil, reticulocyte, and platelet counts [22].
• Aerosolized amphotericin B inhalations as prophylaxis of invasive aspergillus infections during prolonged neutropenia: results of a prospective randomized multicenter trial [23].
• Four of 28 patients with congenital neutropenia displayed a point mutation in the tested cytoplasmic region of the G-CSF receptor gene [24].
• In conclusion, neutropenia and defective chemotaxis did not result in severe clinical infection in SDS [25].

Anatomical context of Neutropenia

• Previous studies have suggested that recombinant methionyl granulocyte colony-stimulating factor (G-CSF) can reduce chemotherapy-related neutropenia in patients with cancer [26].
• The principal toxic reaction was neutropenia; 11 ganciclovir recipients had an absolute neutrophil count below 0.75 x 10(9) per liter, as compared with 3 placebo recipients (P = 0.052) [16].
• Increase in Candida krusei infection among patients with bone marrow transplantation and neutropenia treated prophylactically with fluconazole [27].
• Cells from rheumatoid arthritis patients without neutropenia, cells from patients with drug-induced neutropenia without rheumatoid arthritis, or plasma from FS patients failed to suppress the colony forming unit in culture [28].
• Two patients with classic rheumatoid arthritis developed severe neutropenia and increased numbers of large granular lymphocytes in the blood and bone marrow [29].

Gene context of Neutropenia

• Granulocyte colony-stimulating factor (GCSF) is the principal growth factor regulating the maturation, proliferation and differentiation of the precursor cells of neutrophilic granulocytes and is used to treat neutropenia [30].
• In approximately 20% of cases of severe congenital neutropenia (SCN), mutations are found in the gene encoding the granulocyte colony-stimulating factor receptor (G-CSF-R) [31].
• Cohen syndrome is an autosomal recessive condition associated with developmental delay, facial dysmorphism, pigmentary retinopathy, and neutropenia [32].
• In summary, gibbon IL-3 is a growth factor that can synergize with other CSFs to enhance proliferation of myeloid-committed progenitors, suggesting that combinations of CSFs may have clinical utility in patients with neutropenia of various etiologies [33].
• Recently, we described a case of severe neonatal alloimmune neutropenia (NAIN) caused by an alloantibody against a variant of the CD11b subunit (Mart alloantigen) [34].

Analytical, diagnostic and therapeutic context of Neutropenia

• We measured the number of days of neutropenia, rate of hospitalization, number of days in the hospital, number of days the patient received parenteral antibiotics, and number of culture-positive infections [35].
• In six such patients, the incidences and duration of neutropenia and thrombocytopenia were greater than in 25 similar allograft recipients treated with azathioprine alone [36].
• Host risk factors include diabetes mellitus, neutropenia, sustained immunosuppressive therapy, chronic prednisone use, iron chelation therapy, broad-spectrum antibiotic use, severe malnutrition, and primary breakdown in the integrity of the cutaneous barrier such as trauma, surgical wounds, needle sticks, or burns [37].
• Our study demonstrates that substitution of prostacyclin for heparin in doses that do not cause hypotension, does not prevent neutropenia or alter the diminished neutrophil adhesiveness that occurs during heparin hemodialysis [38].
• A patient with well documented cyclic neutropenia (CN) was given chronic lithium therapy as well as a short course of plasmapheresis with therapeutic intention [39].

References