Neutropenia treatment

Anderson, D.R., Holmes, W.W., Lee, R.B., Dalai, S.J., Hurst, C.G., Maimer, B.I., Newmark, J., Smith, W.J. (2006). Sulfur mustard-induced neutropenia treatment with gran-uloc de colony-stimulating factor. Mil. Med. 171 448-53. 

Anderson DR, Holmes WW, Lee RB, Dalai SJ, Hurst CG, Maliner BI, Newmark J, Smith WJ. 2006. Sulfur mustard-induced neutropenia treatment with granulocyte colony-stimulating factor. Mil Med 171 448 53. 

Ghaznavi S, Nakic M, Rao P, Hu J, Brewer JA, Hannestad J, Bhagwagar Z. Rechallenging with clozapine following neutropenia treatment options for refractory schizophrenia. Am J Psychiatry 2008 165(7) 813-8. 

The oxa2ohdinedione trimethadione [127-48-0] C H NO (50), at one time the dmg of choice for the treatment of absence sei2ures, has been replaced by ethosuximide (41) and valproate (49). (50) has a distinct profile from that of phenytoin but causes photophobia and night blindness in approximately 30% of the patients taking it and has the CNS and sedative properties seen for other anticonvulsants together with moderate neutropenia, hepatitis, and skin rashes (13). Trimethadione does not appear to produce its effects via modulation of GABA-mediated responses. 

Capecitabine is used for the treatment of colorectal and breast cancers. It is contraindicated in patients with known hypersensitivity to capecitabine or any of its components or to 5-fluorouracil and in patients with known dihydropyrimidine dehydrogenase (DPD) deficiency. The use of capecitabine is restricted in patients with severe renal impairment. The drag can induce diarrhea, sometimes severe. Other side effects include anemia, hand-foot syndrome, hyperbilirubinemia, nausea, stomatitis, pyrexia, edema, constipation, dyspnea, neutropenia, back pain, and headache. Cardiotoxicity has been observed with capecitabine. A clinically important drag interaction between capecitabine and warfarin has been demonstrated. Care should be exercised when the drag is co-administered with CYP2X9 substrates. 

Decitabine is specifically indicated for the treatment of multiple types of myelodysplastic syndromes and chronic myelomonocytic leukemia. As anticipated, use of decitabine is associated with bone marrow suppression including neutropenia and thrombocytopenia which are the most frequently observed serious adverse effects. 

Neutropenia is a drop in the number of circulating leukocytes, especially neutrophils. It can be induced by a variety of drugs. Treatment with cytotoxic antineo-plastic drags usually results in severe neutropenia, which can be treated with colony-stimulating factors (G-CSF, GM-CSF). 

The drug was subsequently reintroduced for treatment-resistant or treatment-intolerant patients in the UK and USA in 1990. The drug is completely free of extrapyramidal side effects but has to be monitored for the development of neutropenia and agranulocytosis. Other problems include sialorrhoea, sedation, reduction in seizure... 

Immunocompetent patients generally do not require reassessment after treatment. Patients with neutropenia exhibit an increased risk of dissemination of infection, and therefore should be monitored for signs of systemic fungal infection. Due to an increased risk of recurrence, HIV-positive patients should routinely be evaluated for recurrence at each visit. 

Bone marrow suppression ZDV Onset Few weeks to months Symptoms Fatigue, risk of T bacterial infections due to neutropenia anemia, neutropenia 1. Advanced HIV 2. High dose ZDV 3. Preexisting anemia or neutropenia 4. Concomitant use of bone marrow suppressants Avoid in patients with high risk for bone marrow suppression avoid other suppressing agents monitor CBC with differential at least every 3 months Switch to another NRTI D/C concomitant bone marrow suppressant, if possible for anemia Identify and treat other causes consider erythropoietin treatment or blood transfusion, if indicated for neutropenia Identify and treat other causes consider filgrastim treatment, if indicated... 

Lenalidomide was approved recently for the indication of myelodysplastic syndrome where the 5q deletion is present. Since lenalidomide is an analog of thalidomide, all the same precautions must be taken to prevent phocomelia. The time to maximum lenalidomide concentrations occurs 0.5 to 4 hours after the dose. The terminal half-life ranges from 3 to 9 hours. Approximately 65% of lenalidomide is eliminated unchanged in the urine, with clearance exceeding the glomerular filtration rate. To date, no pharmacokinetic studies have been done in patients with renal dysfunction. Lenalidomide is used in the treatment of myelodysplastic syndrome and multiple myeloma. Other side effects are neutropenia, thrombocytopenia, deep vein thrombosis, and pulmonary embolus. 

Neutropenia occurs when the percent of mature neutrophils plus the percent of bands (or immature neutrophils) times the WBC count is less than 500/mm3 (0.5 x 109/L). The risk of infection increases as the extent of neutropenia becomes severe and the duration increases. The assessment of infection is different in the neutropenic cancer patient. First, WBC counts may be profoundly low, so no left shift is available to evaluate. Second, there is no pus without WBCs. Some bacterial pneumonias may not be readily apparent by chest x-ray. Third, if patients are receiving steroids as part of the cancer treatment, fever curves may be blunted or absent. When a patient does have a fever and is neutropenic, prompt initiation of anti-infectives is necessary. 

Fever, rigors, chills, malaise headaches, myalgia Nausea, emesis Neutropenia Hepatic enzyme elevation Cutaneous—alopecia, transient, mild rashlike reaction Acetaminophen (APAP). NSAID if APAP is not effective. Meperidine for severe chills and rigors. Bedtime administration. 5-HT3 antagonist, prochlorperazine, metoclopramide, fluids Weekly complete blood count reduce dose by 30-50% Liver function tests (LFTs) weekly withhold treatment until LFTs normalize restart at 30-50% dose reduction reversible on dose reduction or cessation. Interferon is contraindicated in patients with psoriasis because exacerbation of psoriasis has been noted during IFN therapy. 

O A risk assessment should be performed at presentation of febrile neutropenia to identify low-risk patients for potential outpatient treatment. Patients who do not meet low-risk criteria should be hospitalized for immediate parenteral administration of broad-spectrum antibacterials before culture results are obtained. 

The success of the treatment of febrile neutropenia hinges on the adequate recovery of the absolute neutrophil count and either optimal antimicrobial coverage of identified organisms or empirical coverage of unidentified organisms. 

It is clear that patients with febrile neutropenia represent a heterogeneous group. Some patients are at lower risk and potentially could be treated as outpatients, thereby avoiding the risk and cost of hospitalization. The Multinational Association for Supportive Care in Cancer (MASCC) has validated a risk-assessment tool that assigns a risk score to patients presenting with febrile neutropenia7 (Table 96-3). Patients with a risk-index score of 21 or greater are identified as low risk and are candidates for outpatient therapy (discussed under Treatment ). 

The CSFs should not be used routinely for treatment of febrile neutropenia in conjunction with antimicrobial therapy.5 However, the use of CSFs in certain high-risk patients with hypotension, documented fungal infection, pneumonia, or sepsis is reasonable. A recent meta-analysis demonstrated that hospitalization and neutrophil recovery are shortened and that infection-related mortality is marginally improved.14 As with prophylactic use of these agents, cost considerations limit their use to high-risk patients. 

For patients receiving oral antibiotics either prophylacti-cally or as treatment of febrile neutropenia, counsel them that initial or persistent fever should be reported promptly and that compliance with the regimen is critical. Patients also should have easy access to medical care and adequate caregiver support. Provide information on drug interactions and adverse effects. 

Lyman GH, Kuderer NM. The economics of the colony-stimulating factors in the prevention and treatment of febrile neutropenia. Crit Rev Oncol Hematol 2004 50 129-146. 

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