Neutropenia in cancer patients

G. Other applications Leukine has been effective in producing increases in normally functioning neutrophils, eosinophils, and monocytes in AIDS patients and patients with leukopenia. Leukine may prolong survival when used as adjuvant therapy in patients with stage III or IV malignant melanoma. Leukine has also been effective in abrogating chemotherapy-related neutropenia in cancer patients, with a reduction in the severity and duration of chemotherapy-induced myelosuppression. 

A key controversy in the management of febrile neutropenia in cancer patients is the optimal time to stop empirical antimicrobial therapy in patients who remain persistently febrile. Patients individual risk of severe infection (determined by extent and duration of neutropenia, as well as other risk factors) helps to guide treatment decisions in this setting. 

A-II, were identified. Protein expression profiles determined by MS are thus useful for idenfilying treatment-responsive proteins [25], Toxicity can be severe in case of chemotherapy. MS-based techniques may also be applied to reduce side effects. A study evaluated the association between exposure to unbound docetaxel and neutropenia in cancer patients and identified factors influencing unbound docetaxel clearance. Pharmacokinetic studies and toxicity assessments were performed during the first cycle of therapy. Total docetaxel concentrations were determined by HPLC-MS-MS. The authors conclude that as exposure to unbound docetaxel is closely related to drug-induced hematologic toxicity, this needs to be considered in future pharmacological investigations [26]. 

Malik lA, Mold 1, Aziz Z, Khan S, Suleman M. A randomized comparison of fluconazole with amphotericin B as empiric anti-fungal agents in cancer patients with prolonged fever and neutropenia. Am J Med 1998 105(6) 478-83. 

Johansen HK, Gotzsche PC. Amphotericin B lipid soluble formulations vs amphotericin B in cancer patients with neutropenia. Cochrane Database Syst Rev 2000 CD000969. 

In mnrine studies, quinolones have been effective in controlling endogenous gramnegative systemic infections following radiation. Qninolones are also effective in preventing endogenous Klebsiella and Psendomonas infections. In addition, penicillin snpplementation has prevented treatment failnres in cancer patients with treatment-induced neutropenia (2). 

Consensus guidelines provide useful information regarding the management of febrile episodes in cancer patients with neutropenia. However, therapy (including initial empirical regimens, modifications, and duration of treatment) must be individuahzed based on individual patient parameters and response to therapy. 

Owing to the potential morbidity and mortality of infections in neutropenic cancer patients, measures have been taken to prevent these complications through a number of environmental modifications and prophylactic antimicrobial regimens. The goal of antimicrobial prophylaxis in cancer patients is to decrease the number and severity of systemic infections during prolonged periods of neutropenia. Decisions regarding prophylactic antimicrobials must be made with the realization of associated issues, such as resistance concerns. 

Pizzo PA, Hathorn JW, Hiemenz J, et al. A randomized trial comparing ceftazidime alone with combination antibiotic therapy in cancer patients with fever and neutropenia. N Engl J Med 1986 315 552-558. 

Administration of the probiotic E. faecium strain probably leads to the competition with and elimination of pathogenic bacteria from the intraepithelial niche. Therefore it can be considered that application of non-pathogenic E. faecium can be a promising method for elimination of pathogenic bacteria in the case of inflammatory bowel disease and colon cancer. The same strain of E. faecium was nsed also for the prevention of febrile neutropenia in lenkemic patients. Tolerance of therapy was excellent without significant adverse effects. However, the administration of the enterococcal strain was not effected in the prevention of febrile neutropenia bnt no febrile episode or infection provoked by the probiotic strain E. faecium was noticed (Mego et al. 2005a, 2006). 

Clinical use and toxicity Interferon alpha is approved for use in chronic hepatitis A and B infections, Kaposi s sarcoma, papillomatosis, and topically for genital warts. Another possible use of interferons is to prevent herpes zoster vims dissemination in cancer patients. Toxic effects include dose-limiting neutropenia, gastrointestinal irritation, fatigue, myalgia, mental confusion, and a reversible cardiomyopathy. 

G. MoUneux, PEGfilgrastim using PEGylation technology to improve neutropenia support in cancer patients. Anticancer Drugs 14 (2003) 259-264. 

Aapro MS, Bohlius J, Cameron DA, Dal Lago L, DonneUy JP, Kearney N, et al. 2010 update of EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphoproUferative disorders and solid tumours. Eur J Cancer 2011 47(l) 8-32. 

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. 

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 ). 

Neutropenia is a condition characterized by a decrease in blood neutrophil count below 1.5 X 109 cells per litre a normal blood count is (2.0-7.5) X 109 cells per litre. Its clinical symptoms include the occurrence of frequent and usually serious infections, often requiring hospitalization. Neutropenia may be caused by a number of factors (Table 10.6), at least some of which are responsive to CSF treatment. Particularly noteworthy is neutropenia triggered by administration of chemotherapeutic drugs to cancer patients. Chemotherapeutic agents (e.g. cyclophosphamide, doxorubicin and methotrexate), when administered at therapeutically effective doses, often induce the destruction of stem cells and/or compromise stem cell differentiation. 

Neulasta, Pegfilgrastim, G-CSF-PEG Amgen, Inc. Infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelo-suppressive anti-cancer drugs Jan. 2002... 

Unlabeled uses Lithium carbonate (300 to 1,000 mg/day) has improved the neutrophil count in patients with cancer chemotherapy-induced neutropenia, in children with chronic neutropenia, and in AIDS patients receiving zidovudine. 

---