Myelosuppression, chemotherapy-induced

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. 

Neutropenia is a common adverse effect of the cytotoxic drugs used to treat cancer and increases the risk of serious infection in patients receiving chemotherapy. Unlike the treatment of anemia and thrombocytopenia, transfusion of neutropenic patients with granulocytes collected from donors is performed rarely and with limited success. The introduction of G-CSF in 1991 represented a milestone in the treatment of chemotherapy-induced neutropenia. This growth factor dramatically accelerates the rate of neutrophil recovery after dose-intensive myelosuppressive chemotherapy (Figure 33-5). It reduces the duration of neutropenia and usually raises the nadir count, the lowest neutrophil count seen following a cycle of chemotherapy. 

The authors of a study in 101 patients concluded that in addition to the dose of chemotherapy and the administration of hemopoietic growth factors, poor performance status and a high concentration of soluble p75-R-TNF can predict the occurrence of chemotherapy-induced myelosuppression in lymphoma (39). 

Voog E, Bienvenu J, Warzocha K, Moullet I, Dumontet C, Thieblemont C, Monneret G, Gutowski MC, Coiffier B, Salles G. Factors that predict chemotherapy-induced myelosuppression in lymphoma patients role of the tumor necrosis factor ligand-receptor system. J Clin Oncol 2000 18(2) 325-31. 

There were no major differences in the adverse effect profiles in 42 patients with breast cancer randomized to filgrastim (G-CSF) or molgramostim (GM-CSF) (SEDA-22, 407). There were no significant differences in the adverse effects profiles and severity of adverse effects in 181 patients with cancers randomized to receive filgrastim (G-CSF) or sargramostim (GM-CSF) for chemotherapy-induced myelosuppression (6). 

Oprelvekin has thrombopoietic activity and has been licensed to prevent severe thrombocytopenia and reduce the need for platelet transfusion after myelosuppressive chemotherapy (1). Common adverse effects included myalgia and arthralgias, fatigue, headache, and conjunctival injection. Peripheral edema, dyspnea, pleural effusions, tachycardia, and anemia were supposedly the result of oprelvekin-induced fluid retention (SEDA-20, 336) (SEDA-21, 376). Atrial flutter or fibrillation were sometimes noted. 

L. E. Friberg, A. Henningsson, H. Maas, L. Nguyen, and M. O. Karlsson, Model of chemotherapy-induced myelosuppression with parameter consistency across drugs. J Clin Oncol 20 4713 721 (2002). 

Myelosuppressant chemotherapy, in bone marrow transplantation, to reduce length of drug-induced neutropenia (aplastic anemia, hairy cell leukemia, AIDS)... 

Oprelvekin is an interleukin. Interleukin 11 (lL-11) is a thrombopoietic growth factor that directly stimulates the proliferation of hematopoietic stem cells and megakaryocyte progenitor cells and induces megakaryocyte maturation, resulting in increased platelet production. It prevents severe thrombocytopenia and reduces the need for platelet transfusions following myelosuppressive chemotherapy in patients with nonmyeloid malignancies. 

A 52-year-old woman with chemotherapy-induced myelosuppression took voriconazole 400 mg twice per day for suspected IPA. Four days after voriconazole therapy, the patient developed arrhythmias followed by... 

Oxidative stress reduces the rate of cell proliferation, and that occurring during chemotherapy may interfere with the cytotoxic effects of antineoplastic drugs, which depend on rapid proliferation of cancer cells for optimal activity. Antioxidants detoxify ROS and may enhance the anticancer effects of chemotherapy. For some supplements, activities beyond their antioxidant properties, such as inhibition of topoisomerase II or protein tyrosine kinases, may also contribute. ROS cause or contribute to certain side effects that are common to many anticancer drugs, such as gastrointestinal toxicity and muagenesis. ROS also contribute to side effects that occur only with individual agents, such as doxorubicin-induced cardiotoxicity, cisplatin-induced nephrotoxicity, and bleomycin-induced pulmonary fibrosis. Antioxidants can reduce or prevent many of these side effects, and for some supplements the protective effect results from activities other than their antioxidant properties. Certain side effects, however, such as alopecia and myelosuppression, are not prevented... 

Dercksen MW, Hoekman K, ten Bokkel Huinink WW, Rankin EM, Dubbelman R, van Tinteren H, Wagstaff J, Pinedo HM. Effects of interleukin-3 on myelosuppression induced by chemotherapy for ovarian cancer and small cell undifferentiated tumours. Br J Cancer 1993 68(5) 996-1003. 

Prior myelotoxic chemotherapy and/or radiotherapy appear to be major risk factors in determining the severity of neutropenia (1,13). Doses of 200 and 250 mg/m over short infusion times induce minimal myelosuppression in patients who have had minimal prior therapy (26,30) however, seven patients (1.6%) died because of toxicity in another trial in patients with ovarian cancer who had received extensive previous chemotherapy deaths were due to sepsis or severe neutropenia (13). 

A type B ADR encountered with a number of drugs from varying classes of therapeutic agents is drug-induced myelosuppression. Although myelosuppression is an accepted type A ADR of cytotoxic chemotherapy, type B ADR class of myelosuppression is usually far more insidious and may occur up to several months following the last course of drug therapy. 

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