Thrombocytopenia chemotherapy-induced

Neumega Oprelvekin Genetics Institute Prevention of severe chemotherapy-induced thrombocytopenia... 

Severe thrombocytopenia and reduction of the need for platelet transfusions Chemotherapy-induced thrombocytopenia Nov. 1997... 

Neumega (rIL-11) Approved (1997) Prevention of chemotherapy-induced thrombocytopenia Genetics Institute... 

F. Role in therapy According to Micro-medex, treatment of severe chemotherapy-related thrombocytopenia is hmited to platelet transfusions. There is a need for an alternative, especially due to the frequent use of myeloid colony-stimulating factors (G-CSF, GM-CSF) to reduce febrile neutropenia although effective, their use increases the risk of acute and prolonged thrombocytopenia, and the need for platelet transfusions. Other cytokines, such as interleukin-1 and interleukin-6, have been investigated as a means of ameliorating chemotherapy-induced thrombocytopenia, but results have been equivocal. 

G. Other considerations Recombinant human oprelvekin has been designated an orphan product for use in the prevention of chemotherapy-induced thrombocytopenia. 

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. 

Issac C, Robert NJ, Bailey FA, Schuster MW, et al. 1997. Randomized placebo-controlled study of recombinant human interleukin 11 to prevent chemotherapy induced thrombocytopenia in patients with breast cancer receiving dose-intensive cyclophosphamide and doxorubicin. J Clin Oncol. 15 3368-3377. 

Recombinant thrombopoietin is still an investigational agent. The primary focus of current clinical trials is for the treatment of chemotherapy-induced thrombocytopenia and thrombocytopenia accompanying hematologic stem cell transplantation. Other trials are looking into the possibility of administering thrombopoietin to normal donors in order to increase the number of cells recovered by platelet apheresis. Approval of the latter application will require that thrombopoietin be shown to have an excellent short- and long-term safety profile. 

Vadhan-Raj S. Clinical experience with recombinant human thrombopoietin in chemotherapy-induced thrombocytopenia. Semin Hematol 2000 37(2 Suppl 4) 28-34. 

Renal cell carcinoma Prevention of chemotherapy-induced thrombocytopenia Hepatitis B prevention Vaccination of infants against H. influenzae type B and hepatitis B... 

Neumega (rIL-11, lacks N-terminal proline of native human molecule produced in E. coli) Genetics Institute prevention of chemotherapy-induced thrombocytopenia 1997 (US)... 

Kaye, J.A. 1998. FDA licensure of NEUMEGA to prevent severe chemotherapy-induced thrombocytopenia. Stem Cells 16, 207-223. 

Items 9-10 After undergoing surgery for breast cancer, a 53-year-old woman is scheduled to receive four cycles of cancer chemotherapy. The cycles are to be administered every 3-5 weeks. Her first cycle was complicated by severe chemotherapy-induced thrombocytopenia. 

Persistent or recurrent cutaneous T-cell lymphoma Prevention of severe chemotherapy-induced thrombocytopenia Moderate to severe active rheumatoid arthritis Moderate to severe active rheumatoid arthritis Anemia related to AZT therapy in HIV-infected patients Anemia associated with chronic renal failure... 

The overriding conclusion from murine models of chemotherapy workis that it is very difficult to obtain a reliable neutropenia of sustained duration in mice, without unacceptable systemic toxicity. The relevance of the models to the human situation is, therefore, opentoquestion.lt is evident that the effects of rhMIP-laand BB-10010 on chemotherapy-induced neutropenia and thrombocytopenia in the mouse are erratic because of the practical difficulties experienced with these animal models. They suggest that a study on human patients would be the best way of advancing knowledge in the area of hematopoietic stem cell protection. 

Vermes A, Guchelaar HJ, Dankert J. Prediction of flucytosine-induced thrombocytopenia using creatinine clearance. Chemotherapy 2000 46(5) 335 1. 

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. 

Thrombopoietin is an endogenous colony-stimulating factor that increases the number of megakaryocyte colonies in bone marrow and also induces maturation of megakaryocytes (1). Recombinant thrombopoietin is indicated for correction of thrombocytopenia, induced by chemotherapy or radiotherapy (1). It has been tested in subcutaneous doses up to 5 micrograms/kg/day, resulting in increased numbers of platelets at 7 days, with a peak count at 17 days (1). 

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. 

Adachi JD, Bensen WG, Kassam Y el al (1987) Gold induced thrombocytopenia 12 cases and a review of the literature. Semin Arthritis Rheum 16 287-293 Andersohn F, Konzen C, Garbe E (2007) Non-chemotherapy dmg-induced agranulocytosis a systematic review of case reports. Ann Intern Med 146 657-665 Andres E, Maloisel F (2008) Idiosyncratic drug-induced agranulocytosis ot acute neutropenia. Curr Opin Hematol 15 15-21... 

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