Lymphoproliferative diseases

Mycophenolate mofetil (CellCept) inhibits DNA and RNA synthesis and has been shown to have a specific lymphocyte antiproliferative effect. Although not FDA approved for this indication, oral mycophenolate mofetil appears effective in the treatment of moderate to severe plaque psoriasis. The usual dose is 500 mg orally four times a day, up to a maximum of 4 g/day. Common adverse effects include GI toxicity (diarrhea, nausea, vomiting), hematologic effects (anemia, neutropenia, thrombocytopenia), and viral and bacterial infections. Lymphoproliferative disease or lymphoma has been reported. 

L., Geha, R., Roncarolo, M.G., Oettgen, H., De Vries, J.E. and Terhorst, C., 1998, The X-hnked lymphoproliferative disease gene product, SAP regulates signals induced through the co-receptor, SLAM. Nature, 395 462-464. 

Goreva, O.B., Grishanova, A.Y., Mukhin, O.V., et al. (2003) Possible prediction of the efficiency of chemotherapy in patients with lymphoproliferative diseases based on MDRl gene G2677T and C3435T polymorphisms. Bull. Exp. Biol. Med. 136, 183-185. 

Special Precautions Risk of infections, leukopenia, thrombocytopenia, lymphoma, posttransplant lymphoproliferative disease or other malignancies Pregnancy Category C... 

Southern blotting and polymerase chain reaction are being used for detecting B- and T-cell clonality in lymphoproliferative diseases, including mantle cell lymphoma and lymphoma of the breast (Medeiros and Carr, 1999). Molecular genetic tests are currently important ancillary tools for the diagnosis and classification of malignancy, and their role is likely to increase in the future. 

In lymphoproliferative disease, sensory-motor neuropathy may be a result of diffuse malignant nerve infiltration or immune-mediated mechanisms [120], Syndromes similar to Guillain Barre syndrome sometimes occur among patients with lymphoproliferative disease, but in this group, it is uncertain whether cancer by itself favors the development of Guillain-Barre syndrome by suppressing immunosurveillance mechanisms [121]. 

Sunil-Chandra NP, Amo J, Fazakerley J, Nash AA. Lymphoproliferative disease in mice infected with gammaherpesvirus 68. Am J Pathol 1994 145 818-26. 

Martin-Gomez MA, Pena M, Cabello M, Burgos D, Gutierrez C, Sola E, Acedo C, Bailen A, Gonzalez-Molina M. Posttransplant lymphoproliferative disease a series of 23 cases. Transplant Proc 2006 38 2448-50. 

IMATINIB CICLOSPORIN t plasma concentrations of cidosporin, with risk of nephrotoxicity, myelosuppression, neurotoxicity and excessive immunosuppression, with risk of infection and post-transplant lymphoproliferative disease Inhibition of metabolism of cidosporin Monitor plasma cidosporin levels to prevent toxicity... 

CICLOSPORIN AZOLES - ITRACONAZOLE, KETOCONAZOLE, VORICONAZOLE t plasma concentrations of ciclosporin, with risk of nephrotoxicity, myelosuppression, neurotoxicity, excessive immunosuppression, with risk of infection and post-transplant lymphoproliferative disease Inhibition of CYP3A4-mediated metabolism of ciclosporin these inhibitors vary in potency. Ketoconazole and itraconazole are classified as potent inhibitors. Effect not clinically relevant with fluconazole Avoid co-administration with itraconazole or ketoconazole. Consider alternative azole but need to monitor plasma ciclosporin levels to prevent toxicity... 

Development of rat models for clinical ATL has required the use of immunodeficient rats. Ohashi et al. (1999) demonstrated that an ATL-like lymphoproliferative disease could be established in adult nude (nu/nu) rats following inoculation of some HTLV-l-immortalized cell lines. This led to studies that examined methods of protection against tumor development, including adoptive transfer of T cells (Kaimagi et al., 2000) and Tax-specific peptide vaccines (Hanabuchi et al., 2001). 

High-dose chemotherapy with cyclophosphamide, vincristine, prednisolone, and intrathecal methotrexate given for post-transplant lymphoproliferative disease was suggested to have favored the occurrence of acute ciclosporin neurotoxicity (headache, fever, seizures, and visual agnosia) in a 9-year-old cardiac transplant patient (239). Ciclosporin serum concentrations were normal and a further similar episode occurred on ciclosporin readministration. 

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