tacrolimus and pirarubicin

A 69-year-old woman, who had been diagnosed as having Sjögren's syndrome at 37 years old and mixed connective tissue disease at 42 years old, was under treatment with oral prednisolone. In 2009, she was diagnosed as having active systemic lupus erythematosus, and started on treatment with tacrolimus at 3 mg/day. In 2010, para-aortic lymphadenopathy and superficial multiple lymphadenopathy were detected. Tacrolimus was discontinued. Axillary lymph node biopsy revealed Epstein-Barr (EB) virus-negative CD5-positive diffuse large B-cell lymphoma (DLBCL). The patient was classified into clinical stage IIIA and as being at high risk according to the international prognostic index. After the discontinuation of tacrolimus, the lymph nodes reduced temporarily in size. In January 2011, the lymphadenopathy increased again, and the patient received a total of 8 courses of therapy with rituximab, pirarubicin, vincristine, cyclophosphamide and prednisolone, followed by intrathecal injection to prevent central nervous system infiltration, which was followed by complete remission. In February 2012, fluorodeoxyglucose positron emission tomography showed relapse in multiple lymph nodes and central nervous system infiltration. The patient was considered to have iatrogenic lymphoproliferative disorder classified as "other iatrogenic immunodeficiency-associated lymphoproliferative disorders" by the WHO, and this is the first reported case of CD5-positive DLBCL and central nervous system infiltration following administration of the drug. The patient was considered to have a poor prognosis as EB virus was negative, discontinuation of tacrolimus was ineffective and there was evidence of central nervous system infiltration.

Topics: Aged; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; CD5 Antigens; Cyclophosphamide; Doxorubicin; Female; Herpesvirus 4, Human; Humans; Iatrogenic Disease; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Lymphoma, Large B-Cell, Diffuse; Mixed Connective Tissue Disease; Prednisolone; Rituximab; Sjogren's Syndrome; Tacrolimus; Vincristine

Tetrahydropyranyladriamycin (THP), a derivative of anthracycline, exhibits a stronger antiproliferative activity and a lower cardiotoxicity than the other anthracyclines. The value of THP as an immunosuppressant has not been examined yet, whereas cyclophosphamide, which is another antiproliferative drug, has shown promise as an immunosuppressant in concordant xenotransplantation.. The effect of THP on the marginal zone in the spleen and anti-species antibody production was evaluated and was compared with that of cyclophosphamide in a concordant xenogeneic splenocyte injection model (hamster-to-rat). Next, THP was used as monotherapy for hamster-to-rat heart transplantation to substantiate the potency of its immunosuppressive activity in concordant xenotransplantation. Finally, combination therapy with THP plus FK506 was tried.. THP (5 mg/kg) suppressed the expansion of the marginal zone more than did cyclophosphamide (40 mg/kg) and inhibited the production of antispecies antibody as much as did cyclophosphamide (40 mg/kg) in the splenocyte injection model. THP monotherapy could prolong the survival of hamster-to-rat heart grafts up to 14.5 +/- 3.2 days (n = 21). The rejected grafts in the THP-treated animals did not show any histologic evidence of vascular endothelial damage but did exhibit a mononuclear cell infiltration. Combination therapy with THP plus FK506 provided excellent graft survival.. THP can prevent early phase humoral rejection in concordant xenotransplantation.

Topics: Animals; Antibodies, Heterophile; Cricetinae; Cyclophosphamide; Doxorubicin; Drug Therapy, Combination; Graft Rejection; Graft Survival; Heart Transplantation; Immunosuppressive Agents; Male; Mesocricetus; Myocardium; Rats; Rats, Wistar; Spleen; Tacrolimus; Transplantation, Heterologous; Transplantation, Heterotopic

Topics: Animals; Antibodies, Heterophile; Cricetinae; Doxorubicin; Drug Therapy, Combination; Graft Rejection; Heart Transplantation; Immunoglobulin M; Immunosuppressive Agents; Male; Mesocricetus; Rats; Rats, Wistar; Tacrolimus; Transplantation, Heterologous