sirolimus and Purpura--Thrombotic-Thrombocytopenic

We describe an infant who developed juvenile myelomonocytic leukemia (JMML) at the age of 6 months. Myeloproliferation was effectively controlled by low-dose cytosine arabinoside and 13-cis retinoic acid therapy. Two years after therapy for JMML was stopped, at the age of 5 years, the patient developed autoimmune thrombotic thrombocytopenic purpura (TTP). TTP was transiently controlled by plasma exchange, prednisolone, rituximab, and cyclophosphamide, but relapsed within a short time. Long-term control of TTP was established by sirolimus. Somatic N-RAS G38A→Gly13Asp substitution was restricted to hematopoietic cells. The somatic N-RAS mutation may link myeloproliferation and autoimmunity.

Topics: Age of Onset; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Child, Preschool; Cytarabine; Genes, ras; Humans; Infant; Isotretinoin; Leukemia, Myelomonocytic, Juvenile; Mutation; Purpura, Thrombotic Thrombocytopenic; Sirolimus

Thrombotic microangiopathy (TMA) in renal transplantation (RTX) generally develops during treatment with calcineurin inhibitors. We present a RTX case that developed TMA under everolimus treatment. A 40-year-old woman received a kidney allograft from her 77-year-old mother. She initially received tacrolimus, mycophenolate mofetil and steroids. She was discharged with a creatinine level of 2.2 mg/dl after treatment for a cellular rejection attack within the first two weeks after transplantation. Later on, tacrolimus was replaced with everolimus. One year later, she presented with fever and increased creatinine level (4 mg/dl), anemia and thrombocytopenia. Her peripheral blood smear revealed signs of microangiopathic hemolysis. Bone marrow examination revealed an increased number of megakaryocytes. We diagnosed the case as TMA and initiated plasma exchange, I.V. pulse steroid treatment and stopped everolimus. This approach improved laboratory and clinic abnormalities. The development of TMA after treatment with everolimus and the exclusion of other possible causes suggested TMA associated with proliferating signal inhibitors (PSIs) in our case.

Topics: Adult; Everolimus; Female; Humans; Immunosuppressive Agents; Kidney Transplantation; Purpura, Thrombotic Thrombocytopenic; Sirolimus

Thrombotic microangiopathy (TMA) remains a serious event. We report a case of occurrence of TMA in the immediate postoperative period after a living-related renal transplantation. A distinguished feature of the case was major, early involvement of the retina with marked by decreased visual acuity along with thrombocytopenia and renal functional impairment. The syndrome was reversible with plasma exchange and conversion from tacrolimus to sirolimus. The patient's renal function is excellent at 11 months after transplantation. Decreased visual acuity and cotton wool exudates may be the first manifestation of posttransplant TMA.

Topics: Adolescent; Female; Humans; Immunosuppressive Agents; Kidney Transplantation; Plasma Exchange; Purpura, Thrombotic Thrombocytopenic; Retina; Sirolimus

Topics: Biopsy, Needle; Female; Follow-Up Studies; Humans; Immunohistochemistry; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Purpura, Thrombotic Thrombocytopenic; Risk Assessment; Severity of Illness Index; Sirolimus; Transplantation Immunology; Transplantation, Homologous

Topics: Combined Modality Therapy; Female; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Transplantation; Middle Aged; Plasma Exchange; Purpura, Thrombotic Thrombocytopenic; Sirolimus; Tacrolimus