Carfilzomib
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Haemolytic and uraemic-syndrome: case report A 66-year-old man developed haemolytic and uraemic-syndrome during treatment with carfilzomib for myeloma. The man had a history of smoking (ceased), high BP and excess weight. Four years previously, he presented with IgG Kappa multiple myeloma and received bortezomib, thalidomide, dexamethasone and melphalan, with autologous haematopoietic stem cells transplantation. Complete remission was achieved. A consolidation treatment with bortezomib, thalidomide and dexamethasone was started. After 18 months, biological progression was observed. Six months later, he stated receiving a 2nd line treatment with dexamethasone, lenalidomide and carfilzomib [route and dosage not stated]. Within 6 months complete remission was obtained and treatment was continued for 21 months. The last treatment cycle was started a month prior to his hospitalisation (cumulative dose of carfilzomib: 6228mg). Other than chemotherapy, he was receiving a combination of nebivolol and hydrochlorothiazide, aspirin [acetylsalicylic acid], cotrimoxazole [sulfamethoxazole-trimethoprim], folic acid and valaciclovir. Eight days after the end of the 22nd cycle of chemotherapy, he was hospitalised due to a deterioration of his general condition associated with asthenia and anorexia. He exhibited arterial hypertension. Laboratory results showed anaemia, thrombocytopenia and acute oligo-anuric renal failure, complicated by severe metabolic acidosis and hyperkalaemia. An abdominal and pelvic CT scan. Additional laboratory tests confirmed the mechanical haemolytic nature of the anaemia. The man’s treatment was started with emergency haemodialysis. With the presumed diagnosis of thrombotic microangiopathy from the outset, he was treated with plasma exchanges with a substitution for fresh frozen plasma. He exhibited few diarrhoeal stools after admission, but the stool cultures were sterile. Urine cytobacteriological tests and blood cultures were also sterile. He tested negative for hepatitis B, C and HIV serological tests. The autoimmunity test was negative. Normal results of serum protein electrophoresis and the serum free light chain assay confirmed the lack of myeloma progression. After normalisation of ADAMTS-13 activity, plasma exchanges were discontinued. However, the signs of haemolysis persisted, and he remained anuric and on haemodialysis. The complement test results normalised. A possibility of haemolytic and uraemic-syndrome secondary to carfilzomib was hypothesiesed. Therefore, chemotherapy was discontinued, and symptomatic treatments and haemodialysis were continued. This allowed good control of BP and hydration status. Twenty-five days after the last administration of carfilzomib, the signs of haemolysis persisted, and he remained anuric and on haemodialysis. Then, eculizumab was started. After the first infusion, haptoglobin levels became measurable again. After the second infusion, the significant reoccurrence of diuresis was observed. The last haemodialysis session was performed on the d
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