pentostatin and Hemolytic-Uremic-Syndrome

Many drugs have been reported to cause thrombotic microangiopathy (TMA), often described as thrombotic thrombocytopenic purpura (TTP) or hemolytic-uremic syndrome (HUS). We recently established criteria to evaluate the evidence for a causal association of a drug with TMA and then we systematically reviewed all published reports of drug-induced TMA (DITMA) to determine the level of evidence supporting a causal association of the suspected drug with TMA. On the basis of this experience, we used these evaluation criteria to assess the Oklahoma TTP-HUS Registry patients who had been previously categorized as drug-induced, 1989-2014. We also reviewed the experience of the BloodCenter of Wisconsin with testing for drug-dependent antibodies reactive with platelets and neutrophils in patients with suspected immune-mediated DITMA, 1988-2014. Among 58 patients in the Oklahoma Registry previously categorized as drug-induced (15 suspected drugs), 21 patients (three drugs: gemcitabine, pentostatin, quinine) had evidence supporting a definite association with TMA; 19 (90%) of the 21 patients had quinine-induced TMA. The BloodCenter of Wisconsin tested 40 patients with suspected DITMA (eight drugs); drug-dependent antibodies, supporting a definite association with TMA, were identified in 30 patients (three drugs: oxaliplatin, quinine, vancomycin); 28 (93%) of the 30 patients had quinine-induced TMA. Combining the data from these two sources, 51 patients (five drugs) have been identified with evidence supporting a definite association with TMA. DITMA was attributed to quinine in 47 (92%) of these 51 patients.

Topics: Ambulatory Care Facilities; Antibodies; Deoxycytidine; Gemcitabine; Hemolytic-Uremic Syndrome; Humans; Oklahoma; Organoplatinum Compounds; Oxaliplatin; Pentostatin; Purpura, Thrombotic Thrombocytopenic; Quinine; Registries; Thrombotic Microangiopathies; Vancomycin; Wisconsin

Topics: Antibiotics, Antineoplastic; Hemolytic-Uremic Syndrome; Humans; Interferon-alpha; Lymphoma, T-Cell, Cutaneous; Male; Middle Aged; Pentostatin

We present a case of a patient who developed all manifestations of thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS) acutely following treatment of cutaneous T-cell lymphoma (CTCL, Sezary syndrome) with deoxycoformycin (pentostatin). Symptoms and signs included severe thrombocytopenia and microangiopathic hemolytic anemia; hallucinations, confusion and disorientation; oliguric acute renal failure requiring hemodialysis; and fever. No other etiology for these symptoms and signs was present. Complete recovery followed treatment for one month with plasma exchange and glucocorticoids. During the succeeding 20 months she has remained well and her CTCL remains stable on no further treatment. This case and two previously published cases suggest that acute and severe TTP-HUS may be a dose-dependent toxicity of deoxycoformycin (pentostatin).

Topics: Enzyme Inhibitors; Female; Glucocorticoids; Hemolytic-Uremic Syndrome; Humans; Middle Aged; Pentostatin; Plasma Exchange; Purpura, Thrombotic Thrombocytopenic; Sezary Syndrome

A hypercalcemic patient with adult T-cell leukemia was treated with deoxycoformycin (DCF) in a dose of 5 mg/m2 daily for three days. Several days later, severe thrombocytopenia appeared abruptly and then microangiopathic hemolytic anemia ensued. Subsequently, renal failure and hypertension developed, and the patient died seven weeks after DCF therapy. Needle necropsy of the kidney showed glomerular damage including swelling of endothelial cells, mesangiolysis and segmental collapse. This is the second reported case of hemolytic-uremic syndrome due to DCF.

Topics: Fatal Outcome; Female; Hemolytic-Uremic Syndrome; Humans; Leukemia, T-Cell; Middle Aged; Pentostatin