Aplastic Anemia and Severe Myelosuppression with Boceprevir or Simeprevir-Containing Hepatitis C Virus Treatment

ABSTRACT The addition of the new protease inhibitors (PIs) to peg-interferon (IFN) and ribavirin (RBV), approved for chronic hepatitis C, has clearly improved sustained virological response (SVR) rates although several adverse events have been reported with this regimens, including mild hematological toxicity. Moreover, severe pancytopenia and aplastic anemia during triple therapy with telaprevir has recently been described in seven patients. We report here two cases of severe agranulocytosis/aplastic anemia using boceprevir or simeprevir in interferon-based combination and 2 additional cases of severe myelosupression in IFN-free therapy with sofosbuvir and simeprevir plus RBV. Our observations suggest that PIs could have a sort of class-effect in developing severe hematologic toxicity or, at least, an additive interaction with other potentially myelotoxic agents such as IFN or RBV that are used in the classical regimens against HCV. Unfortunately, the mechanisms behind this phenomenon are currently unknown. In conclusion, given the lifethreatening character of these complications, close monitoring is mandatory in patients under PIs based therapy to promptly detect serious hematological toxicities and to carefully evaluate treatment discontinuation. Prospective studies assessing the usefulness of RBV in the era of new IFN-free combinations are needed.

Aplasia medular asociada al uso de ticlopidina / Bone marrow aplasia associated to the use of ticlopidine: report of one case

We report a 58 years old male that developed a bone marrow aplasia associated to the use of ticlopidine, prescribed after coronary artery stenting. The patient developed a pneumonia as a complication. He was admitted to the Intermediate Treatment Unit, receiving wide spectrum antimicrobial therapy and a granulocyte colony stimulating factor (Neupogen(r)) with favourable response. Ticlodipine is an effective anti-platelet agent, but has serious hematological and other side effects. Its prescription requires a close follow up and search for complications

GM-CSF and low-dose araC treatment of AML in prolonged hypoplasia with residual leukemic cells after induction chemotherapy

We describe a case with acute myelogenous leukemia (AML; M2) who developed prolonged marrow hypoplasia with residual leukemic blasts and recurrent infections after induction chemotherapy. He was treated successfully with a sequential treatment of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) and low-dose cytosine arabinoside (LD AraC). To the best of our knowledge this is the first reported case of a successful treatment of a patient with AML, who showed prolonged markedly hypocellular bone marrow with significant residual leukemic cells after induction chemotherapy, with a sequential treatment of GM-CSF and LD AraC.

Alteraçöes hematológicas em pacientes expostos cronicamente ao benzeno / Hematological abnormalities in patients chronically exposed to benzene

Foram apresentadas as alteraçöes hematológicas do sangue periférico e da medula óssea em pacientes expostos cronicamente ao benzeno. Foram descritos a biotransformaçäo metabólica e os possíveis mecanismos envolvidos neste tipo de toxicidade. Os dados hematológicos do sangue periférico säo mostrados e avaliados em sua importância, sendo a macrocitose e a linfocitopenia sinais precoces de toxicidade ao benzeno. As alteraçöes da medula óssea observadas säo demonstradas pelos métodos complementares citológico e histológico. A anormalidade histológica de maior importância foi a hipocelularidade global devida, principalmente, ao setor granulocítico. Foi observado também aumento do percentual de eosinófilos, de mastócitos e de atipias no setor megacariocítico. Foram observadas alteraçöes de caráter inflamatório e ressaltada a presença de sinais de dismielopoiese. Foram enfatizadas a necessidade da valorizaçäo das alteraçöes hematológicas do sangue periférico e a visäo crítica e global desse importante problema de saúde pública

Trichloroethylene toxicity in mice: a biochemical, hematological and pathological assessment.

Oral administration of trichloroethylene (TCE; 0, 500, 1000 and 2000 mg/kg/day) to male mice once daily, 5 days a week for a period of 28 days, caused a significant increase in liver weight, degeneration/necrosis of hepatocytes and characteristics proliferation of endothelial cells of hepatic sinusoids. Increase in kidney weight, glomerular nephrosis, degeneration/desquamation of tubular epithelium and characteristic amyloid deposition in glomeruli were observed only in the group of mice treated with 2000 mg/kg TCE. These changes occurred concurrently with a significant increase in total protein and free sulphydryl contents, elevated activities of acid phosphatase and catalase and decreased activity of delta-aminolevulinic acid dehydratase (delta-ALAD) indicating the sensitivity of liver and kidney as target tissues in TCE-toxicity. Hematological studies showed a significant increase in RBC counts and a reduction in WBC counts without any statistically significant change in the hemoglobin, urea nitrogen, creatinine and uric acid levels in the blood of TCE-exposed mice. A dose-related increase in cell density and acid phosphatase activity with a parallel significant decrease in the activity of delta-ALAD were observed in the bone marrow, which appear to be responsible for hematological alterations in TCE-exposed mice. The results suggest that early metabolic, pathological and hematological perturbations following a short-term exposure of TCE in mice, can provide the basis for its documented potential for chronic effects like blood dyscrasia and cancer.