Platelet transfusions and bleeding complications associated with plasma exchange catheter placement in patients with presumed thrombotic thrombocytopenic purpura.

INTRODUCTION: Bleeding risk because of thrombocytopenia in patients with thrombotic thrombocytopenic purpura (TTP) often causes concern during placement of the central venous catheter for plasma exchange. This perceived risk of bleeding often triggers prophylactic platelet transfusion; however, the risk of platelet transfusion is unknown. METHODS: Single institution review of bleeding episodes after catheter insertion in patients with suspected TTP. RESULTS: Fifty-five thrombocytopenic patients with presumed TTP underwent a total of 57 catheter insertion attempts. There were no major bleeding complications and no bleeding that required invasive intervention. Fourteen patients with a median platelet count of 12,000/µL were transfused with platelets prior to catheter placement. Five (35%) of the transfused patients had minor bleeding complications that did not require intervention. In the nontransfused group, 12 (28%) patients had minor bleeding that did not require invasive intervention and three patients experienced bleeding episodes that resolved after applying direct pressure. Eight (15%) patients died during admission. Mortality in the transfused group was 43% versus 5% in the nontransfused group. In general, patients receiving platelet transfusion prior to catheter insertion were more acutely ill. CONCLUSION: There were no major bleeding complications associated with plasma exchange catheter insertion in thrombocytopenic patients with presumed TTP. In light of the uncertain risk of platelet transfusion in patients with TTP, it may be reasonable to forgo prophylactic platelet transfusion prior to catheter placement.

Ulceration of Striae distensae in high-grade glioma patients on concurrent systemic corticosteroid and bevacizumab therapy.

Striae distensae (stretch marks) are a common complication seen in patients on chronic corticosteroid therapy. Under certain circumstances, primary brain tumor patients require chronic corticosteroid therapy and can suffer from striae distensae. Bevacizumab, a humanized monoclonal antibody to vascular endothelial growth factor-A (VEGF-A) is now more widely used for the treatment of primary brain tumors. In this paper, we present four cases of ulcerated striae distensae in primary brain tumor patients on concurrent corticosteroid and bevacizumab therapy. Because of bevacizumab's effects on wound healing and its recent accelerated approval for recurrent glioblastoma multiforme (GBM), the most common malignant primary brain tumor in adults, this novel skin complication should be considered in patients on concurrent corticosteroid and bevacizumab therapy.

Acute leukemia associated with valproic acid treatment: a novel mechanism for leukemogenesis?

Valproic acid has been previously associated with hematologic toxicity, including a reversible myelodysplasia-like syndrome without chromosomal abnormalities. We now report three cases of acute leukemia with features of secondary leukemia associated with valproic acid therapy: two cases of acute myelogenous leukemia with multilineage dysplasia, one with trisomy 8 and one with monosomy 7, and one case of secondary acute lymphoblastic leukemia with del (7) (q22q34), del (9) (q21.11q22), del (11) (q12q23). One patient had a previous myelodysplastic syndrome while on valproic acid. Valproic acid has been previously shown to be a histone deacetylase inhibitor. Inhibition of histone deacetylase causes a relaxation of chromatin structure and thus increases susceptibility to DNA damage and sensitizes cells to radiation. We propose that valproic acid therapy may lead to secondary leukemia by increasing DNA damage through chronic inhibition of histone deacetylase.

Phase I study of temozolomide and escalating doses of oral etoposide for adults with recurrent malignant glioma.

BACKGROUND: Although temozolomide is active against recurrent malignant glioma, responses in many patients are modest and short-lived. Temozolomide may prove more effective in combination with other agents. Therefore, combination oral chemotherapy for these patients is a particularly attractive approach. METHODS: The authors conducted a Phase I study of temozolomide in combination with escalating doses of oral etoposide (VP-16) to determine the maximum tolerated doses of these two agents when given together. The temozolomide dose was fixed at 150 mg/m(2) per day on Days 1-5. The oral VP-16 was escalated in cohorts of 3 to 6 patients by numbers of days of VP-16 administered: 50 mg/m(2) per day, Days 1-5 (dose level 1), Days 1-8 (dose level 2), Days 1-12 (dose level 3), Days 1-16 (dose level 4), and Days 1-20 (dose level 5). Therapy was given in 28-day cycles. RESULTS: Of the 29 patients enrolled, 26 were fully evaluable and 3 were partially evaluable for toxicity. The 29 patients received a total of 92 cycles. The median age of the patients was 49 years (range, 28-76 years). Diagnoses included glioblastoma (n = 19), gliosarcoma (n = 3), anaplastic astrocytoma (n = 5), and anaplastic oligoastrocytoma (n = 2). The median time from diagnosis to disease recurrence was 8 months (3-188 months). Twenty patients were treated at the first disease recurrence, seven at the second, and two at the third. Twenty-four patients (83%) were receiving anticonvulsants and 24 were receiving dexamethasone. All patients had received previous radiation, and 25 of 29 had been treated with chemotherapy previously. Of the 3 patients at dose level 1, none had dose-limiting toxicity (DLT). Of the 6 patients at dose level 2, 1 patient had DLT: Grade 3 thrombocytopenia resulting in a > 2-week delay in starting the next cycle of chemotherapy. Of the 6 patients at dose level 3, 1 patient had DLT: death due to pneumonia. There were 2 DLTs in the 7 patients at dose level 4: fever, neutropenia, and herpes zoster infection in 1 patient and death due to pneumonia in another. Seven patients had been started at dose level 5 when DLT was established at dose level 4: of the 5 fully evaluable and 2 partially evaluable patients at dose level 5, there was no DLT. CONCLUSIONS: The maximum tolerated dose of temozolomide and oral VP-16 in this heavily treated group of patients with recurrent malignant glioma is temozolomide 150 mg/m(2) per day for 5 days and oral VP-16 50 mg/m(2) per day for 12 days.