Thomas Coyle

Rituximab as an adjunct to plasma exchange in TTP: a report of 12 cases and review of literature.

Idiopathic thrombotic thrombocytopenic purpura (TTP) is caused by the production of autoantibodies against the Von Willebrand factor cleaving enzyme. This provides a rationale for the use of rituximab in this disease. We report a retrospective review of 12 patients treated with rituximab for TTP refractory to plasma exchange. Eleven patients were treated during initial presentation, and one patient was treated for recurrent relapse. Ten patients responded to treatment. Median time to response after first dose of rituximab was 10 days (5–32). Of the 11 patients treated during initial presentation, nine remain free of relapse after a median follow‐up of 57+ months (1+–79+). Two patients died during initial treatment. One patient was lost to follow‐up 1 month after achieving complete response. The patient treated for recurrent disease during second relapse remained disease free for 2years, relapsed and was treated again with rituximab, and was in remission for 22 months. She relapsed again, was retreated, and has now been in remission for 21+ months. We conclude that rituximab is an useful addition to plasma exchange treatment in TTP, but its exact role and dosing need to be verified in prospective studies. J. Clin. Apheresis, 2008.

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

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.

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.

PPX and Concurrent Radiation for Newly Diagnosed Glioblastoma Without MGMT Methylation: A Randomized Phase II Study: BrUOG 244.

Purpose: Efficacy signals but substantial myelosuppression were demonstrated in a single arm phase II study of paclitaxel poliglumex (PPX) in combination with temozolomide (TMZ) and radiation therapy (RT) for first-line treatment of glioblastoma. The objective of this randomized phase II trial was to assess the efficacy and safety of single-agent PPX with RT (PPX/RT) versus TMZ with RT (TMZ/RT) for glioblastoma without O6-methylguanine-DNA methyltransferase (MGMT) methylation. Materials and Methods: Patients with glioblastoma with unmethylated MGMT without prior chemotherapy or RT were eligible. Patients were randomly assigned 2:1 to PPX, 50 mg/m2/wk for 6 weeks, or standard TMZ, with concurrent 60.0 Gy RT. One month after completion of chemoradiation all patients received standard maintenance TMZ. The primary endpoint was progression-free survival (PFS). Results: Of the 164 patients enrolled, 86 were MGMT unmethylated. Of these, 63 patients were randomized (42 to PPX/RT and 21 to TMZ/RT). Fifty-nine patients could be analyzed. The median PFS was 9 months in the PPX/RT group and 9.5 months in the TMZ/RT group (hazard ratio in the PPX/RT group, 1.10; 95% confidence interval, 0.79-2.08; P=0.75). Median overall survival was 16 versus 14.8 months for PPX/RT and TMZ/RT groups, respectively (hazard ratio, 1.44; 95% confidence interval, 0.75-2.77; P=0.27). In the PPX and TMZ groups 44% versus 22% of patients, respectively, experienced one or more grade 3 or higher toxicities during chemoradiation. Conclusions: PPX/RT did not improve PFS or overall survival. This study provides an effective trial design for screening RT sensitizers in glioblastoma.

Crizotinib in anaplastic lymphoma kinase-positive anaplastic large cell lymphoma in the setting of renal insufficiency: a case report

BackgroundIn vitro studies confirmed cytoreductive anti-tumor activity of crizotinib in experimental models of anaplastic large cell lymphoma in 2007. One case series and a few case reports describe the use of crizotinib in relapsed or refractory anaplastic lymphoma kinase-positive anaplastic large cell lymphoma. Even though data are limited regarding the dose of crizotinib in renal insufficiency, our case was successfully treated with a lower dose of crizotinib.Case presentationWe report the case of a 48-year-old white man who had progressive disease after three prior cycles of cyclophosphamide, doxorubicin, vincristine and prednisone and three cycles of ifosfamide, carboplatin, and etoposide, and was not a candidate for high-dose chemotherapy and transplant due to poor performance status and renal insufficiency; he had a complete and durable response to single agent crizotinib. Crizotinib was given at a reduced dose (250 mg once daily) due to his renal insufficiency. He has been in complete remission for more than 2 years.ConclusionsOur experience confirms the activity of crizotinib in this disease; it suggests that long-term treatment with crizotinib is a reasonable option in patients who are not candidates for more aggressive therapy and indicates that crizotinib can be used successfully at reduced doses in patients with pre-existing renal insufficiency. The role and timing of crizotinib in anaplastic lymphoma kinase-positive anaplastic large cell lymphoma is unclear, but the current literature that we review here provides promising results that may lead to studies of crizotinib earlier in the course of disease.

Von Willebrand Factor for Menorrhagia: A Survey and Literature Review

von Willebrand disease (VWD) is the most common congenital bleeding disorder. In women, menorrhagia is the most common bleeding symptom, and is disabling with iron deficiency anaemia, high health cost and poor quality of life. Current hormonal and non‐hormonal therapies are limited by ineffectiveness and intolerance. Few data exist regarding von Willebrand factor (VWF), typically prescribed when other treatments fail. The lack of effective therapy for menorrhagia remains the greatest unmet healthcare need in women with VWD. Better therapies are needed to treat women with menorrhagia.