Leslie Zypchen

Fludarabine and rituximab for relapsed or refractory hairy cell leukemia

The purine analogs, pentostatin and cladribine, induce high remission rates when used as first-line monotherapy for hairy cell leukemia (HCL); however, patients continue to relapse. Re-treatment with the same or alternate purine analog produces lower response rates and a shorter duration of response. Fludarabine is another purine analog widely used in indolent lymphoid cancers, often in combination with rituximab, but there are few reports of its use in HCL. We identified 15 patients treated in British Columbia with fludarabine and rituximab (FR) from 2004 to 2010 for relapsed/refractory HCL after first-line cladribine (n = 3) or after multiple lines of therapy (n = 12). All patients with available response data responded to FR. With median follow-up of 35 months, 14 patients remain progression-free, whereas 1 patient has developed progressive leukemia and died. Five-year progression-free and overall survivals are 89% and 83%, respectively. FR is a safe and effective therapeutic option for relapsed/refractory HCL.

Improved Survival in HIV-Associated Diffuse Large B-Cell Lymphoma with the Addition of Rituximab to Chemotherapy in Patients Receiving Highly Active Antiretroviral Therapy

Abstract Purpose: Recent trials suggest serious toxicity in HIV-associated non-Hodgkin’s lymphoma (NHL) with rituximab (R) and chemotherapy (CT), offsetting the benefit of rituximab. Method: We retrospectively reviewed experience with CHOP-R vs. CT in 40 patients with HIV-associated diffuse large B-cell lymphoma (DLBCL) diagnosed between December 1992 and February 2006, all of whom were treated with curative intent. Results: In a univariate analysis, International Prognostic Index (IPI) score, prior AIDS, HAART, and rituximab were significant for overall survival (OS). In a multivariate analysis, IPI 0-1 (p < .02), no prior AIDS (p < .0002), and receiving CHOP-R (p < .01) were significant for improved OS, and HAART use (p < .09) retained a trend for improved OS. The hazard ratio (HR) for patients with high IPI receiving CHOP-R was 0.3 (95% CI 0.1-0.8). Patients without prior AIDS receiving CHOP-R had an HR of 0.5 (95% CI 0.1-1.7). The OS at 30 months in patients not receiving HAART was 0%. With HAART, OS was 33% for CT and 86% for CHOP-R; HR for CHOP-R was 0.4 (95% CI 0.1-1.2). Toxic deaths were 3 (33%) for CHOP-R and 6 (25%) for CT (p = ns); all toxic deaths with CHOP-R were in patients not receiving HAART. Rituximab-treated patients had a lower death rate from lymphoma (CHOP-R, 2 [16%] vs. CT, 15 [63%]; p < .04), and overall mortality (CHOP-R, 5 [42%] vs. CT, 21 [88%]; p < .01). Conclusion: These retrospective data suggest that fatal toxicity of rituximab in HIV-NHL is not increased provided HAART is used, that the addition of rituximab to CT improved outcome, and that further prospective trials investigating this issue are warranted.

Diagnosis and management of iliofemoral deep vein thrombosis: clinical practice guideline

Venous thromboembolism, presenting as deep vein thrombosis (DVT) or pulmonary embolism, affects over 35 000 Canadians each year.[1][1] It is associated with substantial morbidity, mortality and burden on the Canadian health care system, with one-month mortality rates estimated at 6% for DVT and 12%

Published guidelines versus real-life practice in the diagnosis and treatment of essential thrombocythemia.

intensity [RIC]), primary disease, and status at transplant. Thrombocytopenia was distinguished as persistent or transient in the presence of a or <30 day duration of platelet count reduction, respectively. Clinical conditions related or associated with the development of thrombocytopenia (i.e. cGVHD, infectious complications, relapse, microangiopathy, or other) were evaluated. Quantitative variables were tested for normal distribution using the Shapiro-Wilk test. Comparisons between groups were performed with t test or U-Mann Whitney test, depending on Shapiro-Wilk test results. g tests were used to analyze categorical values; when assumptions for g test were not verified, Fisher’s exact test was used. Survival curves were estimated using the Kaplan-Meier method. Overall survival (OS) was analyzed using log-rank tests and Cox proportional hazard models, after the proportional hazards assumption had been verified.