Western Intravascular Lymphoma (IVL): Case Series of Published Reports Between 1994-2014

Introduction: IVL is rare entity that often associated with disseminated aggressive pattern and fatal clinical course. It is characterized byproliferation of clonal lymphoma cells within blood vessel lumina of various organs that can represent diagnostic challenge due to with non-specific symptoms. IVL is categorized as a subset of large cell non-Hodgkin lymphoma and divided into western and Asian types. We hereby present this systematic review to better describe the salient features of the western subtype, treatment options and overall prognosis. Methods:A systematic review of the Medline and Embase databases via OVID engine was conducted to search for primary articles and case reports under keywords “intravascular lymphoma”,” angiotropic lymphoma” and “malignant angioendotheliomatosis”. Search was limited to publications between January 1994 and April 2014 including all the following; human cases, English language, pathologically confirmed cases and western subtype. Asian variants and cases without sufficient information were excluded. End points were overall survival and treatment, in addition to description of western types and related demographics. Chi-square test was used to analyze categorical covariates data. Student T test was used to compare subgroups means for continuous covariates. Statistical analysis was performed using SAS 9.3 software. Results: A total of 155 patients (Pts) were identified with western type IVL. 53% of cases were males (n=82) and median age on presentation was 64 years (median for B-cell and T-cell IVL 64 & 54 respectively). B-cell IVL (77%, n=119) was the most common subtype (T-cell 9%, NK-cell 1%, unspecified 13%).All cases staged as stage IV with 14% bone marrow involvement (n=21). Presenting symptoms were fever (52%), neurological (51%), fatigue (46%), skin lesions (28%), night sweats (23%), weight loss (23%), edema (22%), gastrointestinal (14%), respiratory (14%), genitourinary (7%), musculoskeletal (5%) and cardiovascular (1%). Median over-all survival from diagnosis was 5 months (mean B-cell 10.8 months, T-cell 10.4,P=0.9472). Fifty seven percent of pts treated with chemotherapy (19% CHOP, 16% R-CHOP 25, and 21% other). Pts treated with chemotherapy had mean survival of 16 months (95% confidence interval [CI] 12-20 months) compared to 2 months (95% CI: 2-4 moths) for those who did not receive chemotherapy (P<0.0001). The median survival of B and T-cells was similar in chemo treated pts (10.4, 10.8 respectively, P=0.9472). Rituximab was used in 19% of pts while 10% treated with intravenous methotrexate (MTX) regimen. In B-cell pts treated with R-CHOP vs CHOP, the mean survival was 21.2 and 10.2 months respectively, P<0.0247, while those treated with MTX vs no MTX mean OS was 37.4 and 14.3 months respectively, P=0.115, and rituximab vs no rituximab mean OS were 19.5 and 14.7 respectively, P=0.2294. In all pts treated with chemotherapy, median survival of those who received MTX was 25 months (95% CI 11.3-38.7) versus a mean OS of 14.3 months (95% CI 10.4-10.8) for those who did not receive MTX (P=0.0232). Conclusions: Western IVL is an aggressive type of lymphoma with a relative poor prognosis. In this systemic review, we found no statistical difference in OS between B- and T-cell types. In chemotherapy treated B-cell IVL, MTX and rituximab clinically prolonged survival but were not statistically significant. However, those who received RCHOP had better OS than those who received CHOP therapy. In all pts treated with chemotherapy, MTX significantly prolonged survival. The addition of MTX to all patients with IVL and rituximab for B-cell IVL to the backbone of multi-agent chemotherapy maybe beneficial and the use of CNS directed therapy should be considered.