The natural history of intravascular lymphomatosis

Intravascular lymphomatosis (IVL) is a rare and clinically devastating form of extranodal B-cell non-Hodgkin's lymphoma. We performed a comprehensive analysis of the literature on IVL's published between 1959 and 2011 and evaluated the natural history as well as identified prognostic and predictive factors in patients. Nonparametric two-tailed Mann-Whitney U-test and Mantel-Cox log rank test were used to evaluate the survival intervals and prognostic factors. Multivariate analysis of variance (MANOVA) and chi-squared statistics were carried out to examine treatment-related predictive factors. Of the 740 patients with IVL, 651 (88%) had a diagnosis of B-cell lymphoma, 45 (6%) with T-cell lymphoma, and 12 patients (2%) with NK cell lymphoma. Central nervous system (CNS) IVL had the highest proportion of postmortem diagnosis, 250 (60%) compared to 21 (8%) of skin, 28 (11%) of bone marrow (BM) and spleen, and 17 (7%) of lung IVL's. Age <70 years (P = 0.0073), non-CNS site of initial diagnosis (P = 0.0014), lactate dehydrogenase (LDH) <700 (P = 0.0112), and rituximab treatment (P < 0.0001) were favorable prognostic factors. Gender, ethnicity, hemoglobin, BM biopsy, and the type of imaging studies used were not significant. Rituximab and doxorubicin treatment worked significantly better in patients with age >71 and LDH >577 compared to nonrituximab, nondoxorubicin regimens (MANOVA 2 degrees of freedom, P = 0.0345), with a median time from treatment to death of 20.0 (95% confidence interval [CI] 14.0-N/A, n = 14) months versus 2.0 (95%CI 0.5-N/A, n = 5) (χ(2) = 4.7, P = 0.0304). Patients with CNS IVL relapsed primarily in the CNS (88%) while same-organ relapse occurred less frequently in skin (23%), BM and spleen (50%) and lung (20%) IVL's. Our results indicate that IVL is primarily a disease of B-lymphoma cells. Timely diagnosis and treatment with rituximab-based chemotherapy improve patient survival. The pattern of recurrence is different between CNS IVL and IVL's in other organs.