High Incidence of Asian Variant Intravascular Large B-Cell Lymphoma (IVL) among IVL in Japan: Clinicopathologic Study of 95 Patients.

IVL is a rare form of aggressive B-cell lymphoma characterized by multifocal and predominant growth within vessels. Although its neurologic and dermatologic manifestations at diagnosis have been well documented, clinical courses of IVL are protean by patients. Systematic strategies for diagnosis and treatment of IVL are still to be established. To address these issues, we retrospectively analyzed a series of patients with IVL. This study was conducted by a refractory lymphoma study group, supported by the Ministry of Labor, Health and Welfare of Japan, and approved by the institutional review board of each participating institution. Both histopathological findings of IVL and positive reactions for at least one B-cell antigens (CD20, CD19 or CD79a) were required for inclusion. There were 95 patients (49 males and 46 females), with a median age of 67 years old (range 41–85). Most patients of IVL were associated with poor prognostic factors; i.e., 95% had more than 1 site of extranodal involvement, 91% had stage III/IV disease, 82% showed performance status greater than 1, and 94% had serum lactate dehydrogenase higher than normal level. Eighty-five percent was classified to the high-risk group of the International Prognostic Index (IPI). Therefore, IPI is not useful for the prognostification of IVL. Thirty-five patients (37%) were positive for CD5. Hemophagocytosis in the bone marrow, a key pathologic criterion for Asian variant of IVL (AIVL; Murase et al: Brit J Haematol 2000), was noted in 53 of 79 patients (67%) with available information. All these 53 patients met the clinical and laboratory criteria for AIVL, including anemia, thrombocytopenia, hepatosplenomegaly, and absence of tumor formation. In contrast, no hemophagocytosis was observed in 13 patients who did not meet the criteria. Patients with IVL were further characterized by the presence of B symptoms (76%), neurologic abnormality (27%), skin lesion (13%), and leukocytopenia (<4x10⁹/L; 27%). Bone marrow involvement was identified in 76% of the patients. Leukemic lymphoma cells were noted in 28% of the patients. Since 16 patients were diagnosed at autopsy, and 4 died shortly after the diagnosis or failed to follow, 75 were enrolled for analyses of prognostic factors. Univariate analyses for overall survival showed no use of anthracycline containing regimen (p=0.001), older age (p=0.005), lower platelet count (<100x10⁹/L; p=0.006), and higher serum soluble IL-2 receptor (5x10³U/mL or more; p=0.017) as unfavorable prognostic factors. Multivariate analysis using Cox regression model revealed that all these three factors were independent and significant prognostic factors (no anthracycline regimen: p=0.002, Hazard ratio [HR] 3.25, 95% confidence interval [CI] 1.53–6.90; age by 10 years: p=0.014, HR 1.36, 95%CI 1.07–1.66; and platelet <100x10⁹/L: p=0.037, HR 2.12, 95%CI 1.05–4.31). These findings suggest patients with IVL should be treated chemotherapy containing anthracyclines.