Blastic variant of mantle cell lymphoma:: a rare but highly aggressive subtype

The blastic variant (BV) form of mantle cell lymphoma (MCL) Is considered to be a very aggressive subtype of non-Hodgkin's lymphoma (NHL). In order to determine Its clinico-biological features and response to therapy we studied 33 patients (17%) out of 187 suffering from MCL who were diagnosed with a BV of MCL. Blastic variant was diagnosed according to histopathological patterns, Immunophenotyping, and bcl1 gene rearrangement and/or cyclin DI overexpression. Three patients Initially diagnosed with large cell NHL were classified as BV. Patients received front-line therapy including CHOP-like regimen or CVP (n = 29), or chlorambucil (n = 4) and CHOP or ESAP as second-line therapy. High-dose Intensification with stem cell transplantation (SCT) was performed in 11 cases (autoSCT, n = 8; alloSCT, n = 3). All but two patients were in complete remission (CR) at the time of transplant (CRI, n = 5; CR2, n = 4). Clinical and biological characteristics did not differ from those of the common form of MCL. The median age was 62 years (29-80), with a sex ratio (MIF) of 2.6:1. Of the 33 patients, 66% had extranodal site Involvement, 85% had an Ann Arbor stage IV, and 82% had peripheral lymphadenopathy. Circulating lymphomatous cells were seen in 48% of cases. Twelve patients (36%) entered a CRI with a median duration of 11 months. Fifteen patients (46%) failed to respond and rapidly died of progressive disease. Second-line therapy led to a 26% (6/23) CR2 rate. Nine patients relapsed after high-dose therapy. Twenty-two of the 33 patients (66%) died of refractory or progressive disease. Median overall survival (OS) time was 14.5 months for the 33 BV patients as compared to 53 months for the 154 patients with a common form of MCL, P < 0.0001. In the univariate analysis, OS was influenced by age, extranodal site involvement, circulating lymphomatous cells, and international prognosis Index (IPI). In the multivariate analysis, only IPI affected OS: patients with IPI greater than or equal to2 had 8 months median OS as compared to 36 months median OS for patients with IPI <2, P = 0.003. Blastic variant is one of the worst forms of NHL. An improved recognition of BV of MCL Is required, particularly in high-grade CD5(+) NHL using Immunophenotyping and bcl1 molecular study. Standard therapy using anthracycline or even high-dose Intensification produce poor results and an alternative treatment should be proposed to such patients.