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

Abstract

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 D1 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 (CR1, 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 (M/F) 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 CR1 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 Ͻ0.0001. 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 у2 had 8 months median OS as compared to 36 months median OS for patients with IPI Ͻ2, 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. Leukemia (2001) 15, 1785-1791.

Immunohistochemical detection of cdc2 is useful in predicting survival in patients with mantle cell lymphoma

“…Both IPI and clinical stage have been found to be prognostically important in some but not all studies of mantle cell lymphoma. [2][3][4][5] In our study, no statistical significance was found with IPI except when the cutoff was lowered to 1. As shown in Table 1, there were only seven (23%) patients in our study who have an IPI of r1, which relatively limits the prognostic utility of IPI for most mantle cell lymphoma patients.…”

“…A number of previous studies have reported the prognostic values of various clinical, pathologic, and biologic markers for mantle cell lymphoma patients. [2][3][4][5][6][7][8][9][10][11][16][17][18] Most mantle cell lymphoma patients present with a high clinical stage and widespread disease, and the prognostic value of IPI is controversial among studies. 2,4 Some biologic markers are promising, and these markers include p53 mutations and loss of p27, which have been found to correlate with worse clinical outcome in some studies.…”

“…2,3 Various studies have been performed in evaluating the prognostic importance of a number of clinical, pathologic, and biologic markers. For the pathologic parameters, blastoid and mantle zone mantle cell lymphoma have been reported to correlate with shorter and longer survival respectively, 4,5 although the frequencies of these mantle cell lymphoma variants are relatively low. For the clinical parameters, patient age, the presence of splenomegaly or anemia, but not international prognostic index (IPI) and Ann Arbor clinical stage, were found to be associated with survival in one study.…”

Blastic mantle cell lymphoma developing concurrently in a patient with chronic myelogenous leukemia and a review of the literature

“…Morphologically, MCL consists of a monotonous proliferation of small-to medium-sized lymphocytes with scant cytoplasm, variably irregular nuclei with condensed chromatin, and inconspicuous nucleoli [21]. There is a blastic variant that has a very poor prognosis with a median survival of 14.5 months [7,[22][23][24]. Immunophenotypically, the neoplastic lymphocytes express pan B-cell markers CD19, CD20, and CD22, the T-cell marker CD5, strong sIg expression, kappa/lambda restriction, and absence of CD10 and CD23 [21,25].…”

Nodal and leukemic small B-cell neoplasms

“…59,[61][62][63] 63,64 MCL is typically positive for the B-cell markers CD19 and CD20 with surface immunoglobulin light chain restriction, positive for CD5, FMC7, and Cyclin D1, and negative for CD23. Absence of CD5 expression has been reported in a minority of cases, perhaps 5-10% of MCL overall.…”