Complex karyotype in mantle cell lymphoma is a strong prognostic factor for the time to treatment and overall survival, independent of the MCL international prognostic index

Abstract

Mantle cell lymphoma (MCL) is usually an aggressive disease. However, a few patients do have an "indolent" evolution (iMCL) defined by a long survival time without intensive therapy. Many studies highlight the prognostic role of additional genetic abnormalities, but these abnormalities are not routinely tested for and do not yet influence the treatment decision. We aimed to evaluate the prognostic impact of these additional abnormalities detected by conventional cytogenetic testing, as well as their relationships with the clinical characteristics and their value in identifying iMCL. All consecutive MCL cases diagnosed between 1995 and 2011 at four institutions were retrospectively selected on the basis of an informative karyotype with a t(11;14) translocation at the time of diagnosis. A total of 125 patients were included and followed for an actual median time of 35 months. The median overall survival (OS) and survival without treatment (TFS) were 73.7 and 1.3 months, respectively. In multivariable Cox models, a high mantle cell lymphoma international prognostic index score, a complex karyotype, and blastoid morphology were independently associated with a shortened OS. Spleen enlargement, nodal presentation, extra-hematological involvement, and complex karyotypes were associated with shorter TFS. A score based on these factors allowed for the identification of "indolent" patients (median TFS 107 months) from other patients (median TFS: 1 month). In conclusion, in this multicentric cohort of MCL patients, a complex karyotype was associated with a shorter survival time and allowed for the identification of iMCL at the time of diagnosis.

Complex karyotype in patients with mantle cell lymphoma predicts inferior survival and poor response to intensive induction therapy

“…10,12,13,15 Espinet et al described loss(17p) as being prognostic in a multivariable model, 9 and Sarkozy et al reported that it was prognostic in univariable but not multivariable modeling. 12 More recently, Eskelund et al used data from the Nordic MCL trials to demonstrate that in patients aged <66 years, TP53 mutations were associated with inferior OS (HR, 6.2; P<.01) and time to disease recurrence (HR, 6.9; P<.01), with a median OS of 1.8 years. 16 In addition, they demonstrated that TP53-mutated cases had an inferior response to intensive induction therapy.…”

Mantle cell lymphoma: 2019 update on the diagnosis, pathogenesis, prognostication, and management

“…TP53 ‐mutated MCL patients generally have a poor prognosis and have a poor response to standard frontline chemoimmunotherapy . Patients with a complex karyotype, defined as having three or more chromosomal abnormalities in addition to t(11;14) or additional chromosomal abnormalities detected by array CGH (comparative genomic hybridization) generally have poorer outcomes …”

Negative prognostic impact of low absolute CD4+ T cell counts in peripheral blood in mantle cell lymphoma

“…Given this heterogeneity and the limited discriminatory power of the International Prognostic Index (IPI), the simplified MCL IPI (sMIPI) including age, performance status, white blood cell counts, and lactate dehydrogenase (LDH) level enables assessment of the prognosis of individual patients. As sMIPI was developed from patients with advanced stage disease in the pre‐rituximab era, and the variables of sMIPI were just a reflection of tumor burden and serve as indirect markers for the biological characteristics of MCL, many other prognostic factors were analyzed such as Ki‐67, TP53, stage, serum β2‐microglobulin, chromosome karyotype, and other parameters . Unfortunately, little research into MCL took the host immunity and tumor microenvironment into account.…”

“…As sMIPI was developed from patients with advanced stage disease in the pre-rituximab era, (3) and the variables of sMIPI were just a reflection of tumor burden and serve as indirect markers for the biological characteristics of MCL, many other prognostic factors were analyzed such as Ki-67, TP53, stage, serum b2-microglobulin, chromosome karyotype, and other parameters. (1,3,4) Unfortunately, little research into MCL took the host immunity and tumor microenvironment into account. More and more evidence has proved the interaction among lymphoma cells, stromal cells, and immune cells.…”