High Mantle Cell Lymphoma International Prognostic Index Research Articles

Overexpression of the key metabolic protein CPT1A defines mantle cell lymphoma patients with poor response to standard high-dose chemotherapy independent of MIPI and complement established highrisk factors.

The variable outcome to standard immunochemotherapy for mantle cell lymphoma (MCL) patients is a clinical challenge. Established risk factors, including high MCL International Prognostic Index (MIPI), high proliferation (Ki-67), non-classic (blastoid/pleomorphic) morphology, and mutated TP53, only partly identify patients in need of alternative treatment. Deepened understanding of biological factors that influence time to progression and relapse would allow for an improved stratification, and identification of novel targets for high-risk patients. We performed gene expression analyses to identify pathways and genes associated with outcome in a cohort of homogeneously treated patients. In addition to deregulated proliferation, we show that thermogenesis, fatty acid degradation and oxidative phosphorylation are altered in patients with poor survival, and that high expression of carnitine palmitoyltransferase 1A (CPT1A), an enzyme involved in fatty acid degradation, can specifically identify high-risk patients independent of the established high-risk factors. We suggest that complementary investigations of metabolism may increase the accuracy of patient stratification and that immunohistochemistry- based assessment of CPT1A can contribute to defining high-risk MCL.

Identification of miRNA-34a and miRNA-155 as prognostic markers for mantle cell lymphoma.

ObjectiveMicroRNAs (miRNAs) with functional relevance have not been previously identified in mantle cell lymphoma (MCL). Here, we aimed to evaluate the relationships between miR-34a and miR-155-5p and MCL clinicopathology and prognosis.MethodsSeventy-five paraffin-embedded tissue samples from patients with MCL who completed at least four cycles of chemotherapy from January 2006 to October 2016, and 27 samples from control patients with reactive lymphoid hyperplasia (RLH), were collected. MiRNA expression levels were measured by qRT-PCR.ResultsThe miR-155-5p levels were significantly higher in patients with MCL than in the controls. The Eastern Cooperative Oncology Group (ECOG) ≥ 2 and Sex-Determining Region Y-Box transcription factor 11 (SOX11) < median value (M) groups presented lower miR-34a expression than the ECOG < 2 and SOX11 ≥ M groups, respectively. MiR-155-5p expression differed between low, intermediate, and high MCL International Prognostic Index risk groups. The AUCs of miR-34a and miR-155-5p were 0.5819 and 0.7784, respectively. The median survival times of the miR-34a ≤ 0.2150 and miR-155-5p > 2.11 groups were shorter than those of the miR-34a > 0.2150 and miR-155-5p ≤ 2.11 groups, respectively.ConclusionsLow miR-34a and elevated miR-155-5p levels may be correlated with poor prognosis in MCL.

Mantle cell lymphoma may have a different clinical course in Mexican Mestizos: Real-world data from a single center.

The biology of some hematological diseases varies among different populations. No previous studies have evaluated the clinical behavior of mantle cell lymphoma (MCL) in México. This is a retrospective review of MCL cases seen in Mexico from January 2003 to June 2020. A total of 12 cases were identified. There were nine males and three females; median age was 56 years. Eight patients had a high MCL international prognostic index score, one was intermediate, and three were low. Five patients had circulating malignant monoclonal cells. Initial treatment included rituximab, cyclophosphamide, daunorubicin, vincristine, and prednisone (R-CHOP) and CHOP. Subsequent treatment included hematopoietic stem cell transplantation in five patients; two were given maintenance therapy. Splenectomy was done in four patients. Median overall survival (OS) for all the patients has not been reached and exceeds 162 mos: OS at 162 mos was 56%. Achieving a complete remission (CR) after the first treatment was a significant prognostic factor, with a median OS exceeding 141 mos in patients achieving CR, and 16 mos among those not achieving CR (p = 0.0006). Some of MCL patients in Mexico have an indolent clinical course, particularly patients who achieve a CR to initial treatment and who undergo splenectomy.

Mantle Cell Lymphoma: An Immunomorphologic Study with SOX11 from a Tertiary Care Cancer Centre in Southern India

Introduction: Mantle Cell Lymphoma (MCL) is a relatively rare Non-Hodgkin Lymphoma (NHL) of mature B cells forming 5-7% of NHL. SOX11 has emerged as a useful antibody in the diagnosis of MCL with prognostic significance. Aim: To evaluate the immunomorphologic features and significance of SOX11 expression in MCL at a tertiary care cancer institute. Materials and Methods: This was a descriptive study which was conducted at a tertiary care cancer centre in Southern India over a period of five years from January 2013 to December 2017. Seventy six cases of newly diagnosed MCL with paraffin blocks were included in the study. Immunohistochemistry (IHC) with a panel of antibodies including SOX11 was carried out on Formalin Fixed Paraffin Embedded (FFPE) sections. Morphologic, immunologic findings were analysed and correlated with clinical data and survival, using Chi-square and Independent sample t-test to compare data and Kaplan-Meir method with Log Rank test for survival analysis. Results: Mantle Cell Lymphoma (MCL) formed in 5.8% of NHL with a striking male predominance (M:F ratio, 4.4:1), with mean age of 58 years at presentation and females at a younger age. Nearly 80% of patients presented at an advanced stage. Cervical lymphadenopathy was the most common presenting feature, followed by involvement of the gastrointestinal tract. There were 59 cases of classic and 17 cases of blastoid and pleomorphic MCL, with diffuse pattern being the most common in 36 (47.4%) cases. In the present study, 64 (92.8%) cases expressed SOX11 and showed heterogeneous staining with high expression in 34 (53.1%) cases and low expression in 30 (46.9%) cases. Ki-67 proliferation of more than 30% was seen in 52 (68.4%) cases and 30% or less in 24 (31.6%) cases. None of these findings had statistically significant correlation with survival, though high Ki-67, high MCL International Prognostic Index (MIPI) and blastoid/pleomorphic cases had relatively worse Overall Survival (OS). Conclusion: MCL is a disease of the elderly and in the present study it affected females at a slightly younger age as compared to males. SOX11 expression was heterogeneous in neoplastic cells and was complementary to cyclin D1 for diagnosis of MCL however, the staining intensity had no effect on survival.

P53 is associated with high-risk and pinpoints TP53 missense mutations in mantle cell lymphoma.

SummarySurvival for patients diagnosed with mantle cell lymphoma (MCL) has improved drastically in recent years. However, patients carrying mutations in tumour protein p53 (TP53) do not benefit from modern chemotherapy‐based treatments and have poor prognosis. Thus, there is a clinical need to identify missense mutations through routine analysis to enable patient stratification. Sequencing is not widely implemented in clinical practice for MCL, and immunohistochemistry (IHC) is a feasible alternative to identify high‐risk patients. The aim of the present study was to investigate the accuracy of p53 as a tool to identify patients with TP53 missense mutations and the prognostic impact of overexpression and mutations in a Swedish population‐based cohort. In total, 317 cases were investigated using IHC and 255 cases were sequenced, enabling analysis of p53 and TP53 status among 137 cases divided over the two‐cohort investigated. The accuracy of predicting missense mutations from protein expression was 82%, with sensitivity at 82% and specificity at 100% in paired samples. We further show the impact of p53 expression and TP53 mutations on survival (hazard ratio of 3·1 in univariate analysis for both), and the association to risk factors, such as high MCL International Prognostic Index, blastoid morphology and proliferation, in a population‐based setting.

Mantle Hücreli Lenfoma Hastalarımızın Klinik ve Laboratuvar Özellikleri: Kesitsel Bir Çalışma

Mantle cell lymphoma (MCL) comprises less than 10% of non-Hodgkin's lymphoma cases. Major independent risk factors are identified as the MCL International Prognostic Index (MIPI) and Ki-67 proliferation index of tumor. The aim of this study is retrospectively evaluate MCL patients treated and followed-up in our department. Materials and Methods: This study included 27 MCL patients medical records of whom could be reached. The data was reviewed to figure out MIPI score, bone marrow involvement, extranodal involvement, treatment protocols, treatment response, relapse status, and transplant history. Patients were followed-up for a mean duration of 64.4 (1-246) months. Subsequent to the first-line treatment, complete response was achieved in 17 (63%) and partial response was achieved in 3 (11%) patients, whereas 7 (26%) patients experienced disease progression. Median PFS following first-line treatment was 29 (3-120) months. Based on the classification by MIPI scoring, low-risk patients had significantly longer median survival than that of high-risk patients (194 months vs 126 months, p=0.04), and the patients at moderate-risk had significantly longer PFS compared to high-risk patients (41month vs 3 months, p=0.025). Median age, stage III-IV, and short duration of PFS in patients with high MIPI score were our findings in parallel with available literature. R-hyper-CVAD/MTX-AraC was mostly preferred first-line treatment at our center with a shorter median PFS compared to literature. Given the expanding use of target-driven therapies for MCL, we believe our results are noteworthy in comparing such therapies with pre-existing therapies.

Effect of prognostic classification on temsirolimus efficacy and safety in patients with relapsed or refractory mantle cell lymphoma: a retrospective analysis.

BackgroundTemsirolimus, a selective inhibitor of the mammalian target of rapamycin, has demonstrated clinical benefit versus investigator’s choice (INV) of therapy in patients with relapsed/refractory mantle cell lymphoma (MCL).MethodsThis post hoc study retrospectively assigned simplified Mantle Cell Lymphoma International Prognostic Index (MIPI) scores (ie, secondary MIPI) based on parameters at the time of randomization in patients with MCL (N = 162) who received temsirolimus 175 mg once weekly for 3 weeks followed by once-weekly 75 mg or 25 mg or the INV of active therapy. Outcomes were analyzed according to the low-, intermediate- or high-risk category.ResultsPatient distribution by MIPI risk category was 31%, 39%, and 30% in the low-, intermediate-, and high-risk groups, respectively. Among patients in all categories, objective response rate (complete response + partial response) was higher in patients in the temsirolimus 175/75-mg group versus the INV group, respectively: 42% versus 0% (low-risk); 33% versus 5% (intermediate-risk); 10% versus 0% (high-risk). Median progression-free survival was significantly longer with temsirolimus 175/75 mg versus INV, respectively, in patients with intermediate (4.3 vs 1.9 months; P = 0.035) or high (4.5 vs 1.6 months; P = 0.0025) risk, and a trend toward improvement was observed in patients with low risk (5.3 vs 2.6 months; P = 0.091). Improvement in median overall survival was observed with temsirolimus 175/75 mg versus INV in low-risk patients (18.0 vs 10.5 months, respectively; P = 0.069).ConclusionsThis analysis suggests that, compared with INV, temsirolimus demonstrated benefit in all MIPI risk categories in patients with MCL. In all treatment groups, patients with high secondary MIPI scores at baseline faced a dismal prognosis.Trial registrationClinicalTrials.gov NCT00117598.Electronic supplementary materialThe online version of this article (doi:10.1186/s40164-015-0006-1) contains supplementary material, which is available to authorized users.

Mantle cell lymphoma epidemiology: a population-based study in France.

Only limited population-based data are available on mantle cell lymphoma (MCL), a relatively rare and aggressive mature B cell non-Hodgkin lymphoma (NHL) entity. We conducted an epidemiological study based on the three French registries devoted to haematological malignancies over the period 2002-2006. Main clinical features and management characteristics were collected. Incidence and survival rates were estimated, and independent prognostic factors were analysed. MCL was diagnosed in 135 patients between 2002 and 2006. Seventy-four percent of patients were men. Age-standardised incidence rate of MCL (per 100,000) was 1.1 in men and 0.26 in women. Median age at diagnosis was 72 years (range 30-92). Advanced-stage (III or IV) disease was diagnosed in 81.5 % of patients, and 55 % of them were identified as high risk according to MCL International Prognostic Index (MIPI). Median net survival time was 41 months (95 % confidence interval (CI), 38-62). Main independent prognostic factors were age at diagnosis, performance status and use of rituximab in first-line treatment. Median overall survival was 36 months (95 % CI, 27-40) for high MIPI and 60 months (95 % CI, 35-74) for low/intermediate MIPI patients (p = 0.02). This study confirms that MCL remains an aggressive NHL with a median overall survival less than 4 years and demonstrates that the use of rituximab has modified overall survival duration.

Is Early Hematopoietic Stem-Cell Transplantation Necessary in Mantle-Cell Lymphoma?

Is Early Hematopoietic Stem-Cell Transplantation Necessary in Mantle-Cell Lymphoma?

Detection of gene copy number aberrations in mantle cell lymphoma by a single quantitative multiplex PCR assay: clinicopathological relevance and prognosis value

The t(11;14)(q13;q32) is the hallmark of mantle cell lymphoma (MCL). Additional genetic alterations occur in the majority of cases. This study aimed to design a polymerase chain reaction (PCR) assay to determine the incidence and relevance of recurrent gene copy number aberrations in this disease. Forty-two MCL cases with frozen- or paraffin-embedded (FFPE) tissues were selected. Three different quantitative Multiplex PCR of Short Fluorescent Fragments (QMPSF) assays were designed to simultaneously analyse eight genes (CDKN2A, RB1, ATM, CDK2, TP53, MYC, CDKN1B, MDM2), to analyse the 9p21 locus (CDKN2A/CDKN2B) and FFPE tissues. Gains of MYC, CDK2, CDKN1B, and MDM2 were observed in 10% of cases. Losses of RB1, CDKN2A, ATM or TP53 were observed in 38%, 31%, 24% and 10% of cases, respectively. Analysis of the 9p21 locus indicated that, in most cases, tumours displayed a complete inactivation of p14(ARF)/p15I(NK4B)/p16I(NK4A). CDKN2A and MYC aberrations were associated with a high MCL international prognostic index (MIPI). CDK2/MDM2 gains and CDKN2A/TP53 losses correlated with an unfavourable outcome. PCR experiments with frozen and FFPE-tissues indicated that our approach is valid in a routine diagnostic setting, providing a powerful tool that could be used for patient stratification in combination with MIPI in future clinical trials.