Mantle cell lymphoma patients in first relapse: we pretty much know what to do.
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ABSTRACT:
SUBMITTER: Quaglia FM
PROVIDER: S-EPMC8378770 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:In young and fit patients with mantle cell lymphoma (MCL), intensive induction therapy followed by a consolidative autologous haematopoietic cell transplant (autoHCT) is the standard of care in the front-line setting. Recently, time-to-event analysis has emerged as an important risk assessment tool in lymphoma, though its impact in MCL is not well defined. We utilized the Center for International Blood and Marrow Transplant Research database to evaluate the effect of post-autoHCT time to relapse on overall survival (OS) over time in 461 patients who underwent autoHCT within 12 months of MCL diagnosis. On multivariate analysis, the impact of relapse on OS was greatest at the six-month [hazard ratio (HR) = 7·68], 12-month (HR = 6·68), and 18-month (HR = 5·81) landmark timepoints. Using a dynamic landmark model we demonstrate that adjusted OS at five years following each landmark timepoint improved with time for relapsing and non-relapsing patients. Furthermore, early relapse (<18 months) following autoHCT defines a high-risk group with inferior post-relapse OS. This retrospective analysis highlights the impact of time to relapse on OS in MCL patients undergoing up-front autoHCT and emphasizes the need to consider novel therapeutic approaches for patients suffering early relapse.
| S-EPMC8627449 | biostudies-literature
Project description:Mantle cell lymphoma (MCL) is a heterogeneous disease with high relapse rates. Limited data guide the use of surveillance imaging following treatment. We constructed a retrospective cohort from two academic institutions of patients with MCL who completed first-line therapy and underwent follow-up for relapse, analyzing the effect of surveillance imaging on survival. Of 217 patients, 102 had documented relapse, with 38 (37%) diagnosed by surveillance imaging and 64 (63%) by other methods. Relapse diagnosis by surveillance imaging had no significant advantage in overall survival from diagnosis date (hazard ratio [HR] = 0.80, p = .39) or relapse date (HR = 0.72, p = .22). Of 801 surveillance images, PET/CT had a positive predictive value (PPV) of 24% and number needed-to-scan/treat (NNT) of 51 to detect one relapse, and CT had a PPV of 49% and NNT of 24. For MCL after first-line therapy, relapse detection by surveillance imaging was not associated with improved survival and lacks clinical benefit.
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Project description:Mantle cell lymphoma (MCL) is a rare lymphoid malignancy with a poor prognosis characterised by frequent relapse and short durations of treatment response. Most patients present with aggressive disease, but there exist indolent subtypes without the need for immediate intervention. The very heterogeneous behaviour of MCL is genetically characterised by the translocation t(11;14)(q13;q32), leading to Cyclin D1 overexpression with distinct clinical and biological characteristics and outcomes. There is still an unfulfilled need for precise MCL prognostication in real-time. Machine learning and deep learning neural networks are rapidly advancing technologies with promising results in numerous fields of application. This study develops and compares the performance of deep learning (DL) algorithms and radiomics-based machine learning (ML) models to predict MCL relapse on baseline CT scans. Five classification algorithms were used, including three deep learning models (3D SEResNet50, 3D DenseNet, and an optimised 3D CNN) and two machine learning models based on K-nearest Neighbor (KNN) and Random Forest (RF). The best performing method, our optimised 3D CNN, predicted MCL relapse with a 70% accuracy, better than the 3D SEResNet50 (62%) and the 3D DenseNet (59%). The second-best performing method was the KNN-based machine learning model (64%) after principal component analysis for improved accuracy. Our optimised CNN developed by ourselves correctly predicted MCL relapse in 70% of the patients on baseline CT imaging. Once prospectively tested in clinical trials with a larger sample size, our proposed 3D deep learning model could facilitate clinical management by precision imaging in MCL.
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Project description:While classical nodal mantle cell lymphoma (cMCL) is often associated with involvement of multiple extranodal sites, isolated extranodal disease (ED) at the time of diagnosis is a rare event; data on the outcome of these forms are lacking. On behalf of the European MCL Network, we conducted a retrospective analysis on the clinical characteristics and outcomes of MCL presenting with isolated or predominant ED (MALT MCL). We collected data on 127 patients with MALT MCL diagnosed from 1998 to 2015: 78 patients (61%) were male with a median age of 65 years. The involved sites include: upper airways + Waldeyer ring (40; 32%), gastrointestinal tract (32; 25%), ocular adnexa (17; 13%), oral cavity and salivary glands (17; 13%) and others (13; 1%); 7 patients showed multiple extranodal sites. The median follow-up was 80 months (range: 6-182), 5-year progression-free survival (PFS) was 45% (95% CI: 35-54) and 5-year overall survival (OS) was 71% (95% CI: 62-79). In an explorative setting, we compared MALT MCL with a group of 128 cMCL patients: MALT MCL patients showed a significantly longer PFS and OS compared with nodal cMCL; with a median PFS of 4.5 years vs 2.8 years (p?=?0.001) and median OS of 9.8 years vs 6.9 years (p?=?0.018), respectively. Patients with MALT MCL at diagnosis showed a more favorable prognosis and indolent course than classical nodal type. This clinical variant of MCL should be acknowledged to avoid possible over-treatment.
| S-EPMC7000480 | biostudies-literature
Project description:Mantle cell lymphoma (MCL) is a rare, B cell non-Hodgkin's lymphoma with highly heterogeneous clinical presentation and aggressiveness. First-line treatment consists of intensive chemotherapy with autologous stem cell transplant for the fit, transplant eligible patients, or less intensive chemotherapy for the less fit (and transplant-ineligible) patients. Patients eventually relapse with a progressive clinical course. Numerous therapeutic approaches have emerged over the last few years which have significantly changed the treatment landscape of MCL. These therapies consist of targeted approaches such as BTK and BCL2 inhibitors that provide durable therapeutic responses. However, the optimum combination and sequencing of these therapies is unclear and is currently investigated in several ongoing studies. Furthermore, cellular therapies such as chimeric antigen receptor (CAR) T cells and bispecific T cell engager (BiTe) antibodies have shown impressive results and will likely shape treatment approaches in relapsed MCL, especially after failure with BTK inhibitors. Herein, we provide a comprehensive review of past and ongoing studies that will likely significantly impact our approach to MCL treatment in both the frontline (for transplant eligible and ineligible patients) as well as in the relapsed setting. We present the most up to date results from these studies as well as perspectives on future studies in MCL.
| S-EPMC7302387 | biostudies-literature
Project description:SAMHD1 (sterile alpha motif domain and histidine-aspartate domain-containing protein 1) is a deoxynucleoside triphosphate triphosphohydrolase regulating innate immune and modulating DNA damage signaling. It plays an important role in the development of some tumors. SAMHD1 was also reported as a barrier to cytarabine, a common chemotherapy drug for mantle cell lymphoma (MCL), and as a biomarker of grim prognosis for acute myelocytic leukemia (AML) patients. However, SAMHD1 expression and function in MCL have not been well-defined. In the present study, we evaluated SAMHD1 expression by immunohistochemistry and its gene structure by Sanger sequencing in MCL. Our results showed that SAMHD1 was positive in 36 (62.1%) patients. Importantly, SAMHD1-positive patients were associated with lower chemotherapy response rate (p = 0.023) and shorter overall survival (p = 0.039) than SAMHD1-negative cases. These results suggest that SAMHD1 is an adverse biomarker for MCL patients, which is due to the high expression of SAMHD1 and rapid cell proliferation. These findings were confirmed in an in vitro study using the siRNA technique. Silencing the SAMHD1 gene in the MCL cell line Jeko-1 significantly decreased cell proliferation and increased cell apoptosis. The MCL cell line with SAMHD1 knockdown showed lower Ki-67 proliferation index, higher caspase-3, and higher sensitivity to cytarabine. Furthermore, for the first time, four previously unreported missense mutations (S302Y, Y432C, E449G, and R451H) in exon 8 and exon 12 of the SAMHD1 gene were discovered by sequencing. The mutations had not been found to corelate with SAMHD1 protein expression detected by immunohistochemistry. The biological functions of this mutated SAMHD1 remain to be investigated.
| S-EPMC8719590 | biostudies-literature
Project description:SILAC analysis of fludarabine resistance in human Mino cells.
2015-08-03 | PXD002034 | Pride
Project description:BackgroundHigh-dose therapy and autologous stem cell transplantation (ASCT) improves outcomes for patients with mantle cell lymphoma (MCL), but relapse ultimately occurs in most patients. Recently presented interim results from a phase III prospective trial suggest maintenance rituximab (MR) after ASCT for MCL improves progression-free survival (PFS). The maturation of these data and any benefit of MR on overall survival (OS) remain to be defined.Patients and methodsIn this retrospective study, we examined a cohort of consecutive patients with MCL that underwent ASCT for MCL at our center and evaluated their outcomes according to whether they received MR after ASCT (n = 50) or did not (n = 107). MR was treated as a time-dependent covariate to account for variation in timing of its initiation.ResultsMR was associated with an improved PFS [hazard ratio (HR) 0.44; confidence interval (CI) (0.24-0.80), P = 0.007] and overall survival (OS; HR 0.46; CI 0.23-0.93, P = 0.03) following a multivariate adjustment for confounding factors with a median follow-up of ?5 years. Grade 4 neutropenia was increased (34% versus 18%, P = 0.04) in the MR group, but no effect on the rate of mortality unrelated to relapse was observed.ConclusionsThese data support that MR after ASCT for MCL confers a benefit in PFS and additionally suggest it may improve OS. General application of this strategy will require confirmation of benefit in prospective randomized trials.
| S-EPMC4621031 | biostudies-literature
Project description:Gene expression analyis of primary MCL including IGHV mutated and unmutated cases Gene set analysis was perfomed in MCL samples, comparing IGHV mutated cases vs. IGHV unmutated cases
2013-06-25 | GSE36000 | GEO
Project description:As the survival of patients with mantle cell lymphoma (MCL) continues to improve, patients are increasingly being treated with multiple regimens. However, outcome after each line remains poorly characterized in the modern era. To address this knowledge gap, we retrospectively studied 404 consecutive MCL patients who were managed between 2000 and 2014 at Memorial Sloan Kettering Cancer Center. Histologic diagnosis was centrally confirmed, and patients were followed longitudinally from diagnosis throughout their disease course. Progression-free survival (PFS) and overall survival (OS) were determined by Kaplan-Meier method. The median OS and PFS after first-line treatment were 9.7 and 4.0 years, respectively. After second-line therapy, the median OS and PFS were 41.1 and 14.0 months, third line were 25.2 and 6.5 months, and fourth line were 14.4 and 5.0 months. In patients less than 65 years, stem cell transplant (SCT)-based frontline regimens were associated with improved PFS compared with non-SCT regimens (median PFS: 86.2 versus 40.0 months; P < 0.01), with a trend toward longer OS (median OS: 165.0 versus 120.0 months; P = 0.06). Early treatment failure after first-line regimens was associated with worse OS (5.9 versus 2.5 years; P < 0.01). Our study should facilitate establishing proper endpoints for future clinical trials using novel treatment approaches.
| S-EPMC6527702 | biostudies-literature