Outcome of Deferred Initial Therapy in Mantle-Cell Lymphoma

Martin, Peter; Chadburn, Amy; Christos, Paul J.; Weil, Karen; Furman, Richard R.; Ruan, Jia; Elstrom, Rebecca; Niesvizky, Rubén; Ely, Scott; DiLiberto, Maurizio; Melnick, Ari; Knowles, Daniel M.; Chen‐Kiang, Selina; Coleman, Morton; Leonard, John P.

doi:10.1200/jco.2008.19.6121

Cited by 305 publications

(185 citation statements)

References 25 publications

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“…Accordingly, it is difficult to compare the results of regimens applied in different phase II studies. In keeping with these concepts, 19 of 20 patients in this study had a low risk or intermediate MIPI score and in fact some authors have even suggested a watch and wait strategy in such low risk patients [13]. However, if therapy has to be initiated the combination of rituximab and chlorambucil represents a very attractive therapeutic approach with very few side effects even when compared to the recently presented data on bendamustine in indolent and mantle cell lymphoma [14].…”

supporting

confidence: 53%

Chlorambucil in indolent mantle cell lymphoma – just another old drug for a new disease?

Dreyling

Polliack²,

Tadmor

2011

Leukemia & Lymphoma

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supporting

confidence: 53%

Chlorambucil in indolent mantle cell lymphoma – just another old drug for a new disease?

Dreyling

Polliack²,

Tadmor

2011

Leukemia & Lymphoma

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“…In patients with SLL, a WW strategy is indicated as an initial approach, with treatment considered only for patients with disease-related symptoms or progressive or advanced stage disease [12]. A small subset of MCL, identified by lack of SOX11 expression, is associated with indolent behaviour and favorable prognosis with no need for immediate treatment, compared to the common SOX11+MCL [13]. These patients are generally asymptomatic, with a normal serum lactate dehydrogenase level and no lymphadenopathies.…”

Section: Introductionmentioning

confidence: 99%

Whole body magnetic resonance in indolent lymphomas under watchful waiting: The time is now

et al. 2017

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The indolent non-Hodgkin lymphomas (i-NHLs) are characterised by 'indolent' clinical behaviour with slow growth and prolonged natural history. The watchful waiting (WW) strategy is a frequently employed treatment option in these patients. This implies a strict monitoring by imaging examinations, including 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG-PET/CT) and CT. A major concern is radiation exposure due to regularly monitoring by conventional imaging procedures. Several studies have demonstrated the reliability of whole-body magnetic resonance imaging (WB-MRI) for lymphoma staging. WB-MRI could be useful for active surveillance in iNHLs providing the suspect of disease progression that can be then confirmed by additional diagnostic procedures, including 18F-FDG-PET/CT. The directive 2013/59 by the European Union claims that if a radiation-free imaging technique allows obtaining the same diagnostic results, it should be invariably used.In this setting, WB-MRI may be considered a reasonable option in i-NHLs under WW, replacing imaging modalities that cause exposure to ionising radiations. This will help to reduce the cancer risk in i-NHL patients for whom chemo-/radiotherapy remain the usual treatment options following the usually long WW phase. The scientific community should raise the awareness of the risk of ionising radiations in i-NHLs and the emphasise the need for establishing the proper place of WB-MRI in lymphoma imaging. Key Points• Watchful waiting is a reasonable option in patients with indolent non-Hodgkin lymphomas.• Imaging is crucial to monitor patients with indolent nonHodgkin lymphomas.• CT and 18 F-FDG-PET/CT are commonly used, implying a substantial radiation exposure.• WB-MRI is highly reliable in lymphoma staging.• WB-MRI may be considered to monitor indolent nonHodgkin lymphomas under watchful waiting.

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“…Most MCL cases have a rapid evolution and an aggressive behavior with an unfavorable outcome with current therapies (5). Paradoxically, a subset of patients follows an indolent clinical evolution with stable disease even in the absence of chemotherapy (6,7). This favorable behavior has been associated with IGHV-mutated (8,9) and lack of expression of SOX11 (10, 11), a transcription factor highly specific of MCL that contributes to the aggressive behavior of this tumor (12).…”

mentioning

confidence: 99%

Landscape of somatic mutations and clonal evolution in mantle cell lymphoma

Beà

Valdés-Mas

Navarro

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

457

342

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Mantle cell lymphoma (MCL) is an aggressive tumor, but a subset of patients may follow an indolent clinical course. To understand the mechanisms underlying this biological heterogeneity, we performed whole-genome and/or whole-exome sequencing on 29 MCL cases and their respective matched normal DNA, as well as 6 MCL cell lines. Recurrently mutated genes were investigated by targeted sequencing in an independent cohort of 172 MCL patients. We identified 25 significantly mutated genes, including known drivers such as ataxia-telangectasia mutated (ATM), cyclin D1 (CCND1), and the tumor suppressor TP53; mutated genes encoding the anti-apoptotic protein BIRC3 and Toll-like receptor 2 (TLR2); and the chromatin modifiers WHSC1, MLL2, and MEF2B. We also found NOTCH2 mutations as an alternative phenomenon to NOTCH1 mutations in aggressive tumors with a dismal prognosis. Analysis of two simultaneous or subsequent MCL samples by whole-genome/whole-exome (n = 8) or targeted (n = 19) sequencing revealed subclonal heterogeneity at diagnosis in samples from different topographic sites and modulation of the initial mutational profile at the progression of the disease. Some mutations were predominantly clonal or subclonal, indicating an early or late event in tumor evolution, respectively. Our study identifies molecular mechanisms contributing to MCL pathogenesis and offers potential targets for therapeutic intervention.next-generation sequencing | cancer genetics | cancer heterogeneity M antle cell lymphoma (MCL) is a mature B-cell neoplasm characterized by the t(11;14)(q13;q32) translocation leading to the overexpression of cyclin D1 (1). CCND1 is a weak oncogene that requires the cooperation of other oncogenic events to transform lymphoid cells (2). Molecular studies have identified alterations in components of the cell-cycle regulation, DNA damage response, and cell survival pathways (3, 4), but the profile of mutated genes contributing to the pathogenesis of MCL and cooperating with CCND1 is not well defined (1). Most MCL cases have a rapid evolution and an aggressive behavior with an unfavorable outcome with current therapies (5). Paradoxically, a subset of patients follows an indolent clinical evolution with stable disease even in the absence of chemotherapy (6, 7). This favorable behavior has been associated with IGHV-mutated (8, 9) and lack of expression of SOX11 (10, 11), a transcription factor highly specific of MCL that contributes to the aggressive behavior of this tumor (12). However, the molecular mechanisms responsible for this clinical heterogeneity are not well understood.To gain insight into the molecular pathogenesis of MCL we performed whole-genome sequencing (WGS) and whole-exome sequencing (WES) of 29 MCL and further investigated mutated genes in an expanded series of patients. We also analyzed the subclonal heterogeneity of the tumors and their modulation during the evolution of the disease. Results Landscape of Mutations in MCL.We performed WGS and WES of 4 and 29 MCL, respectively. These patients were re...

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Outcome of Deferred Initial Therapy in Mantle-Cell Lymphoma

Abstract: In selected asymptomatic patients with MCL, deferred initial treatment ("watch and wait") is an acceptable management approach.

Cited by 305 publications

References 25 publications

Chlorambucil in indolent mantle cell lymphoma – just another old drug for a new disease?

Chlorambucil in indolent mantle cell lymphoma – just another old drug for a new disease?

Whole body magnetic resonance in indolent lymphomas under watchful waiting: The time is now

Landscape of somatic mutations and clonal evolution in mantle cell lymphoma

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