Follicular Lymphoma: Prognostic Factors, Conventional Therapies, and Hematopoietic Cell Transplantation

Sehn, Laurie H.; Fenske, Timothy S.; Laport, Ginna G.

doi:10.1016/j.bbmt.2011.11.012

Cited by 19 publications

(13 citation statements)

References 84 publications

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“…by guest www.bloodjournal.org From associated with transformation in multiple studies. 2,17,20,22,23,58 If poor outcome in patients with BCL2-mutant FL is also widely replicated, this might serve as the foundation for further studies in FL. In particular, the assessment of BCL2 mutation status along with FLIPI could allow better stratification of FL patients in future clinical trials.…”

Section: Discussionmentioning

confidence: 99%

“…2015;125(4):658-667) Introduction Follicular lymphoma (FL) has a highly variable clinical course. [1][2][3] Although some patients do well for decades, often with limited therapy, at some point 30% to 50% of patients experience histologic transformation to a more aggressive lymphoma, usually diffuse large B-cell lymphoma (DLBCL). [4][5][6][7][8][9][10][11] This transformation, which is thought to reflect the acquisition of new genetic abnormalities leading to further genomic instability, [12][13][14][15][16] has generally been associated with a poor clinical outcome.…”

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confidence: 99%

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BCL2 mutations are associated with increased risk of transformation and shortened survival in follicular lymphoma

Correia¹,

Schneider²,

Dai³

et al. 2015

Blood

114

107

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Key Points• BCL2 mutations in FL correlate with activationinduced cytidine deaminase expression and frequently alter the amino acid sequence of the protein.• Mutations in the BCL2 coding sequence at diagnosis are associated with shortened time to transformation and earlier death due to lymphoma.Follicular lymphoma (FL), an indolent neoplasm caused by a t(14;18) chromosomal translocation that juxtaposes the BCL2 gene and immunoglobulin locus, has a variable clinical course and frequently undergoes transformation to an aggressive lymphoma. Although BCL2 mutations have been previously described, their relationship to FL progression remains unclear. In this study, we evaluated the frequency and nature of BCL2 mutations in 2 independent cohorts of grade 1 and 2 FLs, along with the correlation between BCL2 mutations, transformation risk, and survival. The prevalence of BCL2 coding sequence mutations was 12% in FL at diagnosis and 53% at transformation (P < .0001). The presence of these BCL2 mutations at diagnosis correlated with an increased risk of transformation (hazard ratio 3.6; 95% CI, 2.0-6.2; P < .0001) and increased risk of death due to lymphoma (median survival of 9.5 years with BCL2 mutations vs 20.4 years without; P 5 .012).In a multivariate analysis, BCL2 mutations and high FL international prognostic index were independent risk factors for transformation and death due to lymphoma. Some mutant Bcl-2 proteins exhibited enhanced antiapoptotic capacity in vitro. Accordingly, BCL2 mutations can affect antiapoptotic Bcl-2 function, are associated with increased activationinduced cytidine deaminase expression, and correlate with increased risk of transformation and death due to lymphoma. (Blood. 2015;125(4):658-667) Introduction Follicular lymphoma (FL) has a highly variable clinical course. [1][2][3] Although some patients do well for decades, often with limited therapy, at some point 30% to 50% of patients experience histologic transformation to a more aggressive lymphoma, usually diffuse large B-cell lymphoma (DLBCL). [4][5][6][7][8][9][10][11] This transformation, which is thought to reflect the acquisition of new genetic abnormalities leading to further genomic instability, [12][13][14][15][16] has generally been associated with a poor clinical outcome. 17 Retrospective analyses from the prerituximab era have reported a median survival of only 1 to 2 years after transformation, 18,19 although a recent prospective observational study suggests somewhat better survival after transformation in the rituximab era. 20 At the present time, the FL international prognostic index (FLIPI), which integrates patient characteristics at diagnosis, is the gold standard for predicting FL clinical outcome. 21,22 There is, however, considerable interest in identifying characteristics of the FL cells themselves that might also impact prognosis. 22,23 The BCL2 gene is critical for FL pathogenesis. 24,25 Originally identified because of its translocation to the immunoglobulin heavy chain (IGH) locus as a part of the t(14;18) ...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

BCL2 mutations are associated with increased risk of transformation and shortened survival in follicular lymphoma

Correia¹,

Schneider²,

Dai³

et al. 2015

Blood

114

107

View full text Add to dashboard Cite

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“…More recently, the American Society of Clinical Oncology (ASCO) proposed a modified Delphi approach and established the steps involved in detail, recognizing the importance of such methods for the development of guidelines when evidencebased data is scarce. 18 What differentiates this manuscript from the many other excellent reviews on the role of HSCT in patients with FL 17,26,27 is the fact that, in the current paper, the recommendations following the exhaustive review of the literature result from a systematic and objective procedure, rather than summarizing the pre-established views of a limited number of authors. Consensus methods increase the objectivity of experts' recommendations by guaranteeing that all participants involved in the process will be able to express their opinions and that all views will be equally valued.…”

Section: *Partial Consensus Onlymentioning

confidence: 99%

Indications for hematopoietic stem cell transplantation in patients with follicular lymphoma: a consensus project of the EBMT-Lymphoma Working Party

et al. 2013

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The aim of this project was to define indications for hematopoietic stem cell transplantation in follicular lymphoma in Europe. In the absence of evidence-based data, a RAND-modified Delphi procedure was used by an expert panel. After pre-defining statements, these were individually/anonymously scored by each participant using a 9-point scale. Consensus was reached that: 1) high-dose therapy with autologous stem cell rescue is not an appropriate option to consolidate first remission in patients responding to immuno-chemotherapy outside clinical trials; 2) in patients with first chemo-sensitive relapse, high-dose therapy with autologous stem cell rescue is an appropriate option to consolidate remission, especially in patients with a short response after immuno-chemotherapy or with high-risk FLIPI; 3) high-dose therapy with autologous stem cell rescue is also appropriate in second/subsequent chemo-sensitive relapses; 4) allotransplant (preferably a reduced intensity conditioning-allotransplant) should be considered at relapse after high-dose therapy with autologous stem cell rescue. No consensus was reached on the role of high-dose therapy with autologous stem cell rescue in low-risk first relapse, or on when an allotransplant should be preferred over high-dose therapy with autologous stem cell rescue. In the absence of evidence-based data, the consensus method used was a valuable tool to define indications for hematopoietic stem cell transplant in follicular lymphoma.

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“…9,10,45 Moreover, several reports have found no difference in outcome between FL grades 3a and 3b when treated with anthracycline-based therapy, and molecular studies identified comparable gene expression profiles between FL grade 3a and FL grade 3b. [11][12][13][14] These findings, the advent of new-targeted therapies, and the clinical followup with limited sampling of the disease (ie, peripheral blood, fine needle aspiration biopsies) strictly demand new diagnostic tools able to differentiate such similar diseases.…”

Section: Discussionmentioning

confidence: 99%

The miR-17-92 microRNA cluster: a novel diagnostic tool in large B-cell malignancies

Fassina

Marino

Siri

et al. 2012

Laboratory Investigation

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Diffuse large B-cell lymphoma (DLBCL) can present as de novo or can arise through the transformation of many indolent lymphomas, including follicular lymphoma (FL). The morphological differentiation between germinal center-DLBCL (GC-DLBCL) and high-grade (grade 3) FL could be challenging; the accurate sub-classification of large B-cell lymphomas is mandatory in order to select the most appropriate among the new-targeted therapies. Recent expression profiling studies reported microRNAs (miRNAs) (and miR-17-92 cluster, in particular) as useful tools in differentiating DLBCL and FL. However, these preliminary results are based on cell line-derived data or did not consider grade 3 FL cases. To investigate this point, 36 cases of GC-DLBCL and 18 cases of grade 3 non-transforming FL were considered. All diagnoses were based on the World Health Organization criteria and were confirmed by clinical, histological, and immunohistochemical data. Six members of the miR-17-92 cluster (ie, miR-18b, miR-19b, miR-20a, miR-92, miR-93, and miR-106a) and two control miRNAs (ie, miR-150 and miR-210) were quantified by quantitative reverse transcription-polymerase chain reaction. All the considered miR-17-92 cluster miRNAs were significantly overexpressed in GC-DLBCL, being miR-20a and miR-106a the most dysregulated (Po0.001). Receiver operating characteristics (ROCs) analysis was used to find the optimal cut-off in distinguishing the two histotypes. The ROC estimated thresholds for miR-18b, miR-19b, miR-20a, miR-92, and miR-106a displayed a sensitivity level higher than 0.80 in achieving the GC-DLBCL diagnosis. The classification tree built on the six thresholds allowed the correct identification of 35/36 GC-DLBCL (97.2%). Profiling the miR-17-92 cluster is a promising investigative method for differentiating GC-DLBCL from high-grade FL. Subject to the validation of these findings in further larger studies; miR-17-92 cluster could represent a reliable, standardizable diagnostic tool for the sub-classification of large B-cell lymphoid neoplasm.

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Follicular Lymphoma: Prognostic Factors, Conventional Therapies, and Hematopoietic Cell Transplantation

Cited by 19 publications

References 84 publications

BCL2 mutations are associated with increased risk of transformation and shortened survival in follicular lymphoma

BCL2 mutations are associated with increased risk of transformation and shortened survival in follicular lymphoma

Indications for hematopoietic stem cell transplantation in patients with follicular lymphoma: a consensus project of the EBMT-Lymphoma Working Party

The miR-17-92 microRNA cluster: a novel diagnostic tool in large B-cell malignancies

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