Cyclin D1 Polymorphisms as Predictive and Prognostic Molecular Markers in 90 Mantle Cell Lymphoma Patients Treated with R-HyperCVAD.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1581-1581
Author(s):  
Michael A. Thompson ◽  
Tapan M. Kadia ◽  
B. Nebiyou Bekele ◽  
Michael Wang ◽  
Jorge E. Romaguera
Keyword(s):  
Molecular Markers ◽  
Cyclin D1 ◽  
Mantle Cell Lymphoma ◽  
Clinical Characteristics ◽  
Cell Lymphoma ◽  
Response Rates ◽  
Genotype Frequency ◽  
Free Survival ◽  
Mantle Cell ◽  
Exon 4

Abstract Background Mantle cell lymphoma (MCL) is an aggressive lymphoma with poor prognosis. Prognostic and predictive molecular markers may aid in identification of patients that may benefit from clinical trials of novel therapies. Cyclin D1 is a highly specific marker of MCL. Alternative splicing in the cyclin D1 gene (CCND1) is modulated by a frequent A/G polymorphism located within the splice donor region of exon 4. CCND1 genotype is associated with the age of onset of HNPCC and with shortened event free survival and greater risk of local relapse in resectable non-small cell lung cancer. Methods Samples were collected from 90 MCL patients treated with R-HyperCVAD from 1999 to 2002. The DNA was produced from peripheral blood lymphocytes and bone marrow using the Genomic extraction Kit (Promega, Madison, WI). The CCND1 exon 4 (codon 242) polymorphism was evaluated using pyrosequencing in the M. D. Anderson Cancer Center core facility as previously described (Kong et al. Cancer Res60:249–52, 2000). Genotype groups were correlated with clinical characteristics under an IRB approved protocol. Results The CCND1 genotype frequency for 90 MCL patients was G/G 20%, G/A 54%, A/A 26%. Clinical characteristics were not statistically significantly different between genotype groups. 89 patients were evaluable for response. The ORR at 6 cycles was 100% for all subjects. The CR+CRu rates were G/G 95%, G/A 85%, A/A 96% (p=0.048). The PR rate was higher for patients with genotype G/A (15%) compared to G/G (6%) and A/A (4%). There were no statistically significant differences with respect to failure free survival (FFS) between groups (p=0.361), although there was a trend for a higher FFS in the A/A genotype group. In addition, overall survival (OS) was higher for A/A genotype patients at 61 vs. 49 months for the other genotypes (p=0.01). Discussion In a previous study of 42 MCL patients the CCND1 genotype frequency was: G/G 31%, G/A 55%, and A/A 14% (Howe and Lynas. Haematologica86:563–9, 2001). They showed that CCND1 polymorphisms did not affect prognosis. However, the chemotherapy regimens were not defined in that study. In our study, a larger number of patients were treated homogeneously with the chemotherapy regimen of R-HyperCVAD. Response rates were high and differed slightly by CCND1 polymorphism. The OS was increased for the A/A genotype with a trend for higher FFS. The discrepancy with prior studies may be related to subject genotype frequencies, treatment regimen, and other factors. The CCND1 polymorphisms may have a different predictive yield with other treatment regimens - eg, bortezomib or mTOR inhibitors. Conclusions Response rates were high in all CCND1 genotype groups, but CR rates were lower in the G/A genotype patients. The OS was increased for the A/A genotype with a trend for higher FFS. Future studies should evaluate the role of CCND1 polymorphisms with other active agents against MCL.

Rituximab and CHOP Induction Therapy for Newly Diagnosed Mantle-Cell Lymphoma: Molecular Complete Responses Are Not Predictive of Progression-Free Survival

2002 ◽  
Vol 20 (5) ◽  
pp. 1288-1294 ◽  
Author(s):  
Orion M. Howard ◽  
John G. Gribben ◽  
Donna S. Neuberg ◽  
Michael Grossbard ◽  
Christina Poor ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Induction Therapy ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
Response Rates ◽  
Molecular Response ◽  
Newly Diagnosed ◽  
Chop Chemotherapy ◽  
Free Survival ◽  
Mantle Cell

PURPOSE: To evaluate the efficacy of rituximab and cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) induction therapy in patients with newly diagnosed mantle-cell lymphoma (MCL). PATIENTS AND METHODS: From March 1997 to May 1999, 40 previously untreated patients with stage II through IV MCL were treated with six cycles of rituximab and CHOP chemotherapy in a phase II trial. Pretreatment and interval peripheral-blood (PB) and bone marrow (BM) specimens were also analyzed by polymerase chain reaction (PCR) for tumor-specific BCL-1/immunoglobulin H (IgH) translocations and clonal IgH rearrangements. Study end points included clinical and molecular response rates and long-term progression-free survival (PFS). RESULTS: Forty-eight percent of patients achieved a complete response (CR)/CR unconfirmed (CRu), and 48% of patients obtained a partial response (PR). However, 28 of the 40 patients have already relapsed or developed progressive disease with a median PFS of 16.6 months. Twenty-five patients had PCR-detectable BCL-1/IgH or clonal IgH products in PB or BM at diagnosis. Nine of the 25 informative patients had no evidence of PCR-detectable disease in PB or BM after rituximab and CHOP therapy. However, patients who achieved molecular remissions in PB or BM had PFS similar to patients without molecular remissions (16.5 v 18.8 months, P = .51). CONCLUSION: Favorable clinical and molecular response rates associated with rituximab and CHOP chemotherapy do not translate into prolonged PFS in MCL. Nevertheless, rituximab and combination chemotherapy may transiently clear PB or BM of detectable tumor cells, prompting additional consideration of antibody-based in vivo purging in subsequent clinical trials.

scholarly journals A147 PRIMARY COLONIC MANTLE CELL LYMPHOMA: A RARE ENTITY

2021 ◽  
Vol 4 (Supplement_1) ◽  
pp. 138-140
Author(s):  
K Donaldson ◽  
S Nassiri ◽  
D Chahal ◽  
M F Byrne
Keyword(s):  
Case Report ◽  
Cyclin D1 ◽  
Mantle Cell Lymphoma ◽  
Transverse Colon ◽  
Cell Lymphoma ◽  
Rapid Progression ◽  
Rare Entity ◽  
Gi Bleeding ◽  
Gi Tract ◽  
Mantle Cell

Abstract Background Mantle cell lymphoma (MCL) is an aggressive subtype of B-cell non-Hodgkin lymphoma (NHL), often diagnosed at later stages with secondary gastrointestinal (GI) involvement. Primary GI MCL is rare and is not often discussed in the literature. Aims To increase awareness of a rare condition that is likely to be encountered but can be challenging to diagnose. Methods Case report and review of the literature. Results Case Report A 78-year-old man with multiple untreated vascular risk factors including atrial fibrillation and type 2 diabetes presented with acute onset left hemiplegia, dysarthria, and imaging consistent with a left pontine stroke. As part of his workup he underwent a CT abdomen/pelvis identifying an 11 x 5 cm intraluminal mass in the transverse colon. Previous screening colonoscopies, for family history of colon cancer, were notable for tubular adenomas without high-grade dysplasia at 13, 12, 10, 7, and 2 years prior to admission. The patient had 16 pounds of weight loss without other constitutional symptoms, change in bowel habits or evidence of GI bleeding. Bloodwork was notable for microcytic anemia (Hemoglobin 91 g/L, MCV 75 fL), from a normal baseline one year prior, without other cytopenias. C-reactive protein (44 mg/L) and GGT (164 U/L) were elevated. Other liver enzymes, lactate dehydrogenase, and electrolytes were normal. Colonoscopy revealed numerous polypoid lesions throughout the entire colon and a large non-obstructive mass with submucosal appearance in the transverse colon. Biopsies were taken from the large mass and one of the smaller polypoid lesions. Histology showed a sheet-like infiltrate of small lymphocytes within the lamina propria. Immunohistochemical staining was positive for CD20, BCL2, Cyclin D1, equivocal for CD5, and negative for BCL6 and CD3. Ki67 index approached 30%. A diagnosis of colonic MCL was made. Literature Review Primary MCL of the GI tract is rare, accounting for only 1 to 4% of all GI malignancies. There is a male and Caucasian predominance with a median age of 68 years at diagnosis. Presenting complaints may include abdominal pain, anorexia, and GI bleeding. Typical endoscopic features are small nodular or polypoid tumors, between 2mm and 2 cm in size, along one or more segments of the GI tract referred to as multiple lymphomatous polyposis (MLP). A single colonic mass is infrequently seen, highlighting the importance of endoscopy for diagnosis, as subtle findings may be missed on radiographic evaluation. Biopsies for immunohistochemistry are essential to distinguish MCL from other NHLs, as almost all cases express cyclin D1. Despite aggressive immunochemotherapy, prognosis is often poor due to MCL’s rapid progression and early relapse. Conclusions Primary GI MCL is a rare entity. Awareness is essential as evaluation and management differ from lymphoma at other sites, and other GI malignancies. Funding Agencies None

Cyclin D1 as an Aid in the Diagnosis of Mantle Cell Lymphoma in Skin Biopsies: A Case Report

2001 ◽  
Vol 23 (5) ◽  
pp. 470-476 ◽  
Author(s):  
Brent R. Moody ◽  
Nancy L. Bartlett ◽  
David W. George ◽  
Caroline R. Price ◽  
Wayne A. Breer ◽  
...  
Keyword(s):  
Case Report ◽  
Cyclin D1 ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Mantle Cell ◽  
Skin Biopsies

scholarly journals Therapeutic Activity of Lenalidomide in Mantle Cell Lymphoma and Indolent Non-Hodgkin’s Lymphomas

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Marco Gunnellini ◽  
Lorenzo Falchi
Keyword(s):  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Single Agent ◽  
Response Rates ◽  
Prognostic Scores ◽  
Cell Transplant ◽  
Survival Times ◽  
Phase Ii Studies ◽  
Mantle Cell ◽  
Hodgkin's Lymphomas

Mantle cell lymphoma (MCL) comprises 3–10% of NHL, with survival times ranging from 3 and 5 years. Indolent lymphomas represent approximately 30% of all NHLs with patient survival largely dependent on validated prognostic scores. High response rates are typically achieved in these patients with current first-line chemoimmunotherapy. However, most patients will eventually relapse and become chemorefractory with poor outcome. Alternative chemoimmunotherapy regimens are often used as salvage strategy and stem cell transplant remains an option for selected patients. However, novel approaches are urgently needed for patients no longer responding to conventional chemotherapy. Lenalidomide is an immunomodulatory drug with activity in multiple myeloma, myelodisplastic syndrome and chronic lymphoproliferative disorders. In phase II studies of indolent NHL and MCL lenalidomide has shown activity with encouraging response rates, both as a single agent and in combination with other drugs. Some of these responses may be durable. Optimal dose of lenalidomide has not been defined yet. The role of lenalidomide in the therapeutic armamentarium of patients with indolent NHL or MCL will be discussed in the present paper.

Antitumoral Activity of Lenalidomide in In Vitro and In Vivo Models of Mantle Cell Lymphoma Involves the Destabilization of Cyclin D1/p27KIP1 Complexes

2013 ◽  
Vol 20 (2) ◽  
pp. 393-403 ◽  
Author(s):  
Alexandra Moros ◽  
Sophie Bustany ◽  
Julie Cahu ◽  
Ifigènia Saborit-Villarroya ◽  
Antonio Martínez ◽  
...  
Keyword(s):  
Cyclin D1 ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Antitumoral Activity ◽  
In Vivo Models ◽  
Mantle Cell

MCL-049: Clinical Characteristics and Outcomes of Primary Versus Secondary Gastrointestinal (GI) Mantle Cell Lymphoma (MCL)

2020 ◽  
Vol 20 ◽  
pp. S257-S258
Author(s):  
Yucai Wang ◽  
Aung Tun ◽  
Alessia Castellino ◽  
David Inwards ◽  
Thomas Witzig ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Clinical Characteristics ◽  
Cell Lymphoma ◽  
Mantle Cell

scholarly journals Dysregulation of cyclin D1 by translocation into an IgH gamma switch region in two multiple myeloma cell lines [see comments]

Blood ◽  
1996 ◽  
Vol 88 (2) ◽  
pp. 674-681 ◽  
Author(s):  
M Chesi ◽  
PL Bergsagel ◽  
LA Brents ◽  
CM Smith ◽  
DS Gerhard ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Cyclin D1 ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Myeloma Cell ◽  
Switch Region ◽  
Chromosomal Locus ◽  
Multiple Myeloma Cell ◽  
Mantle Cell ◽  
Switch Regions

Translocations involving the IgH locus at chromosomal locus 14q32.3 are a common event in many B-cell malignancies. The translocations, which generally occur into JH and switch regions, are mediated by errors in the two developmentally regulated, lymphocyte-specific pathways: VDJ- and switch-mediated recombination. Dysregulation of cyclin D1 by a t(11;14)(q13;q32) translocation occurs in most cases of mantle-cell lymphoma and in approximately 30% of multiple myeloma (MM) tumors in which a 14q32 translocation can be detected. We show here that in two of three myeloma lines that overexpress cyclin D1, there is an 11;14 translocation into a gamma switch region, suggesting an error in switch recombination. By contrast, 11;14 translocations in mantlecell lymphoma are invariably into or near a JH segment, suggesting an error in VDJ recombination. This is consistent with the fact that myeloma cells have undergone lgH switch recombination, whereas mantle-cell lymphoma cells generally have not.

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