Computerized image analysis of the Ki-67 proliferation index in mantle cell lymphoma

2015 ◽  
Vol 67 (1) ◽  
pp. 62-69 ◽  
Author(s):  
Yngvild N Blaker ◽  
Marianne Brodtkorb ◽  
John Maddison ◽  
Tarjei S Hveem ◽  
John Arne Nesheim ◽  
...  
Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. LB1-LB1
Author(s):  
Christian H. Geisler ◽  
Erkki Elonen ◽  
Arne Kolstad ◽  
Anna Laurell ◽  
Niels Andersen ◽  
...  

Abstract Mantle cell lymphoma (MCL) is considered incurable, with a median survival of 4 years. Intensive immunochemotherapy and autologous stem-cell (ASC) support has appeared promising in small patient cohorts, but has not been tested in large, consecutive series. Here we report the final results of the 2nd Nordic MCL (MCL2) trial after a median of 3 years follow-up from study entry. Methods: This unrandomized phase-II trial included 159 untreated patients younger than 66 years, 84% stage IV, 128 with classical, 31 with blastoid/pleomorphic cytology. Following 6 cycles of intensive induction immunochemotherapy with alternating cycles of rituximab (R) + maxi-CHOP and R+ high-dose AraC, responders received BEAM/BEAC with in-vivo purged (R) ASC support. Results: 153 patients (96%) responded to induction therapy with CR in 55% and PR in 41%. The 5-year event-free (EFS) and overall survival (OAS) are 63% and 74% respectively on intention-to-treat, and the 144 (91%) responders who completed treatment had 72% 5-year response duration, with plateaus emerging in all three curves at these levels. Figure Figure There were 6 treatment-related deaths (3,8%). Of 77 patients with available primers, 90% had become PCR-negative two months posttransplant; those who remained PCR-negative more than 1 year posttransplant had a significantly longer clinical response duration than patients who did not (P<0.0001). Of 42 stem-cell products assessed 88% were PCR-negative as compared to only 12% in the MCL1 study (P<0.001). In a multivariate analysis including age, sex, international prognostic index (IPI), cytological variants and Ki-67 proliferation index, only IPI and Ki-67 were independent predictors of EFS and response duration respectively, and only IPI and cytological variant of OAS. Compared to the 41 patients of 1st Nordic MCL study who received 4 cycles of maxi-CHOP without rituximab before BEAM or BEAC + ASCT (1), the OAS, EFS and response duration were highly significantly increased. Conclusion: The demonstration of long-term event-free survival in a large, consecutive prospective series now for the first time indicates that intensive immunochemotherapy including AraC and Rituximab with in-vivo purged stem-cell support may cure mantle cell lymphoma.


2016 ◽  
Vol 51 (2) ◽  
pp. 127 ◽  
Author(s):  
Tae-Dong Jeong ◽  
Hyun-Sook Chi ◽  
Min-Sun Kim ◽  
Seongsoo Jang ◽  
Chan-Jeoung Park ◽  
...  

Blood ◽  
2015 ◽  
Vol 126 (5) ◽  
pp. 604-611 ◽  
Author(s):  
Marie-Hélène Delfau-Larue ◽  
Wolfram Klapper ◽  
Françoise Berger ◽  
Fabrice Jardin ◽  
Josette Briere ◽  
...  

Key Points CDKN2A and TP53 deletions remain of bad prognostic value in younger MCL patients treated according to the current standard of care. CDKN2A and TP53 deletions have independent deleterious effects and should be considered for treatment decisions in addition to MIPI and Ki-67 index.


Blood ◽  
2000 ◽  
Vol 95 (2) ◽  
pp. 619-626 ◽  
Author(s):  
Roberto Chiarle ◽  
Leo M. Budel ◽  
Jeffrey Skolnik ◽  
Glauco Frizzera ◽  
Marco Chilosi ◽  
...  

Mantle cell lymphoma (MCL) is an aggressive neoplasm characterized by the deregulated expression of cyclin D1 by t(11;14). The molecular mechanisms responsible for MCL's clinical behavior remain unclear. The authors have investigated the expression of p53, E2F-1, and the CDK inhibitors p27 and p21 in 110 MCLs, relating their expression to proliferative activity (Ki-67). For comparison, they have similarly analyzed low-grade (12 MALT, 16 CLL/SLL) and high-grade (19 DLCL) lymphomas. p53 was detected more frequently in large-cell MCL (l-MCL; 5 of 7) than in classical MCL (s-MCL; 13 of 103) and DLCL (8 of 19). In MCL and DLCL, the percentage of E2F-1+ nuclei was high, correlating with high Ki-67 expression. Most MCLs (91 of 112) and DLCLs (12 of 19) showed a loss of p27; MALT and CLL/SLL, however, were p27 positive. Reverse transcription–polymerase chain reaction and in vitro protein degradation assays demonstrated that MCLs have normal p27 mRNA expression but increased p27 protein degradation activity via the proteasome pathway. Correlation of MCL p53 and p27 expression with clinical data showed an association between reduced overall survival rates and the overexpression of p53 (P = .001), the loss of p27 (P = .002), or both. Loss of p27 identified patients with a worse clinical outcome among p53 negative cases (P = .002). These findings demonstrated that MCL has a distinct cell cycle protein expression similar to that of high-grade lymphoma. The loss of p27 and the overexpression of p53 in MCL are prognostic markers that identify patients at high risk. The demonstration that low levels of p27 in MCL result from enhanced proteasome-mediated degradation should encourage additional clinical trials. (Blood. 2000;95:619-626)


2020 ◽  
Vol 4 (15) ◽  
pp. 3486-3494
Author(s):  
Diego Villa ◽  
Laurie H. Sehn ◽  
Kerry J. Savage ◽  
Cynthia L. Toze ◽  
Kevin Song ◽  
...  

Abstract Rituximab-containing chemotherapy regimens constitute standard first-line therapy for mantle cell lymphoma (MCL). Since June 2013, 190 patients ≥18 years of age with MCL in British Columbia have been treated with bendamustine and rituximab (BR). The overall response rate to BR was 88% (54% complete response). Of these, 61 of 89 patients (69%) aged ≤65 years received autologous stem cell transplantation and 141 of 190 patients (74%) from the entire cohort received maintenance rituximab. Twenty-three patients (12%) had progressive disease, associated with high risk per the Mantle Cell Lymphoma International Prognostic Index (MIPI), Ki-67 ≥50%, and blastoid/pleomorphic histology. Outcomes were compared with a historical cohort of 248 patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP; January 2003 to May 2013). Treatment with BR was associated with significant improvements in progression-free survival (PFS), but not overall survival (OS), compared with R-CHOP in the whole cohort (3-year PFS, 66% BR vs 51% R-CHOP, P = .003; 3-year OS, 73% BR vs 66% R-CHOP, P = .054) and in those &gt;65 years of age (3-year PFS, 56% BR vs 35% R-CHOP, P = .001; 3-year OS, 64% BR vs 55% R-CHOP, P = .063). Outcomes in transplanted patients were not statistically significantly different compared with R-CHOP (3-year PFS, 85% BR vs 76% R-CHOP, P = .135; 3-year OS, 90% BR vs 88% R-CHOP, P = .305), although in multivariate analyses, treatment with BR was associated with improved PFS (hazard ratio, 0.40 [95% confidence interval, 0.17-0.94]; P = .036) but not OS. BR is an effective first-line option for most patients with MCL, however, outcomes are suboptimal for those with high-risk features and further studies integrating novel agents are warranted.


2011 ◽  
Vol 102 (9) ◽  
pp. Sep cover-Sep cover
Author(s):  
Yoshizo Kimura ◽  
Kensaku Sato ◽  
Yutaka Imamura ◽  
Fumiko Arakawa ◽  
Junichi Kiyasu ◽  
...  

Cancer ◽  
2013 ◽  
Vol 119 (18) ◽  
pp. 3318-3325 ◽  
Author(s):  
Zaher I. Chakhachiro ◽  
Rima M. Saliba ◽  
Grace-Julia Okoroji ◽  
Martin Korbling ◽  
Amin M. Alousi ◽  
...  

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