Clonally related composite follicular lymphoma and mantle cell lymphoma with clinicopathologic features and biological implications

2013 ◽  
Vol 44 (12) ◽  
pp. 2658-2667 ◽  
Author(s):  
Shi Wang ◽  
Alexander Tzankov ◽  
Zijun Y. Xu-Monette ◽  
Sylvia Hoeller ◽  
Sa A. Wang ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Clinicopathologic Features ◽  
Mantle Cell

scholarly journals Radioimmunotherapy for Mantle Cell Lymphoma: 5-Year Follow-up of 90 Patients from the International RIT-Registry

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5263-5263
Author(s):  
Karin Hohloch ◽  
Christine Windemuth-Kieselbach ◽  
Pier Luigi Zinzani ◽  
Roberto E. Cacchione ◽  
Wojciech Jurczak ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Mantle Cell Lymphoma ◽  
Board Of Directors ◽  
Research Funding ◽  
Cell Lymphoma ◽  
Primary Therapy ◽  
First Line ◽  
Advisory Committees ◽  
Mantle Cell

To assess the efficacy of radioimmunotherapy (RIT) with 90yttrium-ibrutinib-tiuxetan (90Y-IT) in mantle cell lymphoma, data from 90 patients registered in the RIT Network with a median follow-up (FU) of 5.5 years after RIT were evaluated. 90Y-IT was given as first-line therapy in 45 (50%) (consolidation 44 pts., primary therapy 1 pt.) and at relapse in 45 (50%) patients (consolidation 24 pts., recurrence 12 pts., therapy refractory 3 pts., conditioning 2 pts., other 4 pts.). As a first-line treatment, 30 patients (pts.) (67%) achieved CR, 10 pts. (22%) PR%., 1 pt. (2%) PD, and for 4 pts. (9%) no response data was available. At relapse, CR was achieved in 17 pts. (38%), PR in 6 pts. (13%), SD in 2 pts. (4%), and 6 pts. (13%) had PD, while the response was not documented for 14 pts. (31%). After a median FU of 5.5 years, median PFS for all patients was 2.11 (95%CI: 1.03-2.32) years, and median OS was 4.05 (95%CI 2.79-7.21) years. Eleven pts. (12.2%) developed second malignancy. In conclusion, this is the largest report of MCL pts. treated with 90Y-IT to date. 90Y-IT was most often used as consolidation after first- and second-line chemotherapy and may improve the results achieved using chemoimmunotherapy alone. However, the results are less encouraging compared to treatment with small molecules such as ibrutinib. Disclosures Zinzani: TG Therapeutics: Honoraria, Speakers Bureau; Kyowa Kirin: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Portola: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Immune Design: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sandoz: Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celltrion: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Verastem: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Eusapharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Consultancy. Jurczak:Sandoz: Membership on an entity's Board of Directors or advisory committees, Research Funding; Loxo: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Research Funding; Roche: Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Research Funding; Bayer: Research Funding; Gilead: Research Funding; MorphoSys: Research Funding; Incyte: Research Funding; Novo Nordisk: Research Funding; Servier: Research Funding; TG Therapeutics: Research Funding; Celtrion: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding. Truemper:Seattle Genetics, Inc.: Research Funding; Takeda: Consultancy, Research Funding; Roche: Research Funding; Nordic Nanovector: Consultancy; Mundipharma: Research Funding; Janssen Oncology: Consultancy. Scholz:Janssen-Cilag: Consultancy; Hexal: Consultancy; Takeda: Consultancy; Novartis: Consultancy; Celgene: Consultancy; Pfizer: Speakers Bureau; Roche: Consultancy; GILEAD: Consultancy, Speakers Bureau; Daiichi Sankio: Consultancy. OffLabel Disclosure: Yttrium 90 (90Y) Ibritumomab Tiuxetan (Zevalin) is approved for treatment of patients with relapsed follicular lymphoma and as consolidation therapy after chemo(immuno)therapy of patients with follicular lymphoma.

Successful in vivo purging of CD34-containing peripheral blood harvests in mantle cell and indolent lymphoma: evidence for a role of both chemotherapy and rituximab infusion

Blood ◽  
2000 ◽  
Vol 96 (3) ◽  
pp. 864-869 ◽  
Author(s):  
Michele Magni ◽  
Massimo Di Nicola ◽  
Liliana Devizzi ◽  
Paola Matteucci ◽  
Fabrizio Lombardi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Follicular Lymphoma ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Bone Marrow Involvement ◽  
Hematopoietic Stem ◽  
Mantle Cell

Abstract Elimination of tumor cells (“purging”) from hematopoietic stem cell products is a major goal of bone marrow–supported high-dose cancer chemotherapy. We developed an in vivo purging method capable of providing tumor-free stem cell products from most patients with mantle cell or follicular lymphoma and bone marrow involvement. In a prospective study, 15 patients with CD20+ mantle cell or follicular lymphoma, bone marrow involvement, and polymerase chain reaction (PCR)–detectable molecular rearrangement received 2 cycles of intensive chemotherapy, each of which was followed by infusion of a growth factor and 2 doses of the anti-CD20 monoclonal antibody rituximab. The role of rituximab was established by comparison with 10 control patients prospectively treated with an identical chemotherapy regimen but no rituximab. The CD34+ cells harvested from the patients who received both chemotherapy and rituximab were PCR-negative in 93% of cases (versus 40% of controls;P = .007). Aside from providing PCR-negative harvests, the chemoimmunotherapy treatment produced complete clinical and molecular remission in all 14 evaluable patients, including all 6 with mantle cell lymphoma (versus 70% of controls). In vivo purging of hematopoietic progenitor cells can be successfully accomplished in most patients with CD20+ lymphoma, including mantle cell lymphoma. The results depended on the activity of both chemotherapy and rituximab infusion and provide the proof of principle that in vivo purging is feasible and possibly superior to currently available ex vivo techniques. The high short-term complete-response rate observed suggests the presence of a more-than-additive antilymphoma effect of the chemoimmunotherapy combination used.

Weekly Treatment with a Combination of Bendamustine and Bortezomib in Relapsed or Refractory Indolent Non-Hodgkin’s Lymphoma: A Single- Center Phase 1/2 Study.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1574-1574 ◽  
Author(s):  
Peter R Moosmann ◽  
Marc Heizmann ◽  
Nina Kotrubczik ◽  
Mario Bargetzi ◽  
Martin Wernli
Keyword(s):  
Adverse Events ◽  
Follicular Lymphoma ◽  
Mantle Cell Lymphoma ◽  
Hodgkin’S Lymphoma ◽  
Cell Lymphoma ◽  
Phase 1 ◽  
Hodgkin's Lymphoma ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Mantle Cell

Abstract Besides its established role in the treatment of patients with multiple myeloma, the proteasome inhibitor bortezomib is active in patients with a variety of indolent non-Hodgkin’s lymphomas, notably mantle cell lymphoma and follicular lymphoma. Bendamustine was originally designed as a bifunctional anticancer compound combining an alkylating and an antimetabolite function. It has strong efficacy in non-Hodgkin’s lymphoma and multiple myeloma, and apparently low cross-resistance with other alkylating agents. This open label, single-center phase 1/2 study evaluated a weekly combination of bortezomib and bendamustine in patients with relapsed or refractory indolent non-Hodgkin’s lymphoma. The primary endpoint was to define the maximal tolerated dose (MTD). Secondary endpoints were tolerability and response. On days 1, 8, 15, and 22 of a 35-day cycle, patients received intravenous bolus bortezomib 1.6 mg/m2 for a maximum of 3 cycles. Bendamustine was administered as 30-min. intravenous infusion on days 1, 8, and 15. Dose escalation was started at a dose of 60 mg/m2 bendamustine. Response was assessed at the end of study treatment. Four patients entering the first dose level showed no dose-limiting toxicity (DLT). Thereupon, bendamustine dosage was increased to 80 mg/m2. In 3 out of 5 patients, DLT was observed. Dose-limiting adverse events were grade 3 diarrhea with dehydration, fatigue, and grade 4 thrombocytopenia, respectively. Adverse events with an overall incidence of ≥20% were diarrhea, nausea, vomiting, thrombocytopenia, and fatigue. There were no infectious or dose-limiting neurological adverse events. The 9 patients (7 females) in the phase 1 part of this trial, 5 with relapsed, 4 with refractory stage III (n=2) or stage IV (n=7) disease, received a median of 2 treatment cycles (range 2–3). Median age was 71 yrs (range 55–85). Detailed histological diagnoses were mantle cell lymphoma (n=4), follicular lymphoma (n=4), and Waldenstroem’s macroglobulinemia (n=1). All patients were pretreated (median 3 lines of treatment, range 2–8). Prior treatments comprised rituximab (n=7), anthracyclines (n=4), ibritumomab tiuxetan (n=2), bortezomib (n=2), and autologous stem cell transplantation (n=1). The reasons for not completing the planned 3 treatment cycles were DLT (n=2), and disease progression (n=3). As best response, partial remission was achieved in 6 patients, while disease progressed in 3 patients. Among the different types of lymphoma, partial remissions were observed in all 4 mantle cell lymphoma patients, 1 out of 4 follicular lymphoma patients, and in the Waldenstroem’s macroglobulinemia patient. The trial’s phase 2 part is currently ongoing. In conclusion, weekly bortezomib and bendamustine (1.6 mg/m2 d1, 8, 15, & 22 and 60 mg/m2 d1, 8, & 15 q5w, respectively) was found to have acceptable toxicity. Moreover, this study demonstrates initial evidence of efficacy of the combination in heavily pretreated patients with indolent non-Hodgkin’s lymphoma, particularly mantle cell lymphoma.

Nuclear Expression of the Sox 11 Transcription Factor in Mantle Cell Lymphoma, and Cytoplasmic Expression in Follicular Lymphoma and Multiple Myeloma: Pathogenetic Implications.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2925-2925
Author(s):  
Michael E Williams ◽  
Sarah Rutherford ◽  
Yunjia Tang ◽  
John Cousar
Keyword(s):  
Multiple Myeloma ◽  
Transcription Factors ◽  
Follicular Lymphoma ◽  
Cyclin D1 ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Direct Result ◽  
Cytoplasmic Expression ◽  
Mantle Cell ◽  
Sox11 Expression

Abstract Abstract 2925 Poster Board II-901 Mantle cell lymphoma (MCL) is characterized by nuclear cyclin D1 expression resulting from the t(11;14)(q13;q32). As cyclin D1 overexpression alone is insufficient for B-cell transformation, we have investigated other potentially contributing mutations. Sox11 is a member of a large family of transcription factors containing a DNA-binding high-mobility group (HMG) domain and shares homology with Sox4, which is involved in lymphopoiesis. Recent reports have identified Sox11 expression in the majority of MCL, suggesting it may contribute to pathogenesis (Ek et al, Blood 2008;111:800; Wang et al, Br J Haematol 2008;143:248). Methods: Patients with MCL diagnosed at the Univ. of Virginia from 1997-2008 and for whom nodal, marrow or spleen tissue blocks were available were identified from the Pathology database. Follicular lymphoma (FL), marginal zone lymphoma (MZL), small lymphocytic lymphoma (SLL), hairy cell leukemia (HCL) and multiple myeloma (MM) were also analyzed. Formalin-fixed, paraffin-embedded samples were stained by immunohistochemistry for cyclinD1, Sox11 (rabbit a/Sox11, 1:100, Sigma) and Ki-67. Nuclear and/or cytoplasmic expression was determined by two of us (YT, JC). Results: All MCL samples revealed nuclear cyclin D1 expression. Nuclear but not cytoplasmic Sox11 expression was identified in all 24 non-blastoid and in 5/6 blastoid samples; 1 blastoid sample showed only cytoplasmic Sox11 staining (Table). Four of 5 HCL expressed cyclin D1 but were negative for Sox11; 4/5 MM also were cyclin D1-positive, with 3 positive for cytoplasmic Sox11 including 2 of the cyclin D1-positive cases. All 5 FL showed cytoplasmic Sox11 positivity, whereas all MZL and SLL were negative for cytoplasmic or nuclear staining. Conclusions: Nuclear Sox11 expression was uniformly identified in MCL, with the exception of cytoplasmic expression in a single blastoid case. No nuclear Sox11 was present in HCL or MM despite the expression of cyclin D1, although 3 MM showed cytoplasmic Sox11 staining. These findings suggest that nuclear Sox11 overexpression is not a direct result of dysregulated cyclin D1 signaling but instead occurs by alternative mechanisms. The significance of cytoplasmic staining remains uncertain. A potential pathogenetic role for Sox11 and possibly other Sox family transcription factors warrants further investigation in MCL and other lymphoproliferative neoplasms for diagnostic use and therapeutic targeting. Disclosures: No relevant conflicts of interest to declare.

Clinicopathologic features, management and outcomes of blastoid variant of mantle cell lymphoma: a Nebraska Lymphoma Study Group Experience

2015 ◽  
Vol 57 (6) ◽  
pp. 1327-1334 ◽  
Author(s):  
Vijaya R. Bhatt ◽  
Fausto R. Loberiza ◽  
Lynette M. Smith ◽  
James O. Armitage ◽  
Timothy C. Greiner ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Study Group ◽  
Clinicopathologic Features ◽  
Mantle Cell ◽  
Lymphoma Study Group ◽  
Group Experience

scholarly journals Weekly versus twice weekly bortezomib given in conjunction with rituximab, in patients with recurrent follicular lymphoma, mantle cell lymphoma and Waldenström macroglobulinaemia

2010 ◽  
Vol 151 (4) ◽  
pp. 346-353 ◽  
Author(s):  
Agathoclis Agathocleous ◽  
Ama Rohatiner ◽  
Simon Rule ◽  
Hannah Hunter ◽  
Jonathan Paul Kerr ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Mantle Cell

Influence of rituximab plus bendamustine chemotherapy on the immune system in patients with refractory or relapsed follicular lymphoma and mantle cell lymphoma

2014 ◽  
Vol 56 (4) ◽  
pp. 1123-1125 ◽  
Author(s):  
Kaori Ito ◽  
Masataka Okamoto ◽  
Maiko Ando ◽  
Yukiko Kakumae ◽  
Akinao Okamoto ◽  
...  
Keyword(s):  
Immune System ◽  
Follicular Lymphoma ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Mantle Cell

Successful PBSC Mobilization, Collection, Transplantation and Engraftment after Radioimmunotherapy with Yttrium-90 Ibritumomab Tiuxetan for Non-Hodgkin’s Lymphoma (NHL).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5517-5517 ◽  
Author(s):  
Pamela Ely ◽  
Diane M. Stearns ◽  
Bassem I. Zaki ◽  
Thomas F. Fitzmaurice ◽  
Marc Gautier ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Median Number ◽  
Cell Transplant ◽  
Ibritumomab Tiuxetan ◽  
Autologous Transplant ◽  
Cd34 Cells ◽  
Mantle Cell ◽  
Yttrium 90

Abstract Radioimmunotherapy (RIT) is a useful addition to the armamentarium against NHL. Due to concerns about chronic myelosuppression and the possible inability to mobilize stem cells or tolerate further therapy after RIT, this modality has not been commonly utilized in potential transplant candidates. We report the successful mobilization, collection, transplantation and engraftment of 5 patients with NHL following yttrium-90 ibritumomab tiuxetan. Patients had follicular lymphoma, grade I or II (n=3), transformed follicular lymphoma (n=1) or blastic variant mantle cell lymphoma (n=1). Time from RIT to mobilization was 10 months (median; range 7–27 months). The median number of regimens prior to RIT was 2.5 (range 1–4) including prior autologous transplant (n=1). The median number of regimens following RIT and prior to transplant was 1.5 (range 1–2). All patients exhibited chemosensitive disease. Patients were mobilized with R-ICE/G-CSF (n=4) or G-CSF alone (n=1) and required 2.8 leukaphereses (mean; range 2–5). The CD34 yield was 3.8x106 CD34+ cells/kg (median; range 3.4–5.1x106 CD34+ cells/kg). All patients received busulfan, VP-16, ARA-C and cyclophosphamide (BVAC) as the preparatory regimen. One patient received IL-2 from day 0 to day 11. Time to engraftment was 13 days (median; range 9–19 days) for an absolute neutrophil count (ANC) >500 cells/ml and 23 days (median; range 15–44 days) for a platelet count>20x103/ml. The patient on the IL-2 study showed delayed engraftment of both ANC (day 19) and platelets (day 27). The patient with mantle cell lymphoma, who was undergoing his second autologous transplant, exhibited delayed platelet engraftment (day 44). Time to engraftment did not differ significantly for either ANC (p=0.16) or platelets (p=0.10) in 18 RIT-naïve NHL patients receiving BVAC and an autologous peripheral blood stem cell transplant (PBSC) during the same time period. There were no treatment-related deaths. With a median follow up of 12 months, one patient has died of disease recurrence. Two patients remain in complete remission. Two patients are alive with disease (relapse at 12 months and 14 months) and are currently receiving therapy. No patient has demonstrated laboratory or cytogenetic evidence of a myelodysplastic syndrome. In conclusion, heavily pretreated patients who have received radioimmunotherapy with yttrium-90 ibritumomab tiuxetan and subsequently relapse can successfully undergo mobilization, collection, and autologous PBSC transplant. These patients demonstrate full engraftment, durable remissions and tolerate additional therapy should relapse occur following transplant.

Sign in / Sign up

Export Citation Format

Share Document