Primary Spinal Epidural Mantle Cell Lymphoma: Case Report

Neurosurgery ◽  
2000 ◽  
Vol 47 (5) ◽  
pp. 1239-1242 ◽  
Author(s):  
Maja Barnard ◽  
Bayardo Perez-Ordoñez ◽  
David W. Rowed ◽  
Lee Cyn Ang

Abstract OBJECTIVE AND IMPORTANCE Mantle cell lymphoma is a distinct clinicopathological type of non-Hodgkin's lymphoma that often presents at an advanced stage, with systemic spread. Spinal involvement is uncommon and generally occurs as part of advanced disease or generalized relapses. Primary spinal epidural lymphoma is a rare initial manifestation of non-Hodgkin's lymphoma, and mantle cell lymphoma with initial presentation in the spinal epidural space is extremely rare, having been previously reported in only two cases. CLINICAL PRESENTATION We report a case of a 71-year-old man who presented with increasing weakness and numbness of the legs. Magnetic resonance imaging revealed a spinal epidural mass in the lumbosacral region. INTERVENTION The patient underwent a partial L4 and L5–S1 laminectomy, with incomplete resection of the mass for spinal decompression and tissue diagnosis. Mantle cell lymphoma was diagnosed in the pathological examination. CONCLUSION After radiotherapy, the disease recurred with a soft-tissue mass in the anterior maxillary area of the face. The patient underwent restaging and was treated with chemotherapy, with only a partial response. Mantle cell lymphoma with primary spinal epidural presentation is rare. This diagnosis can be established and other causes of spinal cord compression can be ruled out by obtaining tissue for proper histopathological examinations. Because of its aggressive behavior and poor prognosis, mantle cell lymphoma should be treated using a combined-modality approach.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1574-1574 ◽  
Author(s):  
Peter R Moosmann ◽  
Marc Heizmann ◽  
Nina Kotrubczik ◽  
Mario Bargetzi ◽  
Martin Wernli

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.


2008 ◽  
Vol 26 (27) ◽  
pp. 4473-4479 ◽  
Author(s):  
K. Sue Robinson ◽  
Michael E. Williams ◽  
Richard H. van der Jagt ◽  
Philip Cohen ◽  
Jordan A. Herst ◽  
...  

PurposeBendamustine HCl is a bifunctional mechlorethamine derivative with clinical activity in the treatment of non-Hodgkin's lymphoma. This study evaluated bendamustine plus rituximab in 67 adults with relapsed, indolent B-cell or mantle cell lymphoma without documented resistance to prior rituximab.Patients and MethodsPatients received rituximab 375 mg/m2intravenously on day 1 and bendamustine 90 mg/m2intravenously on days 2 and 3 of each 28-day cycle for four to six cycles. An additional dose of rituximab was administered 1 week before the first cycle and 4 weeks after the last cycle. Sixty-six patients (median age, 60 years) received at least one dose of both drugs.ResultsOverall response rate was 92% (41% complete response, 14% unconfirmed complete response, and 38% partial response). Median duration of response was 21 months (95% CI, 18 to 24 months). Median progression-free survival time was 23 months (95% CI, 20 to 26 months). Outcomes were similar for patients with indolent or mantle cell histologies. The combination was generally well tolerated; the primary toxicity was myelosuppression (grade 3 or 4 neutropenia, 36%; grade 3 or 4 thrombocytopenia, 9%).ConclusionBendamustine plus rituximab is an active combination in patients with relapsed indolent and mantle cell lymphoma.


2019 ◽  
Vol 244 (11) ◽  
pp. 865-872
Author(s):  
Jia He ◽  
Khalid A Hajj ◽  
Christopher M Knapp ◽  
Kathryn A Whitehead

Mantle cell lymphoma is an aggressive subtype of non-Hodgkin’s lymphoma that claims the lives of tens of thousands of people every year. Although combination chemotherapy treatments such as CHOP have yielded promising outcomes in the clinic, the development of chemoresistance in patients has limited their long-term success. The lack of in vitro chemoresistance models has limited our ability to understand the mechanisms by which cells develop resistance, and thus our ability to develop novel therapeutics to overcome this issue. Here, we describe the development of a clinically relevant chemoresistant mantle cell lymphoma model using the JeKo-1 cell line. This was achieved through a stepwise treatment selection strategy using gradually increasing concentrations of CHOP. We show that resistant JeKo-1 cells display strong recovery and fast proliferation after treatment with an IC50 dose of CHOP. We also found that resistant JeKo-1 cells overexpress three oncogenes implicated in the development of mantle cell lymphoma—Cyclin D1, Mcl-1, and Bcl-2—compared to normal JeKo-1 cells. We anticipate that in vitro models such as this one will enable the discovery of new therapeutic strategies for overcoming chemoresistance and improve clinical outcomes in mantle cell lymphoma patients. Impact statement Mantle cell lymphoma remains one of the deadliest subtypes of non-Hodgkin’s lymphoma, in large part because patients become resistant to frontline chemotherapy. The development of strategies to treat advanced disease will be contingent upon testing in appropriate models. Most in vitro models of resistant mantle cell lymphoma are laboratory grade models that do not recapitulate the low level of chemoresistance typically observed in patients, limiting their utility. This study develops a clinically relevant in vitro model that can be used to establish the mechanisms of resistance and test new therapeutics intended to treat recurrent disease.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4946-4946
Author(s):  
Shuichi Ota ◽  
Junji Tanaka ◽  
Masanobu Nakata ◽  
Kiyotoshi Imai ◽  
Masahiro Ogasawara ◽  
...  

Abstract BACKGROUND. Synergistic or additive activities for rituximab and cladribine have been shown in preclinical studies. Indolent Non-Hodgkin’s lymphoma (I-NHL) tends to recur with shortening intervals of remission after standard chemotherapy. New modalities of treatment are necessary. Therefore, we evaluated the feasibility, efficacy, and toxicity of combined regimen that consisted of rituximab plus cladribine plus mitoxantrone (the RCM regimen) in the treatment of patients with relapsed or refractory I-NHL. METHODS. The RCM protocol consisted of rituximab at a dose of 375 mg/m2 on Day 1, cladribine at a dose of 0.09 mg/kg per day on Days 2 through 6, and intravenous mitoxantrone at a dose of 6 mg or 10 mg/m2 per day on Day 2. The RCM courses were repeated at 4-week intervals, for up to 4 cycles. RESULTS. Fourteen patients with I-NHL and one patient with mantle cell lymphoma entered in the study. The median age was 60 (range 47–77) and 8 were females. Histology was small lymphocytic lymphoma (n=1), follicular lymphoma (n=13), mantle cell lymphoma (n=1). Median time from diagnosis to RCM treatment was 3.6 (range 0.2–8.1) years and median number of prior treatment regimen was 2 (range 1–4). Twelve patients (80%) had recurrent disease after prior therapy including high dose therapy with autologous stem cell transplant, and 3 patients (20%) had refractory disease. Thirteen patients were treated on the RCM regimen, and 8 patients (61.5%) achieved a complete response, 3 patients (23.1%) achieved a partial response. Therefore, the overall response rate was 92.3%. Median time to response was 2.8 months (range 1.0–6.7). Median progression free survival of responders was 16.5 (range 1.3–25.5) months. The treatment revealed tolerability, with episodes of severe neutropenia (grade 3 and 4) observed in 12 patients (85.7%), episodes of grade 3 and 4 thrombocytopenia observed in 2 patients (15.4%). However, severe infections were not observed in any patients. CONCLUSIONS. The RCM regimen is highly effective and well tolerated modalities of treatment in heavily pretreated and relapsed or refractory patients with I-NHL.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e19529-e19529
Author(s):  
E. Braun ◽  
D. Katz ◽  
P. Venugopal ◽  
M. Larson ◽  
J. Shammo ◽  
...  

e19529 Background: Radioimmunotherapy is a therapeutic option for relapsed or refractory indolent, follicular and transformed non Hodgkin's lymphoma and mantle cell lymphoma. Although prolongued myelotoxicity has been described with use of iodine I 131 tositumomab (TOSI) and yttrium 90 ibritumomab tiuxetan (IBRI), analysis of toxicity according to patients’ age at therapy still lacks. Methods: Utilizing the Rush University Medical Center database 61 subjects who received RIT between November/2003 and June/2008, either with TOSI or IBRI were divided in 2 groups according to age at time of therapy. Group 1 included patients between 33 and 60 (51.8±6.5) years of age (N=29) and group 2 included patients 61 years old or older (70.1±7.8) (N=32). Parameters compared between groups were: Time to nadir of lowest absolute neutrophil count (ANC), time to recovery ANC above 1000/mcL, time to nadir of lowest hemoglobin levels, time to recovery to hemoglobin levels above 8g/dL, time to lowest platelet count and time to recovery to platelet count above 100,000/mcL. Incidence o myelodysplastic syndrome (MDS) was also compared between groups. Groups characteristics such as sex, type of RIT, presence of disease in bone marrow, FLIPI/IPI and use of G-CSF were noted. Results: There was no significant statistical difference between groups in time (number of days) to achieve nadir of ANC (group 1 85.3±208; group 2 50.3±19.9), nadir of hemoglobin levels (group 1 106±60.6; group 2 84±57.0) and time to nadir of platelet level (group 1 53.5±70.7; group 2 41.8±9.6). There was no statistical significant difference between groups in duration of cytopenias, except for time for platelet recovery which was significant longer in group 2 using the Pearson Correlation analysis. (p=0.008). (Days for platelets recovery to levels above 100,000/mcL group 1 29.4±27.7; group 2 108.8 ±207.3). One patient in group 1 and three patients on group 2 were diagnosed with MDS but were also treated with different chemotherapy regimens. Conclusions: RIT should be considered a safe therapeutic modality in patients with refractory or relapsed indolent, follicular, NHL, transformed and Mantle Cell lymphoma regardless of age. [Table: see text]


2005 ◽  
Vol 23 (4) ◽  
pp. 667-675 ◽  
Author(s):  
Andre Goy ◽  
Anas Younes ◽  
Peter McLaughlin ◽  
Barbara Pro ◽  
Jorge E. Romaguera ◽  
...  

Purpose Evaluate efficacy and toxicity of bortezomib in patients with relapsed or refractory B-cell non-Hodgkin's lymphoma. Patients and Methods Patients were stratified, based on preclinical data, into arm A (mantle-cell lymphoma) or arm B (other B-cell lymphomas) without limitation in number of prior therapies. Bortezomib was administered as an intravenous push (1.5 mg/m2) on days 1, 4, 8, and 11 every 21 days for a maximum of six cycles. Results Sixty patients with a median number of prior therapies of 3.5 (range, one to 12 therapies) were enrolled; 33 patients were in arm A and 27 were in arm B, including 12 diffuse large B-cell lymphomas, five follicular lymphomas (FL), three transformed FLs, four small lymphocytic lymphomas (SLL), two Waldenström's macroglobulinemias (WM), and one marginal zone lymphoma. In arm A, 12 of 29 assessable patients responded (six complete responses [CR] and six partial responses [PR]) for an overall response rate (ORR) of 41% (95% CI, 24% to 61%), and a median time to progression not reached yet, with a median follow-up of 9.3 months (range, 1.7 to 24 months). In arm B, four of 21 assessable patients responded (one SLL patient had a CR, one FL patient had a CR unconfirmed, one diffuse large B-cell lymphoma patient had a PR, and one WM patient had a PR) for an ORR of 19% (95% CI, 5% to 42%). Grade 3 toxicity included thrombocytopenia (47%), gastrointestinal (20%), fatigue (13%), neutropenia (10%), and peripheral neuropathy (5%). Grade 4 toxicity occurred in nine patients (15%), and three deaths from progression of disease occurred within 30 days of withdrawal from study. Conclusion Bortezomib showed promising activity in relapsed mantle-cell lymphoma and encouraging results in other B-cell lymphomas. Future studies will explore bortezomib in combination with other cytotoxic or biologic agents.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e19540-e19540
Author(s):  
Rouslan Kotchetkov ◽  
David Susman ◽  
Lauren Gerard ◽  
Erica DiMaria ◽  
Derek Wayne Nay

e19540 Background: Bendamustine plus rituximab (B+R) was established as a preferred first line therapy for patients with previously untreated indolent non-Hodgkin’s lymphoma based on the BRIGHT and STIL trials. However, only few reports on efficacy and safety data of this combination in the real-world setting are available to-date. Methods: We conducted a retrospective review of patients who received therapy with standard doses of B+R in our cancer center from June 2013 to January 2021. Patients with indolent non-Hodgkin’s lymphoma (iNHL) and mantle cell lymphoma (MCL) who received more than one cycle of B+R were evaluated. Results: Amongst a total of 201 patients 56% were males and 44% females. Median age at B+R initiation was 72 years (range 34-94). Follicular lymphoma (FL) (50.3%), marginal zone lymphoma (MZL) (19.4%), and lymphoplasmacytic lymphoma (LPL) (14.5%) were the most common iNHL. Stage 3 and 4 diseases represented 19.9% and 68.6% of patients. Extranodal disease was found in 35.8%. The proportion of patients with high risk disease was 48.5% for FL (FLIPI ≥3), 86.6% for LPL (WMISS score ≥2), and 80.5% for MCL (MIPI score ≥6.2). Prior history of secondary malignancy had 23.4% of patients; 11.4% patients had ECOG 3. Most common indications for B+R initiation were bulky symptomatic lymphadenopathy (69.1%), cytopenia (36.8%) and constitutional symptoms (36.8%). Fifty-eight percent of patients had more than one indication for therapy. Median number of B+R cycles delivered was 6 (range: 1-6), median dose of bendamustine was 90 mg/m2 (range 45-90). Full doses of treatment were given in 66.7% of patients, reduced in 33.3% with mean dose 78.3 mg/m2. A total of 50.8% completed 6 cycles with no delays, in 49.2% treatment was delayed (mean delay time 1.8 weeks). Overall response was 94.5%, with 77.6% complete and 16.9% partial remission. Median duration of follow-up was 35 months (range: 4-91). At the end of follow-up, event free survival (EFS) was 77.1% and overall survival (OS) was 79.6%. Six percent of patients relapsed, 8% developed secondary hematological malignancies, including 14 cases of aggressive B-cell lymphoma and 2 cases of MDS. 16.9% of patients required support with G-CSF. Grade 3-4 neutropenia was recorded in 22.4%, febrile neutropenia in 7.5%, grade 3-4 anemia in 7.9%, and grade 3-4 thrombocytopenia in 3.9% of patients. Rituximab-associated infusion reactions, skin rash, thrombophlebitis, and infection were the most common non-hematological adverse events. A total of 80.6% of patients proceeded to rituximab maintenance. Conclusions: B+R chemoimmunotherapy is feasible to administer in non-clinical trial setting. Despite more dose reduction as compared to STIL trial, B+R retained its efficacy with comparable EFS and OS. No new adverse events or increase in secondary malignancies were found.


2012 ◽  
Vol 2012 ◽  
pp. 1-4 ◽  
Author(s):  
Christopher B. Tan ◽  
Dhyan Rajan ◽  
Sumreen Majeed ◽  
Shadab Ahmed ◽  
Lester Freedman ◽  
...  

Mantle cell lymphoma (MCL) accounts for less than 10 percent of all non-Hodgkin’s lymphoma (NHL). Pathologic or spontaneous rupture of the spleen has been reported in patients with lymphoma; however only 5 cases have been reported in patients with MCL. Although splenomegaly occurs frequently in patients with MCL, spontaneous splenic rupture is rare. We present a case of a 51-year-old female with MCL, who presented to the medical emergency room with splenic rupture. This case illustrates that clinicians should be aware of the incidence and presentation of patients with MCL and spontaneous splenic rupture, as early detection and heightened suspicion may prevent potentially fatal outcomes.


Sign in / Sign up

Export Citation Format

Share Document