Mantle Cell Lymphoma: Current Concepts
Journal of Hematology & Thromboembolic Diseases

Journal of Hematology & Thromboembolic Diseases
Open Access

ISSN: 2329-8790

+44 7868 792050

Review Article - (2015) Volume 3, Issue 4

Mantle Cell Lymphoma: Current Concepts

Manish K. Pant, Weaam Alshenawy, Ahmed Alrajjal, Hussain Alrobeh and Imad A Tabbara*
George Washington University Medical Center, Pennsylvania Ave NW, Washington, USA
*Corresponding Author: Imad A Tabbara, M.D., FACP, Professor of Medicine, Director Blood & Marrow Stem Cell Transplant Program, George Washington University, 2150 Pennsylvania Avenue, NW, Suite 1-200, Washington, DC 20037, USA, Tel: 202 741 2478, Fax: 202 741 2487 Email:


Mantle Cell Lymphoma is a rare B-cell malignancy that can invade almost any structure in the body and recur after short-lived clinical responses. The pathogenesis and clinical features are well defined, but management has not yet been optimized. Induction with traditional immune-chemotherapy regimens that are used in other non- Hodgkin lymphomas rarely generate durable remissions. Therefore, clinical research is needed to improve treatment of de novo disease and to establish safe and effective regimens for maintenance and salvage options for relapsed or refractory disease. This comprehensive review discusses disease pathogenesis and focuses on emerging treatment paradigms using novel targeted therapies.

Keywords: Mantle cell lymphoma; Cyclin D1; MIPI score; Rituximab; Bortezomib; Ibrutinib; Idelalisib


Mantle cell lymphoma (MCL) is an uncommon but aggressive lymphoma, comprising about 6% of all non-Hodgkin lymphomas [1] with a typical median survival of 5-7 years [2]. Patients are much more commonly male and elderly [3] with a median age of onset of 68 years [4]. The disease is less frequent in Asian countries [4]. Most cases are advanced at presentation and often exhibit complete responses to initial treatment followed by frequent relapses [3].

This neoplasm is characterized by mature B-lymphocytes that infiltrate the lymph nodes, bone marrow, peripheral blood, and extranodal sites [3]. Histologic appearance is homogenous with a background of pink histiocytes that stain positively for cyclin D1, surface immunoglobulin B-cell markers, and CD5 [3]. While the t (11;14) (q13;q32) translocation is present in over 90% of MCL, other translocations have been reported. Disease heterogeneity features both a blastoid variant with a high Kiel 67 (Ki67) proliferation index, as well as a more indolent variant that can be appropriately managed with a watch and wait approach until symptomatic [3].

Younger, fit patients can be managed with intensive cytarabine-containing chemotherapy alternating with hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone combined with rituximab (R-HyperCVAD) with or without autologous stem cell transplantation for consolidation. Other patients receive CHOP-like (cyclophosphamide, doxorubicin, vincristine, prednisone) therapy plus rituximab. Substitution of vincristine with the proteasome inhibitor bortezomib has emerged as a validated treatment for both relapsed and untreated disease.

Awareness of prognostic factors through the validated MIPI score [5], identification of potential transplant candidates, and careful assessment of response to and tolerance of immunochemotherapies, are all crucial determinants of both survival and quality of life.


MCL can be distinguished by immunohistochemistry (IHC) with a profile usually showing positivity for B-cell markers as well as CD5, FMC7, CD43, and cyclin D1. Most cases are negative for CD10 and CD23. The reciprocal translocation t (11;14) results in the overexpression of cyclin D1 [6]. In less than 5% of cases, cyclin D1 and t (11;14) may be negative in MCL if there is an otherwise typical IHC profile, with over half of these cases revealing rearranged CCND2 and consequent overexpression of cyclin D2 mRNA [7]. Most pathologic findings and clinical features of cyclin D1-negative MCL appear similar to those of cyclin D1-positive cases [8], and should be managed the same.


The pathogenesis of mantle cell lymphoma (MCL) occurs through two major events that cause a gain of function and loss of function. Chromosome 11q13 holds the proto-oncogene CCND1, which encodes cyclin D1, and its translocation to chromosome 14q32, the locus of the immunoglobulin heavy chain complex (IGH), deregulates the cell cycle at the G1/S phase transition and makes cyclin D1 constitutively overexpressed in otherwise normal B lymphocytes. Gain of function occurs via t (11;14) translocation, causing BCL-1 over-transcription. Loss of function occurs via 11q22-23 deletion, altering the DNA damage pathway response. Thus, the cyclin D1 protein has a major oncogenic effect through two different mechanisms [9].

MCL carries a high degree of genomic instability, with multiple secondary chromosomal alterations. Its pathogenesis was traditionally thought to derive from naïve B-cells in the pre-germinal center (e.g. mantle zone) since the initial translocation event t (11;14) (q13;q32) occurs during recombination of the V(D)J segments of the IGH variable region (IGHV) in the bone marrow. However, the tumor is composed of mature B lymphocytes. Antigen selection is now thought to play an important role in pathogenesis for the 15-40% of MCLs that carry IGHV hypermutations similar to those in chronic lymphocytic leukemia [10].

Cyclin D1 binds to CDK4 and CDK6, which phosphorylates retinoblastoma 1 (RB1), thereby activating the transcription factor E2F while promoting cyclin E/CDK2 activation to trigger entry into the S phase of the cell cycle [11]. Additional oncogenic interactions by cyclin D1 include chromatin remodeling and histone-modifying enzymes. Secondary chromosome alterations that also affect DNA damage response and cell survival pathways are now thought to facilitate aggressive MCL because the CDKN2A locus (9p21), which encodes for both the CDK inhibitor INK4a and the positive p53 regulator ARF, is frequently deleted in these cases [11].


The round cell variant has a CLL-like clinical presentation that tends to behave more like an indolent lymphoma. These cases usually show a rather low cell proliferation (Ki-67 roughly 10%). On the other hand, a blastoid variant occurring 5% of the time shows a much more aggressive clinical course. Biological factors like high cell proliferation (determined by Ki-67 staining) or p53 mutations and p16 deletions are closely related to this MCL subtype. However, more than 80% of MCL still presents with somewhat intermediate characteristics. Whereas immediate initiation of treatment is indicated for the majority of patients, select cases may be closely observed to more reliably estimate the aggressiveness of the disease [12].

Prognostic Markers

In 2008, Hoster et al. [5] devised a system to categorize MCL patients’ relative survival probability by grading the following risk factors: age, performance status, lactate dehydrogenase (LDH) level, and white blood cell (WBC) count. This system is outlined in Table 1. A MIPI combined biologic index (MIPIb) score of less than 5.7 classifies patients into a low-risk group comprising 44% of patients with a median overall survival (OS) not reached; a score of 5.7 to less than 6.2 yields an intermediate-risk group comprising 35% of patients with median OS of 51 months; and a score of 6.2 or greater falls into the high-risk group with 21% of the patients and median OS of 29 months. It is notable that the number of extranodal sites is not an independent prognostic factor in the MIPI score. Tumor cell proliferation, assessed on paraffin-embedded tissue by Ki-67, showed a median value of 14.5% (range 1.2–91%). This value was also prognostically significant using a cutoff point of 10%, and was independent of the MIPI. Ki-67 of 30% has been proposed by the NCCN as a cutoff for determining the aggressiveness of the disease, but should not constitute an indication to begin treatment [13].

MIPIb Index Score* Risk Patient percentage Overall survival
<5.7 Low risk 44% Not reached
5.7 to £ 6.2 Intermediate risk 35% 51 months
³ 6.2 High risk 21% 29 months

Table 1: MIPI Score. *Survival probability by grading the following risk factors: age, performance status, lactate dehydrogenase (LDH) level, white blood cell (WBC) count, and Ki-67.

Induction Therapy

Stage I and non-bulky Stage II

Localized presentation, which is extremely rare, can be managed with observation, radiation therapy, or a combination of radiation and chemotherapy. Retrospective data suggests that use of radiotherapy with or without chemotherapy engendered significantly better progression-free survival (PFS) at 5 years (73% vs. 13%; p=0.001) with a trend towards overall survival benefit, when compared to patients who did not receive radiation [14]. Radiotherapy as a primary treatment for stage 1-2 MCL patients analyzed retrospectively showed curative results for 3.6% of patients, with 3-year OS of 93% [15].

Bulky Stage II, Stage III, and Stage IV

Enrollment in clinical trials is recommended for eligible patients with systemic disease, in whom no cure is currently available. In highly select cases in which the patient is asymptomatic, advanced disease can also be managed with a watch and wait approach.

R-HyperCVAD (rituximab, cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with high-dose methotrexate and cytarabine) is considered a preferred aggressive regimen in patients who can tolerate considerable toxicity. A phase II study of 97 treatment-naïve patients with advanced MCL showed failure-free survival of 64% and overall survival of 82% at 3 years, and median overall survival not yet reached at 10 years follow-up [16]. The SWOG 0213 phase II multicenter trial of newly diagnosed patients under the age of 70 who received R-HyperCVAD yielded PFS of 4.8 years and OS of 6.8 years, with 2-year PFS of 63% and OS of 76% [17].

The Nordic regimen includes induction immunochemotherapy with rituximab plus maxi-CHOP (cyclophosphamide, vincristine, doxorubicin, prednisone) alternating with rituximab and high-dose cytarabine. The Cancer and Leukemia Group B (CALGB) regimen features induction with rituximab-methotrexate with augmented CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) for at least 2 cycles, with an additional cycle if the bone marrow contains greater than 15% involvement by MCL.

A phase III randomized trial of the German Low Grade Lymphoma study group [18] evaluated the addition of rituximab to CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine, prednisone) in treatment-naïve patients with advanced MCL aged 65 and younger. R-CHOP showed significantly better overall response rate (94% vs. 75%), complete remission rate (34% vs. 7%) and median time to treatment failure (21 months vs. 14 months) than CHOP. However, PFS and OS outcomes were not superior. R-CHOP can also be alternated with R-DHAP (rituximab, dexamethasone, cisplatin, cytarabine) or R-ICE (rituximab, ifosfamide, carboplatin, etoposide) in sequence.

For elderly patients or those with poor performance status, bendamustine plus rituximab (BR) has shown superior PFS than R-CHOP (35 months vs. 22 months; HR=0.49, 95% CI 0.28-0.79; p=0.0044) in primary MCL according to subgroup analysis of the phase III STiL study [19]. Of note, adverse events and grade 3 and 4 toxicities were significantly less in the BR treatment arm.

Another less aggressive induction regimen to gain FDA approval is VR-CAP (bortezomib, rituximab, cyclophosphamide, doxorubicin, prednisone). When compared to R-CHOP in patients who were not transplant-eligible, front-line VR-CAP showed superior PFS (24.7 vs. 14.4 months, p<0.001) and CR rate (48% vs. 41%) with a trend towards OS benefit (64% vs. 54%) in a phase III randomized study [20].

Of note, VR-CAP incurred slightly more high-grade adverse events (93% vs. 84%), but most were considered manageable. VR-CAP was again compared to R-CHOP in a recently published study of 487 patients with at least stage II disease [21]. The median PFS was 14.4 months in the R-CHOP group and 24.7 months in the VR-CAP group (hazard ratio favoring the VR-CAP group, 0.63; p<0.001), and there was consistent progression-free survival benefit across all prespecified subgroups and irrespective of MIPIb and Ki-67 score [21]. VR-CAP is currently the only first-line regimen approved by the FDA.

A Summary of the treatment regimens is presented in Table 2.

Treatment Study Overall response rate (ORR) Overall survival rate (OS) Progression Free Survival (PFS) Failure Free Survival Complete remission rate (CR) Median time to treatment failure (TTTF)
R-HyperCVAD Phase II study of 97 de novo advanced MCL (15) - 82% at 3 years - 64% - -
R-HyperCVAD SWOG 0213 phase II study of de novo pts <70 yo (16) - 76% 4.8 years 2-year PFS of 63% - - -
R-CHOP Phase III study of advanced MCL pts £ 65 yo (17) 95% Not superior Not superior - 34% 21 months
Bendamustine + Rituximab Subgroup analysis of Phase III study (18) - - 35 months - - -
VR-CAP Phase III study (20) - 64% 24.7 vs. 14.4 months - 48% -

Table 2: Induction therapy.

Consolidation therapy

Following successful induction with R-HyperCVAD or CHOP-like immunochemotherapy, high-dose therapy (HDT) with one cycle of etoposide, cytarabine, and rituximab and one cycle of carmustine, etoposide, and cyclophosphamide has been effectively followed by autologous stem cell rescue (ASCR). Thirty-three patients treated at MD Anderson after achieving first remission with HyperCVAD with or without rituximab achieved 5-year disease-free survival of 42% and OS of 77% [22], with 100% OS rate in those patients with a low serum beta-2 microglobulin level. Long-term follow-up showed a median PFS of 42 months and OS of 93 months [23]. Non-randomized analysis suggests an improved PFS in transplanted patients who were induced with HyperCVAD (with or without rituximab) rather than CHOP (with or without rituximab) [24].

Post-induction maintenance therapy with rituximab has been shown to provide extended disease control for patients who cannot undergo high-dose therapy and stem cell transplantation. In one pilot phase II study of 22 patients with newly diagnosed MCL, a dose-reduced R-HyperCVAD (omitting methotrexate and cytarabine) followed by maintenance therapy with rituximab for 5 years yielded a PFS of 37 months and median OS not reached, with acceptable toxicity [25]. Additional studies have also shown promising data for rituximab maintenance after R-CHOP induction [26,27], and it remains unclear whether first-line consolidation with high-dose chemotherapy with autologous stem cell rescue (HDT/ASCR) provides an advantage over rituximab maintenance in patients of any age. No randomized trial data are currently available to compare intensive consolidation regimens against maintenance therapy.

Table 3 provides a summary of the current consolidation/maintenance regimens.

Treatment Study Overall survival rate (OS) Progression Free Survival (PFS) 5-year disease-free survival (DFS)
HyperCVAD +/- Rituximab Long-term follow-up of auto-SCT in pts with diffuse MCL in first CR (21) 77%100% (patients with low serum B2 Microglubulin) 42 months 42%
Long-term follow-up HyperCVAD +/- Rituximab followed by MD Anderson after achieving first remission Mature results of the M.D. Anderson Cancer Center risk-adapted transplantation strategy in MCL (22) 93 months 42 months -

Table 3: First-line consolidation.

Second-line therapy

Second-line consolidation therapy can be pursued with autologous or allogeneic stem cell transplantation (SCT) following non-myeloablative or myeloablative conditioning regimens. A study of 112 patients who had previously failed conventional chemotherapy underwent a preparative conditioning regimen that consisted of etoposide, cyclophosphamide, mesna, and fractionated total-body irradiation (TBI). Patients who were not eligible for TBI because of prior exposure to radiation received BEAM (carmustine–etoposide–cytarabine–melphalan) for conditioning instead. Graft-versus-host disease (GVHD) prophylaxis consisted of a combination of cyclosporin or tacrolimus with mini-dose methotrexate and/or methylprednisolone. Nine patients received interferon-α maintenance after autologous SCT. Allo-SCT in 44 patients resulted in lower recurrence rates but higher treatment-related mortality rates than the 68 patients who underwent high-dose therapy with autologous stem cell transplantation [28]. Outcomes were initially more favorable for the autologous SCT group (significant only for day 100 mortality); however, this pattern changed over time. A plateau was seen amongst the allogeneic SCT group at 44 months after transplantation for OS and at 24 months for DFS, whereas there was a continuous pattern of treatment failure in the autologous SCT group. The improved OS among the allogeneic SCT group was not statistically significant (p>0.05) but the improved DFS was significant (p=0.01). A similar pattern of DFS was observed when 19 patients with chemoresistant disease who underwent allogeneic SCT were compared with 26 patients with chemosensitive disease who underwent autologous SCT (p=0.04). The rate of disease progression was significantly higher in the autologous SCT group (74%; 95% CI 59% to 88%) than in the allogeneic SCT group (19%; 95% CI 9% to 38%) with p=0.003 [28].

Additional regimens suitable for use in first relapse include: bendamustine with or without rituximab [29]; cladribine [30]; FC (fludarabine plus cyclophosphamide) with or without rituximab; FCMR (fludarabine, cyclosphamide, mitoxantrone, and rituximab); FMR (fludarabine, mitoxantrone, and rituximab); PCR (pentostatin, cyclophosphamide, and rituximab); and PEPC (prednisone, etoposide, procarbazine, cyclophosphamide with or without rituximab).

Novel Agents

Bortezomib is approved by the U.S. Food and Drug Administration (FDA) for relapsed or refractory MCL based on the phase II PINNACLE trial, in which bortezomib induced an overall response rate of 33% (CR in 8%), with a median duration of response of 9 months and median time to progression of 6 months [31]. Long-term follow-up confirmed these effects [32]. Bortezomib combined with rituximab has shown activity in heavily pre-treated patients with relapsed/refractory disease.

The immunomodulating agent, lenalidomide, has shown efficacy in relapsed or refractory aggressive non-Hodgkin lymphoma, with subset analysis of MCL patients showing an ORR of 35% and CR rate of 12% at a median follow-up of 12 months in a phase II trial [33]. In this study the duration of response was 16 months, and the median PFS was approximately 9 months.

Another recent phase II study of patients with rituximab-resistant B-cell lymphomas [34] treated 43 patients with lenalidomide 10 mg by mouth daily for 8 weeks followed by 4 weekly doses of rituximab 375 mg/m2 intravenously. Six out of the eleven patients with MCL showed a clinical response (3 CR, 1 Cru, 2 PR); the addition of rituximab did not change the ORR, although two PR improved to CR [4].

The small-molecule Bruton’s tyrosine kinase (BTK) inhibitor, ibrutinib, has shown promising activity in several B-cell malignancies. Subgroup analysis of phase I data in 9 patients with relapsed and/or refractory MCL showed response in 7 patients, including a CR in 3 patients, with no dose-limiting toxicities and no significant myelosuppression even with the full dose of 560 mg daily [35]. A multicenter phase II trial of 111 patients who had been previously treated with bortezomib and/or rituximab-containing regimens, 72% of whom had advanced disease and 42% of whom had high-risk MIPI scores, showed an ORR of 68% with CR rate of 21% after 15 months of ibrutinib [36]. The median duration of response was 17.5 months, median PFS was 14 months, and estimated OS rate at 18 months was 58%. The response rates appeared to increase with longer duration of therapy. In November 2013, the FDA approved ibrutinib to treat MCL on the basis of an “unprecedented” response. The most common adverse event rated grade ≥3 were neutropenia (16%), thrombocytopenia (11%), anemia (10%), pneumonia (6%), diarrhea (6%), fatigue (5%) and dyspnea (5%). The use of ibrutinib causes a transient lymphocytosis that resolves after an average of 8 weeks, and caused grade ≥3 bleeding events in 5% of patients [37]. Thus, ibrutinib is emerging as a potential preferred salvage option due to ease of daily oral dosing and favorable side effect profile.

Although ibrutinib can extend the lives of heavily treated, relapsed, or refractory patients with mantle cell lymphoma (MCL), many become resistant to the drug. Analysis of longitudinal functional genomics in MCL [38] showed that 30% of the patients who developed resistance to ibrutinib expressed high levels of activated phosphatidylinositol-3 kinase (PI3K-AKT) and cyclin-dependent kinase 4 (CDK4). (PI3K-AKT proteins promote survival; CDK4 drives MCL cells through the cell cycle.) These two mechanisms appeared to override ibrutinib’s inhibitory action in resistant cells. An experimental selective CDK4/CDK6 inhibitor, palbociclib, has demonstrated cytotoxicity against the mutated BTKC481S protein.

Stepwise treatment with palbociclib followed by ibrutinib, or palbociclib followed by the PI3K pathway inhibitor, idelalisib, which is FDA-approved to treat CLL, might treat MCL patients who initially do not respond to ibrutinib. Or, the drugs given together might prevent resistance.

A 48-week study using idelalasib [39] evaluated 39 patients with relapsed or refractory mantle cell lymphoma patients who had received a median of four prior therapies. Overall, nine (18%) patients discontinued therapy due to adverse effects including diarrhea, transaminase elevations, pneumonia, and acute renal failure. Thirty-three (84.6%) patients had some reduction in lymph node size, with CR in two (5%) patients, PR in 14 (35%) patients, and stable disease in nineteen (47.5%) patients.

Table 4 provides a summary of the novel agents used in MCL.

Treatment Study Overall response rate (ORR) Overall survival rate (OS) Progression Free Survival (PFS) Failure Free Survival Complete remission rate (CR)
Bortezomib Phase II PINNACLE trial [31] 33% - Median duration of response of 9 months Median time to progression of 6 months  
Lenalidomide Phase II Multicenter Study [32] 35% - 9 months Duration of response was 16 months 12% median follow-up of 12 months
Bruton’s tyrosine kinase (BTK) inhibitor, ibrutinib Phase II multi-center data of 111 previously treated pts [34] 68% 58% at 18 months 17.5 months 14 months 21% after 15 months

Table 4: Novel agents.


Mantle cell lymphoma is an incurable but increasingly well characterized clinicopathologic entity that unfortunately poses persistent obstacles in achieving durable responses with available treatment regimens. Early stage disease is rare, but limited available data suggests that radiation with or without chemotherapy can effectively manage limited, non-bulky distribution. For advanced disease, referral for enrollment in prospective clinical trials should be pursued. Based on individual patients’ performance features, they can be managed up-front with either observation, R-HyperCVAD, CHOP-like chemotherapy, or less aggressive induction regimens including bendamustine and rituximab. Relapsed and refractory disease carries a poorer prognosis, but novel agents including bortezomib, lenalidomide, and ibrutinib have shown promising efficacy and tolerability. Further randomized data are needed to establish clear standards of care and improve rates of survival and quality of life.


  1. (1997) A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin's lymphoma. The Non-Hodgkin's Lymphoma Classification Project. Blood 89: 3909-3918.
  2. Martin P, Chadburn A, Chistos P (2008) Intensive treatment strategies may not provide superior outcomes in mantle cell lymphoma: overall survival exceeding 7 years with standard therapies. Ann Oncol 19:1327-1330.
  3. Jares P, Colomer D, Campo E (2007) Genetic and molecular pathogenesis of mantle cell lymphoma: perspectives for new targeted therapeutics. Nat Rev Cancer 7: 750-762.
  4. Zhou Y, Wang H, Fang W, Romaguer JE, Zhang Y, et al. (2008) Incidence trends of mantle cell lymphoma in the United States between 1992 and 2004. Cancer 113: 791-798.
  5. Hoster E, Dreyling M, Klapper W, Gisselbrecht C, van Hoof A, et al. (2008) A new prognostic index (MIPI) for patients with advanced-stage mantle cell lymphoma. Blood 111: 558-565.
  6. Yatabe Y, Suzuki R, Tobinai K, Matsuno Y, Ichinohasama R, et al. (2000) Significance of cyclin D1 overexpression for the diagnosis of mantle cell lymphoma: a clinicopathologic comparison of cyclin D1-positive MCL and cyclin D1-negative MCL-like B-cell lymphoma. Blood 95: 2253-2261.
  7. Salaverria I, Royo C, Carvajal-Cuenca A, Clot G, Navarro A, et al. (2013) CCND2 rearrangements are the most frequent genetic events in cyclin D1(-) mantle cell lymphoma. Blood 121: 1394-1402.
  8. Fu K, Weisenburger DD, Greiner TC, Dave S, Wright G, et al. (2005) Cyclin D1-negative mantle cell lymphoma: a clinicopathologic study based on gene expression profiling. Blood 106: 4315-4321.
  9. Fernàndez V, Hartmann E, Ott G, Campo E, Rosenwald A (2005) Pathogenesis of mantle-cell lymphoma: all oncogenic roads lead to dysregulation of cell cycle and DNA damage response pathways. J Clin Oncol 23: 6364-6369.
  10. Raffeld M, Jaffe ES (1991) bcl-1, t(11;14), and mantle cell-derived lymphomas. Blood 78: 259-263.
  11. Jares P, Colomer D, Campo E (2012) Molecular pathogenesis of mantle cell lymphoma. J Clin Invest 122: 3416-3423.
  12. Klapper W, Hoster E, Determann O, Oschlies I, van der Laak J, et al. (2009) Ki-67 as a prognostic marker in mantle cell lymphoma-consensus guidelines of the pathology panel of the European MCL Network. J Hematop 2: 103-111.
  13. Leitch HA, Gascoyne RD, Chhanabhai M, Voss NJ, Klasa R, et al. (2003) Limited-stage mantle-cell lymphoma. Ann Oncol 14: 1555-1561.
  14. Abrahamsson A, Albertsson-Lindblad A, Brown PN, Baumgartner-Wennerholm S, Pedersen LM, et al. (2014) Real world data on primary treatment for mantle cell lymphoma: a Nordic Lymphoma Group observational study. Blood 124: 1288-1295.
  15. Romaguera JE, Fayad L, Rodriguez MA, Broglio KR, Hagemeister FB, et al. (2005) High rate of durable remissions after treatment of newly diagnosed aggressive mantle-cell lymphoma with rituximab plus hyper-CVAD alternating with rituximab plus high-dose methotrexate and cytarabine. J Clin Oncol 23: 7013-7023.
  16. Bernstein SH, Epner E, Unger JM, Leblanc M, Cebula E, et al. (2013) A phase II multicenter trial of hyperCVAD MTX/Ara-C and rituximab in patients with previously untreated mantle cell lymphoma; SWOG 0213. Ann Oncol 24: 1587-1593.
  17. Lenz G, Dreyling M, Hoster E (2005) Immunochemotherapy with rituximab and cyclophosphamide, doxorubicin, vincristine, and prednisone significantly improves response and time to treatment failure, but not long-term outcome in patients with previously untreated mantle cell lymphoma: results of a prospective randomized trial of the German Low Grade Lymphoma Study Group (GLSG). J Clin Oncol 23: 1984-1992.
  18. Rummel MJ, Niederle N, Maschmeyer G, Banat GA, von Grünhagen U, et al. (2013) Bendamustine plus rituximab versus CHOP plus rituximab as first-line treatment for patients with indolent and mantle-cell lymphomas: an open-label, multicentre, randomised, phase 3 non-inferiority trial. Lancet 381: 1203-1210.
  19. Cavalli F, Rooney B, Pei L (2014) Randomized phase 3 study of rituximab, cyclophosphamide, doxorubicin, and prednisone plus vincristine (R-CHOP) or bortezomib (VR-CAP) in newly diagnosed mantle cell lymphoma (MCL) patients ineligible for bone marrow transplantation (BMT). J Clin Oncol 32: Abstract 8500.
  20. Robak T, Huang H, Jin J, Zhu J, Liu T, et al. (2015) Bortezomib-based therapy for newly diagnosed mantle-cell lymphoma. N Engl J Med 372: 944-953.
  21. Khouri IF, Saliba RM, Okoroji GJ, Acholonu SA, Champlin RE (2003) Long-term follow-up of autologous stem cell transplantation in patients with diffuse mantle cell lymphoma in first disease remission: the prognostic value of beta2-microglobulin and the tumor score. Cancer 98: 2630-2635.
  22. Tam CS, Bassett R, Ledesma C, Korbling M, Alousi A, et al. (2009) Mature results of the M. D. Anderson Cancer Center risk-adapted transplantation strategy in mantle cell lymphoma. Blood 113: 4144-4152.
  23. Till BG, Gooley TA, Crawford N, Gopal AK, Maloney DG, et al. (2008) Effect of remission status and induction chemotherapy regimen on outcome of autologous stem cell transplantation for mantle cell lymphoma. Leuk Lymphoma 49: 1062-1073.
  24. Kahl BS, Longo WL, Eickhoff JC (2006) Maintenance rituximab following induction chemoimmunotherapy may prolong progression-free survival in mantle cell lymphoma: a pilot study from the Wisconsin Oncology Network. Ann Oncol 17: 1418-1423.
  25. Kluin-Nelemans HC, Hoster E, Hermine O, Walewski J, Trneny M, et al. (2012) Treatment of older patients with mantle-cell lymphoma. N Engl J Med 367: 520-531.
  26. Chang JE, Li H, Smith MR, Gascoyne RD, Paietta EM, et al. (2014) Phase 2 study of VcR-CVAD with maintenance rituximab for untreated mantle cell lymphoma: an Eastern Cooperative Oncology Group study (E1405). Blood 123: 1665-1673.
  27. Hosing C, Saliba RM, McLaughlin P, Andersson B, Rodriguez MA, et al. (2003) Long-term results favor allogeneic over autologous hematopoietic stem cell transplantation in patients with refractory or recurrent indolent non-Hodgkin's lymphoma. Ann Oncol 14: 737-744.
  28. Robinson KS, Williams ME, van der Jagt RH, Cohen P, Herst JA, et al. (2008) Phase II multicenter study of bendamustine plus rituximab in patients with relapsed indolent B-cell and mantle cell non-Hodgkin's lymphoma. J Clin Oncol 26: 4473-4479.
  29. Inwards DJ, Fishkin PA, Hillman DW, Brown DW, Ansell SM, et al. (2008) Long-term results of the treatment of patients with mantle cell lymphoma with cladribine (2-CDA) alone (95-80-53) or 2-CDA and rituximab (N0189) in the North Central Cancer Treatment Group. Cancer 113: 108-116.
  30. Fisher RI, Bernstein SH, Kahl BS, Djulbegovic B, Robertson MJ, et al. (2006) Multicenter phase II study of bortezomib in patients with relapsed or refractory mantle cell lymphoma. J Clin Oncol 24: 4867-4874.
  31. Goy A, Bernstein SH, Kahl BS, Djulbegovic B, Robertson MJ, et al. (2009) Bortezomib in patients with relapsed or refractory mantle cell lymphoma: updated time-to-event analyses of the multicenter phase 2 PINNACLE study. Ann Oncol 20: 520-525.
  32. Zinzani PL, Vose JM, Czuczman MS (2012) Phase II Multicenter Study of the Safety and Efficacy of Single-Agent Lenalidomide in Subjects With Relapsed/Refractory Mantle Cell Lymphoma: Long-term Follow-up Analysis of the NHL-003 Study. Blood 120: Abstract 2738.
  33. Chong EA, Ahmadi T, Aqui NA, Svoboda J, Nasta SD, et al. (2015) Combination of Lenalidomide and Rituximab Overcomes Rituximab Resistance in Patients with Indolent B-cell and Mantle Cell Lymphomas. Clin Cancer Res 21: 1835-1842.
  34. Advani RH, Buggy JJ, Sharman JP, Smith SM, Boyd TE, et al. (2013) Bruton tyrosine kinase inhibitor ibrutinib (PCI-32765) has significant activity in patients with relapsed/refractory B-cell malignancies. J Clin Oncol 31: 88-94.
  35. Wang ML, Rule S, Martin P, Goy A, Auer R, et al. (2013) Targeting BTK with ibrutinib in relapsed or refractory mantle-cell lymphoma. N Engl J Med 369: 507-516.
  36. Chiron D, Di Liberto M, Martin P, Huang X, Sharman J, et al. (2014) Cell-cycle reprogramming for PI3K inhibition overrides a relapse-specific C481S BTK mutation revealed by longitudinal functional genomics in mantle cell lymphoma. Cancer Discov 4: 1022-1035.
  37. Kahl BS, Spurgeon SE, Furman RR, Flinn IW, Coutre SE, et al. (2014) A phase 1 study of the PI3Kδ inhibitor idelalisib in patients with relapsed/refractory mantle cell lymphoma (MCL). Blood 123: 3398-3405.
Citation: Pant MK, Alshenawy W, Alrajjal A, Alrobeh H, Tabbara IA (2015) Mantle Cell Lymphoma: Current Concepts. J Hematol Thrombo Dis 3:215.

Copyright: © 2015 Pant MK, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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