|Year : 2019 | Volume
| Issue : 3 | Page : 226-230
Mantle cell lymphoma: Saudi Lymphoma Group's clinical practice guidelines for diagnosis, management and follow-up
Musa Alzahrani1, Ahmed Sagheir2, Ibraheem Motabi3, Reyad Dada4, Mubarak Al-Mansour5, Hani Alhashmi6, Magdy Kandil7, Ayman Alhejazi8
1 Department of Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia
2 Oncology Institute, John Hopkins Aramco Healthcare, Dhahran, Saudi Arabia
3 Department of Adult Hematology and BMT, Comprehensive Cancer Center, King Fahad Medical City, Riyadh, Saudi Arabia
4 Department of Oncology, King Faisal Specialist Hospital and Research Centre, Jeddah; College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
5 College of Medicine, King Saud Bin Abdulaziz University for Health Sciences; Adult Medical Oncology, Princess Noorah Oncology Center, King Abdulaziz Medical City, Ministry of National Guard Health Affairs-Western Region, Jeddah, Saudi Arabia
6 Adult Hematology and Stem Cell Transplantation Department, King Fahad Specialist Hospital, Dammam, Saudi Arabia
7 Oncology Department, Prince Sultan Military Medical City, Riyadh, Saudi Arabia; Clinical Oncology Department, Cairo University, Giza, Egypt
8 Department of Oncology, King Abdulaziz Medical City, Ministry of National Guard Health Affairs-Central Region, Riyadh, Saudi Arabia
|Date of Web Publication||28-Aug-2019|
Dr. Mubarak Al-Mansour
Adult Medical Oncology, Princess Noorah Oncology Center, King Abdulaziz Medical City, Ministry of National Guard Health Affairs-Western Region, PO Box 9515, Jeddah 21423
|How to cite this article:|
Alzahrani M, Sagheir A, Motabi I, Dada R, Al-Mansour M, Alhashmi H, Kandil M, Alhejazi A. Mantle cell lymphoma: Saudi Lymphoma Group's clinical practice guidelines for diagnosis, management and follow-up. Saudi J Med Med Sci 2019;7:226-30
|How to cite this URL:|
Alzahrani M, Sagheir A, Motabi I, Dada R, Al-Mansour M, Alhashmi H, Kandil M, Alhejazi A. Mantle cell lymphoma: Saudi Lymphoma Group's clinical practice guidelines for diagnosis, management and follow-up. Saudi J Med Med Sci [serial online] 2019 [cited 2022 Jan 28];7:226-30. Available from: https://www.sjmms.net/text.asp?2019/7/3/226/265640
| Introduction|| |
Mantle cell lymphoma (MCL) is a type of B-cell lymphoma that falls in between the indolent and aggressive subtypes of non-Hodgkin's lymphoma (NHL). MCL combines the incurable feature of indolent lymphomas with the clinical course of aggressive lymphomas. According to the Saudi Cancer Registry, in 2015, NHL was the second and fifth most common cancer among Saudi male and female population, respectively, accounting for 6.9% of all cancers. However, the incidence of MCL in Saudi Arabia is yet unknown, whereas in the United States and Europe, MCL constitutes about 7% of adult NHLs.,
In MCL, extranodal involvement is common, including bone marrow and peripheral blood. It also has a peculiar tendency to involve the gastrointestinal (GI) tract. Subclinical GI epithelial invasion without overt colonic polyposis is very common. Therefore, a high index of suspicion is required for detecting GI involvement in MCL patients, especially among those presenting with iron deficiency anemia.
| Methods|| |
A committee comprising experts in hematology and medical oncology was established under the supervision of the Saudi Lymphoma Group and in collaboration with the Saudi Oncology Society. For collecting evidence, a literature search was carried out with relevant keywords using online database search engines such as PubMed/Medline, Web of Science and Scopus. In addition, expert opinion was considered when necessary. The levels of evidence used in developing this guideline were as follows:
- Evidence level (EL)-1 (highest), evidence from Phase III randomized trials or meta-analyses
- EL-2 (intermediate), evidence from well-designed Phase II trials or Phase III trials with limitations
- EL-3 (low), evidence from retrospective or observational studies/reports and/or expert opinion.
This easy-to-follow grading system is convenient for readers to understand and allows an accurate assessment of the guideline's applicability in individual patients.
1. PATHOLOGIC DIAGNOSIS
1.1.1. Excisional lymph node biopsy should be done to diagnose MCL (EL-3)
1.1.2. If excisional lymph node biopsy is not feasible, then an incisional or core needle biopsy should be done (EL-3)
1.1.3. Pathologically, the majority of MCLs consist of small lymphocytes with notched nuclei, and the architectural pattern of the lymph node is usually diffuse but may show a vaguely nodular or mantle zone growth pattern. A number of other morphologic variants have been recognized. The blastoid variant of MCL has a high mitotic rate and is clinically very aggressive. It can also mimic diffuse large B-cell lymphoma (EL-3)
1.1.4. Cyclin D1 expression is a hallmark of MCL. In cyclin D1-negative cases, SOX11 can be useful in the diagnosis (EL-3)
1.1.5. In terms of immunophenotype, MCL cells are typically positive for CD5, FMC7, bright CD20 and CD43, but negative for CD10 and CD23 (EL-3)
1.1.6. In terms of genetic variance, although not specific for MCL and found in other indolent NHLs, almost all MCL cases harbor the cyclin D1 translocation t(11;14) (q13;q32), which can be detected by fluorescence in situ hybridization or the traditional karyotypic analysis (EL-3).
2. DIAGNOSIS AND WORKUP
2.1. Evaluations should include complete history (i.e., age; gender; comorbidities; B-symptoms; Eastern Cooperative Oncology Group performance status; hepatitis or human immunodeficiency virus [HIV] risk factors; medications; allergy to contrast media or drugs as well as social and family history) and physical examination (i.e., of lymph nodes, Waldeyer's ring, spleen, liver, central nervous system, GI tract, lung, bone and skin) (EL-3)
2.2.1. Basic laboratory evaluations of all patients should include complete blood count (CBC) with differential, liver function test as well as routine blood chemistry including lactate dehydrogenase (LDH), electrolytes and calcium (EL-3).
2.2.2. Viral serology
- Hepatitis serology (hepatitis B surface antigen, core antibody and surface antibody as well as hepatitis C virus), and PCR for hepatitis B surface antigen-or core antibody-positive cases (EL-3)
- Testing for HIV is required (EL-3).
- Computed tomography (CT) scan of neck and chest, abdomen and pelvis (CAP) should be performed in all cases (EL-3)
- Whole body positron emission tomography scan should be considered, especially in limited stage disease, prior to curative radiotherapy (EL-3).
2.2.4. Other tests
- Bone marrow biopsy is recommended as part of staging MCL patients (EL-3)
- Upper and lower GI scopes should be considered for patients with GI-related symptoms (EL-3)
- Pregnancy test must be done for women of childbearing age (EL-3).
2.3.1. Mantle Cell Lymphoma International Prognostic Index
18.104.22.168. For MCL patients, the International Prognostic Index (IPI) is not adequate, as this score is not specific
22.214.171.124. The use of a more specific score such as the Mantle Cell Lymphoma International Prognostic Index (MIPI) is recommended. MIPI uses age, performance status, LDH and WBC counts to separate patients into three risk groups (EL-1).
2.3.2. Ki-67: The use of immunohistochemistry stain for Ki-67 can provide an important prognostic value, as it classifies MCL patients into three groups. Patients with Ki-67 <10% have the best outcome (low risk) compared to patients with Ki-67 10%–29% (intermediate risk) and Ki-67 ≥30% (high risk) (EL-1).
3.1. Introduction to management:
- Treatment of MCL is based on the stage, age and comorbidities
- Limited stage is defined as Stage I or II, with no B-symptoms or bulky disease
- Advanced stage is defined as Stage III or IV, presence of B-symptoms or bulky disease regardless of the stage.
3.2. Management of patients with limited stage disease:
3.2.1. Localized disease is extremely rare in MCL
3.2.2. Involved site radiotherapy (ISRT) of 30 Gy or combination of a short treatment with immunochemotherapy (e.g., 3–4 cycles of rituximab plus cyclophosphamide, vincristine, doxorubicin and prednisone (R-CHOP) or R-CHOP-like therapy) followed by ISRT is recommended (EL-3).
3.3. Management of patients with advanced stage disease:
3.3.1. Given that advanced stage disease is relatively uncommon in MCL, there is no “standard” therapy or approach
3.3.2. Most patients have symptomatic disease and require treatment. However, few patients have a course similar to that of indolent lymphomas, and in these cases, a period of observation is recommended (EL-3)
3.3.3. In MCL patients aged ≤60 years, dose-intensified therapies (e.g. autologous stem cell transplant-based regimens) should be considered.,,
3.3.6. Induction therapy
126.96.36.199.1 The preferred regimen for advanced stages is alternating RCHOP/RDHAP (rituximab plus dexamethasone, high-dose cytarabine, and cisplatin) followed by myeloablative autologous stem cell transplant in patients achieving at least a partial response (≥75%),
188.8.131.52.2. Another option is cyclophosphamide, vincristine, doxorubicin and dexamethasone (HyperCVAD) alternated with high-dose methotrexate and cytarabine plus rituximab (EL-2),
184.108.40.206.3. For maintenance after autologous stem cell transplant, rituximab should be given every 8 weeks for 3 years (EL-1).
220.127.116.11. Less aggressive therapies for elderly or unfit patients:
18.104.22.168.1. Combination of bendamustine and rituximab (EL-1),
22.214.171.124.1. RCHOP followed by maintenance rituximab every 8 weeks until progression or intolerance (EL-1)
126.96.36.199.1. Bortezomib, rituximab, cyclophosphamide, doxorubicin and prednisone (VR-CAP) (EL-1)
188.8.131.52.1. Combination of lenalidomide and rituximab (EL-2).
184.108.40.206. Therapy for relapsed/refractory disease
220.127.116.11.1. Ibrutinib in combination or without rituximab (EL-1),,,
18.104.22.168.2. Combination of lenalidomide and rituximab (EL-2),
22.214.171.124.3. Other preferred regimens are Venetoclax  and Acalabrutinib (EL-2).
126.96.36.199. Consolidation after second-line therapy:
188.8.131.52.1 Allogeneic hematopoietic stem cell transplantation should be considered after achieving complete response with second-line therapy, if the patient is eligible for transplant (EL-3)
184.108.40.206.2. Autologous transplant could be considered in relapsed patients if not performed as part of the initial treatment (EL-3).
4. FOLLOW UP
4.1. Every 3 months for 2 years, and every 6 months thereafter
4.2. History and physical examination should be documented in every visit
4.3. CBC with differential count and LDH evaluations should be requested in every visit
4.4. CT of neck and CAP is required 3 months after completion of all therapy, and if the findings are normal, no further routine imaging is required
4.5. Annual influenza immunization is recommended (EL-3).
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Saudi Cancer Registry. Cancer Incidence Report in Saudi Arabia 2015. Riyadh (KSA): Saudi Cancer Registry; 2018.
A clinical evaluation of the international lymphoma study group classification of non-Hodgkin's lymphoma. The non-Hodgkin's lymphoma classification project. Blood 1997;89:3909-18.
Anderson JR, Armitage JO, Weisenburger DD. Epidemiology of the non-Hodgkin's lymphomas: Distributions of the major subtypes differ by geographic locations. Non-Hodgkin's lymphoma classification project. Ann Oncol 1998;9:717-20.
Argatoff LH, Connors JM, Klasa RJ, Horsman DE, Gascoyne RD. Mantle cell lymphoma: A clinicopathologic study of 80 cases. Blood 1997;89:2067-78.
Jazieh AR, Saudi Lung Cancer Guidelines Committee. The lung cancer management guidelines 2012. J Infect Public Health 2012;5 Suppl 1:S4-10.
Mozos A, Royo C, Hartmann E, De Jong D, Baró C, Valera A, et al.
SOX11 expression is highly specific for mantle cell lymphoma and identifies the cyclin D1-negative subtype. Haematologica 2009;94:1555-62.
Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al
. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues (IARC WHO Classification of Tumours). Revised 4th
Edition. Lyon: International Agency for Research on Cancer; 2017.
Jaffe ES. Hematopathology. Philadelphia, PA: London: Saunders; 2010.
Li JY, Gaillard F, Moreau A, Harousseau JL, Laboisse C, Milpied N, et al.
Detection of translocation t(11;14)(q13;q32) in mantle cell lymphoma by fluorescence in situ
hybridization. Am J Pathol 1999;154:1449-52.
Hoster E, Dreyling M, Klapper W, Gisselbrecht C, van Hoof A, Kluin-Nelemans HC, et al.
A new prognostic index (MIPI) for patients with advanced-stage mantle cell lymphoma. Blood 2008;111:558-65.
Hoster E, Rosenwald A, Berger F, Bernd HW, Hartmann S, Loddenkemper C, et al.
Prognostic value of Ki-67 index, cytology, and growth pattern in mantle-cell lymphoma: Results from randomized trials of the European mantle cell lymphoma network. J Clin Oncol 2016;34:1386-94.
Illidge T, Specht L, Yahalom J, Aleman B, Berthelsen AK, Constine L, et al.
Modern radiation therapy for nodal non-Hodgkin lymphoma-target definition and dose guidelines from the international lymphoma radiation oncology group. Int J Radiat Oncol Biol Phys 2014;89:49-58.
Meusers P, Hense J. Management of mantle cell lymphoma. Ann Hematol 1999;78:485-94.
Dreyling M, Lenz G, Hoster E, Van Hoof A, Gisselbrecht C, Schmits R, et al.
Early consolidation by myeloablative radiochemotherapy followed by autologous stem cell transplantation in first remission significantly prolongs progression-free survival in mantle-cell lymphoma: Results of a prospective randomized trial of the European MCL network. Blood 2005;105:2677-84.
Hoster E, Metzner B, Forstpointner R, Pfreundschuh M, Trumper L, Hallek M, et al
. Autologous stem cell transplantation and addition of rituximab independently prolong response duration in advanced stage mantle cell lymphoma. Blood 2009;114:880.
Le Gouill S, Thieblemont C, Oberic L, Moreau A, Bouabdallah K, Gyan E, et al
. Rituximab maintenance after autologous stem cell transplantation prolongs survival in younger patients with mantle cell lymphoma. Blood 2016;128:145.
Pott C, Hoster E, Delfau-Larue MH, Beldjord K, Böttcher S, Asnafi V, et al.
Molecular remission is an independent predictor of clinical outcome in patients with mantle cell lymphoma after combined immunochemotherapy: A European MCL intergroup study. Blood 2010;115:3215-23.
Delarue R, Haioun C, Ribrag V, Brice P, Delmer A, Tilly H, et al.
CHOP and DHAP plus rituximab followed by autologous stem cell transplantation in mantle cell lymphoma: A phase 2 study from the groupe d'etude des lymphomes de l'adulte. Blood 2013;121:48-53.
Romaguera JE, Fayad L, Rodriguez MA, Broglio KR, Hagemeister FB, Pro B, et al.
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 2005;23:7013-23.
Merli F, Luminari S, Ilariucci F, Petrini M, Visco C, Ambrosetti A, et al.
Rituximab plus HyperCVAD alternating with high dose cytarabine and methotrexate for the initial treatment of patients with mantle cell lymphoma, a multicentre trial from Gruppo Italiano Studio Linfomi. Br J Haematol 2012;156:346-53.
Le Gouill S, Thieblemont C, Oberic L, Moreau A, Bouabdallah K, Dartigeas C, et al.
Rituximab after autologous stem-cell transplantation in mantle-cell lymphoma. N Engl J Med 2017;377:1250-60.
Rummel MJ, Niederle N, Maschmeyer G, Banat GA, von Grünhagen U, Losem C, et al.
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 2013;381:1203-10.
Flinn IW, van der Jagt R, Kahl BS, Wood P, Hawkins TE, Macdonald D, et al.
Randomized trial of bendamustine-rituximab or R-CHOP/R-CVP in first-line treatment of indolent NHL or MCL: The BRIGHT study. Blood 2014;123:2944-52.
Lenz G, Dreyling M, Hoster E, Wörmann B, Dührsen U, Metzner B, et al.
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 2005;23:1984-92.
Robak T, Huang H, Jin J, Zhu J, Liu T, Samoilova O, et al.
Bortezomib-based therapy for newly diagnosed mantle-cell lymphoma. N Engl J Med 2015;372:944-53.
Ruan J, Martin P, Shah B, Schuster SJ, Smith SM, Furman RR, et al.
Lenalidomide plus rituximab as initial treatment for mantle-cell lymphoma. N Engl J Med 2015;373:1835-44.
Wang ML, Rule S, Martin P, Goy A, Auer R, Kahl BS, et al.
Targeting BTK with ibrutinib in relapsed or refractory mantle-cell lymphoma. N Engl J Med 2013;369:507-16.
Wang ML, Blum KA, Martin P, Goy A, Auer R, Kahl BS, et al.
Long-term follow-up of MCL patients treated with single-agent ibrutinib: Updated safety and efficacy results. Blood 2015;126:739-45.
Dreyling M, Jurczak W, Jerkeman M, Silva RS, Rusconi C, Trneny M, et al.
Ibrutinib versus temsirolimus in patients with relapsed or refractory mantle-cell lymphoma: An international, randomised, open-label, phase 3 study. Lancet 2016;387:770-8.
Jerkeman M, Eskelund CW, Hutchings M, Räty R, Wader KF, Laurell A, et al.
Ibrutinib, lenalidomide, and rituximab in relapsed or refractory mantle cell lymphoma (PHILEMON): A multicentre, open-label, single-arm, phase 2 trial. Lancet Haematol 2018;5:e109-16.
Wang M, Fayad L, Wagner-Bartak N, Zhang L, Hagemeister F, Neelapu SS, et al.
Lenalidomide in combination with rituximab for patients with relapsed or refractory mantle-cell lymphoma: A phase 1/2 clinical trial. Lancet Oncol 2012;13:716-23.
Davids MS, Roberts AW, Seymour JF, Pagel JM, Kahl BS, Wierda WG, et al.
Phase I first-in-human study of venetoclax in patients with relapsed or refractory non-Hodgkin lymphoma. J Clin Oncol 2017;35:826-33.
Wang M, Rule S, Zinzani PL, Goy A, Casasnovas RO, Smith SD, et al
. Efficacy and safety of acalabrutinib monotherapy in patients with relapsed/refractory mantle cell lymphoma in the phase 2 ACE-LY-004 study. Blood 2017;155:Abstract 155.
Krüger WH, Hirt C, Basara N, Sayer HG, Behre G, Fischer T, et al.
Allogeneic stem cell transplantation for mantle cell lymphoma – Final report from the prospective trials of the East German Study Group Haematology/Oncology (OSHO). Ann Hematol 2014;93:1587-97.
Pedrazzoli P, Baldanti F, Donatelli I, Castrucci MR, Puglisi F, Silvestris N, et al.
Vaccination for seasonal influenza in patients with cancer: Recommendations of the Italian Society of Medical Oncology (AIOM). Ann Oncol 2014;25:1243-7.