Mantle Cell Lymphoma Facts - Donate Today!
Mantle CellLymphoma FactsNo. 4 in a series providing the latest information forpatients, caregivers and healthcare professionalswww.LLS.org Information Specialist: 800.955.4572Highlightsl Mantlecell lymphoma (MCL) is one of severalsubtypes of B-cell non-Hodgkin lymphoma.l MCLusually begins with lymph node enlargement;it can spread to other tissues such as the bonemarrow and liver.l MCLcan involve the gastrointestinal tract.l MCLis distinguished by overexpression of cyclinD1 (a protein that stimulates cell growth) in almostall cases. The overexpression of cyclin D1 is usuallycaused by a rearrangement (translocation) betweenchromosomes 11 and 14.l Anumber of chemotherapy plus rituximab(Rituxan ) combinations are used to treat MCL.l Bortezomib(Velcade ) may be used to treat patientswho have relapsed disease and has been approved foruntreated patients in a combination therapy.l Ibrutinib(Imbruvica ), a Bruton tyrosine kinase(BTK) inhibitor, is approved for patients withrelapsed MCL.l Autologousstem cell transplantation may be usedto treat MCL in first complete remission. Treatmentwith allogeneic stem cell transplantation orreduced-intensity allogeneic stem cell transplantationmay be beneficial for some patients, based upon theavailability of a matched related stem cell donor.l Manyclinical trials are under way to study potentialimprovements in current treatment approaches.This publication was supported in part byIntroductionLymphoma is the general name for many related subtypesof cancer that arise from a type of white blood cell calleda “lymphocyte.” Lymphoma is divided into two majorcategories: Hodgkin lymphoma (HL) and non-Hodgkinlymphoma (NHL). Mantle cell lymphoma (MCL) is one ofabout 70 different subtypes of NHL.Lymphoma may arise in any one of three types oflymphocytes: B lymphocytes (B cells), T lymphocytes (T cells)and natural killer (NK) cells. B lymphocytes make antibodiesto fight infection; T lymphocytes help fight infections andattack cancer cells detected early; and natural killer cellswhich also attack cancer cells and eliminate viruses. B-celllymphomas are more common than T-cell lymphomas.Most lymphocytes are found in the lymphatic system, whichincludes lymph nodes (small bean-shaped structures located inall parts of the body), the spleen and tonsils, for example.This publication includes information about the diagnosisand management of MCL. It also provides specificinformation on the stages and treatment of the disease, newtreatments undergoing investigation and support resources.For additional free information about NHL subtypes, pleasesee The Leukemia & Lymphoma Society (LLS) publicationsNon-Hodgkin Lymphoma and The Lymphoma Guide:Information for Patients and Caregivers.About Mantle Cell LymphomaMantle cell lymphoma (MCL) results from a malignanttransformation of a B lymphocyte in the outer edge of alymph node follicle (the mantle zone). The transformedB lymphocyte grows in an uncontrolled way, resultingin the accumulation of lymphoma cells, which causesenlargement of lymph nodes. Sometimes, when these lymphnodes become very large, or grow in other parts of thebody, they can be called “tumors.” The MCL cells can enterthe lymphatic channels and the blood, and can spread toother lymph nodes or tissues, such as the marrow, liver andgastrointestinal tract.In the United States, there are about 70,800 new cases ofNHL expected in 2014. MCL patients represent only about6 percent (about 4,200 cases) of all new cases of NHL inthe United States. MCL occurs more frequently in olderadults—the average age at diagnosis is the mid-60s. It is moreoften diagnosed in males than in females and white men andwomen are at a higher risk than black men and women foran MCL diagnosis.FS4 Mantle Cell Lymphoma Facts I page 1Revised November 2014
Mantle Cell Lymphoma FactsCausesAbout 85 percent of patients with MCL have acharacteristic genetic lesion that involves chromosome11 and chromosome 14. This is called a “reciprocaltranslocation,” and is abbreviated as t(11;14). Thistranslocation results in short segments of chromosome11 and chromosome 14 exchanging places. The exchangeoccurs at the site of the cyclin D1 gene on chromosome11 and the site of a gene that controls the formation ofantibody molecules on chromosome 14. The t(11;14)triggers an overproduction of cyclin D1, a protein thatcauses tumor cell division and growth. The overproductionof the cyclin D1 protein leads to accumulation of largenumbers of MCL cells. This translocation can be thoughtof as a driver in the behavior of the disease, which likelycomplements other genetic defects leading to MCLdevelopment.In a small proportion of patients t(11;14) is not present.In most of these patients, other genetic changes causeexcess production of cyclin D1. Rarely, MCL arises fromoverexpression of other cyclin genes (e.g., cyclin D2 andcyclin D3).l Leukocytosis(high white blood cell counts) may result if thedisease grows in the peripheral blood, that is, in the arteriesand veins, producing a leukemia phase of the disease.DiagnosisA patient who has a potential diagnosis of lymphomaneeds to make sure that his or her subtype has beencorrectly identified. Treatment depends on knowing thespecific subtype. Each patient should be evaluated by ahematologist/oncologist, a doctor who specializes in treatingpatients who have NHL.Lymphomas are diagnosed by the examination of affectedtissue, obtained from a surgical biopsy, usually of a lymphnode. It is important to be aware that the number of cellsobtained from a fine needle aspiration (FNA) are NOTsufficient to establish a diagnosis.Microscopic examination of tissue from the lymph nodebiopsy can determine if lymphoma is present. A diagnosis ofMCL is made if additional examination of the tissue showsthat the lymphoma cellsl HaveSigns, Symptoms and ComplicationsMost patients with MCL have disease involving multiplelymph nodes and other sites of the body. These sites mayinclude the spleen, marrow and blood, the lymph nodesin the throat (tonsils and adenoids), the liver, or thegastrointestinal tract. MCL cells may enter the brain, lungsand spinal cord, although this is relatively rare.Patients who have MCL may experience loss of appetite andweight loss, fever, night sweats, nausea and/or vomiting,indigestion, abdominal pain or bloating, a feeling of“fullness” or discomfort as a result of enlarged tonsils, liver orspleen, pressure or pain in the lower back that often extendsdown one or both legs, or fatigue from developing anemia.Commonly seen complications from disease progressionmay includel Lowblood cell counts, or cytopenias (neutropenia [lowwhite blood cell counts], anemia [low red blood cellcounts] and/or thrombocytopenia [low numbers ofplatelets]) since the growing lymphoma cells in the bonemarrow crowd out normal blood cells, decreasing bloodcell production.l Gastrointestinal,pulmonary, or central nervous system(CNS) complications because the MCL is extranodal(occurring outside the lymph nodes and in organs).“Multiple small-intestine polyps” may develop in thegastrointestinal tract as a result of the lymphomacell growth.surface markers of B cells (e.g., CD20)l Overexpressl Containthe cyclin D1 protein within the cellsthe translocation 11;14.Blood tests and body imaging scans may also be done todetermine the extent of disease.A hematopathologist (doctor who specializes in examiningtissue and diagnosing disease) will determine if the MCL isthe common type (found in most patients) or a rare blastoidvariant. In the blastoid variant, the cells are bigger and theygrow and divide more rapidly, are more aggressive and aremore challenging to treat. The blastoid variant of MCL maybe present at diagnosis or may emerge over time.StagingStaging determines extent of disease, or how much the cancerhas spread, and where it is located. Staging enables doctors todevelop a prognosis (predicting the future course of diseaseand the chance of survival) and tailor treatment to individualpatients and minimize potential toxic effects of therapy.Tests that are useful in staging of disease includel Completeblood cell counts, to assess the concentrationof red blood cells, white blood cells and plateletsl Bonemarrow aspiration and biopsy, to determinewhether or not the disease has extended beyond thelymph nodes and into the bone marrowFS4 Mantle Cell Lymphoma Facts I page 2
Mantle Cell Lymphoma Factsl Imagingstudies, including computed tomography (CT)scans of the chest, abdomen and pelvis, with or withoutan accompanying positron emission tomography (PET)scan, to determine the metabolic activity of the disease.These imaging tests will be used to understand whetherthe disease is present in the deep lymph nodes, liver,spleen or in other parts of the body (see Figure 1.)l Studiesto check levels of specific proteins in the blood,especially measurements of lactate dehydrogenase (LDH)and beta2-microglobulin, because these are indirectmarkers of disease extent and rate of progression.Figure 1. Lymphoma StagesStage IOne lymph node regionor a single organ.DiaphragmFor additional information about laboratory and imagingtests, see the free LLS publication Understanding Lab andImaging Tests.Treatment PlanningIn order to optimize treatment, doctors determine prognosis(predicting the course of the disease and the chance ofsurvival) so that they can identify patients who may benefitfrom alternate therapy and those who may need lessaggressive therapy. Prognostic indexes help doctors developtreatment strategies based on individual patient risk factors.Once the extent of disease has been determined, somedoctors who care for MCL patients use The MantleCell International Prognostic Index (MIPI) to help plantreatment. Several clinical factors influence prognosisin MCL. The MIPI score was developed based on fourindependent factors at the time of diagnosis that maycorrespond with prognosis: age, performance status(ability to perform activities of daily life), lactatedehydrogenase (LDH) levels and leukocyte (white bloodcell) count. Age and performance status are measuresof chemotherapy tolerance while LDH and leukocytecount are indirect measures of disease activity. Patientsare assigned to a low-risk, intermediate-risk or high-riskcategory based on the number of points assigned to thenumber of factors present.A number of additional factors have been suggested aspotentially important prognostic markers, includingmarkers of cell proliferation (Ki-67), which measureshow fast malignant cells grow; gene expression profiling;minimal residual disease (MRD); MCL cell type; peripheralblood monocyte count (AMC) at diagnosis andbeta2-microglobulin level.Your treatment team may include more than one specialist.It is important for you and members of your treatmentteam to discuss all treatment options, including treatmentsbeing studied in clinical trials.DiaphragmStage IITwo or more lymph noderegions on the same side ofthe diaphragm.Stage IIITwo or more lymph noderegions above and belowthe diaphragm.DiaphragmDiaphragmStage IVWidespread disease inlymph nodes and/or otherparts of the body.For more information about choosing a doctor or atreatment center, see the free LLS publication Choosing aBlood Cancer Specialist or Treatment Center.FS4 Mantle Cell Lymphoma Facts I page 3
Mantle Cell Lymphoma FactsTreatmentMCL is generally considered an aggressive (fast-growing) typeof B-cell non-Hodgkin lymphoma and most MCL patientsreceive treatment following diagnosis and staging. However, fora small number of patients who have slow-growing (indolent)MCL and are otherwise well, doctors may recommend aperiod of close observation, called “watchful waiting.” Thedoctor will want to schedule visits with these patients every 2to 3 months, and do imaging tests every 3 to 6 months. Forpatients with indolent MCL, therapy begins when symptomsbecome more prominent or there are signs of progression (forexample, increasing lymph node size, new pain symptoms ornew enlarged nodes).may offer an alternative to the standard R-CHOP regimenand should be considered as initial (first-line) treatment inthese patients. A study of the Treanda and Rituxan drugcombination showed that it is more effective and less toxicthan CHOP. Clinical studies are evaluating the feasibilityof combining the Treanda and Rituxan regimen withmaintenance Rituxan.Table 1. Types of TreatmentR-CHOP [Rituxan, cyclophosphamide,hydroxydaunomycin (doxorubicin), Oncovin (vincristine), and prednisone]Patients who are having symptoms at diagnosis are notappropriate candidates for watchful waiting, since prompttreatment typically resolves symptoms.VcR-CAP [bortezomib (Velcade), Rituxan,cyclophosphamide, doxorubicin (Adriamycin ) andprednisone]Generally, rituximab (Rituxan ) in combination with otherdrugs is used to treat patients who have MCL. Rituxan is amonoclonal antibody that targets and destroys cells with theCD20 antigen, including MCL cells. A number of studiesshow that patients who are treated with chemotherapy plusRituxan have a higher initial response rate than what mightbe achieved with chemotherapy alone.R-CHOP [Rituxan, cyclophosphamide,hydroxydaunomycin (doxorubicin), Oncovin(vincristine), and prednisone] with an autologous stemcell transplantationIn most practices, standard R-CHOP-based chemotherapyis still a commonly used standard of care. While manyinstitutions recommend a protocol that consolidatesR-CHOP chemotherapy with a subsequent autologous stemcell transplant, other practices may not endorse this approach.A number of variations of standard R-CHOP chemotherapyhave been developed around the world. Recently, theFDA approved bortezomib (Velcade ) in a combinationreferred to as VcR-CAP [bortezomib (Velcade), Rituxan,cyclophosphamide, doxorubicin (Adriamycin ) andprednisone] for previously untreated patients with MCL. TheNordic Lymphoma Study Group has pioneered a protocol—appropriate for fit patients–that uses Maxi-R-CHOP (slightlyhigher CHOP doses) followed by high-dose cytarabine, anagent that many doctors believe is crucial in the treatmentof MCL. The chemotherapy is followed by autologous stemcell transplant. This protocol, which has been used in manycenters, seems to produce very favorable results.Other centers may recommend R-hyperCVAD, a moreintensive chemotherapy. It is an effective regimen and mayincrease response rates, but these treatments can be very toxic,so, typically, they are reserved for healthier, often younger,patients. Younger patients, however, may want to opt for aless intensive approach.For older fit patients without significant coexisting illnessesand those who are not eligible for transplantation, thecombination of bendamustine (Treanda ) and Rituxan (B R)Maxi-R-CHOP, The Nordic Lymphoma StudyGroup Protocol [R-CHOP followed by higher dosesof cytarabine, followed by an autologous stem celltransplant]R-hyperCVAD [Rituxan, cyclophosphamide,vincristine, doxorubicin (Adriamycin ), anddexamethasone alternating with high-dose cytarabineand methotrexate]R-hyperCVAD [Rituxan, cyclophosphamide,vincristine, doxorubicin (Adriamycin), anddexamethasone alternating with high-dose cytarabineand methotrexate] either with or without autologousstem cell transplantationB R [bendamustine (Treanda ) and Rituxan]R-FCM [Rituxan, fludarabine (Fludara ),cyclophosphamide and mitoxantrone]R-DHAP [Rituxan, dexamethasone, cytarabine andcisplatin].R-CVP (Rituxan, cyclophosphamide, vincristine,and prednisone)R-CBP [Rituxan, cyclophosphamide, bortezomib(Velcade ) and prednisone]Note: These are some of the combination chemotherapies.They may or may not be consolidated with an autologousstem cell transplant.FS4 Mantle Cell Lymphoma Facts I page 4
Mantle Cell Lymphoma FactsFor older, less fit MCL patients (who often have coexistingdisease), less intensive approaches are the best option.Single-agent oral Leukeran (chlorambucil) may be a goodchoice for frail elderly patients or for patients with seriouscomorbidities. Less aggressive treatment regimens suchas low-dose Treanda in combination with Rituxan (B R)may also be offered. The combination of oral chlorambucilwith Rituxan may also be considered for these patients; theregimen is well tolerated in most patients. Some elderly frailpatients may benefit from combination R-CVP (Rituxan,cyclophosphamide, vincristine, and prednisone), or evena newer regimen of R-CBP (Rituxan, cyclophosphamide,bortezomib (Velcade ) and prednisone).For more aggressive forms of MCL, if the disease hasspread to the central nervous system (CNS), drugs may beadministered directly into the fluid bathing the spinal canal.This procedure is called “intrathecal therapy (IT).”Patients will be better prepared for their treatments if theyknow how a medication is administered. The drugs fromcombinations listed in Table 1 on page 4, are given indifferent ways includingl Intravenously(IV): Rituxan, doxorubicin, vincristine,methotrexate, cytarabine, fludarabine, mitoxantroneand cisplatin.l IV or, less commonly, by mouth: cyclophosphamidel By mouth: prednisone and dexamethasone.The side effects of combination treatment will depend onmany factors, including the type of treatment and dosage,the age of the patient and coexisting medical conditions.Therapy may cause fever or chills, fatigue, nausea, peripheralneuropathy (tingling, burning, numbness or pain in thehands or feet), changes in blood cell counts, infection, rash,diarrhea, shortness of breath, temporary loss of hair andother side effects. Patients may be less fertile after undergoingcertain cancer treatments.Talk to Your Doctor About Side Effects of Treatment.Side-effects management is important. If you are havingany concerns about your side effects, talk to your doctor ornurses to get help. Most side effects can be managed withtreatment that will not compromise treatment for yourdisease. In fact, aggressive management of side effects oftenleads to better treatment outcomes. Most side effects aretemporary and resolve when treatment is completed.For additional drug information, see the free LLSpublication Understanding Side Effects of Drug Therapyand the Food and Drug Administration (FDA) druginformation webpage ult.htm.Also, see Treatments Under Investigation on page 6.Stem Cell Transplantation. Because outcomes withconventional chemotherapy have been disappointing,autologous stem cell transplantation has been combined withinitial first-line treatment of MCL. The purpose of autologousstem cell transplantation is to enhance the response toinduction therapy and to prolong remission. In autologousstem cell transplantation, a patient’s own stem cells arecollected and stored (harvested). The harvested cells are frozenand then returned to the patient after he or she has receivedintensive high-dose chemotherapy either with or withoutradiation therapy. High-dose chemotherapy with autologousstem cell transplantation has resulted in high rates of clinicalremission for MCL patients when used in first completeremission and may be an option for clinically symptomaticfit younger patients with few or no coexisting illnesses.Autologous transplantation combined with effective inductionagents, including combinations of monoclonal antibodies andchemotherapy, may offer a longer remission in these patients.Recent research suggests that this procedure followed bymaintenance Rituxan may improve progression-free survival.Some older fit patients may be candidates for autologousstem cell transplantation. High-dose chemotherapy andautologous stem cell transplantation is less successful whenused to treat patients who have relapsed or refractory MCLthan when it is used as first-line therapy early in the course ofthe disease.Allogeneic stem cell transplantation involves the transfer ofstem cells from a donor to the patient following high-dosechemotherapy or radiation therapy. This type of transplantis determined by the patient’s medical
Nov 25, 2013 · FS4 Mantle Cell Lymphoma Facts I page 3 ae e mpoma acts l Imaging studies, including computed tomography (CT) scans of the chest, abdomen and pelvis, with or without an accompanying positron emission tomography (PET)
In Non-Hodgkin lymphoma - Follicular lymphoma (36.8%) was the most common, followed by Diffuse large B-cell lymphoma (27.6%). Among 10 cases of Hodgkin lymphoma with marrow infiltration, there were 3 cases of Mixed cellularity, 3 cases of Lymphocyte - depleted clas-sical Hodgkin lymphoma and 1 case of Nodular sclerosis. Further, 2 Cases of Non .
also involved in other B-cell malignancies such as atypical Burkitt/Burkitt-like lymphoma, diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma and multiple myeloma. Besides 8q24 (MYC), other translocation partners for IGK, such as chromosomal regions 1p13, 3q27 (BCL6), 7q21, 16q24 and 18q21 (BCL2), are known.
The following Fact Fluency Card labels are included in this pack: 1. Plus One Facts 2. Plus Two Facts 3. Plus Three Facts 4. Minus One Facts 5. Minus Two Facts 6. Minus Three Facts 7. Facts of Five 8. Doubles Facts (Addition) 9. Doubles Facts (Subtraction) 10. Near Doubles Facts (e.g. 6 7 6 6 1 12 1 13) 11. Facts of Ten: Addition 12.
a mature B-cell lymphoma usually composed of small to . (Swerdlow et al., 2017). Immunophenotypically, the lymphoma cells express common B cell markers, CD5 and Cyclin D1, and lack the expression of CD23 and CD200 (Swerdlow et al., 2016a). The genetic hallmark of MCL is CCND1 translocation with . Cyclin D
Since CD5-negative MCL cases are occasionally reported, reevaluation will be necessary when CD5-negative B-cell lymphoma including MALT lymphoma is suspected and it has an atypical clinical course or is treatment-resistant,keep-ing in mind the possibility of MCL. CD5-negative cases in MCL
Lymphoblastic Lymphoma Lymphoblastic lymphoma represents approxi tl 20% f llNimately 20% of all Non-Hdki'Hodgkin's lymphoma -T-cell 15% -B-cell 3% ALL: Clinical Features Hepatosplenomegaly 68% Splenomegaly63%Splenomegaly 63% Fever 60% Malaise and fatigue 50% Lymphadenopathy 50% Pallor 40% Bl di 48%Bleeding 48% Bone pain 23% CNS signs 5%
Pediatric Cancer CAMPFIRE, NCT04145700 Pediatric Cancer CDK4 & 6 INHIBITOR ABEMACICLIB monarcHER, NCT02675231 Breast Cancer Next MONARCH 1, NCT02747004 . leukemia/small lymphocytic lymphoma, mantle cell lymphoma, and non-Hodgkin's lymphoma. BTK INHIBITOR PIRTOBRUTINIB (LOXO-305)
ACCOUNTING 0452/12 Paper 1 October/November 2019 1 hour 45 minutes Candidates answer on the Question Paper. No Additional Materials are required. READ THESE INSTRUCTIONS FIRST Write your centre number, candidate number and name on all the work you hand in. Write in dark blue or black pen. You may use an HB pencil for any diagrams or graphs. Do not use staples, paper clips, glue or correction .
