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Mantle Cell Lymphoma: Etiology,Manifestation, Prevalence, Treatment,& Survival of a Rare Non-HodgkinLymphomaC A R I S S A O R I G E R , PA - S 2U N I V E R S I T Y O F S O U T H D A K O TA
Objectives01020304Identify characteristicsand manifestations ofMantle cell lymphoma(MCL).Identify theetiology/pathogenesis ofMCL.Discuss the prevalenceand overall survival ofMCL.Discuss treatment andremission of MCL.
Case Study**Disclaimer: consent from patient to share caseDate: 6-14-19CC: “sinus problem”HPI: Patient is a 47 yo male with a history of chronic nasal congestion. He states nothing he has tried seems to clear his symptoms. Iactually saw him back in February when he was complaining of nasal congestion and sinus drainage. He had sinus pressure as well. Hehad been on antibiotics and steroids and seemed to improve, but his symptoms had worsened. He indicates his sense of smell wasdiminished, but he was also complaining of eustachian tube dysfunction and that his ears became plugged and full. Following thatencounter, we placed him on a prednisone taper, some Mucinex, and continued on the Flonase and Allegra and got a CT of thesinuses. CT really did not show anything significant. There was minimal evidence of disease and I had recommended that he stay onthe allergy medicine. He subsequently saw an allergist and was tested and found no significant positives. He is back today because heis frustrated by the nasal congestion that he seems to have chronically. It is worse when he lies down at night. Currently, he is onAstelin and Flonase and his symptoms have not improved. He has had no nosebleeds. Does not describe any other sinus issues. Hedoes display nasal speech today.Additional s/s not listed: Unintentional weight loss of almost 20 pounds, new onset snoring, increased fatigue, dysphagia
Physical Exam/Flexed Scope Evaluation Nose/Nasopharynx: External nose: Normal size and appearance; no tenderness; no discharge; nostrils patent; no evidence of trauma Intranasal exam: Nasal mucosa pink and moist, inferior turbinate normal; middle and superior turbinate normal; septummidline The nose was prepped and the flexible scope was used to evaluate primarily the nasal cavity and nasopharynx. There does appearto be some type of growth in the posterior nasopharynx occluding the nasal choana. It is difficult to tell whether this is posterior nasalcavity tissue or nasopharyngeal tissue or adenoid regrowth.Assessment: Nasopharyngeal massPlan: I had Dr. *** look at it as well. We both agree that there is some suspicious tissue in the back of the nose or in the nasopharynx. This needsto be biopsied. The CT we obtained back in February did not have contrast, but at this point we are going to set him up for direct visualization andbiopsy and possible removal of the tissue, by Dr. ***, under general anesthesia.
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Why Mantle CellLymphoma?
LymphomaHodgkin & non-Hodgkin lymphoma Hodgkin lymphoma – Reed Sternberg cells Non-Hodgkin lymphoma (NHL) – absence of Reed Sternbergcells 60 types of NHLs (Han et. al, 2017) B cell (85-90% of NHLs) T/NK cellAggressive B-cell NHLs – including Mantle Cell lymphoma(MCL).https://www.google.com/url?sa i&url EpxZk&psig AOvVaw3weLWpOoxzEqibgYlqjAbU&ust 1589224013973000&source images&cd vfe&ved 0CAIQjRxqFwoTCOi0tZb qekCFQAAAAAdAAAAABAD
Mantle Cell LymphomaOther names: intermediate lymphocytic lymphoma,mantle zone lymphoma, centrocytic lymphoma, andlymphocytic lymphoma of intermediatedifferentiation2-7% of NHLs (Rule, 2019)Mantle zone of the follicleS/S: Unexplained weight lossFeverNight sweatsLymphadenopathyFatigueAsymptomatic in early 45/secondary-lymphoid-tissue
MCLAdvanced disease1st presentation – usually lymphadenopathy (75%)Extranodal disease – (25%)Common sites: lymph nodes, spleen, waldeyer’s ring, bonemarrow, blood, and extranodal sites (GI, breast, pleura,orbit)CNS involvement is rareUp-to-date (2021).
Etiology/PathogenesisReciprocal translocation of t(11;14) Overexpression of cyclin D1 gene Present in approximately 85%Cellular origins: Classical MCL or “leukemic”variant of MCLCortelazzo & colleagues – genetic predisposition of having 1st degree relative with MCL or NHL (2012).Pesticides, Fungicides, & Herbicides: Alavanja & colleagues – 10 years of exposure led to risk of developing NHL (2014). Hoffman et al. – growing up on a farm increased risk (2015). Kisby – exposure shows oxidative stress, DNA damage, immunosuppression, and neurological disease (2009).
Clinical EvaluationComplete H&PBloodwork (CBCD, CMP, HIV, Serum Immunoglobulins, SPEP, genetic testing, etc. ) LDH & beta2 microglobulinCT/PET scanColonoscopyBone Marrow biopsyTissue biopsyCardiac workup – EKG, Echo, MUGA
odgkin-lymphoma/diagnosis/nhl-staging
PrognosisCopyrights apply
Copyrights apply
Mantle CellInternationalPrognosticIndex (MIPI)Low, intermediate, or high riskECOG – Eastern CooperativeOncology nternational-prognostic-index-mipi#next-steps
Prevalence M F – approx. ¾ of patients are males Median Age: 68 years old Incidence non-Hispanic whites Hispanics, Asian/Pacific Islanders, NH Black (Jain & Wang, 2019). Multivariant Study (Shah, 2019) – Assessed racial and socioeconomic disparities
Inferior OS NH Black Without insurance Community treatment centers Greatest OS in Hispanic
Patient ase StagePrimary or recurrent MCLEF?
Young, Healthy6 Cycles alternating:Rituximab CHOP Cyclophosphamide, hydroxydaunomycin, onvcovin(Vincristine), and prednisoloneRituximab R-DHAP Dexamethasone, cytarabine, and cisplatinORNordic Regimen (6 cycles alternating):Rituximab high-dose cytarabineRituximab Maxi-CHOP Cyclophosphamide, hydroxydaunomycin(Doxorubicin), onvcovin (Vincristine), andprednisone
Autologous Stem Cell TransplantSelf at about allogenic transplants?
Allogeneic Stem Cell Transplant Graft -versus-host disease (GVHD)Advantages (Tam & Khouri, 2009): Graft vs. lymphoma (GVL) – prevent chemoresistanceLimitation:30% transplant-related mortality
High Risk Patients &IndolentHigh-risk patients:Not eligible for high dose intensive chemotherapyImmunochemotherapy: bendamustine-based regimen Rituximab maintenance therapyIndolent or Low risk:Watch & wait
Remission2015 – 584,000 individuals living with history of NHL Estimation 710,000 by 2022 (Spector et al., 2015)Long-term effects: Persistent pain Depression Post-traumatic stress disorder Fatigue Cardiac toxicities Risk of secondary malignancies
Refractory/Relapse of MCLAveraged 5-7 years OSGerson & Colleagues (2019): OS: 139 months High-risk MCL: 37 monthsIncurable with relapse in months - years More aggressive Treatment resistant Relapse commonly occurs in GI (Ahmed et al., 2018)
ResearchCell cycle inhibitors – type ofdrug would be utilized toprevent cell proliferationProteasome inhibitors – blockcellular pathways preventingcell growth and survivalinhibiting the proteinsnecessary for these actions tooccurMonoclonal antibodies –block growth of cancer cellsby attacking cells butminimize harm to normalcellsImmunomodulators – modifymultiplication and growth ofcells of the immune systemTyrosine kinase inhibitors –block signals of proliferationof cellsmTOR inhibitors – reducecyclin D1 expression to slowand inhibit MCL
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the allergy medicine. He subsequently saw an allergist and was tested and found no significant positives. He is back today be cause he is frustrated by the nasal congestion that he seems to have chronically. It is worse when he lies down at night. Currently, he is on Astelin and Flonase and his symptoms have not improved. He has had no nosebleeds.
