Mantle Cell Lymphoma: Causes, Symptoms, Diagnosis and Treatment — Overview, Diagnosis & Treatment Options | MyMedicPlus

Mantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin lymphoma arising from mantle zone B-cells, accounting for approximately 3-6% of all NHLs with approximately 3,000-4,000 new cases per year in the US. Defined by the t(11;14)(q13;q32) translocation causing cyclin D1 (CCND1) overexpression. Predominantly affects males (3:1) in the sixth and seventh decades.

The t(11;14) translocation (CCND1-IGH fusion) causing cyclin D1 overexpression is the universal genetic hallmark, present in essentially 100% of classic MCL. Secondary alterations that confer worse prognosis: TP53 mutation, CDKN2A deletion, and complex karyotype. SOX11 overexpression characterizes conventional nodal MCL, while SOX11-negative leukemic non-nodal MCL is a more indolent variant. No established environmental risk factors.

Lymphadenopathy (peripheral and mediastinal), hepatosplenomegaly, bone marrow infiltration (>70% at diagnosis), and peripheral blood leukemic involvement. GI tract involvement (lymphomatous polyposis) is characteristic. B symptoms (fever >38°C, drenching night sweats, weight loss >10% in 6 months) in some patients. Cytopenias from bone marrow involvement. Blastoid and pleomorphic MCL variants are more aggressive with rapid clinical progression.

Lymph node biopsy (or bone marrow/GI biopsy). IHC: CD20+, CD5+, CD19+, CD23−, CD10−, cyclin D1+ (or SOX11+ in cyclin D1-negative MCL). FISH for t(11;14) confirming CCND1-IGH. Ki-67 proliferation index (>30% defines blastoid/pleomorphic variant). PET/CT for staging. Bone marrow biopsy with PCR for IGH clonotype. MIPI (Mantle Cell Lymphoma International Prognostic Index) scoring. TP53 mutation and p53 IHC as high-risk markers.

Transplant-eligible younger patients: intensive induction (R-CHOP alternating with R-DHAP containing cytarabine, or Nordic regimen with high-dose cytarabine) followed by autologous SCT plus rituximab maintenance. Transplant-ineligible: bendamustine-rituximab (BR) ± ibrutinib; R-CHOP plus ibrutinib. Rituximab maintenance improves PFS. Relapsed/refractory: BTK inhibitors (ibrutinib, acalabrutinib, zanubrutinib) with ORR approximately 60-80%; venetoclax combinations; brexucabtagene autoleucel (KTE-X19) CAR-T cell therapy approved for relapsed MCL with ORR approximately 85%.

Median OS approximately 5-7 years with conventional treatment; improving with BTK inhibitors and CAR-T. High MIPI, blastoid histology, Ki-67 >30%, TP53 mutation: median OS often less than 3 years. Indolent leukemic non-nodal MCL (SOX11-negative): watch-and-wait approach, with median OS exceeding 10 years. Brexucabtagene autoleucel achieves 24% CRR in heavily pre-treated MCL. Disease remains generally incurable for conventional MCL with current therapy.