Mantle Cell Lymphoma

Background

• Mantle cell lymphoma is a type of aggressive non-Hodgkin lymphoma derived from mature B cells normally found in the mantle zone of lymph node (a thin layer surrounding germinal follicles).
• Mantle cell lymphoma is characterized genetically by a t(11;14) (q13;q32) translocation, resulting in cyclin D1 overexpression.
• Incidence is relatively rare; MCL comprises about 6% of all non-Hodgkin lymphomas and most commonly affects men between 50-70 years of age.
• It generally presents at an advanced stage with disseminated disease involving blood, bone marrow, gastrointestinal tract and/or spleen.
• Associated with poor prognosis and a continued high relapse rate after treatment; the MIPI uses clinical features to stratify 5-year overall survival in patients with advanced-stage MCL.
• Often can present with concurrent complications such as tumor lysis syndrome and viral reactivation.

Evaluation

• Suspect mantle cell lymphoma in older male patients, with history of unexplained fevers, weight loss, gastrointestinal symptoms and physical exam findings that may include extensive lymphadenopathy, hepatomegaly and/or splenomegaly.
• Perform the following diagnostic workup and staging:
  • blood tests
    • complete blood count with platelets and differential
    • comprehensive metabolic panel, including serum lactate dehydrogenase (LDH)
    • hepatitis B testing in patients for whom rituximab is being considered
    • immunophenotyping with immunohistochemistry and/or flow cytometry
  • imaging with chest/abdominal/pelvic computed tomography (CT) scan with contrast
  • lymph node biopsy
  • bone marrow biopsy and aspirate
• Diagnosis is established based on:
  • morphology on biopsy of lymph node, tissue, bone marrow, or blood
  • typical immunophenotype on flow cytometry and/or immunohistochemistry
  • detection of cyclin D1 expression or t(11;14) translocation in the context of mature B-cell proliferation
• Differential diagnosis includes chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and marginal zone lymphoma.
• The typical immunophenotype of mantle cell lymphoma (MCL), which helps to establish diagnosis and differentiate MCL from other types of lymphoma, is:
  • CD5 positive
  • CD20 positive
  • CD43 positive
  • CD23 negative or positive
  • cyclin D1 positive
  • CD10 negative or positive

Management

• For the rare patient who presents with stage I-II disease and localized presentation, options include:
  • induction therapy with suggested chemoimmunotherapy regimen, with or without radiation therapy
  • radiation therapy alone
• For patients with stage II bulky or stage III-IV disease, options include:
  • induction therapy with a suggested chemoimmunotherapy regimen
  • enrollment in a clinical trial; for a list of trials for mantle cell lymphoma that are currently recruiting patients, see clinicaltrials.gov
  • active surveillance
• For patients with stage II-IV disease with complete or partial response to induction therapy, consider:
  • consolidation therapy with high-dose chemotherapy followed by autologous stem cell transplantation in first complete response
  • enrollment in a clinical trial; for a list of trials for mantle cell lymphoma that are currently recruiting patients, see clinicaltrials.gov
• In patients who are not candidates for autologous stem cell transplantation, consolidation therapy options include:
  • in those who had induction therapy with R-CHOP, rituximab maintenance
  • in those who did not have induction therapy with R-CHOP, surveillance
• For patients who relapse or with refractory disease, consider:
  • enrollment in a clinical trial; for a list of trials for mantle cell lymphoma that are currently recruiting patients, see clinicaltrials.gov
  • second-line treatment with a suggested regimen
  • radiation therapy
• Surveillance typically includes clinical follow-up with history and physical exam, blood counts, and routine chemistry every 3-6 months for 5 years, then annually or as clinically indicated.