Radiation Oncology/NHL/DLBCL

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Front Page: Radiation Oncology | RTOG Trials | Randomized Trials

Non-Hodgkin lymphoma: Main Page | Randomized
Overview: Overview | Follicular | Diffuse large B-cell | MALT (extranodal marginal zone) | Nodal marginal zone | Mantle cell | CLL/SLL | Lymphoblastic | Burkitt | NK/T cell | Anaplastic large cell | Primary CNS Lymphoma
Treatment: Low grade and follicular | Diffuse and high grade | Marginal zone | Mantle cell | CLL/SLL | Lymphoblastic | Specific sites | Radioimmunotherapy


Contents

[edit] Pathology

  • Morphology - not clinically useful
    • Immunoblastic
    • Centroblastic
    • Anaplastic
    • Multilobated
  • Markers
    • Improved survival
      • Rb (cell cycle)
      • Germinal centre (bcl-6, CD10)
    • Decreased survival
      • CD5 (T-cell lineage)
      • HLA-I, HLA-II (immune)
      • Ki-67 (proliferation)
      • p53+, p21, p27, cyclin D3 (cell cycle)
      • bcl-2, bax, survivin (apoptosis)
      • CD44 (adhesion)
  • Origin
    • Germinal center of activated lymphoid follicle


[edit] Subclassification

  • Gene profiling identified 3 separate subtypes, with different clinical behavior (5-year OS)
    • Activated B-cell - activation of NFkB - 30% survival
    • Germinal B-cell - hypermutations, REL amplification, bcl-2 translocations - 64% survival
    • Primary Mediastinal B-cell - 59% survival
  • Mediastinal B-cell lymphoma is more closely related to nodular sclerosis subtype of Hodgkin lymphoma (clinically and by gene expression profile), than to the other types of B-cell lymphoma
  • Morphologically, there is also a significant overlap with Burkitt's Lymphoma


  • Charite, 2006 (Germany) PMID 16760442 -- "A biologic definition of Burkitt's lymphoma from transcriptional and genomic profiling." (Hummel M, N Engl J Med. 2006 Jun 8;354(23):2419-30.)
    • Gene analysis. 220 mature aggressive B-cell lymphomas. Molecular Burkitt's lymphoma (mBL) signature developed: 58 gene set. Some patients with this signature had morphologic appearance of DLBCL
    • 5-year OS: mBL 75%, GCB-DLBCL 51%, ABC-DLBC 12%
    • Myc locus survival (mBL and DLBCL): breakpoint 15% vs. no breakpoint 44%
    • Conclusion: molecular definition of Burkitt's lymphoma
  • Lymphoma profiling project
    • 2006 PMID 16760443 -- "Molecular diagnosis of Burkitt's lymphoma." (Dave SS, N Engl J Med. 2006 Jun 8;354(23):2431-42.)
      • Gene analysis. 303 patients with aggressive lymphomas, 25 pathological Burkitt's. Gene profile developed.
      • 8 samples submitted as DLBCL had molecular profile of Burkitt's
      • Conclusion: Gene-expression profiling is accurate to differentiate BL and DLBCL
    • 2005 PMID 16046532 -- "Diffuse large B-cell lymphoma subgroups have distinct genetic profiles that influence tumor biology and improve gene-expression-based survival prediction." (Bea S, Blood. 2005 Nov 1;106(9):3183-90.)
      • ABC-DLBCL: trisomy 3, gain of 3q, gain of 18q21-q22, loss of 6q21-q22
      • GCB-DLBCL: gain of 12q12
      • PMBCL: gain of 9p21, gain of 2p14-p16
  • Dana Farber, 2003 PMID 12933571 -- "The molecular signature of mediastinal large B-cell lymphoma differs from that of other diffuse large B-cell lymphomas and shares features with classical Hodgkin lymphoma." (Savage KJ, Blood. 2003 Dec 1;102(12):3871-9.)
    • Gene expression profiles compared. Shared survival pathway between MBCL and HL
  • NCI, 2002 PMID 12075054 -- "The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma." (Rosenwald A, N Engl J Med. 2002 Jun 20;346(25):1937-47.)
    • Biopsy samples of 240 patients examined with DNA microarrays. 17 gene-set predictor developed
    • Gene array independent predictor to IPS
  • Stanford, 2000 PMID 10676951 -- "Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling." (Alizadeh AA, Nature. 2000 Feb 3;403(6769):503-11.)
    • DNA microarrays to conduct a systemic characterization of gene expression
    • Two molecularly distinct types: 1) Germinal Center and 2) Activated B-like
    • OS significantly better for Germinal Center patients


[edit] Primary Mediastinal Large B-cell

  • Epidemiology:
    • 2% of NHL patients
    • Tends to affect younger women
  • Clinical presentation:
    • Rapidly growing (bulky >10cm) mediastinal mass, often with respiratory symptoms
    • Up to 50% can have symptoms of SVC syndrome (facial edeme, neck vein distension, upper extremity edema
  • Pathology
    • Believed to arise from thymic B-cells
    • Have bcl-6 translocation, but also gain in Janus kinase (JAK-2), bcl-2 translocation absent
    • Striking clinical, immunologic, and molecular similarities to Hodgkin's disease (NScHL), but cells retain B-cell differentiation markers (eg CD20), and lack Reed-Sternberg cells
  • Treatment
    • Please see the Specific Sites section for more detail
    • Some evidence that dose-intensified therapy (eg MACOP-B, VACOP-B, DA-EPOCH) may be superior to CHOP. Role of Rituxan is unclear, but magnitude of benefit probably similar to DLBCL
    • Many patients given consolidative RT for bulky/residual disease, but role of RT somewhat unclear
  • Outcome
    • Somewhat more aggressive course, despite younger age, with similar survival as DLBCL
    • Rarity of relapses past 2 years

[edit] Reviews

  • JCO 2005 - PMID 16155024 — "State-of-the-Art Therapeutics: Diffuse Large B-Cell Lymphoma." Coiffier B et al. Journal of Clinical Oncology, Vol 23, No 26 (September 10), 2005: pp. 6387-6393.

[edit] Treatment

Please see Aggressive lymphoma treatment section

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