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Dlbcl Dlbcl Presentation Transcript

  • Dr. S. Moses Arunsingh
  •  Diffuse large B-cell lymphoma (DLBCL) constitutes 30%–58% of lymphoma series.  Commonest lymphoma in adults.
  • Excisional lymph node or extra nodal tissue biopsy providing enough material for formalin-fixed samples. Minimal IHC (CD45, CD20, and CD3) is mandatory. A complete blood count, Routine blood chemistry including lactate dehydrogenase (LDH) and uric acid Human immunodeficiency virus and hepatitis B and C CT chest and abdomen PET scan Bone marrow aspirate and biopsy. Cardiac function (left ventricular ejection fraction) Lumbar puncture in high risk
  • Age > 60 LDH elevated PS 2-4 Stage III or IV Extranodal involvement > 1 Low – 0 or 1 Low intermediate - 2 High intermediate - 3 High – 4 or 5
  • LDH elevated PS 2-4 Stage III or IV Low – 0 Low intermediate - 1 High intermediate - 2 High – 3
  •  Non bulky disease with no adverse features  R-CHOP x 6 cycles every 21 days (IF 3 cycles add RT)  Non bulky disease with adverse features  R-CHOP x 6 cycles every 21 days (IF 3 cycles add RT)  Bulky Disease >= 10cm  R-CHOP x 6 cycles every 21 days + RT
  •  Efficacy of rituximab proven in  MInT compared 6 cycles CHOP with 6 cycles R-CHOP  3year OS 93% vs 84%
  •  RT benefit first proven over CHOP  SWOG 8763 ( PFS 77% vs 64%, OS 82% vs 72%)  BCCA  ECOG 1484
  •  GELA study (LHN 93-4) did not show benefit of RT. But in RT arm, there delays in RT and avoidance of RT in some patients  Retrospective study of 469 patients from MDACC shows that there is improvement in OS and PFS even after addition of Rituximab ( PFS 82% vs 68% and OS 92% vs 73%)  Interestingly the site of IFRT had no failure in MDACC study whereas in the GELA studies there In field failure rate was more than 20%
  •  6 cycles of R-CHOP x 21 days  Rituximab –  GELA (LNH98-5) (OS 43.5% vs 28% at median follow up of 10 years)  MInT  GHSG - R-CHOP 14 superior to RCHOP 21  RICOVER – 60 in 61-80 years of age also showed that dose dense regimen was superior.
  •  Controversial  Most studies are retrospective.  MDACC retrospective study revealed benefit even stage III and IV  Similar study from Duke University showed improved infield control and EFS but no influence on OS.  There are evidences from various single institutional studies that consolidative RT improves LC, PFS and may be OS.
  •  GELA 87-2 found it beneficial . ( No rituximab)  DLCL04 (Italian) and SWOG 9704 did not show survival benefit when added to R CHOP  Benefit in high risk group that was suggested in the GELA study needs further proof
  •  PNS  Testis  Bone marrow involvement  Epidural  Two or more extranodal sites with elevated LDH  Needs CNS prophylaxis. Optimal management not yet decided.  Intrathecal methotrexate/ cytarabine or IV methotrexate
  •  Based on candidacy for HDC / ASCR  If fit for HDC  DHAP, ESHAP, GDP, ICE, MINE, GEMOX  If not then,  CEPP  Bendamustine  DA EPOCH  CEOP  Linoledamide
  •  GC origin seem to have a favorable prognosis but not yet used to guide choice of therapy
  •  High Ki – 67 has poorer prognosis in Non GC like DLBCL  BCL2(+) GCB-DLBCL seems to receive less benefit from R- CHOP  CD30 expression was more frequent in DLBCLs with non- germinal center origin phenotype, BCL2 + DLBCLs
  •  Concurrent MYC rearrangement and t(14:18) (bcl-2) have very poor prognosis  No standard treatment  Median PFS 6 months and OS 8 -13 months
  •  Brentuximab vedotin - CD30-expressing tumors  Crizotinib - ALK-positive DLBCL  Activated B-cell (ABC) genetic subtype – NFKB , Bortezomib  Tositumomab- Anti-CD20 conjugated with radionuclide iodine-131  Ibritumomab tiuxetan- Anti-CD20 conjugated with radioactive isotope (either yttrium-90 or indium-111)  CD 22 – Epratuzumab  Oblimersen sodium – Bcl-2  Fenretinide – Bcl – 2  mTOR inhibitors  Everolimus  Temsirolimus  Syk inhibitors  Fostamatinib  Tamatinib
  •  Gene profiling has shown PMBCL is distinct from DLBCL  CD 19,20,22 ,23, MUM1+ and 21 - . Weak positivity of CD 30 in 80%  No standard therapy is known because of rarity  But treated as per DLBCL protocol.