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![Progressive multifocal leukoencephalopathy
Cause by JC virus in immunocompromised
patients
Present with subacute onset of focal neuro
deficit
Incidence was very low but fatal
In one report incidence was 2.89
case/1,000 patient-years
Blood 2009 114:3675;[abstract 3675]](https://image.slidesharecdn.com/whatyouneedtoknowaboutdlbcl-190402165551/75/What-you-need-to-know-about-dlbcl-35-2048.jpg)
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What you need to know about dlbcl
Diffuse Large B Cell Lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma, characterized by aggressive behavior and a diverse prognosis based on classification and immunophenotype. The main treatment strategy involves immunochemotherapy using R-CHOP, with careful monitoring and prophylaxis for complications such as HIV-related DLBCL. Post-treatment follow-up is essential due to the risk of relapse and long-term effects of therapy.
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What you need to know about dlbcl
- 1. What (do) youneed to know about DLBCL? Dear my fellow internists..
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- 3. Hematologic malignancy Acute Myeloidleukemia and related precursor neoplasms Myeloproliferative neoplasms Myelodysplastic syndrome Mature B-cell disorder Precursor lymphoid neoplasms (ALL) Mature T-cell and NK-cell disorder Plasma cell neoplasms Hodgkin lymphoma Adapted from WHO classification 2017
- 4. Lymphoproliferative disorder Mature B-celldisorder Mature T-cell and NK-cell disorder Hodgkin lymphoma Adapted from WHO classification 2017 Aggressive DLBCL Burkitt lymphoma Mantle cell lymphoma Indolent Follicular lymphoma CLL/SLL Marginal zone lymphoma MCL, HCL, LPL Classical Nodular sclerosis Lymphocyte-rich Mixed cellularity Lymphocyte depleted Nodular lymphocyte-predominant PTCL, NOS CD30+/CD30- ALCL Angioimmunoblastic TCL NK/T cell lymphoma Mycosis fungoides etc...
- 5. Diffuse large Bcell lymphoma The most common subtype of non-Hodgkin lymphoma Medium-to-large size B cell malignancy grows in diffuse pattern
- 6. Diffuse large Bcell lymphoma The most common subtype of non-Hodgkin lymphoma Medium-to-large size B cell malignancy grows in diffuse pattern When can not be put into predefined category we call DLBCL,NOS
- 7. Simplified version ofDLBCL subgroup GCB Non-GCB PMBCL Primary CNS DLBCL High grade DLBCL AIDS-related DLBCL
- 8. Immunophenotype Positive for CD45(leukocyte common antigen) → not positive in erythroid, plasma cell, or other tumors Positive for B cell marker CD19, CD20, CD22, CD79a, PAX5 Negative for T cell marker CD3, CD4, CD8
- 9. Immunophenotype for subgroup Hansalgorithm CD10+ BCL6+ MUM1/IRF4- CD10- GCB BCL6- MUM1/IRF4+ GCB Non-GCB Non-GCB
- 10. Immunophenotype Ki67 → indicateproliferation rate (40-90% or more) MYC and BCL2 co-expression (double expresser) had a poorer prognosis → This is not equal to double hit lymphoma
- 11. AIDS-related DLBCL Associated withvery low CD4+ count (eg. < 50/mL) The prognosis is improved with concurrent ART CNS prophylaxis is recommended in all cases If CD4+ count < 50/mL rituximab should be defer unit CD4+ improved Plasmablastic lymphoma Primary Effusion lymphoma Primary CNS lymphoma Burkitt lymphoma
- 12. Primary mediastinal largeB cell lymphoma Disease involve primarily in mediastinum Typically occur in young female patients Has feature overlapping with Hodgkin lymphoma IHC - similar to DLBCL with CD30+ weakly, CD15- , Bcl6+ Tumor cell has decreased MHC I, II expression and increased PD-ligand R-CHOP with RT or DA-EPOCH-R
- 13. Primary CNS largeB cell lymphoma One of AIDS defining lymphoma Treatment involve high dose of blood brain barrier penetrating chemotherapy HD-MTX HD-AraC Radiation can be used with palliative intention Associated with dementia in elderly (> 60 y)
- 14. High-grade DLBCL Appeared asBurkitt-like DLBCL Medium to large monotonous cells Or blastoid appearance May have starry sky macrophage Have rearrangement of MYC and BCL2 and/or BCL6 (double hit, triple hit) If no such rearrangement → HG-BL, NOS
- 15. Clinical feature Progressive onsetof lymph node enlargement Extranodal involvement as frequent as 40% Common site: GI tract, Waldeyer ring, testes, marrow, etc May have B-symptoms
- 16. Staging of lymphoma A→ asymptomatic B → B symptom Weight loss > 10% Fever Night sweat E → extranodal involvement X → bulky disease (> 8-10 cm)
- 17. Prognosis International prognostic index(IPI) score Developed from pooled data of lymphoma but major population consist of DLBCL Age > 60 years Performance status ECOG > 2 LDH > normal range Extranodal site > 1 Stage II-IV
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- 20. Treatment of DLBCL Pretreatmentevaluation Immunochemotherapy R-CHOP Salvage treatment
- 21. Treatment of DLBCL Pretreatmentevaluation Immunochemotherapy R-CHOP Salvage treatment 3-4 cycles of chemotherapy 2-4 cycles more Assess for response CT, BMA, PET/CT
- 22. Treatment of DLBCL Pretreatmentevaluation Immunochemotherapy R-CHOP Salvage treatment Cardiac function Performance status - HIV - Hepatitis B Comorbidity
- 23. Treatment of DLBCL Pretreatmentevaluation Immunochemotherapy R-CHOP Salvage treatment Rituximab Cyclophosphamide Doxorubicin Vincristine Prednisolone+ CNS prophylaxis
- 24. Treatment of DLBCL Pretreatmentevaluation Immunochemotherapy R-CHOP Salvage treatment ICE ESHAP GDP HyperCVAD Others ASCT
- 25. Follow up aftertreatment After patient achieved CR F/U every 1-2 months After 2 years incidence of relapse is low; F/U every 6-12 months Late relapse may occur after 8 years and can retreat with the same regimen Keep vaccination on schedule after 12 months of treatment
- 26. Rituximab Chimeric monoclonal antibody againstCD20 Exert multiple mechanism of cytotoxicity
- 27. Rituximab efficacy vschemo alone Age Treatment Study outcome Long term outcome GELA LNH-98.5 60-80 y 8R-CHOP vs 8CHOP 2y EFS 57 vs 38% 10y PFS 36.5 vs 20% 10y OS 43.5 vs 27.6% MInT 18-60 y 6R-CHOP-like vs 6CHOP 3y EFS 79 v s 59% 6y EFS 74.3 vs 55.8% 6y PFS 80.2 vs 63.9% 6y OS 90.1 vs 80% N Engl J Med 2002;346:235-42. Blood 2010 116:2040-5. Lancet Oncol. 2006 May;7(5):379-91. Lancet Oncol. 2011 Oct;12(11):1013-22
- 28. Adverse events ofrituximab Infusion reaction Reactivation of hepatitis B virus Rituximab-induced pneumonitis Progressive multifocal leukoencephalopathy (PML) Humoral immune suppression
- 29. Infusion reaction ofrituximab Patients may experience rash, urticaria, angioedema, bronchospasm, fever, chills Onset 30-120 min after infusion Should be closely monitored in the 1st cycle Premedication with paracetamol, antihistamine, steroid After reaction resolve rituximab can be reinitiate at 50% infusion rate
- 30. Patient at risk:HBsAg +ve, HBcAb IgG +ve Chemotherapeutic regimens Low risk: Azathioprine, methotrexate Moderate risk: CHOP, fludarabine, high dose steroid (pred > 20 mg) High risk: rituximab therapy ~ 5X risk Prevention with entecavir, lamivudine up to 12 months after treatment with surveillance Reactivation of HBV J Clin Transl Hepatol. 2016;4(2):143–50.
- 31. Lamivudine vs entecavir Newlydiagnosed DLBCL enter the clinical trial of R-CHOP 21 vs R-CHOP 14 HBsAg positive and HBV DNA < 103 copy/mL Entecavir 0.5 mg vs lamivudine 100 mg Primary endpoint: incidence of HBV related hepatitis Secondary endpoint: HBV reactivation, chemo disruption R-CHOP 21 or R-CHOP 14 1 week before and 6 months after treatment JAMA. 2014;312(23):2521-30.
- 32. Lamivudine vs entecavir JAMA.2014;312(23):2521-30.
- 33. Rituximab-induced interstitial pneumonitis Rarebut potentially fatal complication Present with dyspnea, fever, cough HRCT chest reveal diffuse interstitial pattern PFT had restrict pattern Incidence after the 4th cycle of rituximab Treatment include systemic steroid
- 34. Rituximab-induced interstitial pneumonitis Inone retrospective review of 560 patients receiving R-Chemo or Chemo 329 patients received rituximab Incidence of ILD was 3.95% (13/329) 4 patients had symptomatic disease Leukemia & Lymphoma. 2015;56(6):1659–64.
- 35. Progressive multifocal leukoencephalopathy Causeby JC virus in immunocompromised patients Present with subacute onset of focal neuro deficit Incidence was very low but fatal In one report incidence was 2.89 case/1,000 patient-years Blood 2009 114:3675;[abstract 3675]
- 36. Immune recovery afterrituximab CD19 count Immunoglobulin level Cancers (Basel). 2015;7(1):305–28.
- 37. New form ofrituximab Administered at fix dose of 1,400 mg SC injection on abdominal site Can be used after cycle 1 Substitute for 375 mg/m2 dose
- 38. Rituximab subcutaneous Lancet Haematol.2017;4:e272–82.
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- 41. Conclusion DLBCL is themost common aggressive lymphoma Common subtype DLBCL-NOS, PMBCL, primary CNS, AIDS-related lymphoma The mainstay of therapy is R-chemo for CD20+ disease Long term care for lymphoma survival Disease surveillance Vaccination