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Viral in hemat

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Joydeep Ghosh
Joydeep Ghosh

This document discusses cytomegalovirus (CMV) infections in patients with hematolymphoid malignancies. CMV is a common herpesvirus that can cause disease in immunocompromised patients. The document outlines the virology of CMV, clinical manifestations such as pneumonia and esophagitis, diagnostic methods including PCR and antigen testing, and treatment options like ganciclovir and valganciclovir. It emphasizes that pre-emptive antiviral therapy based on CMV detection can help prevent disease, and that while prophylaxis is not routinely needed, high-risk patients may benefit from monitoring and early treatment if infection is found.

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CMV INFECTIONS IN HEMATOLYMPHOID MALIGNANCIES Joydeep ghosh
INTRODUCTION.. Double stranded DNA virus Herpesviridae family Other members: HSV 1, HSV 2, HHV 6,7,8, VZV Human CMV grows only in human cells and replicates best in human fibroblasts
Prevalence: USA: 60% J Infect Dis. Apr 1995;171(4):1002-6 Homosexuals: 90% Am J Med. Mar 23 1987;82(3 Spec No):593-601 Developing countries: 90% J Health Popul Nutr. 2002;20: 348- 351 At risk: Day care Blood transfusion Transplant pts Prolonged immunosuppression
Routes of transmission: person to person via close contact placenta blood transfusions organ transplantation breast milk sexual transmission
VIROLOGY
HOW DO THEY LOOK LIKE?..
CLINICAL SYNDROMES
PNEUMONIA..
Viral in hemat
DIAGNOSTICS Cathomas et al, Blood, 1993 81: 1909-1914
ESOPHAGITIS 38% alloHSCT pts spectrum of endoscopic lesions is variable patchy erythema, exudates microerosions diffusely edematous mucosa, multiple mucosal erosions, deep ulcers pseudotumors Dx: Endoscopic app.. Immunostains with antibodies Shell vial culture 24-48 hours CMV PCR
HEPATITIS Defined by: Elevated Bil / enzymes No other cause CMV in liver HPE HPE remains the mainstay of diagnosis as just the presence of CMV DNA is not sufficient.
COLITIS Presentations: abdominal pain, watery or bloody diarrhoea, bleeding, obstruction, toxic megacolon, perforation fistula formation Dx s/s Endoscopic app. Tissue diagnosis (culture /HPE /immunostain/ ISH)
Viral in hemat
MDACC 4328 CANCER PATIENTS, 2001-2004
ETHNICITY MATTERS
AGE..
Viral in hemat
MODALITIES OF DIAGNOSIS Culture: in HEL fibroblasts 28 days Cytopathic effects DEAFF ( Detection of early antigen fluorescent foci ) : Sensitivity 78%, specificity 100% 24 hours cell culture Immunostain of encoded proteins
HPE: typical owls eye appearance Tissue immunofluorescence: anti CMV antibodies Electron microscopy ELISAs for CMV antigen in the urine Detection of CMV DNA by PCR CMV antigenemia test
Viral in hemat
Total 543 blood samples were tested CMV viremia detected in 37 episodes out of 28 patients PCR was only positive in 18 episodes AG positive in only 5 viremic episodes Both positive in 14 episodes Out of that 14, in 6 episodes, PCR preceded antigenemia by avg 7 days
Sensitivities: PCR : 86.5% AG : 51.3% Specificities: 100% for both PCR is an earlier marker of viremia
ANTIVIRAL STRATEGIES Prophylactic: anti-viral therapy started at engraftment and continued until at least day 100 post transplant Pre-emptive: Pre-emptive therapy is defined as antiviral treatment initiated based on the detection of primary or reactivated CMV infection by positive CMV cultures, a positive antigenemia (Ag) assay, or positive molecular assays
GANCICLOVIR.. drug of choice for treatment of CMV disease nucleoside analogue that inhibits DNA synthesis Protein UL97 phosphorylates ganciclovir to ganciclovir monophosphate. against CMV, HSV, VZV, and HHV-6, HHV-7, and HHV-
Adverse effects of ganciclovir therapy include fever, rash, diarrhea, and neutropenia, anemia, thrombocytopenia Managed with dose reduction or GCSF
In the treatment of CMV pneumonia, ganciclovir is administered with CMV-specific immune globulin Dosage: 5 mg/kg IV q12hr, over 1 hr x14-21d Maintenance: 5 mg/kg IV qD
VALGANCICLOVIR.. Valganciclovir is a prodrug of ganciclovir that is activated in the gut and liver to ganciclovir. 60% bioavailability. 900mg = 6mg/kg GFR below 10ml/min is a contraindication Oral valganciclovir is as effective as intravenous ganciclovir when used as an initial treatment Valganciclovir: new preparation. CMV retinitis: a simpler, oral treatment. Prescrire Int. Aug 2003;12(66):133-
FOSCARNET Intravenous foscarnet is considered second- line therapy for CMV reactivation or disease; however, for patients developing dose- limiting neutropenia or CMV strains resistant to GCV, it is the drug of choice Similar efficacy compared to GCV(1) Toxicity: renal 1 -- Reusser, P. Et al, Blood 99:11591164.
CIDOFOVIR Toxicity is a major concern: Nausea, vomiting, thrombocytopenia, Neuro/ophthalmologic toxicity Less favorable outcome Some studies have shown around 58% response rate with significant amount of toxicities(1) 1 Ljungman. Blood 97:388392
Viral in hemat
CMV PROPHYLAXIS.. Annals of Oncology17: 10511059, 2006 doi:10.1093/annonc/mdj132 Published online 5 May 2006
Viral in hemat
Viral in hemat
TAKE HOME MESSAGE.. Routine CMV prophylaxis is not indicated CMV monitoring can be done in high risk non HSCT population Fludarabine Alemtuzmab PET treatment is definitely indicated to reduce the chances of CMV syndrome, as they carry a very high mortality rate

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Viral in hemat

  • 1. CMV INFECTIONS IN HEMATOLYMPHOID MALIGNANCIES Joydeep ghosh
  • 2. INTRODUCTION.. Double stranded DNA virus Herpesviridae family Other members: HSV 1, HSV 2, HHV 6,7,8, VZV Human CMV grows only in human cells and replicates best in human fibroblasts
  • 3. Prevalence: USA: 60% J Infect Dis. Apr 1995;171(4):1002-6 Homosexuals: 90% Am J Med. Mar 23 1987;82(3 Spec No):593-601 Developing countries: 90% J Health Popul Nutr. 2002;20: 348- 351 At risk: Day care Blood transfusion Transplant pts Prolonged immunosuppression
  • 4. Routes of transmission: person to person via close contact placenta blood transfusions organ transplantation breast milk sexual transmission
  • 6. HOW DO THEY LOOK LIKE?..
  • 10. DIAGNOSTICS Cathomas et al, Blood, 1993 81: 1909-1914
  • 11. ESOPHAGITIS 38% alloHSCT pts spectrum of endoscopic lesions is variable patchy erythema, exudates microerosions diffusely edematous mucosa, multiple mucosal erosions, deep ulcers pseudotumors Dx: Endoscopic app.. Immunostains with antibodies Shell vial culture 24-48 hours CMV PCR
  • 12. HEPATITIS Defined by: Elevated Bil / enzymes No other cause CMV in liver HPE HPE remains the mainstay of diagnosis as just the presence of CMV DNA is not sufficient.
  • 13. COLITIS Presentations: abdominal pain, watery or bloody diarrhoea, bleeding, obstruction, toxic megacolon, perforation fistula formation Dx s/s Endoscopic app. Tissue diagnosis (culture /HPE /immunostain/ ISH)
  • 17. AGE..
  • 19. MODALITIES OF DIAGNOSIS Culture: in HEL fibroblasts 28 days Cytopathic effects DEAFF ( Detection of early antigen fluorescent foci ) : Sensitivity 78%, specificity 100% 24 hours cell culture Immunostain of encoded proteins
  • 20. HPE: typical owls eye appearance Tissue immunofluorescence: anti CMV antibodies Electron microscopy ELISAs for CMV antigen in the urine Detection of CMV DNA by PCR CMV antigenemia test
  • 22. Total 543 blood samples were tested CMV viremia detected in 37 episodes out of 28 patients PCR was only positive in 18 episodes AG positive in only 5 viremic episodes Both positive in 14 episodes Out of that 14, in 6 episodes, PCR preceded antigenemia by avg 7 days
  • 23. Sensitivities: PCR : 86.5% AG : 51.3% Specificities: 100% for both PCR is an earlier marker of viremia
  • 24. ANTIVIRAL STRATEGIES Prophylactic: anti-viral therapy started at engraftment and continued until at least day 100 post transplant Pre-emptive: Pre-emptive therapy is defined as antiviral treatment initiated based on the detection of primary or reactivated CMV infection by positive CMV cultures, a positive antigenemia (Ag) assay, or positive molecular assays
  • 25. GANCICLOVIR.. drug of choice for treatment of CMV disease nucleoside analogue that inhibits DNA synthesis Protein UL97 phosphorylates ganciclovir to ganciclovir monophosphate. against CMV, HSV, VZV, and HHV-6, HHV-7, and HHV-
  • 26. Adverse effects of ganciclovir therapy include fever, rash, diarrhea, and neutropenia, anemia, thrombocytopenia Managed with dose reduction or GCSF
  • 27. In the treatment of CMV pneumonia, ganciclovir is administered with CMV-specific immune globulin Dosage: 5 mg/kg IV q12hr, over 1 hr x14-21d Maintenance: 5 mg/kg IV qD
  • 28. VALGANCICLOVIR.. Valganciclovir is a prodrug of ganciclovir that is activated in the gut and liver to ganciclovir. 60% bioavailability. 900mg = 6mg/kg GFR below 10ml/min is a contraindication Oral valganciclovir is as effective as intravenous ganciclovir when used as an initial treatment Valganciclovir: new preparation. CMV retinitis: a simpler, oral treatment. Prescrire Int. Aug 2003;12(66):133-
  • 29. FOSCARNET Intravenous foscarnet is considered second- line therapy for CMV reactivation or disease; however, for patients developing dose- limiting neutropenia or CMV strains resistant to GCV, it is the drug of choice Similar efficacy compared to GCV(1) Toxicity: renal 1 -- Reusser, P. Et al, Blood 99:11591164.
  • 30. CIDOFOVIR Toxicity is a major concern: Nausea, vomiting, thrombocytopenia, Neuro/ophthalmologic toxicity Less favorable outcome Some studies have shown around 58% response rate with significant amount of toxicities(1) 1 Ljungman. Blood 97:388392
  • 32. CMV PROPHYLAXIS.. Annals of Oncology17: 10511059, 2006 doi:10.1093/annonc/mdj132 Published online 5 May 2006
  • 35. TAKE HOME MESSAGE.. Routine CMV prophylaxis is not indicated CMV monitoring can be done in high risk non HSCT population Fludarabine Alemtuzmab PET treatment is definitely indicated to reduce the chances of CMV syndrome, as they carry a very high mortality rate