viral in hemat
TRANSCRIPT
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CMV INFECTIONS IN HEMATOLYMPHOID MALIGNANCIES
Joydeep ghosh
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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
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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
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Routes of transmission: person to person via close contact placenta blood transfusions organ transplantation breast milk sexual transmission
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VIROLOGY
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HOW DO THEY LOOK LIKE?..
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CLINICAL SYNDROMES…
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PNEUMONIA..
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DIAGNOSTICS…
Cathomas et al, Blood, 1993 81: 1909-1914
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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
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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.
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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)
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MDACC4328 CANCER PATIENTS, 2001-2004
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ETHNICITY MATTERS…
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AGE..
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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
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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
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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
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Sensitivities: PCR : 86.5% AG : 51.3%
Specificities: 100% for both
PCR is an earlier marker of viremia
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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
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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-
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Adverse effects of ganciclovir therapy include fever, rash, diarrhea, and neutropenia, anemia, thrombocytopenia
Managed with dose reduction or GCSF
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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
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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-
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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 99:1159–1164.
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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 97:388–392
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CMV PROPHYLAXIS..
Annals of Oncology17: 1051–1059, 2006 doi:10.1093/annonc/mdj132 Published online 5 May 2006
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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