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

5. VIROLOGY

6. HOW DO THEY LOOK LIKE?..

7. CLINICAL SYNDROMES…

8. PNEUMONIA..

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)

15. MDACC
4328 CANCER PATIENTS, 2001-2004

16. ETHNICITY MATTERS…

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 99:1159–1164.

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 97:388–392

32. CMV PROPHYLAXIS..
Annals of Oncology17: 1051–1059, 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