SCT Question 4

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Question 4

Your 60 Y/F, CMV seropositive African American patient who is 45 days post-transplant from her haploidentical, CMV-sero negative daughter presents to the Emergency room with fever and dyspnea. GVHD prophylaxis was with post-transplant cyclophosphamide, tacrolimus and mycophenolate mofetil. Physical exam is unremarkable except for hypoxia on room air and tachypnea with faint bi-basal crackles on inspiration. She reports not being able to fill Letermovir because of high insurance copay cost. There is no JVD or LE edema. There are no antecedent URI sx; SARSCOV2 PCR and respiratory viral panel are negative. CXR shows diffuse bilateral infiltrates. CMV PCR for the UL54 gene was positive at 3.4 log copies/mL when drawn during infusion center visit two days ago; it was 2.1 log the week before and negative the week prior to that. WBC ct. is 1000/microL, ANC is 700, PL ct is 34000/microL and the patient still needs red cell transfusions every other week. CD3+ cell count is 85/microL. Tacrolimus level is therapeutic, she is off MMF for ten days now. Non-contrast CT of the chest shows bilateral ground glass opacities.

Following blood cultures, repeat CMV PCR, and administration of broad-spectrum antibiotics the next step in management is

1. Administer ganciclovir 5 mg/kg twice daily

2. Obtain microbial cell free DNA assay (Karius test) and change antifungal ppx from voriconazole to posaconazole

3. Administer methylprednisolone 1 mg/kg every 8 hrs and start letermovir

4. Initiate foscarnet 90 mg/kg twice daily and IV IGG qOD

5. Obtain BAL and adenovirus PCR


Option 4. This patient has CMV pneumonia in the setting of poor graft function and slow T cell recovery, following a haploidentical transplant from her daughter. The obvious choice of giving ganciclovir will put her at risk for further myelosuppression and graft loss, so must always be undertaken with G-CSF given concomitantly in such circumstances. Foscarnet does not cause myelosuppression so is ideal, but requires adequate hydration and electrolyte repletion. Post-transplant CY for GVHD ppx and Donor CMV sero neg/Recipient CMV sero pos combination puts her at high risk of CMV reactivation. Letermovir is the SOC in this situation, but she was unable to afford it. Foscarnet or ganciclovir or mirabivir alone suffice for CMV reactivation without organ involvement, but with concomitant pneumonia most transplant clinicians would administer IV IGG given the severe humoral immune deficit observed at this time. BAL and mcf-DNA assays are very helpful in the longer term management, but without prompt therapy this patient is at very high risk of transplant related mortality.

This is ten days after stopping mycophenolate mofetil by which time one would expect recovery from MMF induced myelosuppression. Given that this is a child into mother transplant, allo-senstization to non-inherited maternal antigens (NIMA) is a possibility. In large studies of HLA mismatched transplants, matching the mismatched donor HLA loci for NIMA reduces GVHD risk, but there is a possibility that allo-sensitization at child birth may increase risk for graft loss in this child into mother transplant, especially in reduced intensity conditioning recipients, as this 60. year old is likely to be.


Department of Medicine

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