High Risk Allogeneic Hematopoietic Cell Transplant (HCT) Patients with Any Level of Cytomegalovirus (CMV) Viremia Should Be Treated with Antiviral Therapy to Prevent Serious CMV Disease

CMV disease in patients undergoing allogeneic HCT is a major source of morbidity and mortality.  CMV PCR allows for earlier detection of viremia and preemptive anti-viral therapy.  A recent study by Milano et al. (Blood 2011) has reported the efficacy of the use of intensive CMV prophylaxis in umbilical cord blood recipients. In this case series (table below), we describe 3 patients in whom active CMV disease was detected in the context of a viral load which fluctuated between very low level viremia (<150 copies/ml) and undetectable.  The patients (3 males, ages 4-11), all received high risk transplants (2 double cord, 1 9/10 URD) for advanced leukemias.  All three received myeloablative doses of total body irradiation and cyclophosphamide and the two cord blood recipients received fludarabine additionally.  All patients were CMV sero-positive while their donors were CMV sero-negative.  They had symptomatic biopsy-proven CMV disease in various locations including the stomach, gallbladder, sinuses and lung.  They were treated with intravenous ganciclovir and Cytogam induction and two transitioned to foscarnet due to myelosuppression. All three recovered from their symptomatic disease, although they continued to have fluctuating positivity of their serum CMV PCR.  This experience at a single institution in the last year suggests that although CMV PCR has reduced the need for prophylactic ganciclovir in patients undergoing allogeneic HCT, active infection can develop in high risk patients even with very low level of viremia. Therefore, an intensive prophylactic strategy and treatment of any level of viremia, along with a high index of suspicion for CMV disease is required in high risk patients. Additionally, tissue diagnosis, especially with unusual organ involvement such as gallbladder in our patient, should be obtained when possible. 

	Patient 1	Patient 2	Patient 3
Age/Sex	11/M	4/M	10/M
Underlying Diagnosis	SAA with secondary M7 AML	High risk pre-B cell ALL	Relapsed pre-B cell ALL
Donor Source	Double umbilical cord (dUCB)	9/10 matched unrelated donor	dUCB
GVHD	None	Grade IV skin, gut, and liver GVHD	Grade III skin and gut GVHD
CMV viral load at biopsy/ Range	<150 copies/ml Not detected - <150	<150 copies/ml Not detected - <150	#1- 400 copies/ml, #2- not detected Not detected - 11,200
Disease	Day +42 Esophagoduodenal endoscopy: Gastritis with CMV inclusions and CMV positive immunohistochemical stain	Day +285 Cholecystectomy: Perforated chronic cholecystitis with hemobilia, CMV PCR pos	Day +162 Left endoscopic sphenoidotomy: Chronic inflammation with shell vial CMV positivity
			Day +286 Lung biopsy: CMV PCR pos
Outcome	Symptoms of gastritis resolved	Gradual but complete recovery after stabilization in the ICU	Symptoms improved, Follow up CT scans  showed improvement