Cytomegalovirus reactivation in lymphoma and myeloma patients undergoing autologous peripheral blood stem cell transplantation.

Background: Cytomegalovirus reactivation is often diagnosed in allogeneic hematopoietic cell transplant recipients and therefore could lead to CMV-related disease, involving many organs in these immunocompromised patients. In contrast, few studies investigated CMV reactivation and end-organ disease in patients undergoing Autologous Peripheral Blood Stem Cell Transplant (ASCT) since they are considered at low risk for both reactivation and disease.

Objectives: The primary outcome of the analysis was to understand the difference in incidence of CMV reactivation between MM and Lymphoma patients. Secondary outcomes included the difference between MM and Lymphoma patients when considering the effect of CMV reactivation on transplant related mortality (TRM) overall survival (OS) progression free survival (PFS), risk factors for reactivation, and median time to reactivation.

Study Design: In this report, we retrospectively compared the incidence, risk factors, and outcome of CMV reactivation in adult patients with Myeloma (MM) and Lymphoma undergoing ASCT at the American university of Beirut Medical Center in Lebanon (AUBMC). A total of 324 consecutive ASCT were performed between January 2005 and March 2016. Serial weekly monitoring for CMV quantification was done using a quantitative PCR, starting from transplantation until the hospital discharge and afterwards based on the clinical symptoms in cases of clinical suspicion of reactivation after discharge from the hospital.

Results: The cumulative incidence of CMV reactivation was 16% (n=53) with a median time of 16 (range, 4-242) days after ASCT. The incidence of reactivation was significantly higher in the MM (22%) and NHL (20%) groups, when compared to the HL (4%) (P=0.001). There was a higher incidence of CMV reactivation according to age (≥50 vs ≤50 years) with higher incidence in the older population 24% vs 10% respectively (p=0.0043). The mean time to CMV reactivation was significantly higher in the NHL group with a mean of 53.7days when compared to the HL and MM groups with mean 19.75days and 12.66 (range, 4-34) days respectively (P=0.003). Twenty-two patients (76%) and three patients (75%) patients required specific antiviral therapy in the MM group and HL groups respectively; which was significantly higher (P<0.001) then the NHL group with 13 (65%) patients requiring specific antiviral therapy. Five patients (1.5%) developed CMV disease at a median of 60days (range, 7-107) post ASCT: there was significant difference in the mean-time to reactivation based on disease type MM versus lymphoma 10 versus 33days (P=0.007). In multivariate analysis, a higher age was associated with an increased risk of CMV reactivation; MM and NHL had higher risk of CMV reactivation when compared to HL, and progressive disease at transplant was associated with increased risk of CMV reactivation. After a median follow-up of 21.5 months (range: 1-125), there was no significant impact on PFS, however there was significant decrease in OS of lymphoma patients who had CMV reactivation when compared to those without CMV reactivation (204 and 112days respectively P=0.045). TRM increased from 1.1% in patients with no CMV reactivation to 13% in patients with CMV reactivation (P=0.003).

Conclusion: Our data suggests that CMV reactivation is not uncommon in ASCT recipients and may contribute to increase TRM. MM patients may have a higher incidence, of CMV reactivation with more anti-viral treatment requirements when compared to lymphoma patients, especially in older population.