Cytomegalovirus reactivation in lymphoma and myeloma patients undergoing autologous peripheral blood stem cell transplantation
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Elsevier B.V.
Abstract
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 53.7 days when compared to the HL and MM groups with mean 19.75 days 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 60 days (range, 7–107) post ASCT: there was significant difference in the mean-time to reactivation based on disease type MM versus lymphoma 10 versus 33 days (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 112 days 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. © 2017 Elsevier B.V.
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Autologous stem cell transplantation, Cytomegalovirus, Lymphoma, Myeloma, Adult, Antineoplastic combined chemotherapy protocols, Cytomegalovirus infections, Disease-free survival, Female, Humans, Immunocompromised host, Male, Middle aged, Multiple myeloma, Patient outcome assessment, Peripheral blood stem cell transplantation, Retrospective studies, Risk factors, Virus activation, Young adult, Aciclovir, Cotrimoxazole, Doxycycline, Ganciclovir, Levofloxacin, Valaciclovir, Valganciclovir, Voriconazole, Antineoplastic agent, Age, Antiviral therapy, Article, Autologous peripheral blood stem cell transplantation, Cardiotoxicity, Cause of death, Colon biopsy, Cytomegalovirus infection, Disease course, Follow up, Herpes simplex, Human, Human tissue, Immunohistochemistry, Infection prevention, Major clinical study, Morning dosage, Mortality, Mycosis, Neutropenia, Outcome assessment, Overall survival, Pneumocystosis, Pneumonia, Polymerase chain reaction, Priority journal, Progression free survival, Quantitative analysis, Retrospective study, Sepsis, Vein occlusion, Virus reactivation, Complication, Disease free survival, Immunocompromised patient, Isolation and purification, Physiology, Risk factor, Virology