Early Human Herpes Virus 6 Infection after Autologous Stem Cell Transplantation: A Multicenter Prospective Observational Study of 196 Patients (VIRAUTO 6)

Introduction Human Herpes Virus 6 (HHV-6) is an opportunistic and potentially life-threatening infectious agent frequently identified after allogeneic hematopoietic cell transplantation (allo-SCT). In autologous hematopoietic stem cell transplantation (ASCT) setting, although the immune system recovery is rapid and the risk of infection lower in ASCT recipients than allo-SCT ones, cell immunity is impaired and some recipients may develop prolonged myelosuppression, delayed platelet recovery, diarrhea, skin rashes compatible with HHV-6 infection. The primary objective was to evaluate the incidence of HHV-6 infection in ASCT recipients; secondary objectives were to analyze the clinical relevance of this infection on hematopoietic reconstitution, CMV co-infections and other infectious and non-infectious complications. Patients and methods From July 2012 to February 2015, 196 patients undergoing ASCT were enrolled in the prospective multicentric VIRAUTO6 study (NCT02090803). HHV-6 DNA load was measured by quantitative PCR in whole blood specimens once during the 7 days before transplantation and prospectively once a week after transplantation until hematopoietic recovery defined as ANC > 1 x 109/L and platelets > 50 x 109/L with transfusion support cessation. Active HHV-6 and CMV infections were defined as 2 consecutive blood HHV-6/CMV DNAemias ≥ 450 copies/mL, one week apart. Chemotherapy related toxicities were assessed according to the WHO classification. Results The median age of this cohort (127 male, 64.8%) was 59.4 (52.5; 64.8) years. Underlying hematological diseases were lymphoma (108, 55.1%), myeloma (86, 43.9%) and leukemia (1, 0.5%). At transplantation, complete remission or very good partial remission were observed in 125 patients (63.8%), and partial response or refractory disease for others (71, 36.2%). Bicnu-Etoposide-Aracytine-Melphalan (BEAM) conditioning regimen was used in 93 patients (47.4%) and melphalan alone conditioning regimen in 87 patients (44.4%). The median follow-up was 16 (14; 20) days. The median ANC and platelets recovery was 9 (7; 12) days and 15 (10; 25) days, respectively. Twenty-two (11.2%) patients developed active HHV-6 infection with a cumulative incidence of 19.2% at 40 days after transplantation. Among them, only one patient had CMV infection in the same period. The onset of active HHV-6 infection occurred with a median of 13 (12; 15.8) days after transplantation and with a median blood HHV-6 DNAemia of 7,035 (1,192; 19,875) copies/mL. HHV-6 infection occurred less frequently in patients with Melphalan conditioning regimen compared to BEAM alone (OR 0.11; 95%CI 0.02-0.47; p HHV-6 disease occurred in 3 patients (1.5% of the cohort): 2 patients had skin rash with positive skin biopsy for HHV-6 DNA and one patient had fever with no other cause than HHV-6 infection. For 2 patients, ganciclovir treatment was introduced for a median of 11.5 (9.8; 13.2) days. Delayed neutrophils and platelets engraftments were noted with an increased median duration of ANC: 11 (9; 16) vs 9 (7; 12) days; p=0.004) and platelets: 25 (14; 29) vs 15 (10; 24) days; p=0.011 recovery in recipients with HHV-6 infection compared to those without HHV-6 infection. The kinetics of platelets recovery according to HHV-6 infection are shown in figure 1. Conclusion This work relates the first prospective multicentric study assessing incidence and clinical impact of HHV-6 infection in ASCT recipients. Our study supports that 11.2% patients undergoing ASCT had HHV-6 Infection with significantly different outcomes, especially delayed hematopoietic reconstitution. Figure 1. platelets recovery > 20 x 109/L ; p-value = 0.009 Figure 1. platelets recovery > 20 x 109/L ; p-value = 0.009 Figure 2. platelets recovery > 50 x 109/L ; p-value = 0.007 Figure 2. platelets recovery > 50 x 109/L ; p-value = 0.007 Disclosures Augeul-Meunier: janssen: Consultancy; gilead: Consultancy. Salles:Novartis: Consultancy, Honoraria; Gilead: Honoraria, Research Funding; Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Mundipharma: Honoraria; Roche/Genentech: Consultancy, Honoraria, Research Funding.