Viral Infection After Unrelated Cord Blood Transplantation In Bordeaux: Incidence and Outcomes. A Single Centre Experience with Eurocord.

Umbilical cord blood is being increasingly used for transplantation, but the ability of neonatal T cells to regulate viral infections seems to be less effective than other stem cell sources. Viral infections remain important cause of morbidity after hematopoietic stem cell transplantation and some virus less monitored could be important pathogens. We performed a retrospective study, using the EUROCORD database, in 45 patients with the aim to analyze the incidence for viral infections in patients transplanted with single or double unrelated cord blood units for hematologic malignancies, during the first two years after transplantation.

Patients received the unrelated umbilical cord blood transplantation at the Bordeaux University Hospital, France, between October 2003 and December 2009. Real-time quantitative polymerase chain reaction was used to measure the EBV and CMV load twice a week and only if presence of symptom for others virus. We included patients with one quantitative positive PCR in blood for EBV, CMV, HHV6 and ADV, one PCR positive for BK virus in urine, and clinical diagnosis for VZV recurrent infections. Herpes virus disease was defined as clinical symptom from the affected organ, combined with the detection of the herpes virus by PCR in organ biopsy or blood.

The median age was 41 years (range 8–63) with 5 patients (11.5%) < 15 years old. Among these 45 patients, 75% had acute leukemia or myeloid malignancies and 25% lymphoid malignancies. Administration of acyclovir for prevention of HSV and CMV infections was carried out in all patients. Grafts have been performed with a single unmanipulated cord blood unit in 73% and two unmanipulated units in 27%. Neutrophil and platelet recoveries were defined as the first of 2 consecutive days during which the ANC in the blood was >0.5×10⁹/L and the platelet count was >20×10⁹/L without transfusion support, median time to neutrophil recovery was 24 d (range 5–56 d) and median time to platelet recovery was 34 d (range 0–88 d). The median number of nucleated cells infused in recipients of cord blood was 2.2×10⁷/kg of the recipient's body weight (range, 0.7×10⁷ to 6.63×10⁷/kg). The median number of CD34+ cells in the cord blood grafts was 0.9×10⁵/kg (range, 0.16×10⁵ to 3.4×10⁵/kg). Conditioning varied according to the patient's disease and disease status with 45% myeloablative and 55% reduced intensity. All patients, except one, received a cyclophosphamide containing regimen and 24.4% patients received antithymocyte globulin prior to transplantation. Prophylaxis for acute GVHD consisted of cyclosporine A and MMF in 91%, cyclosporine A alone for 2 patients, with prednisone for 1 patient and with MTX for 1 patient. Among the whole cohort, we observed 77.7% viral infections: 9/45 experienced at least one positive PCR for EBV of whom 1 had lethal PTLD, 10/45 for CMV with one gastrointestinal disease and 25/45 for HHV6 with three encephalitis, two pneumoniae, five skin rash, three gastrointestinal infections manifested as diarrhea or hemorrhagic colitis, and two hepatitis. Furthermore, we observed 6/45 herpes zoster with one disseminated disease, 7/45 hemorrhagic cystitis resulting of BK virus infection and 3 patients who experienced ADV viremia. At 100 days the cumulative incidence (CI) for any viral infection was about 69%, 51% for HHV6 infection, 35% for HHV6 disease, 13% for CMV infection and disease, 18% for EBV infection, 14% for BK virus hemorrhagic cystitis, 5% for ADV infection and cumulative incidence at 200 days about 5% for VZV. Viral infection or disease did not affect significantly the overall survival of the patients.

Among the various viral infection/diseases, the high CI of HHV6 infection/disease is of concern. Analysis of risk factors for infection and disease in this specific setting is in progress. Although the morbidity is high, thanks to close monitoring and prompt therapeutic intervention when possible, the mortality directly linked to viral infection remains low.

No relevant conflicts of interest to declare.