Patterns of Early Infectious Complications in Adult Unrelated Cord Blood Transplantation (UCBT). A Single Center Experience.

The major cause of non-relapse transplant related mortality (TRM) in UCBT continues to be infectious, with blood stream infections (BSI) constituting the majority of these events. However, CMV antigenemia and BK virus associated late onset hemorrhagic cystitis (LOHC) are increasingly important causes of morbidity and mortality. We review our single institution experience. We identified 13 patients with hematological malignancies in our database that had undergone UCBT in the period June 2002 - January 2005 and analyzed these data to document the incidence and patterns of infectious complications. The median age was 48 (range 19–62) years. All patients received infectious prophylaxis with Ciprofloxacin, Acyclovir, Voriconazole, Bactrim/nebulized Pentamidine. Eleven patients underwent conditioning with standardized Thiotepa/Busulfan/Cytoxan and GVHD prophylaxis with Tacrolimus/Mycphenalate Mofetil/ATG and the remaining 2 patients received TBI based conditioning. The median total nucleated cell (TNC) was 1.70E+07 and the median CD34 (+) cell count was 8.0E+04. The HLA matches were 4/6 in 9, 5/6 in 3 and 6/6 in 1 patient. All patients engrafted with a median time to neutrophil engraftment (TNE) of 25 (range 16–34) days. Twelve of thirteen patients achieved full donor chimerism at day 30 and 10 of 12 patients with full chimerism at day 100. Five patients developed grade II-IV acute GVHD requiring additional steroid therapy and 1 patient died of steroid refractory GVHD at day 50. Four patients had positive blood cultures at transplant. All patients developed documented bacterial infections: Gram positive in 12 (92%) (VRE in 23%, Steotrophomonas maltophilia in 31%); Gram negative in 8 (61%) (E. cloacae in 15%, Acinobacter spp. in 2 cases). Ten patients were CMV seropositive and 9 of these developed antigenemia requiring Gancyclovir/Foscarnet therapy. Nine patients had documented BK viruria with consequent late onset hemorrhagic cystitis (LOHC) and 5 patients developed BK viremia. There was 1 case of fungal BSI, while 8 patients had documented fungal tongue cultures. Four patients had positive bronchial washings (3 bacterial, 1 C. glabrata). Twelve (92%) patients were alive at day 100. Of note 62% of BSI and all cases of LOHC and CMV antigenemia developed after neutrophil engraftment. In our series of patients, viral infections (CMV, BK virus) were the most significant causes of morbidity. The high rate of BSI, especially after myeloid recovery, argues for a major influence of impaired immune recovery.