Infectious complications following T-cell depleted hematopoietic stem-cell transplantation

Abstract

Although sepsis is a common complication during stem-cell transplantation, the prevalence of infections after hematopoietic recovery is less well known. We undertook a retrospective analysis of infectious episodes in patients who underwent allogeneic BM (n = 77) or PBSC (n = 29) grafting from HLA identical siblings. T-cell depletion of the stem-cell grafts with anti CD 52 (CAMPATH-1) Abs was employed for the prevention of GvHD. Patients' median age was 30 (4-54) years. Antibiotic prophylaxis was with oral amphotericin, ofloxacin and i.v. or oral acyclovir. Fever was treated empirically with a third generation cephalosporin and aminoglucosides until results of microbiological cultures became available. Six patients died of graft failure. GvHD was observed in 18% but in no case was it > Grade II. Only seven patients did not develop pyrexia during the initial admission or within 60 days following graft infusion. Median duration of pyrexia was 10 (range 2-49) days. A microbial source was detected in 42% and it was Gram (+) in 86%, Gram (-) in 11% and fungal in 3%. In 16 patients, indwelling venous catheters were removed due to severe infection. Subsequent to the recovery of the blood parameters, the most prevalent infection was by herpes varicella/zoster in 20; another 17 developed herpes simplex. In total 40/102 were re-hospitalized for pyrexia, which in four cases was of unknown origin. Bacterial infections with Staphylococcus Aureus and S. Epidermitis were seen in 10 and seven patients respectively. CMV was detected in seven patients. Thirteen patients died of sepsis and in 10, it was related to GvHD or graft failure. Another 20 died following recurrence of the malignancy. Overall, 39 patients died and 63% survived at a median DFS of 1992 (range 623-5092) days. We conclude that during the initial neutropenic period the dominant infections are by Gram (+) organisms, often associated with indwelling catheters. Once the BM has recovered, the main morbidity is by viral infections, but Gram+ organisms still remain common bacterial pathogens.