Even coagulase negative staphylococcus infections following reduced intensity transplantation are associated with increased transplant complications and poorer overall survival

Abstract

Reduced intensity transplantation (RIT) is associated with lower transplant related mortality (TRM) but the incidence of infectious complications remains controversial. We analyzed the incidence of bacteremia during the first 100 days post-transplantation in 106 patients with various malignancies who underwent a reduced intensity regimen of extracorporeal photopheresis × 2 cycles, pentostatin 8 mg/m2 by continuous intravenous infusion over 48 hours, and total body irradiation 600cGy, followed by allogeneic bone marrow stem cell infusion from a 6/6 HLA matched related donor (n = 68), 5/6 HLA matched related donor (n = 8), 6/6 HLA matched unrelated donor (n = 29), or 5/6 HLA matched unrelated donor (n = 1). GVHD prophylaxis consisted of continuous infusion cyclosporin A and short course methotrexate. All patients received fluoroquinolone prophylaxis until neutrophil engraftment. During the first 100 days post-transplantation, grade 2–4 acute GVHD occurred in 19% of patients, and 56 patients (53%) had positive blood cultures. Median days to positive cultures were 21 (range −7 to 97). Blood cultures were positive for coagulase negative staphylococcus (CoNS) (n = 36: 63%), other gram-positive cocci (GPC) (n = 10: 10%), gram-negative rods (GNR) (n=5: 9%), fungus (n = 3: 5%), gram-positive rods (GPR) (n = 2: 4%), or anaerobes (n = 1: 1%). Recurrent infections (same species >30 days later) occurred in 7 patients (7%), and multiple infections with different organisms occurred in 16 patients (15%). Three patients died of sepsis. The incidence of bacteremia was higher in patients with grade 2–4 acute GVHD versus grade 0–1 acute GVHD (70% versus 45%: p = 0.05), and in mismatched related or matched unrelated transplants versus matched related transplants (66% versus 46%: p = 0.05). Bacteremia was associated with higher day 100 TRM (26% versus 11%: p = 0.06) and lower median overall survival (OS) (9 months versus 35 months: p = 0.01). CoNS bacteremia had similar day 100 TRM as other GPC bacteremia like staphylococcus aureus and enterococcus (22% versus 38%: p = 0.37) and similar day 100 TRM as non-GPC bacteremia (22% versus 30%: p = 0.61). There was a trend towards lower median OS in patients with CoNS bacteremia versus other GPC bacteremia (7 months versus 14 months: p = 0.18). In patients undergoing RIT, CoNS bacteremia, like other bacteremia, was associated with increased TRM and poorer overall survival. Future studies on RIT will need to address the issue of bacteremia, especially CoNS bacteremia.