Degree of mucositis and duration of neutropenia are the major risk factors for early post‐transplant febrile neutropenia and severe bacterial infections after reduced‐intensity conditioning

Abstract

Whether the intensity of the conditioning regimen affects febrile neutropenia (FN) and severe bacterial infections (SBIs) is not well established. We analyzed the risk factors (RFs) for the development of FN and SBI in the first 100d post-transplant in 195 consecutive adult recipients of a reduced-intensity conditioning allogeneic hematopoietic stem cell transplantation (RIC-allo). The RIC regimens consisted of fludarabine plus melphalan (62%) or busulphan (38%) (FluMel or FluBu). SBIs include pneumonia, urinary tract infections, and bacteremia. FN occurred in 141 patients (72%), always in the first 30d post-allo-RIC. However, a SBI occurred in only 27 patients (14%) during this early post-transplant period (<day +30), while 29 evaluable patients (15%) developed a SBI in the intermediate post-transplant period (days +31 to +100). In multivariate analysis, RFs for the development of FN included onset of neutropenia before day +5 after allo-RIC (P<0.02) and NCI CTC grade III-IV mucosal damage in the first 10d post-transplantation (P=0.03). RFs identified to SBI by multivariate analysis included corticosteroid therapy before day +100 (P<0.01), mycophenolate mofetil-based graft-versus-host disease (GVHD) prophylaxis (P<0.01), and previous SBI before day +30 (P<0.01). The rate of SBI from day +30 to +100 varied according to the number of RFs; thus, the rate of SBI was 1% in patients without any RF, 17% in patients with one RF, 29% with one RFs, and 53% in those with all three RFs. After an RIC-allo, FN and early SBI occurred mostly in patients with severe mucositis and early-onset neutropenia, while postengraftment high-dose steroid therapy for acute GVHD was the major RF.