More Infections with Transplantation of Bone Marrow, Versus Peripheral-Blood Stem Cells, from Unrelated Donors

A phase 3 randomized trial of transplantation of bone marrow (BM) versus peripheral-blood (PB) stem cells from unrelated donors showed no significant (sig) differences when comparing 2-year (yr) survival probabilities (Anasetti et al, NEJM 2012;367:1487-96). Infection (infxn) was a pre-specified secondary endpoint in this BMT CTN protocol, sponsored by NHLBI and NCI.  Moderate (mod) or more severe (sev) infxns were reported on an event-driven Case Report Form, excluding those that occurred pre-transplant. Patients (pts) were censored at last follow up, relapse, 2nd transplant, or 2 yrs after transplant, whichever came first. Among 551 pts enrolled at 48 centers between 01/2004 and 10/2009, 499 (249 of the BM arm and 250 on the PB arm) had full audits of infxn data, accounting for 95% of transplanted pts. Overall, 384 pts developed infxns of mod or greater severity:  201 on the BM arm and 183 on the PB arm. Of 1347 infectious episodes (373 sev and 123 life-threatening/fatal [LT/F]), 710 (53%) occurred on the BM arm and 637 (47%) on the PB arm. Cumulative incidence (CumI) described the proportion of pts developing at least one infxn, while multivariate analyses examined the density of infxn episodes. Gray's test for the CumI rates of infxns had p-value 0.013, with 2-yr rate 84.7% (95% confidence interval [CI]: 79.6%, 89.8%) for the BM arm, vs. 79.7% (95%CI: 73.9%, 85.5%) for the PB arm (Fig 1). Among 810 bacterial infxn episodes, 431 were on the BM arm and 379 on the PB arm, with a 2-yr CumI of 72.1% and 62.9% respectively (Fig 2, p=0.003). Of these, 413 were bacterial bloodstream, 123 Clostridium difficile, and 2 atypical mycobacterial infxns; these categories are not mutually exclusive. The Day 100 CumI of bloodstream bacterial infxns was 44.8% (95%CI: 38.5%, 51.1%) for the BM arm vs. 35.0% (95%CI: 28.9%, 41.1%) for the PB arm (p=0.027), possibly related to quicker neutrophil engraftment using PB.

Infxn density was calculated as (# infxn events / 100 pt days at risk). The total infxn density was 0.67 for BM and 0.60 for PB (P=NS). The infxn density of bacterial infxns was 0.4 for both arms. The infxn density for viral infxns was 0.2 in both arms. The 2-yr CumI of CMV was 25.9% (95%CI: 20.2%, 31.6%) for the BM arm, vs. 24.4% (95%CI: 18.8%, 30.0%) for the PB arm (p=0.62). The infxn density for fungal/parasitic infxns was 0.04 and 0.05 for the BM arm and the PB arm, respectively. The 2-yr CumI of 20 cases of aspergillosis was 3.9% (95%CI: 1.2%, 6.6%) for the BM arm, vs. 3.6% (95%CI: 1.0%, 6.2%) for the PB arm (p=0.811). The ongoing morbidity and mortality from infxns following transplantation remain frequent using either graft source, with no observed differences in fungal or viral infxn rates. The higher observed risks of bacterial infxns using BM grafts may suggest either augmented prophylaxis or heightened surveillance after these transplants.

Fig 1.  CumI of Overall Infxns by treatment arm 

Fig 2.  CumI of Bacterial Infxns by treatment arm