Infection Rates among Acute Leukemia Patients Receiving Alternative Donor Hematopoietic Cell Transplantation

Abstract

Alternative graft sources, [umbilical cord blood (UCB), matched unrelated donors (MUD), or mismatched unrelated donors (MMUD)] enable patients without a matched sibling donor to receive potentially curative hematopoietic cell transplantation (HCT). Retrospective studies demonstrate comparable outcomes among different graft sources. However, the risk and types of infections have not been compared among graft sources. Such information may influence the choice of a particular graft source. We compared the incidence of bacterial, viral, and fungal infections in 1,781 adults with acute leukemia who received alternative donor HCT (UCB = 568, MUD = 930, MMUD = 283) between 2008 and 2011. The incidence of bacterial infection at one year was 72%, 59%, and 65% (p<0.0001) for UCB, MUD and MMUD, respectively. Incidence of viral infection at one year was 68%, 45%, 53% (p<0.0001) for UCB, MUD, and MMUD respectively. In multivariable analysis, bacterial, fungal, and viral infections were more common after either UCB or MMUD than MUD, (p<0.0001). Bacterial and viral, but not fungal, infections were more common after UCB than MMUD (p=0.0009 and <0.0001, respectively). The presence of viral infection was not associated with an increased mortality. Overall survival (OS) was comparable among UCB and MMUD patients with Karnofsky performance status (KPS) ≥90%, but was inferior for UCB for patients with KPS < 90%. Bacterial and fungal infections were associated with poorer OS. Future strategies focusing on infection prevention and treatment are indicated to improve HCT outcomes.

Adult Umbilical Cord Blood Transplantation Using Myeloablative Thiotepa, Total Body Irradiation, and Fludarabine Conditioning

“…The majority of patients experienced at least one moderate to severe infection with bloodstream infection being the most common type of serious infection, similar to prior reports of infection burden after UCB transplantation 29–31 . CMV and HHV-6 reactivation also occurred in the majority of patients as previously described in this patient population, although end organ involvement was rare 30, 32 . In the first 100 days after the thiotepa, TBI, and fludarabine regimen, median hospital length of stay was about 44 days, which is similar to that reported after double UCB transplant in a recent registry analysis comparing hospitalization among alternate graft sources 33 .…”

Bacterial bloodstream infections in the allogeneic hematopoietic cell transplant patient: new considerations for a persistent nemesis

“…Ballen et al 23 compared the incidence of bacterial, viral and fungal infections in 1781 adults with acute leukemia who received alternative donor HCT between 2008 and 2011. Over 50% of patients developed bacterial infections by 1 year post HCT.…”

“…In multivariable analysis, bacterial infections were more common after mismatched unrelated donor (MMUD) than matched unrelated donor (MUD) grafts (P = 0.0295) and most common after umbilical cord blood (UCB) vs MUD (Po 0.001) or MMUD grafts (P = 0.0009), likely due to the slower engraftment and delayed immune recovery associated with UCB. 23 Although UCB are associated with increased BSI rates, Sanz et al 24 reported that higher CD8 + cell doses in UCB grafts independently associated with reduced risk of BSI.…”

Engineering cord blood to improve engraftment after cord blood transplant

“…Several groups have shown that T cell immune reconstitution after double or single CBT (with or without serotherapy) is delayed (14,15) and this, along with the naivety of the infused CB T cells, correlates with an increased risk of viral reactivation or infection from latent and lytic viruses like cytomegalovirus (CMV), Epstein Barr virus (EBV) and adenovirus in the post-transplantation period (16)(17)(18). A comparison of immune recovery after double CBT and HLA-matched unrelated donor (MUD) revealed delay in recovery of naive (CD45RO) memory (CD45RO+) CD4 + T cells, CD8 + T cells, and regulatory…”