Comparison of Infection Rates Among Acute Leukemia Patients in Remission Receiving Alternative Donor Hematopoietic Cell Transplantation

Alternative donors (umbilical cord blood (UCB), haploidentical family members, or mismatched unrelated donors (MMUD) allow patients without matched sibling or unrelated (MUD) donors to proceed to a potentially curative HCT. Retrospective studies have shown comparable outcomes among different alternative graft sources, but differences in infection rates have not been well studied. We compared incidences of bacterial, viral, and fungal infections at 1 year post HCT in patients reported to the CIBMTR who were ≥16 years with acute leukemia in remission who received an alternative donor HCT between 2008 and 2011. Patients were included if they had received HCT in 1^st/ 2^nd CR using UCB, 8/8 allele matched MUD or 7/8 antigen/allele MMUD. Recipients of 467 UCB, 869 MUD and 268 MMUD grafts were included. UCB recipients were younger and had better performance status; they were more likely to have acute lymphoblastic leukemia, not receive antithymocyte globulin, and be transplanted in CR 2 with reduced intensity conditioning regimens.  The incidence at 1 year of bacterial, fungal and viral infections in each cohort are shown in Table 1.  There were no differences by pairwise comparisons between UCB and MMUD for bacterial infections (p = 0.18) nor fungal infections (p = 0.52); however, UCB recipients had significantly more viral infections compared to MMUD (p <0.0001).The rate (infections per patient per year) of CMV reactivation/disease and adenoviral infections was higher in UCB recipients; MMUD had a higher rate of EBV reactivation (Table 2).   Infection as a cause of death was similar among the three graft sources at 1 year (41%, 31%, and 38% for UCB, MUD, and MMUD respectively).  Overall survival at 1 year was 50% (46 – 55%), 69% (65 – 72%), and 58% (52 – 64%) for UCB, MUD, and MMUD respectively (p <0.0001) and this difference was driven by higher treatment related mortality (TRM) as relapse was similar across the groups. The survival was slightly higher with MMUD compared to UCB (p<0.04). In conclusion, 1) The incidences of bacterial, fungal, and particularly viral infections are high after alternative donor transplant; 2) Infections are a major cause of death in the first year after alternative donor transplant; 3) The incidence of infection as cause of death was similar among the graft sources; 4) Viral infections are higher in recipients of UCB compared to MMUD.  Future directions will focus on preventative techniques and predictors for infection, particularly for viral infections.

Table 1 Cumulative incidence of infection at 1 year with 95% CI

	UCB	MUD	MMUD	p-value
Bacterial	71% (66-75%)	63% (59-66%)	66% (60-71%)	0.01
Fungal	15% (12-18%)	8% (7-11%)	13% (9-17%)	0.002
Virus (all)	69% (65-73%)	44% (41-47%)	54% (48-60%)	P<0.0001

Table 2 Rate of viral infections per patient per year, stratified by graft source

Virus	UCB	MUD	MMUD	p-value
CMV	0.783	0.411	0.598	<0.001
Adenovirus	0.099	0.034	0.056	0.008
EBV	0.096	0.091	0.152	0.04