Abstract

In URD allogeneic HCT, donor, not recipient, KIR B/x genotype improves leukemia free survival. Decreased rates of CMV reactivation occur in renal transplant recipients with KIR B/x genotypes. We hypothesized that recipients of cells from a KIR B/x genotypic URD will have decreased infectious complications due to enhanced NK cell function. The National Marrow Donor Program (NMDP) prospectively collected data oninfectious complications at 2 week intervals beginning with conditioning until day 100 and then monthly until day 180 after URD HCT for malignant and nonmalignant diseases at 27 centers (n = 211). A subset of these donors (n = 116) had samples available through the NMDP Research Repository for KIR genotyping (A/A: n = 44; B/x: n = 72). The two cohorts had similar characteristics including age, gender, Karnofsky score, disease and disease status, degree of HLA matching, conditioning intensity, graft type, and donor/recipient CMV match and sex match. Infections were characterized as clinical infectious syndromes if no organism was identified or bacterial, fungal, or viral based on the causative organism. Bacterial infections were significantly lower for recipients of a B/x genotypic donor compared to the A/A genotype [68% (57 – 78) vs 86% (75 – 95); p = 0.02]. The cumulative incidence of other infection types was similar between the groups. A Poisson regression model estimated the expected number of infections for a patient observed up until day 180 and determined characteristics associated with specific infections. Donor KIR genotype was considered in every model. Other factors analyzed included patient and donor age, donor/recipient CMV and sex match, disease (leukemia/MDS vs other), disease status, HLA match (well matched vs partially matched vs mismatched), GVHD prophylaxis (CSA/FK based vs other), and graft type. The mean estimated number of infections per patient was as follows: bacterial, 1.138; viral, 0.58; fungal, 0.764; clinical infectious syndromes, 0.506; and total infections, 6.306. Based on these models, a B/x donor was associated with a statistically lower mean ratio of total infections [B/x = 1.00 vs A/A = 1.23 (1.02 – 1.49), p = 0.03] and bacterial infections [B/x = 1.00 vs A/A = 1.50 (1.16 – 1.94), p = 0.002] compared to recipients of an A/A donor. The table shows the other factors associated with total infections and bacterial infections. The use of an A/A donor was associated with a lower mean ratio of fungal infections [B/x = 1.00 vs A/A= 0.40 (0.17 – 0.92), p = 0.03] but similar ratios of viral and clinical infectious syndromes. Multivariate analysis found a similar relative risk of aGVHD II – IV, cGVHD, and survival regardless of donor KIR genotype. The role of donor KIR genotype on post HCT infectious complications is intriguing and warrants further study in larger populations of patients with uniform antimicrobial prophylaxis to better assess clinical impact.

Variable Total Infections Bacterial Infections 
 Ratio of Mean number of infections (95% CI) p-value Ratio of Mean number of infections (95% CI) p-value 
KIR Genotype     
A/A 1.23 (1.02 – 1.49) 0.03 1.50 (1.16 – 1.94) 0.002 
B/x 1.00  1.00  
Patient Age, yrs  <0.0001  0.004 
<10 0.44 (0.34 – 0.88) 0.01 0.60 (0.32 – 1.15) 0.13 
10 – 19 1.23 (0.9 – 1.69) 0.20 1.36 (0.85 – 2.16) 0.20 
20 – 29 0.57 (0.42 – 0.77) 0.0003 0.50 (0.33 – 0.78) 0.002 
30 – 39 1.05 (0.81 – 1.37) 0.71 0.91 (0.64 – 1.30) 0.61 
40 – 49 0.69 (0.51 – 0.94) 0.02 0.84 (0.55 – 1.28) 0.42 
>50 1.00  1.00  
D/R sex match  0.0001  0.009 
F/F 1.00  1.00  
F/M 1.28 (0.95 – 1.72) 0.10 1.22 (0.81 – 1.83) 0.34 
M/F 0.84 (0.60 – 1.17) 0.30 0.76 (0.48 – 1.20) 0.24 
M/M 1.50 (1.14 – 1.97) 0.004 1.40 (0.97 – 2.04) 0.07 
D/R CMV match  <0.0001  0.03 
N/N 0.79 (0.56 – 1.12) 0.18 0.90 (0.59 – 1.37) 0.62 
N/P 1.65 (1.25 – 2.18) 0.0004 1.31 (0.90 – 1.90) 0.16 
P/N higher 0.84 (0.61 – 1.16) 0.29 0.76 (0.49 – 1.16) 0.20 
P/P 1.00  1.00  
Disease status  0.0008  0.0003 
Early 1.14 (0.87 – 1.48) 0.34 1.51 (1.04 – 2.18) 0.03 
Intermediate 0.68 (0.51 – 0.91) 0.01 0.61 (0.40 – 0.92) 0.02 
Advanced 1.23 (0.95 – 1.60) 0.13 1.36 (0.96 – 1.93) 0.09 
Other 1.00  1.00  
Donor Age, yrs  0.022  
20 – 29 0.64 (0.46 – 0.88) 0.006  
30 – 39 0.80 (0.58 – 1.09) 0.16  
40 – 49 0.89 (0.63 – 1.24) 0.48  
>50 1.00   
HLA Match    <0.0001 
Well matched  1.00  
Partially matched  1.54 (1.15 – 2.07) 0.004 
Mismatched  2.87 (2.02 – 4.05) <0.0001 
GVHD Prophylaxis    
CSA/FK based  1.84 (1.30 – 2.60) 0.0005 
Other  1.00  
Variable Total Infections Bacterial Infections 
 Ratio of Mean number of infections (95% CI) p-value Ratio of Mean number of infections (95% CI) p-value 
KIR Genotype     
A/A 1.23 (1.02 – 1.49) 0.03 1.50 (1.16 – 1.94) 0.002 
B/x 1.00  1.00  
Patient Age, yrs  <0.0001  0.004 
<10 0.44 (0.34 – 0.88) 0.01 0.60 (0.32 – 1.15) 0.13 
10 – 19 1.23 (0.9 – 1.69) 0.20 1.36 (0.85 – 2.16) 0.20 
20 – 29 0.57 (0.42 – 0.77) 0.0003 0.50 (0.33 – 0.78) 0.002 
30 – 39 1.05 (0.81 – 1.37) 0.71 0.91 (0.64 – 1.30) 0.61 
40 – 49 0.69 (0.51 – 0.94) 0.02 0.84 (0.55 – 1.28) 0.42 
>50 1.00  1.00  
D/R sex match  0.0001  0.009 
F/F 1.00  1.00  
F/M 1.28 (0.95 – 1.72) 0.10 1.22 (0.81 – 1.83) 0.34 
M/F 0.84 (0.60 – 1.17) 0.30 0.76 (0.48 – 1.20) 0.24 
M/M 1.50 (1.14 – 1.97) 0.004 1.40 (0.97 – 2.04) 0.07 
D/R CMV match  <0.0001  0.03 
N/N 0.79 (0.56 – 1.12) 0.18 0.90 (0.59 – 1.37) 0.62 
N/P 1.65 (1.25 – 2.18) 0.0004 1.31 (0.90 – 1.90) 0.16 
P/N higher 0.84 (0.61 – 1.16) 0.29 0.76 (0.49 – 1.16) 0.20 
P/P 1.00  1.00  
Disease status  0.0008  0.0003 
Early 1.14 (0.87 – 1.48) 0.34 1.51 (1.04 – 2.18) 0.03 
Intermediate 0.68 (0.51 – 0.91) 0.01 0.61 (0.40 – 0.92) 0.02 
Advanced 1.23 (0.95 – 1.60) 0.13 1.36 (0.96 – 1.93) 0.09 
Other 1.00  1.00  
Donor Age, yrs  0.022  
20 – 29 0.64 (0.46 – 0.88) 0.006  
30 – 39 0.80 (0.58 – 1.09) 0.16  
40 – 49 0.89 (0.63 – 1.24) 0.48  
>50 1.00   
HLA Match    <0.0001 
Well matched  1.00  
Partially matched  1.54 (1.15 – 2.07) 0.004 
Mismatched  2.87 (2.02 – 4.05) <0.0001 
GVHD Prophylaxis    
CSA/FK based  1.84 (1.30 – 2.60) 0.0005 
Other  1.00  

Disclosures: No relevant conflicts of interest to declare.

Author notes

Corresponding author