Iron overload is common in patients undergoing allogeneic hematopoietic cell transplantation (HCT) for hematologic disorders. Serum ferritin, a marker of tissue iron overload, was measured immediately before transplant in adult patients undergoing myeloablative HCT from matched sibling or unrelated donors. The effect of elevated pretransplant ferritin (defined as ferritin X1000 ng/ml) on day 100 mortality, overall survival, acute GVHD and infectious complications was assessed. Data on 190 patients were analyzed. In univariate analysis, the highferritin group had increased day 100 mortality (20 vs 9%, P ¼ 0.038), decreased overall survival (log-rank test: P-value ¼ 0.004), increased acute GVHD/death (63 vs 43%, P ¼ 0.009) and increased incidence of blood stream infections (BSIs)/death (60 vs 44%, P ¼ 0.042). In a multivariate analysis, high ferritin was associated with increased risk of death (Cox model: hazard ratio ¼ 2.28, P ¼ 0.004), increased day 100 mortality (generalized linear model (GLM) odds ratio ¼ 3.82, P ¼ 0.013), increased incidence of acute GVHD/death (GLM odds ratio ¼ 3.11, P ¼ 0.001) and increased risk of BSI/death (GLM odds ratio ¼ 1.99, P ¼ 0.032). The results remained similar when serum ferritin was considered a continuous variable. Elevated serum ferritin adversely impacts on overall survival and increases the likelihood of acute GVHD and BSI after allogeneic HCT.
It has been shown that activating killer Ig-like receptor (aKIR) genes are important for control of CMV reactivation after hematopoietic cell transplantation (HCT). To date, using the broad classification of KIR haplotypes A and B, the precise role of individual KIR genes in control of infection cannot be discerned. To address this, a consecutive case series of 211 non T-cell depleted HCT patients all at risk for CMV, were monitored bi-weekly for CMV DNA in plasma by Q-PCR and at intervals for CMV-specific T cell immunity. Comparing patients with CMV reactivation (n=152) to those with no reactivation (n=59), the presence of specific aKIR haplotypes in the donor, but not in the recipient, were associated with protection from CMV reactivation and control of peak plasma CMV DNA (p< 0.001). A donor aKIR profile, predictive for low risk of CMV reactivation, contained either aKIR2DS2 and aKIR2DS4 or had ≥ 5 aKIR genes. Neither donor nor recipient iKIR played a role in a protective effect. CD4+- and CD8+-specific CMV immunity did not explain reduced CMV infection. The initial control of CMV infection after HCT is managed by aKIR functions, and donor aKIR haplotypes deserve further evaluation in donor selection for optimized HCT outcome.
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