The prognostic significance of eosinophilia after allogeneic hematopoietic SCT (HSCT) and the relationship between eosinophilia and acute GVHD are not well studied. We retrospectively analyzed 201 adult patients who underwent their first allogeneic HSCT. Seventy-three (36%) patients developed eosinophilia within the first 100 days after HSCT. Eosinophilia was observed more frequently among those patients with acute GVHD than those without it (48 vs 25%, P ¼ 0.009). However, it was associated with milder acute GVHD and lower incidence of gut and liver acute GVHD. Among patients with acute GVHD, the 3-year OS for patients with and without eosinophilia was 63.4 and 47.2% (P ¼ 0.02), respectively, and 3-year nonrelapse mortality (NRM) was 20.2 and 37.5% (P ¼ 0.01), respectively. Multivariate analysis confirmed that eosinophilia was associated with a better OS (P ¼ 0.03) and lower NRM (P ¼ 0.046) in patients with acute GVHD, whereas it was not associated with a higher relapse rate (P ¼ 0.45). In contrast, eosinophilia was not associated with outcomes in those patients without acute GVHD. In conclusion, eosinophilia was associated with milder acute GVHD and better prognosis among patients with acute GVHD. The pathophysiology behind eosinophilia after allogeneic HSCT remains to be investigated.

Summary:Noninfectious pulmonary dysfunction (NIPD) is a common and often fatal complication associated with allogeneic hematopoietic stem cell transplantation (HSCT). An insertion/deletion polymorphism in the angiotensinconverting enzyme (ACE) gene has been extensively studied in relation to cardiovascular and renal disease, and lung fibrosis. In pulmonary fibrosis, D-allele frequency is significantly higher than in the control population. We hypothesized that a similar mechanism exists between post-HSCT NIPD and pulmonary fibrosis in the absence of HSCT. We retrospectively analyzed the incidence of NIPD and the ACE genotype polymorphism in 118 Japanese patients who underwent HSCT from HLAidentical sibling donors. NIPD occurred in 17 cases. Deletion/deletion genotype carriers were more common in the NIPD group than in the other 101 patients (41.2 vs 11.9%; hazard ratio, 5.19; 95% confidence interval, 1.67-16.21). There were no significant relationships between the clinical characteristics of patients and the development of NIPD. These findings suggest that the ACE genotype is associated with the development of NIPD following HSCT. This study is the first to report the relationship between genetic background and NIPD. Bone Marrow Transplantation (2005) 36, 617-620.

Introduction: Non-infectious pulmonary dysfunction (NIPC) represents a common and often fatal complication of hematopoietic stem cell transplantation (HSCT). Recently, bactericidal/permeability-increasing (BPI) haplotypes were associated with an increased risk of developing airflow decline after HSCT. Objective: In order to clarify whether BPI is involved in the pathogenesis of HSCT-related pulmonary complications, we performed a genetic association study. Methods: In this study, we therefore investigated the relationship between BPI and pulmonary dysfunction within an ethnic group by analyzing the incidence of NIPC based on genotype and the allelic frequency of BPI polymorphisms in 121 Japanese patients who underwent HSCT from HLA-identical sibling donors. We examined BPI-associated single nucleotide polymorphisms (SNPs) (rs5741798, rs1934917, rs5743530, rs2275954), and identified NIPC-associated polymorphisms in 20 patients (16.5%). Results: The allelic frequencies of rs1934917 and rs5743530 are significantly different between patients with and without NIPC (P=0.024 and P=0.015, respectively). For donors, the rs5743530 C allele was more frequent in the NIPC group than in the group without NIPC (P=0.038). No significant relationships were noted between each of the other gene polymorphisms and the development of NIPC. Conclusion: In this Japanese cohort study, two candidate SNPs reached statistical significance in terms of NIPC incidence and our findings suggest that BPI haplotypes contribute to the development of NIPC within an ethnic group.