Clin Microbiol Infect 2012; 18: 997–1003 Abstract In recent years, we have successfully established a novel method of haploidentical haematopoietic stem cell transplantation (HSCT) without in vitro T‐cell depletion. This study was aimed at analysing the incidence and risk factors of invasive fungal infection (IFI) with this transplantation method. The study comprised 291 patients who had undergone haploidentical HSCT from 1 January 2007 to 31 December 2008. IFI was diagnosed according to the European Organization for Research and Treatment of Cancer/Mycoses Study Group 2002 criteria, and only proven or probable cases of IFI were regarded as true cases. A total of 39 patients were documented as having IFI, including four proven cases and 35 probable cases. The median time of diagnosis was 26 days (range: 6–405 days) after transplantation. The cumulative incidence rates of IFI at 40 days, 1 year, 2 years and 3 years after transplantation were 8.25%, 13.1%, 13.4% and 13.4%, respectively. Multivariate analysis identified platelet engraftment time (>17 days) (p 0.027; hazard ratio (HR) 2.432; 95% CI 1.105–5.355), a high risk of underlying disease (p 0.001; HR 2.916; 95% CI 1.515–5.611) and grade III–IV acute graft‐versus‐host disease (p 0.019; HR 2.407; 95% CI 1.154–5.022) as risk factors for IFI. The incidence rates of IFI in patients with no, one, two or three risk factors at 3 years after transplantation were 4.48%, 7.86%, 29.6% and 23.1%, respectively. In conclusion, IFI is an important complication following haploidentical HSCT without in vitro T‐cell depletion.

BackgroundAllogeneic hematopoietic stem cell transplantation (allo-HSCT) has been established as an effective treatment for patients with hematological malignancies. Disease relapse remains a major cause of transplant failure. T cell homeostasis is critical to determine the potency of the GVT effect. Recent studies have shown the association of the CTLA-4 polymorphisms with the outcome after HLA-identical sibling allogeneic HSCT.MethodsIn this study, we focused on four CTLA-4 polymorphisms, and analyzed the impact of donor genotypes and haplotypes on the conditions of 152 acute leukemia patients (ALL 83) after related HLA-haplotype- mismatched transplantation. The four SNP genotypes (−1661, −318, CT60 and +49) were determined by TaqMan SNP genotyping assays.ResultsALL recipients of donors with +49 GG showed significantly lower OS (67.7 vs. 90.3 %, P = 0.015) than those with GA+AA. Multivariate analyses showed that +49 GG was an independent risk factor for OS (HR: 0.306, 95 % CI 0.111–0.842, P = 0.022) .23 ALL patients receiving mDLI showed significantly lower OS with +49 GG donor than those with GA+AA (30.0 vs. 83.1 %, P = 0.003). The haplotype analysis revealed only three haplotypes in the donor population −1661/−318/CT60/+49 i.e., ACGG, ACAA and GTGA, the frequencies were 64.1, 19.4 and 16.5 %, respectively. Donors with and without the ACGG/ACGG haplotype had the same effect on transplant outcomes as those with +49 GG and +49 GA+AA.ConclusionIn summary, the CTLA-4 +49 GG and the haplotype ACGG/ACGG reduced the overall survival in ALL after allo-HSCT from the related HLA-haplotype-mismatched donor, knowledge of the CTLA-4 polymorphism and haplotype may provide useful information for donor selection and individual application of immunosuppressive agents and immunotherapy.

Cytomegalovirus (CMV) infection and delayed immune reconstitution remains a serious obstacle for successful partially matched-related donor transplantation (PMRD). We evaluated 42 patients for the development of CMV-specific CD8+ T lymphocytes (CTL(CMV) ) following granulocyte colony-stimulating factor-primed peripheral blood (PB) and bone marrow (BM) with anti-thymocyte globulin (ATG)-based PMRD. PMRD recipients achieved a high frequency, proliferation capacity, and interferon-γ response of CTL(CMV) at 1 year post transplantation. CTL(CMV) with the central memory CD45RO+CD62L+ cell phenotype expanded in PB and BM-resident CTL(CMV) displayed distinct phenotypes when CMV was reactivated. Although the incidence of CMV reactivation was high in PMRD patients (87.67%), only 11.90% of them developed CMV disease. In conclusion, after PMRD using mixed grafts with ATG-based conditioning, immune recovery to CMV seems to be early and fast, thereby reducing the incidence of CMV disease.

LOSP is a severe complication after allo-HSCT. The correct timing and corticosteroid dosage in the context of broad-spectrum antimicrobial therapy might further improve the outcomes of patients with LOSP.

We concluded that CMV detection in the feces was not a good predictor of CMV enteritis in patients with intestinal GVHD after allo-HSCT.