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Background In unrelated donor allogeneic stem cell transplantation ( URD- SCT), most studies reported that peripheral blood stem cells ( PBSC) resulted in higher incidence of acute and/or chronic graft-versus-host disease ( GVHD) without survival benefits compared with bone marrow (BM). To overcome these shortcomings of PBSC, we have used a risk-adapted GVHD prophylaxis for patients that received HLA-matched URD- SCT, which was adding low-dose rabbit antithymocyte globulin (Thymoglobulin®, 1.25 mg/kg for 2 d) to conditioning in the transplants with PBSC and not BM. Methods To determine whether this strategy is effective, we analyzed 115 adult patients with acute myeloid leukemia who received HLA-matched URD- SCT with PBSC ( n = 70) or BM ( n = 45) using our risk-adapted GVHD prophylaxis strategy. Results The PBSC group showed faster neutrophil (11 d vs. 13 d; P < 0.01) and platelet (12 d vs. 18 d; P < 0.01) engraftment compared with the BM group. No difference was observed in the incidence of acute GVHD grade II-IV at 100 d (54.3% vs. 64.4%; P = 0.38) and chronic GVHD at 4 yr (65.1% vs. 60.0%; P = 0.83). Other outcomes including the incidence of relapse (30.8% vs. 31.2%; P = 0.53), non-relapse mortality (13.5% vs. 6.9%; P = 0.24), disease-free survival (55.7% vs. 61.9%; P = 0.68), and overall survival (62.2% vs. 63.2%; P = 0.96) at 4 yr were not significantly different. Conclusion Our risk-adapted GVHD prophylaxis strategy resulted in similar transplant outcomes including comparable incidence of GVHD between the PBSC and BM groups in HLA-matched URD- SCT. [ABSTRACT FROM AUTHOR]

To weigh the pros and cons of familial-mismatched/haploidentical transplantation (FMT) in patients with high-risk acute myelogenous leukemia, we assessed outcomes of 23 patients who underwent FMT, using reduced-intensity conditioning with total body irradiation 800 cGy/busulfan/fludarabine/antithymocyte globulin without ex vivo T cell depletion, compared to 33 patients who underwent well-matched unrelated donor transplantation (WM-UDT) and 13 who underwent partially matched unrelated donor transplantation (PM-UDT) during the same period. The FMT patients had not only a similar pattern of engraftment and immune reconstitution as the WM-UDT and PM-UDT patients but also comparable incidences and severity of acute and chronic graft-versus-host disease. The FMT patients did not experience any form of engraftment failure. However, the cumulative incidence of cytomegalovirus DNAemia was significantly higher in the FMT group compared with the other groups (P = .036). After a median follow-up of 28 months, overall survival, disease-free survival, relapse, and nonrelapse mortality were 83%, 74%, 20%, and 7%, respectively, for WM-UDT; 51%, 51%, 31%, and 18% for PM-UDT; and 66%, 64%, 26%, and 10% for FMT. This demonstrates a trend for favorable survival outcomes of WM-UDT over FMT and of FMT over PM-UDT. However, we found no significant statistical differences in survival according to donor type. These data need to be interpreted cautiously because of limited power calculations due to the small number of each donor group. This pilot study suggests the feasibility of FMT using our novel regimen with careful evaluation of CMV DNAemia compared with WM-UDT and PM-UDT. Further trials with larger numbers of patients, comparing FMT directly with transplantation with other donor types, are needed. [Copyright &y& Elsevier]

Highlights • The 3-year GVHD-free, relapse-free survival rate for myelodysplastic syndrome was 34.5%. • Circulating blast, cytogenetics, HCT-CI, MAC/RIC, and ATG dose were factors predicting GRFS. • Risk-stratified GRFS rates were 64.9% in low-risk, 33.6% in intermediate-risk, and 6.6% in high-risk patients. • There was an evident impact of RIC and ATG ≥ 7. 5mg/kg on low-risk patients by the other 3 factors. • There was no evident impact of RIC and ATG ≥ 7.5 mg/kg on high-risk patients by the other 3 factors. Graphical Abstract Image, graphical abstract Abstract Graft-versus-host disease–free, relapse-free survival (GRFS) is a composite endpoint that measures survival free of relapse or significant morbidity after allogeneic hematopoietic stem cell transplantation (HSCT). Consecutive adult patients (N = 324) who received HSCT with fludarabine and busulfan–based conditioning for myelodysplastic syndrome (MDS) or secondary acute myeloid leukemia evolved from MDS were retrospectively analyzed. One-year and 3-year GRFS rates were 47.8% and 34.5%, respectively. Three fixed factors (circulating blast > 3%, high cytogenetic risk, and high comorbidity index) and 2 factors (which are) modifiable by clinicians (myeloablative conditioning [MAC] and low-dose [<7.5 mg/kg] antithymocyte globulin [ATG]) were independent factors for poor GRFS. Based on these 5 factors, 3 groups (3-year GRFS: 64.9% in low risk, 33.6% in intermediate risk, and 6.6% in high risk; P <.001) were identified. Fixed factor–adjusted GRFS in patients receiving reduced-intensity conditioning (RIC) plus high-dose ATG (≥7.5 mg/kg) was superior (P <.001) to those receiving MAC and/or low-dose ATG. Favorable influences of RIC plus ATG ≥ 7.5 mg/kg were evident in the low-risk group defined by fixed factors (3-year GRFS, 38.9% versus 4.4%; P <. 001) but were not evident in the high-risk group (3-year GRFS,.0% versus 5.3%; P =.678). Conclusively, this study suggests that risk-adapted selection of conditioning intensity and ATG could improve qualified HSCT outcomes. [ABSTRACT FROM AUTHOR]

CD161 is a type II transmembrane glycoprotein with characteristics of the C-type lectin superfamily, which has recently been shown to promote T cell expansion. In this study, the role of T cells expressing CD161 as a predictor for the occurrence of acute graft-versus-host disease (aGVHD) after allogeneic stem cell transplantation (SCT) was investigated. Sixty-one patients who underwent first allogeneic SCT were enrolled. At engraftment, the expression of CD3, CD4, CD8, CD161, CD16, and CD56 was analyzed by flow cytometry. After adjusting for potential variables by univariate analysis, we performed a multivariate analysis, which revealed a low frequency of CD8 + CD161 + cells ( P = .034) and a high ratio of CD4 + CD161 + to CD8 + CD161 + cells ( P = .001) were associated with the occurrence of aGVHD with a grade of ≥ II. Moreover, the frequency of CD8 + CD161 + T cells was negatively correlated with aGVHD grade. A separate analysis for visceral aGVHD showed similar results, with a low frequency of CD8 + CD161 + T cells ( P = .031) or a high ratio of CD4 + CD161 + to CD8 + CD161 + cells ( P < .001), indicating a high risk. Also, the predictive role of serum IL-17 levels for the occurrence of aGVHD was identified, and RORγT was more highly expressed in CD4 + CD161 + T cells than in CD8 + CD161 + T cells after allogeneic SCT ( P = .032). Although our study was limited by the heterogeneity and small number of patients, these results suggest that the CD8 + subset of CD161 + T cells may have regulatory effects and that they provide a basis for predicting the occurrence of aGVHD after allogeneic SCT. [ABSTRACT FROM AUTHOR]

Cytomegalovirus gastrointestinal (CMV-GI) disease in GI graft-versus-host disease (GI-GVHD) has not been properly evaluated in the era of preemptive therapy for CMV infection. We investigated 103 patients with GI-GVHD who underwent endoscopic biopsies with immunohistochemical staining for CMV. All recipients and/or donors were seropositive for CMV and monitored with a strategy of preemptive therapy based on real-time quantitative polymerase chain reaction. Twenty-six patients (25 %) developed CMV-GI disease, especially in HLA-mismatched transplants ( P = 0.023) and with initial gut involvement of GVHD ( P = 0.009). The CMV-GI diseases were diagnosed at follow-up endoscopies ( n = 10, 39 %), comprising 19 % of 52 patients who underwent follow-up endoscopies, as well as initial endoscopies ( n = 16, 61 %), comprising 16 % of all GI-GVHD patients. In seven cases, either at initial ( n = 5) or follow-up endoscopies ( n = 2), CMV-GI disease was diagnosed in the absence of histopathologic evidence for GI-GVHD. Notably, only 11 patients (42 %) had prior CMV DNAemia before the diagnosis of CMV-GI disease, while 12 (46 %) and three (12 %) had concurrent and no CMV DNAemia, respectively. Sixty-five percent of CMV-GI disease was resolved by additional antiviral therapies, but CMV-GI disease ( P = 0.032) as well as severity of GVHD ( P = 0.001) negatively affected GVHD-specific survival. In conclusion, our data demonstrate that CMV-GI disease was a cause of initial or persistent GI manifestations after the initiation of therapy in a considerable proportion of GI-GVHD. These suggest the necessity of novel strategies to reduce CMV-GI disease as well as an effort to confirm CMV with repeated endoscopies. [ABSTRACT FROM AUTHOR]