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To evaluate the effect of the different doses of antithymocyte globulin (ATG) on the incidence of acute GVHD among patients receiving hematopoietic SCT without ex vivo T-cell-depletion from haploidentical donors, 224 patients with standard-risk hematological malignancy were randomized in this study. One hundred and twelve patients received 6 mg/kg ATG, whereas the remaining patients received 10 mg/kg ATG. This study was registered at http://www.chictr.org as No. ChiCTR-TRC-11001761. The incidence of grade III–IV acute GVHD was higher in the ATG-6 group (16.1%, 95% confidence interval (CI), 9.1–23.1%) than in the ATG-10 group (4.5%, CI, 0.7–8.3%, P =0.005, 95% CI for the difference, −19.4% to −3.8%). EBV reactivation occurred more frequently in the ATG-10 group (25.3%, 17.1–33.5%) than in the ATG-6 group (9.6% (4.0–15.2%), P =0.001). The 1-year disease-free survival rates were 84.3% (77.3–91.3%) and 86.0% (79.2–92.8%) for the ATG-6 group and ATG-10 groups, respectively ( P =0.88). In conclusion, although 6 mg/kg ATG applied in haploidentical transplantation decreased the risk of EBV reactivation compared with 10 mg/kg ATG, this treatment exposes patients to a higher risk for severe acute GVHD.

This study was performed to investigate incidence, causes and factors influencing mortality after haploidentical hematopoietic stem cell transplantation (HSCT) and to compare differences between haploidentical HSCT and HLA-identical sibling HSCT. From January 2000 to June 2011, 1411 patients with acute leukemia or myelodysplastic syndrome were included in this study. Of these patients, 571 received HLA-identical sibling HSCT and 840 received haploidentical HSCT. The cumulative incidence of overall mortality and transplant-related mortality (TRM) after haploidentical HSCT was higher than those after HLA-identical sibling HSCT (38.7% vs 33.3%, P =0.012 and 27.5% vs 19.9%, P =0.002), but the incidence of relapse-related mortality (RRM) did not differ between the two groups (15.6% vs 16.7%, P =0.943). A multivariate analysis suggested that high-risk disease status and haploidentical HSCT correlated with a higher incidence of overall mortality ( P< 0.0001, hazard ratio=1.911 and P =0.019, hazard ratio=1.249); in addition, in haploidentical HSCT, only high-risk disease status correlated with a higher incidence of overall mortality ( P< 0.0001, hazard ratio=1.845). Our study suggested that haploidentical HSCT provided a higher incidence of overall mortality and TRM but the same incidence of RRM compared with HLA-identical sibling HSCT. Therefore, HLA-identical sibling HSCT remains the first choice, but haploidentical HSCT is available for patients without an HLA-identical sibling donor.

Research on the different mechanisms for crossing HLA barriers has progressed over the past 10 years. General outlines have come into view for a solution to this issue and are often presented as ‘haploidentical SCT’ immunology. In this review, we discuss several mechanisms that have recently been described in ex vivo and in vivo settings that can either avoid GVHD or promote hematopoietic reconstitution in haploidentical settings. The host and donor T-cell responses to allogeneic HLA molecules are a fundamental obstacle to the successful application of haploidentical transplantation, which results in unacceptably high incidences of GVHD and graft rejection. Thus, the T-cell response is a central factor in the establishment of a novel haploidentical transplant protocol with superior outcomes.

Prior data indicate similar outcomes after transplants from human leukocyte antigen (HLA)-haplotype-matched relatives, HLA-identical siblings and HLA-matched unrelated donors. We used our prospective data set to answer a clinically important question: who is the best donor for a person with acute leukaemia transplanted in first complete remission. Patients were randomly divided into training (n=611) and validation (n=588) sets. A total of 1199 consecutive subjects received a transplant from an HLA-haplotype-matched relative using granulocyte colony-stimulating factor and anti-thymocyte globulin (n=685) or an HLA-identical sibling (n=514); 3-year leukaemia-free survivals (LFSs) were 75 and 74% (P=0.95), respectively. The multivariate model identified three major risk factors for transplant-related mortality (TRM): older donor/recipient age, female-to-male transplants and donor-recipient ABO major-mismatch transplants. A risk score was developed based on these three features. TRMs were 8%, 15% and 31% for subjects with scores of 0-1, 2 and 3, respectively, (P<0.001). Three-year LFSs were 78%, 74% and 58%, respectively, (P=0.003). The risk score was validated in an independent cohort. In conclusion, our data confirm donor source is not significantly correlated with transplant outcomes. Selection of the best donor needs to consider donor-recipient age, matching for gender and ABO incompatibility among persons with acute leukaemia receiving related transplants under our transplant modality.

Poor graft function (PGF), including early and late PGF, is a serious complication following allotransplant. We recently reported that bone marrow microenvironment abnormalities may occur in cases of late PGF. Whether these abnormalities occur in early PGF remains unknown. To answer this question, we performed a nested case–control study comparing cellular elements of the bone marrow microenvironment in 10 subjects with early PGF, 30 subjects with late PGF and 40 subjects without PGF. Bone marrow endosteal cells, perivascular cells and endothelial cells were analyzed by flow cytometry and by hematoxylin–eosin and immunohistochemical staining in situ . Subjects with early and late PGF had similar abnormalities in these cell types compared with transplant recipients without PGF. However, none of the aforementioned elements of the bone marrow microenvironment were significantly different between early and late PGF patients. Our data suggest that similar abnormalities in the bone marrow microenvironment may occur in early and late PGF post allotransplant. Cellular approaches, such as the administration of mesenchymal stem cells, promise to be beneficial therapeutic strategies in patients with early or late PGF.

Hematopoietic cell transplantation (HCT) activity in China was surveyed to assess its current status. A record number of HCTs (21 884: 16 631 allogeneic (76%) and 5253 autologous (24%)) were reported by 76 centers in China between 1 January 2008 and 30 June 2016. HCT trends included continued growth in transplant activity, a continued rapid increase in haploidentical donors (HID), and slower growth for unrelated donors, matched-related donors (MRD) and cord blood transplantation (CBT). The proportion of HID HCT among allogeneic HCTs increased from 29.6% (313/1062) in 2008 to 48.8% (1939/3975) in 2015, even 51.7% (1157/2237) in the first half of 2016. During this time frame, the proportion of MRD HCTs among allogeneic HCTs decreased from 48.1% (511/1062) to 33.0% (332/3975). The proportion of unrelated donor HCTs among allogeneic HCTs decreased from 20.4 (216/1062) to 13.6% (540/3975). The proportion of CBTs among allogeneic HCTs was increased from 2.1% (22/1062) to 4.2% (184/3975). HCTs have been increasing continuously for all indications except chronic myelogenous leukemia. Severe aplastic anemia is a common HCT indication among non-malignant diseases in China. The number of cases of allogeneic HCT for this disorder has increased annually, from 59 (5.6%) in 2008 to 569 (14.3%) in 2015, even 334 (14.9%) in the first half year in 2016. This survey clearly shows recent trends for HCTs in China.

Encouraging results from a small sample of patients with myelodysplastic syndrome (MDS) undergoing haploidentical donor (HID) hematopoietic stem cell transplantation (HSCT) must be extended. Furthermore, an algorithm derived from a comparison of the outcomes of HID and identical-sibling donor (ISD) HSCT must be established. Therefore, the outcomes of 454 MDS patients who underwent HSCT from HIDs ( n =226) or ISDs ( n =228) between 2003 and 2013 that were reported to the Chinese Bone Marrow Transplantation Registry were analyzed. Among the 3/6 HID ( n =136), 4–5/6 HID ( n =90) and ISD patient groups, the 4-year adjusted cumulative incidences of non-relapse mortality were 34, 29 and 16%, respectively (overall P =0.004), and of relapse were 6, 7 and 10%, respectively (overall P =0.36). The 4-year adjusted probabilities of overall survival were 58, 63 and 73%, respectively (overall P =0.07), and of relapse-free-survival were 58, 63 and 71%, respectively (overall P =0.14); pairwise comparison showed that the difference was only statistically significant in the 3/6 HID vs ISD pair. The data suggest that ISDs remain the best donor source for MDS patients while HIDs (perhaps 4–5/6 HID in particular) could be a valid alternative when an ISD is not available; human leukocyte antigen disparity had no effect on survival among the HID patients.

Many patients who require allogeneic hematopoietic stem cell transplantation (allo-HSCT) lack a human leukocyte antigen (HLA)-matched donor. Here, we report a protocol for haploidentical allo-HSCT that combines granulocyte-colony stimulating factor primed bone marrow (G-BM) and peripheral blood stem cells (PBSC) without in vitro T-cell depletion (TCD). In this study, 171 patients, including 86 in high-risk group, underwent transplantation from haploidentical family donors. All patients achieved sustained, full donor chimerism. One hundred and eleven patients were alive in remission at a median of 682 (253-1502) days. The cumulative incidence of grade III-IV acute graft-versus-host disease (GVHD) was 23% and that of extensive chronic GVHD, 47%; these were not influenced by HLA disparity. Patients younger than 15 years had less grade III-IV acute GVHD than older patients (P=0.044). The 2-year probability of relapse was 12% for standard-risk disease and 39% for high-risk disease. The 2-year probability of leukemia-free survival (LFS) was 68% for standard-risk patients and 42% for high-risk patients (P=0.0009). Grade III-IV acute GVHD was associated with better LFS (P=0.0017). The results require confirmation and show that G-BM combined with PBSC from haploidentical family donors, without in vitro TCD, may be used as a good source of stem cells for allo-HSCT.

In this paper, the mixing and combustion at low-heat release in a turbulent mixing layer are studied numerically using large eddy simulation. The primary aim of this paper is to successfully replicate the flow physics observed in experiments of low-heat release reacting mixing layers, where a duty cycle of hot structures and cool braid regions was observed. The nature of the imposed inflow condition shows a dramatic influence on the mechanisms governing entrainment, and mixing, in the shear layer. An inflow condition perturbed by Gaussian white noise produces a shear layer which entrains fluid through a nibbling mechanism, which has a marching scalar probability density function where the most probable scalar value varies across the layer, and where the mean-temperature rise is substantially over-predicted. A more sophisticated inflow condition produced by a recycling and rescaling method results in a shear layer which entrains fluid through an engulfment mechanism, which has a non-marching scalar probability density function where a preferred scalar concentration is present across the thickness of the layer, and where the mean-temperature rise is predicted to a good degree of accuracy. The latter simulation type replicates all of the flow physics observed in the experiment. Extensive testing of subgrid-scale models, and simple combustion models, shows that the WALE model coupled with the Steady Laminar Flamelet model produces reliable predictions of mixing layer diffusion flames undergoing with fast chemistry.

This study evaluates the prognostic significance of quantitative chimerism to monitor minimal residual disease and predict relapse in acute leukemia (AL) patients following allogeneic hematopoietic SCT (HSCT). The quantitative chimerism levels of 129 AL patients were measured using RQ-PCR based on 29 sequence polymorphisms. Receiver-operating characteristic curve indicated that the optimal cutoff point to predict an inevitable relapse was 1.0%, which results in 100.0% sensitivity and 79.6% specificity.The relapse rate of patients with chimerism >1.0% at 2 years was 55.0%, whereas that for patients with chimerism <1.0% was 0%( P =0.000). Quantitative chimerism >1.00% indicated a higher probability of relapse. Cox multivariate analysis indicated that quantitative chimerism >1.00% was associated with lower disease-free survival (hazard ratio (HR)=10.825; 95% confidence interval (CI) =4.704–24.912, P =0.000) and lower OS (HR=8.681; 95% CI=3.728–20.212, P =0.000). Patients (24/47 with quantitative chimerism >1.00%) who received preemptive modified DLI immunotherapy had significantly lower relapse rate (37.5%) than those ( n =9) who did not (100%; P =0.001). Thus, quantitative chimerism is an independent prognostic factor that predicts clinical outcomes after HSCT and provides a guide for suitable interventions.