No abstract

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 ¼ 0.005, 95% CI for the difference, À 19.4% to À 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 ¼ 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 ¼ 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. INTRODUCTIONAntithymocyte globulin (ATG) has been used in the conditioning regimen to prevent severe GVHD in haploidentical hematopoietic SCT (HSCT), and our previous study presented encouraging results. 1 However, the limitations associated with the use of ATG as a regimen for in vivo T-cell depletion (TCD) include the occurrence of delayed immune reconstitution and an increased risk of severe infections, depending on the dose of ATG administered. 2 Several previous studies have suggested suitable doses of ATG in matched unrelated transplantations. 3,4 However, to date, the optimal dose of ATG with respect to the prevention of severe GVHD following the haploidentical transplantation is unknown.In our recently reported retrospective study, we reduced the total dose of ATG from the traditional 10 mg/kg in our classic regimen to 6 mg/kg for refractory/relapsed patients undergoing haploidentical HSCT. We observed that the reduction of the total dose of ATG to 6 mg/kg produced similar rates of engraftment, GVHD and survival compared with the 10 mg/kg dose of ATG. 5 Based on these findings, we set out to extend the use of 6 mg/kg ATG to standard-risk patients. Therefore, we initiated the current prospective randomized study to evaluate the effect of the two different doses of ATG in conditioning regimens on graft failure, GVHD, relapse and survival among standard-risk patients receiving haploidentical HSCT. We postulated that the use of 6 mg/kg ATG might reduce adverse events without increasing the risk of GVHD.

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.

To evaluate the prognostic significance of Wilms' tumor gene 1 (WT1) expression for monitoring minimal residual disease and predicting relapse in patients with acute leukemia (AL) following allogeneic hematopoietic SCT (allo-HSCT), the WT1 expression levels of 138 AL patients were measured using real-time quantitative reverse transcription PCR at designed time points after allo-HSCT. All patients were divided into four groups based on the HSCT outcomes and intervention application. A low level of WT1 expression following HSCT indicated a low risk of relapse, whereas WT1 expression 41.05% was indicative of a higher probability of relapse. Only the advanced stage of disease (hazard ratio (HR) ¼ 2.73; 95% confidence interval (CI) ¼ 1.337-5.573, P ¼ 0.006) and a WT1 expression X0.60% (HR ¼ 4.774; 95% CI ¼ 2.410-9.459, P ¼ 0.000) were associated with lower disease-free survival. Relapse (HR ¼ 0.119; 95% CI ¼ 0.056-0.250, P ¼ 0.000) and a WT1 expression X0.60% (HR ¼ 2.771; 95% CI ¼ 1.316-5.834, P ¼ 0.007) were associated with lower OS. In conclusion, the WT1 expression level is an independent prognostic factor that can predict clinical outcomes for AL patients after HSCT and provide a guide for suitable interventions.

Allogeneic hematopoietic SCT is indicated for children whose disease demonstrates dismal prognosis with chemotherapy. This study aims to analyse the most recent outcomes of unmanipulated haploidentical (HID) HSCT for paediatric patients with acute leukaemia. Those from matched sibling donors (MSD) HSCT provided a parallel cohort to illustrate the benefits of HID. Conditioning regimen was modified BuCy2. Anti-thymoglobulin was used for HID. Mobilised marrow and blood stem cells were used as the grafts. All patients in HID achieved neutrophil recovery and 96.7% platelet recovery. In HID, the incidences of acute GVHD 3-4 and extensive chronic GVHD were 14.3 and 26.6%. Play-performance score 90-100% was recorded in 79.7% of all survivors. The 5-year leukaemia-free survival (LFS) in CR1, CR2, beyond CR2 or non-remission were 68.9%, 56.6%, 22.2% and 82.5%, 59.4%, 42.9% for ALL and AML, respectively. In MSD group, LFS for ALL and AML in CR1 were 62.5 and 71.7%. Outcomes of the HID HSCT for paediatric patients with acute leukaemia showed benefits that were similar to those of the parallel cohort of MSD HSCT. 3,4 Hence, the domestic indications for allogeneic HSCT in paediatric patients with acute leukaemia cover more subtypes of disease. 5 For paediatric patients requiring allogeneic HSCT, it is widely accepted that grafts from matched sibling donors (MSDs) result in the best outcomes among various sources of stem cells. For patients lacking a suitable HLA-compatible related donor, alternative options include unrelated donors or umbilical cord blood followed by a haploidentical donor (HID) among family members. At present, there is no international or regional consensus or recommendation to guide alternative options for alternative donors. Haematopoietic cells from relatives who are HLA HID are an immediate almost available source of grafts for HSCT candidates. For HSCT with related HIDs, extensive T-cell depletion or CD34 þ cell selection in vitro, mega-dose infusion and other supportive techniques have increased the rate of engraftment, reduced TRM and improved survival. 6,7 The latest reports of T-cell depletion HSCT from HID parental donors showed improved outcomes in the recent treatment era, with 5-year OS rates of 65% and 74% for very high-risk ALL and AML patients, respectively. 8 At our institution, promising results with unmanipulated, HID HSCT have been achieved in adult patients without ex vivo T-cell depletion, demonstrating outcomes similar to those with MSDs and well-matched unrelated HSCT. 9,10 The short-term efficacy and