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Abstract Introduction Invariant natural killer T cells (iNKTs) are a rare but vital subset of immunomodulatory T cells and play an important role in allogeneic hematopoietic stem cell trans-plantation (HSCT). The association of donor characteristics with the number and frequency of the iNKTs subsets in allografts remains poorly understood. In this paper, we prospectively investigate the association of donor characteristics with iNKTs dose and frequency in granulocyte–colony-stimulating factor (G-CSF) mobilized marrow and peripheral blood harvests. Materials and methods 100 bone marrow (BM) units and 100 peripheral blood (PB) units from 100 healthy donors were examined. Parameters including donor age, sex, weight, height, BMI and blood count [including white blood cells (WBCs), lymphocytes and monocytes] at three time points [donor's steady state before G-CSF administration, the day of G-BM harvesting and the day of G-PB apheresis] were analyzed to explore the impact of donor characteristics on iNKTs composition in BM and PB grafts. Results Multivariate analysis showed monocyte counts before G-BM harvest could predict higher frequency of iNKTs in WBC (OR = 2.593, 95%CI: 1.128–5.961, p = 0.025), higher total CD4+ iNKTs dose (OR = 2.250, 95%CI: 1.011–5.008, p = 0.047) and higher total iNKTs dose (OR = 2.662, 95%CI: 1.187–5.970, p = 0.017) in mixture allografts. Discussion The results suggested that monocyte counts pre G-BM harvest could predict the yield of total CD4+ iNKTs and total iNKTs in mixture allografts. The male and older donors were associated with a higher dose of total CD4− iNKTs in mixture allografts. Highlights • Monocyte before G-BM harvest predicted iNKT/WBC, iNKT/T and iNKTs dose in allograft. • Weight and monocyte pre-mobilization were positively associated with iNKT/T. • Allografts from male and elder donors contained higher dose of CD4− iNKTs. • 100 G-BM and 100 G-PB units from 100 healthy donors examined in this study. [ABSTRACT FROM AUTHOR]

We retrospectively investigated outcomes of haploidentical donor ( HID) transplant for adults with standard-risk acute lymphoblastic leukaemia ( ALL) in first complete remission ( CR1) compared with human leucocyte antigen ( HLA)-matched sibling donor ( MSD) and HLA-matched unrelated donor ( MUD) transplants. A total of 348 adult patients were enrolled, including 127 HID, 144 MSD and 77 MUD recipients. The cumulative incidence of grade II- IV acute graft- versus-host disease ( aGVHD) was 39·5%, 24·0% and 40·3% for HID, MSD and MUD, respectively ( P = 0·020). However, there was no difference in grade III- IV aGVHD (11·4%, 7·7%, 13·5%, respectively, P = 0·468). The 5-year cumulative transplant-related mortality was 16·4%, 11·6% and 19·6% ( P = 0·162), the 5-year relapse rate post-transplantation was 14·8%, 21·1% and 16·7% ( P = 0·231), the 5-year overall survival was 70·1%, 73·7% and 69·8% ( P = 0·525), and the 5-year disease-free survival was 68·7%, 67·3% and 63·7%, respectively ( P = 0·606). Furthermore, the 3-year GVHD-free, relapse-free survival was not different (50·8%, 54·9% and 52·2%, respectively, P = 0·847). Our results indicate that the outcomes of HID transplants are equivalent to those of MSD and MUD, and that HID transplantation is a valid alternative for standard-risk adults with ALL in CR1 who lack matched donors. [ABSTRACT FROM AUTHOR]

Use of high-dose, post-transplant cyclophosphamide (PTCy) results in low rates of graft-versus-host-disease (GVHD) and favorable immune reconstitution, although with higher rates of relapse and somewhat high rates of graft failure. We hypothesized that permissible dose reduction of PTCy might be feasible. The current study attempts to establish a murine model and focus on regulatory T cells (Tregs) to clarify the immunological mechanisms for GVHD prevention by low-dose PTCy. In addition, a prospective, clinical cohort study in haploidentical, T-cell replete transplantation is initiated to support the rational. We found that acute GVHD could be alleviated by low-dose PTCy and could be further mitigated after the combined use of low-dose PTCy and antithymocyte globulin (ATG) in mice. Flow-cytometric analyses in mice showed that low-dose PTCy could increase the number of Tregs and the effect on Tregs is significantly prominent with the combined use of low-dose PTCy and ATG. In the clinical cohort study, the cumulative incidence of grades II-IV acute GVHD in combined treatment cohort with low-dose PTCy and ATG/granulocyte colony-stimulating factor (G-CSF) (17%; 95% CI, 5–29%) was significantly lower than both that in matched-pair cohort (33%; 95% CI, 25–41%; P = 0.04) and that in historical cohort (56%; 95% CI, 42–70%; P < 0.001). In-vivo immune reconstitution analysis showed that low-dose PTCy could facilitate suppressive Tregs reconstitution. In conclusion, low-dose PTCy is sufficient for GVHD abrogation under lymphopenic situation and can enhance the protective effect of ATG/G-CSF on GVHD. Intensified conditioning followed by low-dose PTCy might be a feasible option for patients undergoing haploidentical transplantation. [ABSTRACT FROM AUTHOR]