Impact of a novel prognostic model on allogeneic hematopoietic stem cell transplantation outcomes in patients with CMML.

Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell malignancy, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curable treatment. The outcomes after transplant are influenced by both disease characteristics and patient comorbidities. To develop a novel prognostic model to predict the post-transplant survival of CMML patients, we identified risk factors by applying univariable and multivariable Cox proportional hazards regression to a derivation cohort. In multivariable analysis, advanced age (hazard ratio [HR] 3.583), leukocyte count (HR 3.499), anemia (HR 3.439), bone marrow blast cell count (HR 2.095), and no chronic graft versus host disease (cGVHD; HR 4.799) were independently associated with worse survival. A novel prognostic model termed ABLAG (Age, Blast, Leukocyte, Anemia, cGVHD) was developed and the points were assigned according to the regression equation. The patients were categorized into low risk (0-1), intermediate risk (2, 3), and high risk (4-6) three groups and the 3-year overall survival (OS) were 93.3% (95%CI, 61%-99%), 78.9% (95%CI, 60%-90%), and 51.6% (95%CI, 32%-68%; p < .001), respectively. In internal and external validation cohort, the area under the receiver operating characteristic (ROC) curves of the ABLAG model were 0.829 (95% CI, 0.776-0.902) and 0.749 (95% CI, 0.684-0.854). Compared with existing models designed for the nontransplant setting, calibration plots, and decision curve analysis showed that the ABLAG model revealed a high consistency between predicted and observed outcomes and patients could benefit from this model. In conclusion, combining disease and patient characteristic, the ABLAG model provides better survival stratification for CMML patients receiving allo-HSCT.

Haploidentical transplantation compared with matched sibling and unrelated donor transplantation for adults with standard-risk acute lymphoblastic leukaemia in first complete remission.

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.

[Analysis of Clinical Features and Risk Factors for Oral Ulcers and Bloodstream Infection in Patients with Hematopoietic Stem Cell Transplantation].

OBJECTIVE: To investigate the risk factors of oral ulcers and bloodstream infection in patients with hematopoietic stem cell transplantation. METHODS: The clinical data of 401 hematopoietic stem cell transplant patients in the First Affiliated Hospital of Zhengzhou University from January 2020 to December 2021 were retrospective analyzed, and the risk factors of oral ulcers and bloodstream infection statistical and analyzed. RESULTS: Among the 401 patients, the incidence of oral ulcers was 61.3% (246/401), and the incidence of bloodstream infection was 9.0% (36/401). A total of 40 strains of pathogenic bacteria were isolated from 36 patients, including 26 strains of Gram negative strains (65%), 13 strains of Gram positive strains (32.5%), and 1 strain of fungi (2.5%). Single-factor analysis showed that oral hygiene was associated with the occurrence of bloodstream infection, and the Multi-factor analysis showed that age ≥14 years old, disease diagnosis of leukemia, and allogeneic hematopoietic stem cell transplantation were risk factors for oral ulcers. CONCLUSION: The incidence of oral ulcers in patients with hematopoietic stem cell transplantation is high. The age ≥14 years, disease diagnosis of leukemia, and allogeneic hematopoietic stem cell transplantation were risk factors for oral ulcers in patients, and oral hygiene was associated with the occurrence of bloodstream infection.

The impact of donor characteristics on the invariant natural killer T cells of granulocyte-colony-stimulating factor-mobilized marrow grafts and peripheral blood grafts.

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.

Low-dose post-transplant cyclophosphamide can mitigate GVHD and enhance the G-CSF/ATG induced GVHD protective activity and improve haploidentical transplant outcomes.

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.