[Efficacy analysis of anti-thymocyte globulin regimens with different timing strategies for matched sibling donor hematopoietic stem cell transplantation].

Objective: To compare the effects of two administration time strategies for rabbit antihuman thymocyte immunoglobulin (rATG) of 5mg/kg total dose in matched sibling donor hematopoietic stem cell transplantation (MSD-HSCT) . Methods: This study retrospectively analyzed the clinical data of 32 patients who received MSD-HSCT with 5 mg/kg rATG conditioning regimen at the Department of Hematology of the First Medical Center of the People's Liberation Army General Hospital from October 2020 to April 2022. The patients were classified into two groups: the 4d-rATG group (16 cases), who received antithymocyte globulin (ATG) from day -5 to day -2, and the 2d-rATG group (16 cases), who received ATG from day -5 to day -4. Between the two groups, the transplantation outcomes, serum concentrations of active antithymocyte globulin (ATG) in patients from -4 days to 28 days after graft infusion (+28 days), and the reconstitution of lymphocyte subsets on days +30, +60, and +90 were compared. Results: The cumulative incidences of acute graft-versus-host disease at 100 days after graft infusion were 25.0% (95% CI 7.8% -47.2% ) and 18.8% (95% CI 4.6% -40.2% ) (P=0.605) in the 4d-rATG group and 2d-rATG group, respectively. The 1-year cumulative incidences of chronic graft-versus-host disease were 25.9% (95% CI 8.0% -48.6% ) and 21.8% (95% CI 5.2% -45.7% ) (P=0.896). The 1-year cumulative incidence of relapse was 37.5% (95% CI 18.9% -65.1% ) and 14.6% (95% CI 3.6% -46.0% ) (P=0.135), and the 1-year probabilities of overall survival were 75.0% (95% CI 46.3% -89.8% ) and 100% (P=0.062). The total area under the curve (AUC) of serum active ATG was 36.11 UE/ml·d and 35.89 UE/ml·d in the 4d-rATG and 2d-rATG groups, respectively (P=0.984). The AUC was higher in the 4d-rATG group than that in the 2d-rATG group (20.76 UE/ml·d vs 15.95 UE/ml·d, P=0.047). Three months after graft infusion, the average absolute count of CD8(+) T lymphocytes in the 4d-rATG group was lower than that in the 2d-rATG group (623 cells/µl vs 852 cells/µl, P=0.037) . Conclusion: The efficiencies of GVHD prophylaxis in MSD-PBSCT receiving 4d-ATG regimen and the 2d-rATG regimen were found to be similar. The reconstruction of CD8(+)T lymphocytes in the 2d-rATG group was better than that in the 4d-rATG group, which is related to the lower AUC of active ATG after transplantation.

[Effect of ruxolitinib combined with glucocorticoid on cytomegalovirus activation in acute graft-versus-host disease].

Objective: To observe the effect of ruxolitinib combined with glucocorticoid on cytomegalovirus (CMV) activation in patients with acute graft-versus-host disease (aGVHD) . Methods: The clinical data of 195 patients who underwent allogeneic hematopoietic stem cell transplantation in the Department of Hematology of the First Medical Center of the People's Liberation Army General Hospital from August 2018 to September 2020 were retrospectively analyzed. According to the severity of aGVHD, the patients were divided into the non-GVHD group, aGVHD grade Ⅰ group, aGVHD grade Ⅱ-Ⅳ group, and aGVHD grade Ⅲ/Ⅳ group. In addition, they were classified into two subgroups according to the first-line treatment regimen for aGVHD: combined regimen group (ruxolitinib combined with glucocorticoid) and classical regimen group (glucocorticoid alone) . The cumulative incidence of CMV activation, the duration of CMV activation, and the duration of CMV negativity in each subgroup at 90 and 180 days after transplantation were analyzed. The overall survival and disease-free survival rates of patients in both regimens were compared. Results: Sixty-four (32.8%) patients in the group did not develop aGVHD. The numbers of patients with grade Ⅰ, Ⅱ-Ⅳ, and Ⅲ/Ⅳ aGVHD were 30 (15.4%) , 101 (51.8%) , and 14 (7.2%) , respectively. Compared with patients in the classical regimen, no significant difference was observed in the cumulative incidence of CMV activation, duration of CMV activation, and duration of CMV negativity in patients with grade Ⅰ-Ⅳ aGVHD in the combined regimen at 90 and 180 days after transplantation (P>0.05) . Further analysis of patients with grade Ⅱ-Ⅳ and Ⅲ/Ⅳ aGVHD showed that the cumulative incidence of CMV activation, duration of CMV activation, and duration of CMV negativity did not show significant difference between the two treatment regimens (P>0.05) . In addition, there was no significant difference in the overall survival and disease-free survival rates of patients in both regimens (P>0.05) . Conclusion: Ruxolitinib combined with glucocorticoid as the first-line therapy for aGVHD did not increase the risk of CMV activation.

[Clinical outcomes of peripheral blood stem cell transplantation for aggressive peripheral T-cell lymphoma].

Objective: To evaluate clinical outcomes of autologous and allogeneic peripheral blood stem cell transplantation (PBSCT) for aggressive peripheral T-cell lymphoma (PTCL). Methods: From June 2007 to June 2017, clinical data of PTCL patients who underwent PBSCT were assessed retrospectively. Results: Among 41 patients, 30 was male, 11 female, and median age was 38(13-57) years old. Seventeen patients with autologous PBSCT (auto-PBSCT) and 24 patients with allogeneic PBSCT (allo-PBSCT) were enrolled in this study. Eight patients (8/17, 47.1%) in auto-PBSCT group were ALK positive anaplastic large cell lymphoma (ALCL), 7 patients (7/24, 29.2%) with NK/T cell lymphoma and 9 patients (9/24, 37.5%) with PTCL-unspecified (PTCL-U) in allo-PBSCT group (P=0.035). There were 58.8% patients (10/17) in complete response (CR) status and 11.8% (2/17) in progression disease (PD) status before transplantation in auto-PBSCT group, and 8.3% (2/24) in CR status and 45.8% (11/24) in PD status before transplantation in allo-PBSCT group (P=0.026). The 2-years cumulative overall survival (OS) were (64.0±10.8)% and (53.5±9.7)% for auto-PBSCT and allo-PBSCT respectively (P=0.543). The 2-years cumulative disease-free survival (DFS) were (57.1±12.4)% and (53.5±10.6)% for auto-PBSCT and allo-PBSCT respectively (P=0.701). In patients with dead outcomes after PBSCT, 83.3% (5/6) of death cause was relapse in auto-PBSCT and 41.7% (5/12) of death cause was relapse in allo-PBSCT. Conclusion: Both auto-PBSCT and allo-PBSCT were effective for PTCL. Allo-PBSCT maybe was better than auto-PBSCT for high-risk PTCL with poor prognosis.

A minicircuitry comprised of microRNA-9 and SIRT1 contributes to leukemogenesis in t(8;21) acute myeloid leukemia.

OBJECTIVE: The AML1-ETO fusion protein (AE) resulting from the t(8;21) translocation is highly related to the pathogenesis and development of leukemia. microRNA-9 (miR-9) acts as a tumor suppressor gene in AE-positive acute myeloid leukemia (AML). Silent mating type information regulation 2 homolog-1 (SIRT1) is overexpressed in most cancer cells by increasing proliferation as a tumorigenic gene. The present study was performed to investigate the underlying interaction between miR-9 and SIRT1 in AE-positive AML. PATIENTS AND METHODS: Expression of miR-9 and SIRT1 in AE-positive AML patients, healthy donors and AML cell lines were detected by qPCR. Relevance between miR-9 and SIRT1 was assessed by plasmid transfection, Western blot and correlation analysis. Luciferase assay was used to confirm the target gene of miR-9. Knockdown of SIRT1 in different cell lines was achieved by shRNA transfection and CCK-8 assay was used to investigate the effects on cell proliferation. RESULTS: The miR-9 expression was lower in AE-positive cell lines compared to that in other AE-negative AML cell lines, while expression of SIRT1 was higher in AE-positive cell lines. Expression of miR-9 was also downregulated in adult primary t(8;21) AML patients compared to healthy donors. The over-expression of miR-9 decreased luciferase activity of wild-type SIRT1, which was recovered after transfection with mutant SIRT1. The miR-9 directly targets SIRT1 by binding to its 3'-untranslated region and reducing its protein levels. Importantly, miR-9 and SIRT1 mRNA levels were inversely correlated in AE-positive AML cell lines and t(8;21) AML primary leukemia cells. Knockdown of SIRT1 levels using shSIRT1 inhibited cell proliferation in AE-positive AML cell lines. CONCLUSIONS: SIRT1 is the target gene of miR-9 and the signaling pathway connecting miR-9 and SIRT1 is a therapeutic target for t(8;21) AML.

Haploidentical, unmanipulated G-CSF-primed peripheral blood stem cell transplantation for high-risk hematologic malignancies: an update.

Emerging data demonstrate promising results of related haploidentical allogeneic hematopoietic stem cell transplantation (haplo-HCT) for the treatment of hematologic malignancies. Data about G-CSF primed PBSC as reliable source of graft with myeloablative conditioning are lacking. We updated the outcomes in 130 adult patients with high-risk hematologic malignancies who received haplo-PBSC transplantation consecutively under busulfan-based conditioning. PBSC were freshly isolated and infused without ex vivo T-cell depletion into the recipients. Myeloid recovery was achieved in 99.2% patients with full donor chimerism. The cumulative incidence of acute grade 3-4 GvHD, overall and extensive chronic GvHD was 14.9%, 38.6% and 16.5%, respectively. The 3-year non-relapse mortality rate was 24.1%. Non-remission prior to transplant was associated with higher incidence of relapse (P=0.006), inferior overall survival (P=0.017) and leukemia-free survival (P=0.024). These data suggest that PBSC is a reliable graft source in haploidentical, unmanipulated transplant settings under myeloablative conditioning in patients with high-risk hematologic malignancies.