Comparison of autologous, matched sibling, and alternative donor stem cell transplant outcomes for acute myeloid leukemia patients in first remission: A propensity score matching study.

Autologous hematopoietic stem cell transplantation (auto-HSCT), matched sibling donor HSCT (MSD-HSCT), and alternative donor HSCT (AD-HSCT) are viable post-remission treatment options for acute myeloid leukemia (AML). A total of 283 de novo favorable- and intermediate-risk AML patients, based on the ELN 2022 criteria, in first complete remission were initially included for propensity score matching. Following the matching process, 126 patients were selected for further analysis, with 42 patients in each of the auto-HSCT, MSD-HSCT, and AD-HSCT groups. Among the AD-HSCT group, 38 of 42 (90.5%) patients received haploidentical HSCT. In patients with persistent undetectable measurable residual disease (uMRD) before transplant (n = 83), overall survival (OS) was similar across the groups. However, auto-HSCT showed a trend of increased disease-free survival (DFS) compared to AD-HSCT (HR 2.85, P = 0.09), resulting in a 3-year DFS and OS of 79.1% and 82.8%, respectively. In the non-persistent uMRD group (n = 38), auto-HSCT exhibited a tendency to increase the risk of relapse, particularly when compared to AD-HSCT (HR 0.24, P = 0.07), but this did not result in inferior OS. The monthly direct medical cost per patient within the first 2 years after HSCT was significantly lower in auto-HSCT compared to MSD-HSCT (P = 0.015) and AD-HSCT (P < 0.001). Our results provide evidence for the use of auto-HSCT as a viable therapeutic option for favorable- and intermediate-risk de novo AML patients in first complete remission with persistent uMRD. Additionally, our findings demonstrated a notable cost advantage associated with auto-HSCT compared to MSD-HSCT and AD-HSCT.

WT1 gene mutations impact post-transplant relapse in myelodysplastic syndrome with excess blasts 2 patients.

Wilms tumor 1 (WT1) gene mutations are infrequent in myelodysplastic syndrome (MDS), but MDS with WT1 mutations (WT1mut) is considered high risk for acute myeloid leukemia (AML) transformation. The influence of WT1 mutations in patients with MDS after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is unclear. We performed a retrospective analysis of 136 MDS with excess blasts 2 (MDS-EB2) patients with available WT1 status who underwent their first allo-HSCT between 2017 and 2022 in our center. There were 20 (20/136, 15%) cases in the WT1mut group and 116 (116/136, 85%) cases in the WT1 wild-type (WT1wt) group. WT1mut patients had a higher 2-year cumulative incidence of relapse (CIR) than WT1wt cases (26.2% vs. 9.4%, p = 0.037) after allo-HSCT. Multivariate analysis of relapse showed that WT1 mutations (HR, 6.0; p = 0.002), TP53 mutations (HR, 4.2; p = 0.021), and ≥ 5% blasts in bone marrow (BM) at transplantation (HR, 6.6; p = 0.004) were independent risk factors for relapse. Patients were stratified into three groups according to the risk factors. Two-year CIR differed significantly in high-, intermediate-, and low-risk groups (31.8%, 11.6%, and 0%, respectively). Hence, WT1 mutations may be related to post-transplant relapse in patients with MDS-EB2, which warrants further study.

Prophylactic therapy using epigenetic agents for RUNX1::RUNXT1-positive high-risk AML after Allo-HSCT.

Disease recurrence is the leading cause of treatment failure in patients with RUNX1::RUNXT1-positive acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Post-transplant maintenance therapy, guided by monitoring minimal residual disease (MRD), is commonly administered; however, relapse rates remain high. This prospective study aimed to assess the effectiveness and safety of epigenetic agents as prophylactic therapy in patients with RUNX1::RUNXT1-positive AML. Thirty high-risk patients received prophylactic therapy (n = 17 and n = 13 in the chidamide and AZA groups, respectively) between January 2019 and July 2023. 34 high-risk patients who received preemptive treatment due to molecular relapse were included in the analysis. The two-year relapse-free survival (RFS) and overall survival (OS) were significantly higher in the prophylactic group compared to the preemptive group (82.82% vs. 51.38%, P = 0.014; 86.42% vs. 56.16%, P = 0.025, respectively); 2-year cumulative incidence of relapse rates were 13.8% and 36.40%, respectively (P = 0.037). In conclusion, prophylactic therapy with epigenetic agents may improve long-term prognosis and is well-tolerated in patients with RUNX1::RUNXT1-positive high-risk AML. Timely post-transplant prophylactic therapy may be more effective than preemptive therapy based on positive MRD results.

Ceftazidime-avibactam in the treatment of bacteremia due to carbapenem-resistant gram-negative bacteria in hematological patients: Experience in a single center.

INTRODUCTION: Limited experience exists with ceftazidime-avibactam (CAZ-AVI) in treating bacteremia caused by carbapenem-resistant Enterobacterales (CRE) and Pseudomonas aeruginosa (CRPA) in hematological patients. METHODS: We performed a single-center, retrospective, observational study including patients who received CAZ-AVI for bacteremia due to CRE or CRPA between 2018 and 2022. The primary outcome was 30-day survival. We conducted a multivariable analysis to identify predictors of survival. RESULTS: 56 patients were included and 57 (41 CRE and 16 CRPA) strains were isolated. 35 strains produced carbapenemase, including 25 metallo-beta-lactamase (MBL) and 10 serine-beta-lactamase. 48 patients (85.7 %) received combination therapy. All patients with MBL-CRE bacteremia (n = 24) received combination therapy with aztreonam (AZT). The susceptibility rates to CAZ-AVI were only 26.8 % (11/41) in CRE and 80.0 % (8/10) in CRPA. The 30-day survival rates were 85.0 % (34/40) in the CRE group and 81.3 % (13/16) in the CRPA group. In patients with MBL-CRE bacteremia, the 30-day survival was as high as 91.7 % (22/24) due to combination with AZT. Ceftazidime did not influence the activity of aztreonam-avibactam against MBL-CRE in-vitro. Multivariable cox analysis revealed neutropenia >14 days (P = 0.002, HR: 34.483, 95%CI: 3.846-333.333) and a higher Pitt bacteremia score (P = 0.005, HR: 2.074, 95%CI: 1.253-3.436) were risk factors for 30-day survival. CONCLUSIONS: CAZ-AVI is highly effective in treating bacteremia due to CRPA and serine-beta-lactamase CRE. The combination of avibactam with AZT is highly effective in treating bacteremia due to AZT-resistant MBL producers.

Haematopoietic stem cell transplantation for hepatitis-associated aplastic anaemia and non-hepatitis-associated aplastic anaemia: A propensity score-matched analysis.

To validate the efficacy and safety of haematopoietic stem cell transplantation (HSCT) in hepatitis-associated aplastic anaemia (HAAA) patients, we reviewed 260 patients who underwent HSCT for acquired aplastic anaemia and eventually included 30 HAAA patients and 90 non-HAAA patients using propensity score matching. In the HAAA group, the estimated 5-year overall survival rate (75.8% vs. 86.5%, p = 0.409), failure-free survival (FFS) rate (74.0% vs. 83.2%, p = 0.485), graft-versus-host disease (GVHD)-free FFS rate (61.2% vs. 67.6%, p = 0.669) after HSCT were slightly lower but not statistically significant than those in the non-HAAA group. Both groups did not significantly differ in engraftment, post-transplant severe infection, cytomegalovirus (CMV) or Epstein-Barr virus viraemia, or GVHD incidences. The patterns of immune reconstitution were broadly consistent between the two groups. When stratifying HAAA patients according to donor type, no significant differences in survival, transplant-related mortality, or GVHD cumulative incidences were observed. CMV viraemia (68.7% vs 8.3%, p = 0.009) occurred more commonly in haploidentical donor (HID) transplants than in matched sibling donor transplants. However, early CMV disease incidence (5.6% vs. 0.0%, p = 1.000) was low. Overall, the post-transplant outcomes of HAAA patients were comparable to those of non-HAAA patients after balancing potential confounders, and HID-HSCT can offer an alternative curative option for HAAA.

Outcomes of allogeneic or autologous stem cell transplantation followed by maintenance chemotherapy in adult patient with B-ALL in CR1 with no detectable minimal residual disease.

Autologous haematopoietic stem cell transplantation (auto-HSCT) as a treatment for B-cell acute lymphoblastic leukaemia (B-ALL) has been rigorously debated in recent years. We retrospectively analysed the outcomes of 355 adult patients with B-ALL in first complete remission who had received auto-HSCT or allogeneic HSCT (allo-HSCT) in our centre. The treatment efficacy was evaluated from a model stratified on the risk classification and minimal residue disease (MRD) status after three chemotherapy cycles. Auto-HSCT demonstrated comparable 3-year overall survival (OS) (72.7% vs. 68.5%, p = 0.441) and leukaemia-free survival rates (62.8% vs. 56.1%, p = 0.383) compared to allo-HSCT for patients with negative MRD, while the advantage of lower non-relapse mortality (1.5% vs. 25.1%, p < 0.001) was offset by a higher cumulative incidence of relapse (CIR) rates (35.7% vs. 18.9%, p = 0.018), especially in high-risk patients. For patients at high risk and with positive MRD, there was a lower trend of 3-year OS (50.0% vs. 66.0%, p = 0.078) and significantly higher CIR rates (71.4% vs. 39.1%, p = 0.018) in auto-HSCT. However, no significant interaction was observed in the tests. In conclusion, auto-HSCT appears to be an attractive treatment for patients with negative MRD after three chemotherapy cycles. For MRD-positive patients, allo-HSCT may be a more effective treatment.

The Composite Immune Risk Score predicts overall survival after allogeneic hematopoietic stem cell transplantation: A retrospective analysis of 1838 cases.

There has been little consensus on how to quantitatively assess immune reconstitution after hematopoietic stem cell transplantation (HSCT) as part of the standard of care. We retrospectively analyzed 11 150 post-transplant immune profiles of 1945 patients who underwent HSCT between 2012 and 2020. 1838 (94.5%) of the cases were allogeneic HSCT. Using the training set of patients (n = 729), we identified a composite immune signature (integrating neutrophil, total lymphocyte, natural killer, total T, CD4+ T, and B cell counts in the peripheral blood) during days 91-180 after allogeneic HSCT that was predictive of early mortality and moreover simplified it into a formula for a Composite Immune Risk Score. When we verified the Composite Immune Risk Score in the validation (n = 284) and test (n = 391) sets of patients, a high score value was found to be associated with hazard ratios (HR) of 3.64 (95% C.I. 1.55-8.51; p = .0014) and 2.44 (95% C.I., 1.22-4.87; p = .0087), respectively, for early mortality. In multivariate analysis, a high Composite Immune Risk Score during days 91-180 remained an independent risk factor for early mortality after allogeneic HSCT (HR, 1.80; 95% C.I., 1.28-2.55; p = .00085). In conclusion, the Composite Immune Risk Score is easy to compute and could identify the high-risk patients of allogeneic HSCT who require targeted effort for prevention and control of infection.

Comparison of porcine ALG and rabbit ATG on outcomes of HLA-haploidentical hematopoietic stem cell transplantation for patients with acquired aplastic anemia.

OBJECTIVE: To evaluate the efficacy and safety of P-ALG (porcine anti-lymphocyte globulin) and R-ATG (rabbit anti-thymocyte globulin) in the conditioning regime for patients with acquired aplastic anemia who underwent HLA-haploidentical hematopoietic stem cell transplantation (halpo-HSCT). METHODS: A total of 91 patients with acquired aplastic anemia who received haplo-HSCT at our center between January 2014 and December 2020 were retrospectively reviewed. Twenty-eight patients were in the P-ALG group while sixty-three patients were in the R-ATG group. RESULTS: The median time was 11 versus 13 days (P = 0.294) for myeloid engraftment and 12.5 versus 15 days (P = 0.465) for platelet engraftment in the P-ALG and R-ATG groups, respectively. There were no significant difference in 5-year overall survival (74.83% ± 8.24% vs 72.29% ± 6.26%, P = 0.830), GVHD-free, failure-free survival (71.05% ± 8.65% vs 62.71% ± 6.22%, P = 0.662), failure-free survival (74.83% ± 8.24% vs 66.09% ± 5.84%, P = 0.647) and transplantation-related mortality (25.17% ± 8.24% vs 26.29% ± 6.22%, P = 0.708) between the two groups. The incidence of aGVHD (acute graft versus host disease) (65.39% ± 9.33% vs 62.71% ± 6.30%, P = 0.653), II-IV aGVHD (38.46% ± 9.54% vs 35.64% ± 6.24%, P = 0.695), III-IV aGVHD (19.23% ± 7.73% vs 10.53% ± 4.07%, P = 0.291), cGVHD (chronic graft versus host disease) (22.22% ± 12.25% vs 22.31% ± 6.30%, P = 0.915), and moderate to severe cGVHD (5.56% ± 5.40% vs 9.28% ± 4.46%, P = 0.993) were not significantly different. Similar outcomes were observed between the P-ALG and R-ATG groups for severe bacterial infection (17.9% vs 25.4%, P = 0.431), invasive fungal diseases (3.6% vs 9.5%, P = 0.577) and graft rejection (0% vs 9.5%, P = 0.218). However, the incidence of cytomegalovirus infection and Epstein-Barr virus infection was significantly lower in the P-ALG group (46.4% vs 71.4%, P = 0.022; 3.6% vs 25.4%, P = 0.014). CONCLUSION: The efficacy and safety of P-ALG were similar with R-ATG in the setting of haplo-HSCT for patients with acquired aplastic anemia patients. P-ALG could be an alternative for R-ATG.

Outcome of autologous stem cell transplantation in patients with favorable-risk acute myeloid leukemia in first remission.

OBJECTIVE: To evaluate the efficacy of autologous hematopoietic stem cell transplantation (auto-HSCT) in patients with favorable-risk acute myeloid leukemia in first remission. METHOD: Twenty patients who received auto-HSCT at our center between January 2014 and January 2021 were retrospectively reviewed. RESULTS: Until last follow-up, three patients in the cohort were dead due to relapse. The estimated 1-year and 5-year overall survival were 95.00% ± 4.87% and 83.82% ± 8.58%, respectively. The estimated 5-year RFS and CIR (cumulative incidence of relapse) were 85.00% ± 7.98% and 15.00% ±7.98%, respectively. CONCLUSION: The outcome of auto-HSCT in patients with favorable-risk acute myeloid leukemia in first remission was excellent and auto-HSCT could be an effective treatment for these patients.

CD11c participates in triggering acute graft-versus-host disease during bone marrow transplantation.

CD11c is a canonical dendritic cell (DC) marker with poorly defined functions in the immune system. Here, we found that blocking CD11c on human peripheral blood mononuclear cell-derived DCs (MoDCs) inhibited the proliferation of CD4+ T cells and the differentiation into IFN-γ-producing T helper 1 (Th1) cells, which were critical in acute graft-versus-host disease (aGVHD) pathogenesis. Using allogeneic bone marrow transplantation (allo-BMT) murine models, we consistently found that CD11c-deficient recipient mice had alleviated aGVHD symptoms for the decreased IFN-γ-expressing CD4+ Th1 cells and CD8+ T cells. Transcriptional analysis showed that CD11c participated in several immune regulation functions including maintaining antigen presentation of APCs. CD11c-deficient bone marrow-derived DCs (BMDCs) impaired the antigen presentation function in coculture assay. Mechanistically, CD11c interacted with MHCII and Hsp90 and participated in the phosphorylation of Akt and Erk1/2 in DCs after multiple inflammatory stimulations. Therefore, CD11c played crucial roles in triggering aGVHD and might serve as a potential target for the prevention and treatment of aGVHD.

Comparative Study of Mizoribine and Mycophenolate Mofetil Combined with a Calcineurin Inhibitor-Based Immunosuppressive Regimen in Patients with Alternative Donor Hematopoietic Cell Transplantation.

Cytomegalovirus (CMV) infection and graft-versus-host disease (GVHD) remain the major causes of nonrelapse mortality (NRM) in patients following alternative donor hematopoietic stem cell transplantation (HCT). Mizoribine (MZR) showed an anti-CMV effect in addition to its immunosuppressive effect in patients with renal transplantation. In this study, we aimed to evaluate the efficacy and safety of MZR combined with a calcineurin inhibitor (CNI) as a method of prophylactic immunosuppression in recipients following alternative donor HCT. Eighty patients were enrolled in the study and randomized to the MZR (n = 40) or MMF (n = 40) cohort before transplantation conditioning. Analyses involved a comparison of the outcomes between the 2 cohorts, as well as risk analyses of early nonrelapse mortality (NRM) and severe CMV infection. In contrast to MMF, MZR was associated with a lower but statistically nonsignificant median CMV DNA peak load (P = .075), significantly fewer episodes of persistent/refractory infection (odds ratio [OR], .12), and a lower failure rate of CMV treatment (OR, .82), but a significantly higher rate of hyperuricemia (OR, 2.75). Transplantation efficacy was comparable in the 2 cohorts regarding engraftment, the development of secondary poor graft function and GVHD, and the estimated OS and PFS. The 1-year NRM of the MZR cohort did not differ from that of the MMF cohort, whereas the rate of 1-year NRM caused by viral infections was reduced in the MZR cohort and was of borderline statistical significance (P = .05). In the multivariate analysis, lower doses of CD34+ cells in grafts (hazard ratio [HR], 3.65) and persistent/refractory CMV infections (versus no CMV infection: HR, 7.31; versus CMV infection that was not persistent/refractory: HR, 4.46) were predictors of increased 1-year NRM. The use of MMF (versus MZR cohort: OR, 11.54) and grade II-IV acute GVHD (OR, 15.32) were independent risk factors for developing persistent/refractory CMV infection. When combined with CNIs, MZR functioned well in terms of both immunosuppression and reduced severity of CMV infection; however, further studies are warranted to verify its use as a potential immunosuppressant for alternative donor HCT.

Conditioning Regimen of 5-Day Decitabine Administration for Allogeneic Stem Cell Transplantation in Patients with Myelodysplastic Syndrome and Myeloproliferative Neoplasms.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment for patients with myelodysplastic syndromes (MDS) and myelodysplastic/myeloproliferative neoplasms (MDS/MPN). However, post-HSCT relapse remains a major cause of treatment failure. Here we assessed the efficacy of a new conditioning regimen comprising decitabine (Dec), busulfan (Bu), cyclophosphamide (Cy), fludarabine (Flu), and cytarabine (Ara-c) for allo-HSCT in patients with MDS and MDS/MPN. A total of 48 patients were enrolled, including 44 with MDS and 4 with chronic myelomonocytic leukemia (CMML). Patients received Dec 20 mg/m2/day on days -9 to -5, combined with a Bu/Cy/Flu/Ara-c-modified preparative regimen. At a median follow-up of 522 days (range, 15 to 1313 days), the overall survival (OS) was 86%, relapse incidence was 12%, and nonrelapse mortality was 12%. The incidence of severe acute (grade III-IV) graft-versus-host disease (GVHD) was 23% and that of chronic GVHD was 15%. At 2 years, OS was 74% and 86%, respectively for high-risk and very-high-risk patients with MDS. Survival was promising in patients with poor-risk gene mutations, such as TP53 and ASXL1 (88%), and in those with ≥3 gene mutations (79%). Results of immunomonitoring studies revealed that proper natural killer cells made essential contributions to these favorable clinical outcomes. Overall, this new regimen was associated with a low relapse rate, low incidence and severity of GVHD, and satisfactory survival in allo-HSCT recipients with MDS and MDS/MPN.

Combination treatment of rituximab and donor platelets infusion to reduce donor-specific anti-HLA antibodies for stem cells engraftment in haploidentical transplantation.

BACKGROUND: Donor-specific anti-human leukocyte antigen (HLA) antibodies (DSAs) in recipients is a risk factor for donor stem cell graft failure in haploidentical hematopoietic stem cell transplantation (haplo-HSCT), and the treatment to reduce the levels of DSAs is not unanimous. This study was to analysis the role of DSAs for stem cell engraftment and to discuss the effective treatment to reduce DSAs in haplo-HSCT. METHODS: We retrospectively evaluated the levels of DSAs and the effect of the combination treatment of rituximab and donor platelets (PLTs) for donor stem cell engraftment in haplo-HSCT patients from June 2016 to March 2018 at our center. RESULTS: Nine patients (11.5%) out of the total 78 patients were DSAs-positive and multivariate analysis revealed DSAs was the only factor that affected engraftment. Seven out of the 9 DSAs (+) patients received therapy: Four had antibodies against donor HLA class I (HLA-I) antigens and were administered two therapeutic amounts of donor apheresis platelets (platelet count approximately 3-5 × 1011 ) before donor stem cell infusion and the other three patients received a combination therapy of donor apheresis platelets and rituximab due to the antibodies against both donor HLA-I antigens and HLA class II (HLA-II) antigens. All the seven patients achieved donor stem cell engraftment successfully, and the DSAs levels decreased rapidly after transplantation. CONCLUSIONS: DSAs is an important factor affecting engraftment in haplo-HSCT. Donor platelet transfusion is one simple and effective treatment for HLA-I DSAs, and a combination therapy should be administered if patients have both HLA-I and HLA-II antibodies.

A novel approach of torque control for maxillary displaced incisors.

Effective torque control is crucial for the successful treatment of impacted incisors; however, torque control is often a challenge with the use of conventional bracket systems, especially when the adjacent teeth require opposite torque managements. A novel approach of torque control for adjacent anterior teeth is introduced in this case report. A 12-year-old boy had an impacted maxillary right central incisor with the adjacent teeth severely displaced. The treatment plan was to regain space and pull the impacted incisor into the dentition. An upper removable appliance was first used to regain space for the impacted central incisor, followed by a spontaneous eruption of the impacted incisor. Subsequently, fixed appliances were bonded to level and align the dentition. However, the crown of the maxillary right central incisor was found to be tipped lingually, while the maxillary right lateral incisor was tipped labially. Traditional torque control, including torque bend and the use of a Warren spring, were first used for the correction, but they were ineffective due to the overlap of the root apex of the maxillary central incisor and lateral incisor. After the roots were separated with a V-shaped curve, auxiliary brackets were bonded on the gingival one-third areas of the maxillary incisors and canine with nickel-titanium wires used for the torque control. This approach of using the auxiliary brackets and wires was demonstrated to be efficient and effective in the torque control of adjacent anterior teeth with opposite torque control requirements. The final result and the 2-year follow-up records demonstrated the proper torque of anterior teeth and good and stable dental and profile esthetics.

Effect of Antithymocyte Globulin Source on Outcomes of HLA-Matched Sibling Allogeneic Hematopoietic Stem Cell Transplantation for Patients with Severe Aplastic Anemia.

We wanted to evaluate efficacy of porcine antithymocyte globulin (ATG) in HLA-matched sibling donor allogeneic hematopoietic stem cell transplantation (MSD-HSCT) for patients with severe aplastic anemia (SAA). The clinical data of 113 SAA patients who received MSD-HSCT from January 2005 to November 2016 were analyzed retrospectively. Of these, 58 patients received rabbit ATG as a part of conditioning regimen (R-ATG group), whereas the other 55 patients received porcine ATG (P-ATG group). Patient baseline characteristics and donor conditions of the 2 groups were similar, except patients were older and more received peripheral blood stem cell transplantation in the P-ATG group. All patients engrafted in 2 groups. There were significant differences in the incidence of acute (20.7% ± 5.3% versus 43.4% ± 7.0%, P = .015) and chronic graft-versus- host disease (GVHD; 20.1% ± 5.8% versus 46.0% ± 7.9%, P = .003) between the R-ATG and P-ATG groups. However, there were no significant differences in terms of 3-year overall survival (93.1% ± 3.3% versus 84.4% ± 5.7%, P = .235), grades III to IV acute GVHD (3.4% ± 2.4% versus 12.3% ± 4.7%, P = .098), moderate to severe chronic GVHD (12.6% ± 4.9% versus 11.5% ± 4.9%, P = .905), or graft rejection (7.4% ± 3.6% versus 5.5% ± 3.1%, P = .852). There was also no significant difference with regard to the incidence of severe bacterial infection (P = .075), invasive fungal disease (P = .701), or cytomeglovirus viremia (P = .770). P-ATG showed satisfactory efficacy and safety compared with R-ATG in the setting of MSD-HSCT for SAA patients. P-ATG could be a potential alternative preparation for R-ATG, further offering the advantage of lower costs.

Tri-allelic patterns at the D7S820 locus detected in two generations of a Chinese family.

Alleles at the D7S820 STR locus have 6-14 different numbers of a four-nucleotide (GATA) repeat motif arranged in tandem. The D7S820 tri-allelic pattern is rare and has not been reported in the Chinese population. In this study we report a three-banded pattern at the D7S820 locus observed in a Chinese family, in which four family members in two generations had tri-allelic D7S820 genotype 10-11-12 and one family member had an abnormal bi-allele genotype 10-11. All of the four tri-allelic cases had the genotype 10-11-12, probably due to three copies of the D7S820 STR sequence in all cells (Type 2 tri-allelic pattern), and deduced alleles 10-11 were a linked inheritance in this family.

Successful treatment of a 3-year-old boy with hepatitis-associated aplastic anemia with combination of auto-umbilical cord blood transplantation and immunosuppressive therapy.

In this work we describe a 3-year-old boy with hepatitis-associated aplastic anemia (HAAA) treated successfully with autologous cord blood transplantation combined with immunosuppressive therapy. There is little previous experience in the utility of autologous cord blood transplantation in the treatment of HAAA. Nowadays, for patients born after 1980, an HLA matched sibling donor is not usually available because of the family planning policy in our country. So more and more parents choose to preserve the umbilical cord blood for their children. We consider it a new effective choice for the treatment of HAAA, especially for the pediatric patients.

Endoplasmic reticulum stress regulates rat mandibular cartilage thinning under compressive mechanical stress.

Compressive mechanical stress-induced cartilage thinning has been characterized as a key step in the progression of temporomandibular joint diseases, such as osteoarthritis. However, the regulatory mechanisms underlying this loss have not been thoroughly studied. Here, we used an established animal model for loading compressive mechanical stress to induce cartilage thinning in vivo. The mechanically stressed mandibular chondrocytes were then isolated to screen potential candidates using a proteomics approach. A total of 28 proteins were identified that were directly or indirectly associated with endoplasmic reticulum stress, including protein disulfide-isomerase, calreticulin, translationally controlled tumor protein, and peptidyl-prolyl cis/trans-isomerase protein. The altered expression of these candidates was validated at both the mRNA and protein levels. The induction of endoplasmic reticulum stress by mechanical stress loading was confirmed by the activation of endoplasmic reticulum stress markers, the elevation of the cytoplasmic Ca(2+) level, and the expansion of endoplasmic reticulum membranes. More importantly, the use of a selective inhibitor to block endoplasmic reticulum stress in vivo reduced the apoptosis observed at the early stages of mechanical stress loading and inhibited the proliferation observed at the later stages of mechanical stress loading. Accordingly, the use of the inhibitor significantly restored cartilage thinning. Taken together, these results demonstrated that endoplasmic reticulum stress is significantly activated in mechanical stress-induced mandibular cartilage thinning and, more importantly, that endoplasmic reticulum stress inhibition alleviates this loss, suggesting a novel pharmaceutical strategy for the treatment of mechanical stress-induced temporomandibular joint diseases.

Ursodeoxycholic acid does not reduce SARS-CoV-2 infection in newly allogeneic hematopoietic stem cell transplantation recipients: a prospective NICHE cohort.

Introduction: Retrospective studies have suggested that Ursodeoxycholic Acid (UDCA) provide a protective effect against SARS-CoV-2 infection, particularly in patients with liver disease. However, it is uncertain whether this finding can be extended to the allogeneic hematopoietic stem cell transplantation (allo-HSCT) cohort. Therefore, we aim to examine the protective potential of UDCA against SARS-CoV-2 infection in recently received allo-HSCT patients. Methods: During the initial Omicron variant wave in China (December 2022 to February 2023), we conducted a prospective observational study involving 91 hospitalized patients who had undergone allo-HSCT within the previous 6 months as part of the National Longitudinal Cohort of Hematological Diseases (NICHE). Throughout hospitalization, we continuously monitored the status of COVID-19 using SARS-CoV-2 PCR kits or SARS-CoV-2 Antigen Rapid Tests. Results: Among these patients, 67.0% (n = 61) were confirmed to have contracted SARS-CoV-2 infection. For the 52 patients evaluated, 23.1% experienced a severe or critical clinical course. There was no difference in the infection rate or severity of COVID-19 between the UDCA group and the non-UDCA group. We found that only patients transplanted between 3 and 6 months ago demonstrated a higher risk of SARS-CoV-2 infection compared to those who received allo-HSCT within 3 months (Odds Ratio [OR]: 3.241, 95% Confidence Interval [CI]: 1.287-8.814, P = 0.016). But other clinical factors, such as administration of UDCA, showed no difference. Notably, only age ≥38 years old remained as an independent risk factor for a severe clinical course of SARS-CoV-2 infection (OR: 3.664, 95% CI: 1.129-13.007, P = 0.035). Conclusion: The effectiveness of UDCA in protecting newly allo-HSCT recipients against SARS-CoV-2 infection remains unconfirmed. Presently, the most effective strategy appears to be minimizing exposure to SARS-CoV-2. Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT04645199, identifier NCT04645199.