Severe aplastic anemia patients with infection who received an allogeneic hematopoietic stem cell transplantation had a better chance: Long-term outcomes of a multicenter study.

Background and aims: How to select the treatment is a challenge for the management of acquired patients with infections. This study aimed at comparing the outcomes of SAA with infections who had an allogeneic hematopoietic stem cell transplantation (allo-HSCT)with that of patients who had an infection and received non-HSCT therapy. Methods: We retrospectively compared the outcomes of patients with acquired SAA and infections who had an allo-HSCT (n = 141) with that of patients who had an infection and received non-HSCT therapy (n = 186) between July 2004 and January 2020. Results: The treatment-related mortality (TRM) of grade 1-2 infections in the HSCT and non-HSCT groups was 24.99% and 13.68%, respectively (P = 0.206), while the TRM of grade 3-4 infections was lower in the HSCT group than that observed in the non-HSCT group (18.54% vs. 33.33%, P = 0.036). At 6 months post-treatment, 91.30% patients in the HSCT group and 8.78% patients in the non-HSCT group had achieved a normal blood profile (P < 0.0001). The time required to discontinue transfusions of red blood cells and platelets in the non-HSCT group was longer than in the HSCT group (P < 0.0001). Estimated overall survival (OS) at 6 years was similar in the two groups (75.5% ± 3.9% vs. 76.3% ± 3.1%, P = 0.996), while the estimated failure-free survival (FFS) at 6 years was 75.2% ± 3.8% in the HSCT group and 48.9% ± 3.7% in the non-HSCT group (P < 0.0001). Multivariate analysis showed that younger age, lower grade of infection (grade 1-2), and SAA (vs. very SAA) were favorable factors for OS (P < 0.05), and that the choice of HSCT and younger age were favorable factors for FFS (P < 0.0001). Conclusion: These results suggest that allo-HSCT has a better chance of a successful outcome than non-HSCT in SAA patients with an infection.

Inefficacy of Immunosuppressive Therapy for Severe Aplastic Anemia Progressing From Non-SAA: Improved Outcome After Allogeneic Hematopoietic Stem Cell Transplantation.

BACKGROUND AND AIMS: This study aimed at comparing the efficacy and safety of severe aplastic anemia (SAA) cases that had met the criteria for SAA at the time of diagnosis (group A) with SAA that had progressed from non-SAA (NSAA) (group B), both undergoing first-line immunosuppressive therapy (IST). Additionally, group B was compared with SAA that had progressed from NSAA and who had been treated by allogeneic hematopoietic stem cell transplantation (allo-HSCT) (group C). METHODS: We retrospectively compared 608 consecutive patients in group A (n = 232), group B (n = 229) and group C (n = 147) between June 2002 and December 2019. Six months after treatment, the rate of overall response and the fraction of patients who had achieved normal blood values, treatment-related mortality (TRM), secondary clonal disease, 5-year overall survival (OS) and failure-free survival (FFS) were indirectly compared between group A and group B, group B and group C. RESULTS: Six months after treatment, the rate of overall response and the fraction of patients who had achieved normal blood values in group A was higher than in group B (65.24% vs. 40.54%, P < 0.0001; 23.33% vs. 2.25%, P < 0.0001); the same was true for group C (92.50% vs. 2.25%, P < 0.0001). The rate of relapse in group B was higher than in group C (P < 0.0001), but there were no differences in TRM and secondary clonal disease (P > 0.05). There were no differences in estimated 5-year OS between groups A and B (83.8% ± 2.6% vs. 85.8% ± 2.6%, P = 0.837), or between B and C (85.8% ± 2.6% vs. 77.9% ± 3.4%, P = 0.051). The estimated 5-year FFS in groups A and C was higher than for group B (57.1% ± 3.3% vs. 39.7% ± 3.4%, P < 0.001; 76.7% ± 3.5% vs. 39.7% ± 3.4%, P < 0.0001). CONCLUSION: These results indicate that IST is less effective in SAA progressing from non-SAA but allo-HSCT can improve outcomes.

Comparison of efficacy and health-related quality of life of first-line haploidentical hematopoietic stem cell transplantation with unrelated cord blood infusion and first-line immunosuppressive therapy for acquired severe aplastic anemia.

We retrospectively compared the efficacy and health-related quality of life (HRQoL) of (1) first-line haploidentical hematopoietic stem cell transplantation (haplo-HSCT, n = 146) combined with unrelated cord blood (UCB) infusion and (2) first-line immunosuppressive therapy (IST, n = 219) in acquired severe aplastic anemia (SAA) patients. At 6 months post treatment, 90.30% patients in the haplo-HSCT group and 18.78% patients in the IST group achieved normal blood routine (P < 0.0001). The time required to discontinue red blood cells and platelets transfusion in the IST group were longer than in the haplo-HSCT group (P < 0.0001). The estimated overall survival at 4 years was similar (80.1 ± 3.5% vs. 80.1 ± 3.0%, P = 0.726); the estimated failure-free survival (FFS) at 4 years was 77.8 ± 3.7% in the haplo-HSCT group and 48.0 ± 3.6% in the IST group (P < 0.0001). Patients treated with haplo-HSCT scored significantly better in the HRQoL than treated with IST (P < 0.0001). In the multivariate analysis, first-line haplo-HSCT was the favorable factor for FFS and HRQoL (P < 0.0001). These results suggest that first-line haplo-HSCT combined with UCB infusion might provide a better chance of success and HRQoL than first-line IST for SAA patients.

Successful treatment of acute B lymphoblastic leukemia relapse in the skin and testicle by anti-CD19 CAR-T with IL-6 knocking down: a case report.

BACKGROUND: Extramedullary relapse is an important cause of treatment failure among patients with acute lymphoblastic leukemia (ALL). This type of relapse is commonly observed in the central nervous system, while it is rare in the testicles and skin. Chimeric antigen receptor-modified T cell (CAR-T) therapy targeting CD19 has shown to be a beneficial treatment approach for relapsed/refractory B cell acute lymphoblasticleukemia (r/r B-ALL). Yet, few studies have reported data regarding the treatment of extramedullary B-ALL relapse, especially both in skin and testicle, with CAR-T therapy. CASE PRESENTATION: Here we reported a single case of a patient with relapsed B-ALL in skin and testicle who was successfully treated by the shRNA-IL6-modified anti-CD19 CAR-T(ssCAR-T-19) therapy. A 29-year-old man with relapsed B-ALL in skin and testicle was enrolled in clinal trial involving the shRNA-IL6-modified anti-CD19 CAR-T(ssCAR-T-19) therapy (ClinicalTrials.gov number, NCT03919240). The patient had toxicity consistent with the grade 1 cytokine release syndrome. CONCLUSIONS: ssCART-19 therapy may be used to effectively eliminate infiltrating leukemia cells in the skin and testicle with mild toxicity, which could be a much safer approach to bridge allo-HSCT, thus further improving the patient's outcome. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT03919240, Registered 18 April 2019, retrospectively registered.

Application of alkaloids in reversing multidrug resistance in human cancers.

Multidrug resistance (MDR) in human cancer is one of greatest challenges in cancer therapy. Natural products, especially the alkaloids, exert reversed effects on MDR with low toxicity, by interacting with various targets. In this review article, we summarize the recent progress made in the research of the main alkaloids, including classification, function, mechanism, research status, and application in reversing MDR.

Serum C1q/TNF-related protein 9 is not related to nonalcoholic fatty liver disease.

AIMS: C1q/TNF-related protein 9 (CTRP9) is an adipokine mainly secreted by white adipose tissue and plays protective roles in energy metabolism. However, information regarding the role of CTRP9 in nonalcoholic fatty liver disease (NAFLD) is scarce. Here we aimed to ascertain the clinical relevance between circulating CTRP9 levels and NAFLD through a cross-sectional study. METHODS: The study enrolled 82 NAFLD adults and 79 sex- and age-matched non-NAFLD controls. Serum CTRP9 was measured via ELISA method. Metabolic parameters were also determined. RESULTS: Although serum CTRP9 level seems to be higher in NAFLD adults, there was no significant difference among the ultrasonographic degrees of NAFLD (P = 0.275). Further, after adjustment for BMI in the multinomial logistic regression model, no significant odds ratio difference was observed for NAFLD among the CTRP9 tertiles. Moreover, binary logistic regression models demonstrated that, body mass index (BMI) and alanine aminotransferase (ALT) but not CTRP9 were independent factors related to NAFLD. Besides, serum CTRP9 was positively correlated with BMI, waist circumference, Fasting insulin, HbA1c, and HOMA-IR in all subjects. BMI was the independent factor associated with serum CTRP9. CONCLUSIONS: Serum CTRP9 is not independently related to NAFLD. The association between serum CTRP9 and NAFLD might be due to the influence of obesity.

Effects of major parameters of nanoparticles on their physical and chemical properties and recent application of nanodrug delivery system in targeted chemotherapy.

Chemotherapy is still one of the main cancer therapy treatments, but the curative effect of chemotherapy is relatively low, as such the development of a new cancer treatment is highly desirable. The gradual maturation of nanotechnology provides an innovative perspective not only for cancer therapy but also for many other applications. There are a diverse variety of nanoparticles available, and choosing the appropriate carriers according to the demand is the key issue. The performance of nanoparticles is affected by many parameters, mainly size, shape, surface charge, and toxicity. Using nanoparticles as the carriers to realize passive targeting and active targeting can improve the efficacy of chemotherapy drugs significantly, reduce the mortality rate of cancer patients, and improve the quality of life of patients. In recent years, there has been extensive research on nanocarriers. In this review, the effects of several major parameters of nanoparticles on their physical and chemical properties are reviewed, and then the recent progress in the application of several commonly used nanoparticles is presented.

[Anti-tumor immune response of dendritic cells derived from lymphoma cells transduced with recombinant adenovirus encoding human P53].

This study was aimed to investigate the immunological effect of modified dendritic cells (DC) which inducing cytotoxic T cells (CTL) against lymphoma cells. The DC were isolated from the lymph node and peripheral blood of patients with diffuse large B cell lymphoma (DLBCL). DC were transfected with recombinant adenovirus vector carrying human p53 gene (rAd-p53-DC). The expression of p53 gene was detected by flow cytometry. Western-blot was used to detect the expression of P53. ELISA was used to detect IL-12 level in supernatant. The mixed lymphocyte reaction (MLR) was used to detect the proliferative ability of auto-lymphocyte stimulated by DC. The lactate dehydrogenase (LDH) release test was used to determine the cytotoxicity of CTL. The results indicates that the expressions of DC surface molecule (except for CD1a) such as CD83, CD80, CD86 and HLA-DR were significantly higher in experiment group than that in control group and blank control group. The secretion of IL-12 in supernatant was higher in experiment group than that in control group. The autologous T lymphocyte proliferation and cytotoxic activity against the same kind of DLBL-cells increased in experiment group as compared with control group and blank control group (P < 0.05). The ability to stimulate T lymphocyte proliferation increased with the rising of the ratio of DC and T lymphocyte. However, there was statistically significant difference between rAd-p53-DC derived from Lymph node and peripheral blood (P < 0.05). It is concluded that rAd-p53-transfected DC can induce CTL response in vitro against lymphoma cells.