[Impact of SARS-CoV-2 infection on graft composition and early transplant outcomes following allogeneic hematopoietic stem cell transplantation].

Objective: To assess the feasibility of using donors with novel coronavirus disease 2019 (COVID-19) for allogeneic hematopoietic stem cell transplantation (allo-HSCT) when there are no other available donors and allo-HSCT cannot be delayed or discontinued. Methods: Seventy-one patients with malignant hematological diseases undergoing allo-HSCT between December 8, 2022, and January 10, 2023, were included. Of these, 16 received grafts from donors with mild COVID-19 (D-COVID(+) group) and 55 received grafts from donors without COVID-19 (D-COVID(-) group). The graft compositions were compared between the two groups. Engraftment, acute graft-versus-host disease (aGVHD), overall survival (OS), and relapse were also evaluated. Results: There were no serious side effects or adverse events in the D-COVID(+) group. The mononuclear cell dose and CD34(+) cell dose were comparable between the two groups, and no additional apheresis was required. There were no significant differences in the lymphocyte, monocyte, and T-cell subset doses between the two groups. The median natural killer cell dose in the D-COVID(+) group was significantly higher than that in the D-COVID(-) group (0.69×10(8)/kg vs. 0.53×10(8)/kg, P=0.031). The median follow-up time was 72 (33-104) days. All patients achieved primary engraftment. The 60-day platelet engraftment rates in the D-COVID(+) and D-COVID(-) groups were 100% and (96.4±0.2) %, respectively (P=0.568). There were no significant differences in neutrophil (P=0.309) and platelet (P=0.544) engraftment times. The cumulative incidence of grade 2-4 aGVHD was (37.5±1.6) % vs. (16.4±0.3) % (P=0.062), and of grade 3-4 aGVHD was 25.0% ±1.3% vs. 9.1% ±0.2% (P=0.095) in the D-COVID(+) and D-COVID(-) groups, respectively. The probabilities of 60-day OS were 100% and 98.1% ±1.8% (P=0.522) in the D-COVID(+) and D-COVID(-) groups, respectively. There was no relapse of primary disease during the study period. Conclusion: When allo-HSCT cannot be delayed or discontinued and no other donor is available, a donor with mild COVID-19 should be considered if tolerable. Larger sample sizes and longer follow-up periods are required to validate these results.

[Comparison of clinical features of hemorrhagic cystitis after haploidentical and matched sibling donor allogeneic hematopoietic stem cell transplantation].

Objective: To compare incidence and clinical features of hemorrhage cystitis (HC) after haploidentical donor (HID) allogeneic hematopoietic stem cell transplantation (HSCT) and matched sibling donor (MSD) HSCT. Methods: Medical records of 609 (including 406 HID-HSCT and 203 MSD-HSCT cases) hematologic malignancies patients treated with HSCT undergoing myeloablative conditioning regimen from January 2011 to December 2012 were analyzed retrospectively. Results: HC occurred 183 in HID and 17 ones in MSD respectively. The cumulative incidence of HC in HID group was higher than in MSD group[ (45.6±2.5) % vs (8.5±2.0) %, χ(2)=77.331, P<0.001], and the cumulative incidence of severe HC (grade 3-4) in HID cases was also higher than in MSD ones[ (11.2±1.9) % vs (2.1±1.1) %, χ(2)=12.883, P<0.001]. All HCs were occurred within 180 days in both groups. The median time to onset in two groups were 27 days after HSCT (range 0-177 days) and 29 days after HSCT (range 6-72 days) respectively (P=0.766) . The median duration of HC in two groups were 21 days (range 3-157 days) and 13 days (range 5-67 days) , respectively (P=0.182) . The total efficiency of treatment in two groups were 69.9% and 70.6% respectively (χ(2)=0.003, P=1.000) . Conclusion: The cumulative incidences of HC and severe HC were higher in HID cases than in MSD ones. The median time to onset and median duration of HC and therapeutic outcome between HID and MSD were comparable.

FOXM1 recruits nuclear Aurora kinase A to participate in a positive feedback loop essential for the self-renewal of breast cancer stem cells.

Substantial evidence suggests that breast cancer initiation, recurrence and drug resistance is supported by breast cancer stem cells (BCSCs). Recently, we reported a novel role of Aurora kinase A (AURKA) in BCSCs, as a transactivating co-factor in the induction of the c-Myc oncoprotein. However, the mode of action and transcriptional network of nuclear AURKA in BCSCs remain unknown. Here, we report that nuclear AURKA can be recruited by Forkhead box subclass M1 (FOXM1) as a co-factor to transactivate FOXM1 target genes in a kinase-independent manner. In addition, we show that AURKA and FOXM1 participate in a tightly coupled positive feedback loop to enhance BCSC phenotype. Indeed, kinase-dead AURKA can effectively transactivate the FOXM1 promoter through a Forkhead response element, whereas FOXM1 can activate AURKA expression at the transcriptional level in a similar manner. Consistently, breast cancer patient samples portrayed a strong and significant correlation between the expression levels of FOXM1 and AURKA. Moreover, both FOXM1 and AURKA were essential for maintaining the BCSC population. Finally, we demonstrated that the AURKA inhibitor AKI603 and FOXM1 inhibitor thiostrepton acted synergistically to inhibit cytoplasmic AURKA activity and disrupt the nuclear AURKA/FOXM1-positive feedback loop, respectively, resulting in a more effective inhibition of the tumorigenicity and self-renewal ability of BCSCs. Collectively, our study uncovers a previously unknown tightly coupled positive feedback signalling loop between AURKA and FOXM1, crucial for BCSC self-renewal. Remarkably, our data reveal a novel potential therapeutic strategy for targeting both the cytoplasmic and nuclear AURKA function to effectively eliminate BCSCs, so as to overcome both breast cancer and drug resistance.

[Study and application of dual interventional embolization in patients with acute gastroesophageal variceal bleeding].

From Nov. 1991 to Nov. 1992, twelve cases of acute massive gastro-esophageal variceal bleeding with liver function grading III had been treated with dual interventional embolization (DIE). Hemostasis were successful in all patients during the acute phase. Ten partial splenic embolization (PSE) cases with their hypersplenism cured or improved. The liver function in survived cases were improved with various degree after DIE. The mechanism of DIE in the treatment of acute gastro-esophageal variceal bleeding had been discussed and the alterations in portal pressure, the histopathology of the spleen, the peripheral hematologic changes as well as the complications after DIE were analysed and discussed. The authors claimed that DIE is an alternative method in treating the advanced cirrhosis complicating massive variceal bleeding.