The consensus in 2018 from The Chinese Society of Haematology (CSH) on the monitoring, treatment, and prevention of leukaemia relapse after allogeneic haematopoietic stem cell transplantation (HSCT) facilitated the standardization of clinical practices in China and progressive integration with the world. To integrate recent developments and further improve the consensus, a panel of experts from the CSH recently updated the following consensus: (1) integrate risk-adapted, measurable residual disease (MRD)-guided strategy on modified donor lymphocyte infusion (DLI) and interferon-α into total therapy, which was pioneered and refined by Chinese researchers; (2) provide additional evidence of the superiority of haploidentical HSCT (the dominant donor source in China) to matched HSCT for high-risk populations, especially for pre-HSCT MRD-positive patients; (3) support the rapid progress of techniques for MRD detection, such as next-generation sequencing (NGS) and leukaemia stem cell-based MRD detection; and (4) address the role of new targeted options in transplant settings. In conclusion, the establishment of a "total therapy" strategy represents a great step forward. We hope that the consensus updated by Chinese scholars will include the latest cutting-edge developments and inspire progress in post-HSCT relapse management.

Chimeric Antigen Receptor T (CAR-T) cell therapy has significantly advanced in treating B-cell acute lymphoblastic leukemia (B-ALL) and has shown efficacy in managing relapsed B-ALL after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Donor-derived CAR-T cell offer both high efficacy and rapid response. Although promising results exist, current research lacks definitive evidence of long-term survival benefits for patients treated with donor-derived CAR-T therapy. We report the long-term survival of 32 patients with post-transplant relapsed B-ALL treated with donor-derived CD19 CAR-T cell, achieving either complete Remission (CR) or CR with incomplete peripheral blood recovery (CRi). The median follow-up was 42 months, with 2-year overall survival (OS) and event-free survival (EFS) rates of 56.25% and 50.0%, respectively. The 5-year OS and EFS rates were 53.13% and 46.88%, with no new long-term adverse events observed. These findings demonstrate good long-term safety, supporting donor-derived CAR-T cell as a recommended treatment option for relapsed B-ALL patients post-transplantation. Trial registration: https://www.chictr.org.cn/showproj.html?proj=14315 . Registration number: ChiCTR-OOC-16008447.

In this editorial, we offer our perspective on the groundbreaking study entitled "Hypoxia and inflammatory factor preconditioning enhances the immunosuppressive properties of human umbilical cord mesenchymal stem cells", recently published in World Journal of Stem Cells. Despite over three decades of research on the clinical application of mesenchymal stem cells (MSCs), only a few therapeutic products have made it to clinical use, due to multiple preclinical and clinical challenges yet to be addressed. The study proved the hypoxia and inflammatory factor preconditioning led to higher immunosuppressive effects of MSCs without damaging their biological characteristics, which revealed the combination of inflammatory factors and hypoxic preconditioning offers a promising approach to enhance the function of MSCs. As we delve deeper into the intricacies of pretreatment methodologies, we anticipate a transformative shift in the landscape of MSC-based therapies, ultimately contributing to improved patient outcomes and advancing the field as a whole.

YAP1 plays a dual role as an oncogene and tumor suppressor gene in several tumors; differentiating between these roles may depend on the YAP1 phosphorylation pattern. The specific function of YAP1 in B cell acute lymphoblastic leukemia (B-ALL), however, is currently unclear. Thus, in the present study, the role of YAP1 in B-ALL was investigated using relevant cell lines and patient datasets.

The effects of shRNA-mediated knockdown on YAP1 and LATS1 levels in the NALM6 and MOLT-4 cell lines were examined using Western blotting, quantitative real-time polymerase chain reaction, flow cytometry, immunostaining, and nude mouse subcutaneous tumorigenesis experiments. Gene expression levels of Hippo pathway-related molecules before and after verteporfin (VP) treatment were compared using RNA-Seq to identify significant Hippo pathway-related genes in NALM6 cells.

Patients with ALL showing high YAP1 expression and low YAP1-Ser127 phosphorylation levels had worse prognoses than those with low YAP1 protein expression and high YAP1-Ser127 phosphorylation levels. YAP1-Ser127 phosphorylation levels were lower in NALM6 cells than in MOLT-4 and control cells; YAP1 was distributed in the nuclei in NALM6 cells. Knockdown of YAP1 inhibited MOLT-4 and NALM6 cell proliferation and arrested the NALM6 cell cycle in the G0/G1 phase. Before and after VP treatment, the expression of the upstream gene LATS1 was upregulated; its overexpression promoted YAP1-Ser127 phosphorylation. Further, YAP1 was distributed in the plasma.

LATS1 may downregulate YAP1-Ser127 phosphorylation and maintain B-ALL cell function; thus, VP, which targets this axis, may serve as a new therapeutic method for improving the outcomes for B-ALL patients.

Objective: To investigated the safety and efficacy of donor-derived CD19+ or sequential CD19+ CD22+ chimeric antigen receptor T-cell (CAR-T) therapy in patients with B-cell acute lymphoblastic leukemia (B-ALL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: The data of 22 patients with B-ALL who relapsed after allo-HSCT and who underwent donor-derived CAR-T therapy at the Zhujiang Hospital of Southern Medical University and the 920th Hospital of Joint Logistics Support Force of the People's Liberation Army of China from September 2015 to December 2022 were retrospectively analyzed. The primary endpoint was overall survival (OS), and the secondary endpoints were event-free survival (EFS), complete remission (CR) rate, and Grade 3-4 adverse events. Results: A total of 81.82% (n=18) of the 22 patients achieved minimal residual disease-negative CR after CAR-T infusion. The median follow-up time was 1037 (95% CI 546-1509) days, and the median OS and EFS were 287 (95% CI 132-441) days and 212 (95% CI 120-303) days, respectively. The 6-month OS and EFS rates were 67.90% (95% CI 48.30%-84.50%) and 58.70% (95% CI 37.92%-79.48%), respectively, and the 1-year OS and EFS rates were 41.10% (95% CI 19.15%-63.05%) and 34.30% (95% CI 13.92%-54.68%), respectively. Grade 1-2 cytokine release syndrome occurred in 36.36% (n=8) of the patients, and grade 3-4 occurred in 13.64% of the patients (n=3). Grade 2 and 4 graft-versus-host disease occurred in two patients. Conclusion: Donor-derived CAR-T therapy is safe and effective in patients with relapsed B-ALL after allo-HSCT.