Allogeneic hematopoietic stem cell transplantation (HSCT), the most widely used potentially curable cellular immunotherapeutic approach in the treatment of hematological malignancies, is limited by life-threatening complications: graft versus host disease (GVHD) and infections especially viral infections refractory to antiviral drugs. Adoptive transfer of virus-specific T cells is becoming an alternative treatment for infections following HSCT. We report here the results of a phase I/II multicenter study which includes a series of adenovirus-specific T cell (ADV-VST) infusion either from the HSCT donor or from a third party haploidentical donor for patients transplanted with umbilical cord blood (UCB). Fourteen patients were eligible and 11 patients received infusions of ADV-VST generated by interferon (IFN)-γ-based immunomagnetic isolation from a leukapheresis from their original donor (42.9%) or a third party haploidentical donor (57.1%). One patient resolved ADV infection before infusion, and ADV-VST could not reach release or infusion criteria for two patients. Two patients received cellular immunotherapy alone without antiviral drugs as a pre-emptive treatment. One patient with adenovirus infection and ten with adenovirus disease were infused with ADV-VST (mean 5.83 ± 8.23 × 103 CD3+IFN-γ+ cells/kg) up to 9 months after transplantation. The 11 patients showed in vivo expansion of specific T cells up to 60 days post-infusion, associated with adenovirus load clearance in ten of the patients (91%). Neither de novo GVHD nor side effects were observed during the first month post-infusion, but GVHD reactivations occurred in three patients, irrespective of the type of leukapheresis donor. For two of these patients, GVHD reactivation was controlled by immunosuppressive treatment. Four patients died during follow-up, one due to refractory ADV disease. Adoptive transfer of rapidly isolated ADV-VST is an effective therapeutic option for achieving in vivo expansion of specific T cells and clearance of viral load, even as a pre-emptive treatment. Our study highlights that third party haploidentical donors are of great interest for ADV-VST generation in the context of UCB transplantation. (N° Clinical trial.gov: NCT02851576, retrospectively registered).

Background: Hematological medicine is a practical discipline that is difficult to study. Problem-based learning (PBL) is an innovative student-centered teaching method wherein students define their own learning objectives from clinically based problems. Considering that WeChat is the most popular communication app in China, we selected it as a new platform for online PBL to reduce the limitations of traditional PBL in hematology teaching. Objective: This study aims to explore a new pedagogical method called WeChat-PBL, which is based on real micro clinical cases for postgraduates majoring in hematology and to demonstrate its feasibility and acceptability. Methods: A total of 48 hematological postgraduates and 7 tutors participated in this study. We divided the participants into 7 groups where students can learn theoretical knowledge. After each course, the members of each group were required to complete in-class quizzes. Moreover, the students and tutors were required to fill out periodic (after each class) and overall (after each semester) evaluations. Results: A total of 8 micro clinical cases were presented in WeChat-PBL. The average quiz score for acute myelogenous leukemia, chronic myeloid leukemia, multiple myeloma, acute promyelocytic leukemia, and lymphoma were 89.0%, 86.0%, 83.4%, 88.8%, and 77.5%, respectively. Periodic evaluations showed that both students and tutors were satisfied with the process of WeChat-PBL. The overall evaluation results showed that WeChat-PBL was able to positively impact the learning experiences of hematological postgraduates. Conclusions: Our results indicate the feasibility and acceptability of the WeChat-PBL teaching method for postgraduates majoring in hematology.

A pandemic designated as Coronavirus Disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading worldwide. Up to date, there is no efficient biomarker for the timely prediction of the disease progression in patients. To analyze the inflammatory profiles of COVID-19 patients and demonstrate their implications for the illness progression of COVID-19. Retrospective analysis of 3,265 confirmed COVID-19 cases hospitalized between 10 January 2020, and 26 March 2020 in three medical centers in Wuhan, China. Patients were diagnosed as COVID-19 and hospitalized in Leishenshan Hospital, Zhongnan Hospital of Wuhan University and The Seventh Hospital of Wuhan, China. Univariable and multivariable logistic regression models were used to determine the possible risk factors for disease progression. Moreover, cutoff values, the sensitivity and specificity of inflammatory parameters for disease progression were determined by MedCalc Version 19.2.0. Age (95%CI, 1.017 to 1.048; P < 0.001), serum amyloid A protein (SAA) (95%CI, 1.216 to 1.396; P < 0.001) and erythrocyte sedimentation rate (ESR) (95%CI, 1.006 to 1.045; P < 0.001) were likely the risk factors for the disease progression. The Area under the curve (AUC) of SAA for the progression of COVID-19 was 0.923, with the best predictive cutoff value of SAA of 12.4 mg/L, with a sensitivity of 83.9% and a specificity of 97.67%. SAA-containing parameters are novel promising ones for predicting disease progression in COVID-19.

Classical BCR-ABL-negative myeloproliferative neoplasms are a heterogeneous group of hematologic malignancies, including essential thrombocythemia, polycythemia vera, and primary myelofibrosis. Monocytes, immune cells derived from hematopoietic stem cells, exhibit significant heterogeneity and contribute to immune regulation through cytokine secretion and differentiation into dendritic cells and macrophages. Aberrant monocytes are associated with the prognosis of MPNs, particularly PMF. Furthermore, these altered monocytes play a critical role in the pathogenesis and progression of MPNs. This review aims to explore the heterogeneity of different monocyte subsets during homeostasis and focuses on the potential mechanisms by which monocytes contribute to the development and progression of MPNs.

Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) are chronic hematological malignancies characterized by driver and nondriver mutations, leading to a deregulated immune system with aberrant cytokines and immune cells. Understanding the gene mutation landscape and immune state at various disease stages is crucial for guiding treatment decisions. While advanced techniques like single-cell RNA sequencing and mass cytometry provide valuable insights, their high costs and complexity limit clinical application. In contrast, bulk RNA sequencing (RNA-Seq) offers a cost-effective complementary approach for evaluating genetic mutations and immune profiles. Peripheral blood and bone marrow samples from treatment-naïve patients diagnosed with polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) were analyzed using RNA sequencing. Additionally, data from the microarray datasets [GSE26049, GSE2191] were included in this study. Bioinformatics methods were employed to interpret gene mutations and immune landscapes in MPN patients. Our findings demonstrate the potential value of RNA-Seq in identifying gene mutations and characterizing the immune profile, including immune cell infiltration, cytokine profiles, and distinct immune-related pathways involved in the development of MPN. Bulk RNA-Seq is a feasible tool for routine clinical practice, providing comprehensive insights into the immune and genetic landscape of MPNs. This approach could enhance personalized treatment strategies and improve prognostic accuracy, ultimately contributing to better management of MPN patients.