Chimeric antigen receptors T (CAR-T) cell therapy of cancer is a rapidly evolving field. It has been shown to be remarkably effective in cases of hematological malignancies, and its approval by the FDA has significantly increased the enthusiasm for wide clinical usage and development of novel CAR-T therapies. However, it has also challenged physicians and investigators to recognize and deal with treatment-associated toxicities. A total of 2592 patients were included from 84 eligible studies that were systematically searched and reviewed from the databases of PubMed, de, the American Society of Hematology and the Cochrane Library. The meta-analysis and subgroup analysis by a Bayesian logistic regression model were used to evaluate the incidences of therapy-related toxicities such as cytokine release syndrome (CRS) and neurological symptoms (NS), and the differences between different targets and cancer types were analyzed. The pooled all-grade CRS rate and grade ≥ 3 CRS rate was 77% and 29%, respectively, with a significantly higher incidence in the hematologic malignancies (all-grade: 81%; grade ≥ 3: 29%) than in solid tumors (all-grade: 37%; grade ≥ 3: 19%). The pooled estimate NS rate from the individual studies were 40% for all-grade and 28% for grade ≥ 3. It was also higher in the hematologic subgroup than in the solid tumors group. The subgroup analysis by cancer type showed that higher incidences of grade ≥ 3 CRS were observed in anti-CD19 CAR-T therapy for ALL and NHL, anti-BCMA CAR-T for MM, and anti-CEA CAR-T for solid tumors, which were between 24–36%, while higher incidences of grade ≥ 3 NS were mainly observed in CD19-ALL/NHL (23–37%) and BCMA-MM (12%). Importantly, subgroup analysis on anti-CD19 CAR-T studies showed that young patients (vs. adult patients), allologous T cell origin (vs. autologous origin), gamma retrovirus vector, and higher doses of CAR-T cells were associated with high-grade CRS. On the other hand, the patients with NHL (vs ALL), administered with higher dose of CAR-T, and adult patients (vs. young patients) had an increased incidence of grade ≥ 3 NS events. This study offers a comprehensive summary of treatment-related toxicity and will guide future clinical trials and therapeutic designs investigating CAR T cell therapy.

• Focuses on the PI3K/AKT axis– its core link to cancer metabolic reprogramming (especially the Warburg Effect) and interaction with key glucose metabolic enzymes (HK, LDHA, etc.), as well as their impacts. • 2. Introduces the non-canonical/moonlighting functions of these glucose metabolic enzymes. • 3. Provides theoretical basis and potential targets for tumor metabolism research and targeted therapy, along with current research challenges and future directions.

The first-line therapy for primary immune thrombocytopenia (ITP) is steroids, but about one-third of patients do not respond to steroids. Recent studies have shown megakaryocyte (MK) growth and development abnormalities and poorly compensated thrombopoiesis. Here, we attempted to determine the impact of MK morphological classification on steroid response. We enrolled 170 adult patients with primary ITP and divided them into steroid-sensitive ITP (109/170) and non-steroid-sensitive ITP (61/170) groups. In the univariate logistic model, female, reduced thrombocytogenic MK count (TMC), increased granular MK count to total MK count ratio (GMC/TM ratio), and elevated naked nucleus MK count to TM count ratio were significantly associated with steroid-sensitive ITP. In the multivariate logistic model, sex, reduced TMC, and increased GMC/TM ratio were independent predictors of steroid-sensitive ITP diagnosis. Based on the regression parameters, we established a predictive index with weighted risk score of 1 assigned each to sex, TMC, and GMC/TM ratio. A predictive index ≥2 points had the best area under the curve value (0.63) with 47.7% sensitivity and 78.7% specificity for predicting steroid sensitivity. These findings may help guide early treatment strategies in ITP.

OBJECTIVE: The occurrence of cryptic Philadelphia (Ph) chromosome translocation is rare in BCR-ABL1-positive acute lymphoblastic leukemia (BCR-ABL1+ ALL) and is of unknown significance in the tyrosine kinase inhibitor (TKI) era. METHODS: We retrospectively studied a series of adult patients receiving TKI-based therapy to evaluate the prognostic impact of the normal karyotype (NK) (n=22) in BCR-ABL1+ ALL by comparison with the isolated Ph+ karyotype (n=54). RESULTS: There were no statistically significant differences in clinical characteristics and complete remission rate between the [...] OBJECTIVE: The occurrence of cryptic Philadelphia (Ph) chromosome translocation is rare in BCR-ABL1-positive acute lymphoblastic leukemia (BCR-ABL1+ ALL) and is of unknown significance in the tyrosine kinase inhibitor (TKI) era. METHODS: We retrospectively studied a series of adult patients receiving TKI-based therapy to evaluate the prognostic impact of the normal karyotype (NK) (n=22) in BCR-ABL1+ ALL by comparison with the isolated Ph+ karyotype (n=54). RESULTS: There were no statistically significant differences in clinical characteristics and complete remission rate between the

Pure erythroid leukemia (PEL) is an extremely rare subtype of acute myeloid leukemia (AML), accounting for only 1% of cases, marked by complex karyotypes, dismal prognosis, and lack of standardized treatment. This study reports four cases of PEL with rapidly progressive clinical manifestations, including fever, marked conjugated hyperbilirubinemia, extreme elevations of lactate dehydrogenase (LDH) and ferritin, splenomegaly, ascites, and hepatic failure. Malignant erythroid infiltration of the hepatic sinusoids may be a pathological mechanism responsible for acute liver failure in PEL. Among the four patients, three died of liver failure, while one achieved sustained remission after early diagnosis and intensive multi-agent chemotherapy. Overall, this study highlights the urgency of early identification of this fatal PEL subtype, clarifies the mechanisms underlying its jaundice and hepatic failure, and emphasizes timely intervention to improve patient outcomes.