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Introduction: Numerous AI‐based systems are being developed to evaluate peripheral blood (PB) smears, but the feasibility of these systems on different smear preparation methods has not been fully understood. In this study, we assessed the impact of different smear preparation methods on the robustness of the deep learning system (DLS). Methods: We collected 193 PB samples from patients, preparing a pair of smears for each sample using two systems: (1) SP50 smears, prepared by the DLS recommended fully automated slide preparation with double fan drying and staining (May–Grunwald Giemsa, M–G) system using SP50 (Sysmex) and (2) SP1000i smears, prepared by automated smear preparation with single fan drying by SP1000i (Sysmex) and manually stained with M–G. Digital images of PB cells were captured using DI‐60 (Sysmex), and the DLS performed cell classification. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were used to evaluate the performance of the DLS. Results: The specificity and NPV for all cell types were 97.4%–100% in both smear sets. The average sensitivity and PPV were 88.9% and 90.1% on SP50 smears, and 87.0% and 83.2% on SP1000i smears, respectively. The lower performance on SP1000i smears was attributed to the intra‐lineage misclassification of neutrophil precursors and inter‐lineage misclassification of lymphocytes. Conclusion: The DLS demonstrated consistent performance in specificity and NPV for smears prepared by a system different from the recommended method. Our results suggest that applying an automated smear preparation system optimized for the DLS system may be important. [ABSTRACT FROM AUTHOR]

Objectives: Hemorrhagic events are a rare but potentially fatal complication in patients with polycythemia vera (PV). Methods: We analyzed the characteristics of hemorrhagic events in 267 patients with PV. Results: A median follow-up of 4.8 years revealed that 23 (8.6%) hemorrhagic events occurred. Significantly more hemorrhagic events occurred in younger patients aged below 60 years (n = 72) than in older patients aged 60 years or above (n = 191) (n = 12 [16.7%] vs. n = 11 [5.8%], respectively, P = 0.012). In univariate analysis among the younger patients, white blood cell (WBC) count ≥ 15 × 109/L (hazard ratio [HR] = 7.746, 95% confidence interval [CI] 2.082-28.830, P = 0.002), palpable splenomegaly (HR = 5.629, 95% CI 1.193–26.550, P = 0.029), and JAK2V617F allele burden ≥ 80% (HR = 22.850, 95% CI 2.885–181.00, P = 0.003) were associated with an increased risk of hemorrhagic events. In multivariate analysis, JAK2V617F allele burden ≥ 80% (HR = 9.394, 95% CI 1.046–84.380, P = 0.046) was a significant risk factor. Conclusions: There is an increased risk of hemorrhagic events after diagnosis in younger PV patients with a high JAK2V617F allele burden, high WBC count or palpable splenomegaly. It is important to consider treatment options that aim to avoid hemorrhagic events by reducing the JAK2V617F allele burden in younger PV patients. Plain language summary: Polycythemia vera (PV) is a subtype of Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) that results in the overproduction of red blood cells (RBCs) due to persistent activation of the JAK2-STAT5 pathway caused by mutations in the Janus kinase 2 (JAK2) gene. Complications associated with elevated RBC counts include thrombosis, hemorrhage, and microvascular symptoms (such as headache and erythromelalgia) due to microcirculatory insufficiency, resulting in reduced quality of life. Hemorrhagic events are a rare but potentially fatal complication in patients with PV. However, specific risk factors for hemorrhagic events in PV remain to be elucidated. In this study, we sought to analyze the association between clinical characteristics and hemorrhagic events in 267 patients with PV in order to clarify the characteristics of these events. We found that patients with PV younger than 60 years, those with a high JAK2V617F allele burden (≥ 80%) (hazard ratio [HR] = 22.850, 95% confidence interval [CI] 2.885–181.000, P = 0.003), a higher white blood cell (WBC) count (WBC ≥ 15 × 109/L) (HR = 7.746, 95% CI 2.082–28.830, P = 0.002)or palpable splenomegaly (HR = 5.629, 95% CI 1.193–26.550, P = 0.029) at diagnosis may be at an increased risk of hemorrhagic events after diagnosis. Based on these observations, it would be important to consider the potential benefits of drug therapies aimed at reducing the JAK2V617F allele burden in younger patients with PV. Here, we suggest that these therapies may help to reduce the incidence of hemorrhagic events. [ABSTRACT FROM AUTHOR]

The article discusses the use of l‐asparaginase (l‐Asp) monotherapy in treating acute fulminant chronic active Epstein–Barr virus infection, a life-threatening condition. Two rare cases of patients with high EBV-DNA levels and organ dysfunction were successfully treated with l‐Asp, leading to the initiation of hematopoietic stem cell transplantation (HSCT). The study found that l‐Asp may be an effective bridging therapy to reduce tumor burden before HSCT in such cases, as CAEBV tumor cells have low levels of asparagine synthetase, potentially contributing to the drug's effectiveness. [Extracted from the article]

The discovery of induced pluripotent stem cells (iPSCs) has created promising new avenues for therapies in regenerative medicine. However, the tumorigenic potential of undifferentiated iPSCs is a major safety concern for clinical translation. To address this issue, we demonstrated the efficacy of suicide gene therapy by introducing inducible caspase-9 (iC9) into iPSCs. Activation of iC9 with a specific chemical inducer of dimerization (CID) initiates a caspase cascade that eliminates iPSCs and tumors originated from iPSCs. We introduced this iC9/CID safeguard system into a previously reported iPSC-derived, rejuvenated cytotoxic T lymphocyte (rejCTL) therapy model and confirmed that we can generate rejCTLs from iPSCs expressing high levels of iC9 without disturbing antigen-specific killing activity. iC9-expressing rejCTLs exert antitumor effects in vivo. The system efficiently and safely induces apoptosis in these rejCTLs. These results unite to suggest that the iC9/CID safeguard system is a promising tool for future iPSC-mediated approaches to clinical therapy.

Summary: Risk‐adapted therapy is recommended to prevent major clinical complications, such as thrombo‐haemorrhagic events, in patients with essential thrombocythaemia (ET). In this study, we analysed the association between non‐driver gene mutations and thrombo‐haemorrhagic events in 579 patients with ET. ASXL1 and TP53 mutations were frequently identified in patients with ET complicated by thrombosis (22.7% and 23.1%, respectively), and the DNMT3A mutation was frequently identified in patients who experienced haemorrhage (15.2%). Multivariate analyses of thrombosis‐free survival (TFS) revealed that ASXL1 and TP53 mutations are associated with thrombosis (hazard ratio [HR] = 3.140 and 3.752 respectively). Patients harbouring the ASXL1 or TP53 mutation had significantly worse TFS rates than those without mutation (p = 0.002 and p < 0.001 respectively). Furthermore, JAK2V617F‐mutated patients with accompanying ASXL1 mutations showed significantly shorter TFS compared with those without ASXL1 mutations (p = 0.003). Multivariate analyses of haemorrhage‐free survival (HFS) revealed that the DNMT3A mutation (HR = 2.784) is associated with haemorrhage. DNMT3A‐mutated patients showed significantly shorter HFS than those without the mutation (p = 0.026). Non‐driver gene mutations should be considered in treatment strategies and may provide important information for personalised treatment approaches. [ABSTRACT FROM AUTHOR]

Since MPL mutation is a rare driver gene mutation found in a small number of essential thrombocythemia (ET) patients, the clinical characteristics of patients with MPL mutations and their association with thrombotic events have not yet been elucidated in Japan. We enrolled 579 Japanese ET patients based on the diagnostic criteria of the WHO classification 2017 and compared clinical characteristics of MPL-mutated patients (n = 22; 3.8%) to JAK2V617F-mutated (n = 299; 51.6%), CALR-mutated (n = 144; 24.9%), and triple-negative (TN) (n = 114; 19.7%) patients. Thrombosis during follow up was observed in 4 out of 22 (18.2%) in the MPL-mutated group, which was the highest among all driver gene mutation groups (JAK2V617F-mutated, 8.7%; CALR-mutated, 3.5%; TN,1.8%). The MPL- and JAK2V617F-mutated groups had worse thrombosis-free survival (TFS) than the CALR-mutated (p = 0.043) and TN groups (p = 0.006). Univariable analysis revealed that a history of thrombosis was a possible risk factor for thrombosis among MPL-mutated patients (hazard ratio: 9.572, p = 0.032). MPL-mutated ET patients should require more intensive management to prevent recurrence of thrombosis. [ABSTRACT FROM AUTHOR]