Dasatinib, a second-generation tyrosine kinase inhibitor, has been reported to have immunomodulatory effects. Epstein-Barr virus (EBV)-associated lymphoproliferative disorders (EBV-LPD) occur in immunocompromised patients, such as those receiving methotrexate or other immunosuppressive drugs or after allogenic transplantation. EBV-LPD is also reported to be a rare side effect in patients receiving long-term dasatinib or imatinib. The present report describes a 60-year-old woman with Philadelphia chromosome-positive acute lymphoblastic leukemia who was treated with dasatinib and prednisolone for induction of remission. Fever, enlargement of the tonsils, multiple cervical lymphadenopathies and a splenic mass emerged after 1 month of treatment. Histopathological analysis of tonsil biopsy specimens showed diffuse proliferation of CD20-positive atypical cells with large, irregular nuclei. Some of these cells were positive for EBV-encoded small RNA, and her peripheral blood was positive for EBV-DNA (4.9 Log IU/mL), leading to a diagnosis of EBV-LPD. After discontinuation of dasatinib, her high fever and cervical lymphadenopathies disappeared without recurrence. The subsequently removed splenic mass was largely composed of non-neoplastic cytotoxic T cells resulting from a reaction to EBV-infected B cells. EBV-LPD should be included in the differential diagnosis of patients who develop lymphadenopathy during dasatinib treatment, regardless of its duration.

ETV6::LYN fusion gene is recognized as one of the genetic alterations responsible for myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions (MLN-TK) according to the 2022 WHO classification. However, the clinical features and pathogenesis of MLN-TK with ETV6::LYN are not well defined because of the rarity of the disease. Here, we report an MLN-TK patient with ETV6::LYN that manifested as myeloproliferative neoplasms (MPN) with eosinophilia, myelofibrosis, and T-lymphoblastic lymphoma (T-LBL), which eventually led to acute myeloid leukemia. Targeted RNA sequencing of both lymph node specimens diagnosed with T-LBL and bone marrow specimens diagnosed with MPN specimens detected an identical ETV6::LYN fusion gene. Whole exome sequencing (WES) detected several identical missense and nonsense mutations in both specimens. Detected mutations were not found to be relevant to pathogenesis of T-LBL and MPN in previous reports and were considered variants of uncertain significance. Based on the WES results, ETV6::LYN fusion gene was considered the driver gene essential for the pathogenesis of MPN-TK with ETV6::LYN.

The optimal follow-up protocol for primary central nervous system lymphoma (PCNSL) is unclear. This is the first study to evaluate the benefit of structured follow-up imaging of PCNSL with respect to the timing of relapse. A total of 198 PCNSL patients (57.1% males) diagnosed between 2003 and 2020 were included. The data were collected retrospectively from 8 hospitals in Finland. Relapse detection details included structured follow-up imaging (sMRI) studies, additional imaging (aMRI) studies based on patients' new symptoms, and all outpatient and emergency visits. Overall survival (OS) with respect to the relapse detection method, sMRI versus aMRI, was also evaluated. Relapse was diagnosed in 71 patients (35.9%), 66.1% of whom experienced relapse during the first 2years after diagnosis. During the first year, 48.3% (14/29) of the relapses were detected via sMRI, and 51.7% (15/29) via aMRI. During the second year, the percentages were 33.3% and 66.7%, respectively. More than 5years after the diagnosis, all the relapses were detected via aMRI. To observe one relapse during the first year, 9.4 sMRI studies were needed. Overall survival after relapse (OS2) was 4.0months for the patients whose first relapse was detected via sMRI and 3.0months for those whose first relapse was detected via aMRI (P = 0.203). We found that structured imaging was beneficial for relapse detection during the first year after PCNSL diagnosis. A minor trend towards better survival after relapse was observed for patients who experienced relapse according to structured imaging.

Relapsed or refractory T-cell acute lymphoblastic leukemia/lymphoma (r/r T-ALL/LBL) are frequently aggressive and associated with unfavorable prognoses. Pan-targeted Chimeric Antigen Receptor (CAR) T-cell therapy have shown promising results in clinical trials. In recent years, CD7 CAR T-cell and CD5 CAR T-cell demonstrate effectiveness in treating r/r T-ALL/LBL patients with bone marrow infiltration. However, nearly half of r/r T-ALL/T-LBL patients are accompanied by extramedullary disease (EMD), where comprehensive data on the efficacy and safety of CAR T-cell therapy remain limited. Additionally, CD7 CAR T-cell and CD5 CAR T-cell therapy can cause severe immunodeficiency and hematologic toxicity, complicating with difficult immune reconstitution. This review provides an in-depth analysis of the safety profile and adverse events associated with CAR T-cell therapy in r/r T-ALL/LBL, with a a particular emphasis on its impact in patients with EMD.

Although rearrangement of the MYC oncogene (MYC-R) is frequently observed in aggressive B-cell lymphomas, it is extremely rare in T-cell malignancies. A 64-year-old man who had been under observation for several years because of asymptomatic pulmonary extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALToma) was admitted to our hospital because of poor general condition and hypotension. Blood tests revealed thrombocytopenia and elevated serum lactate dehydrogenase levels, whereas computed tomography revealed systemic lymphadenopathy and splenomegaly. An inguinal lymph node biopsy precipitated a diagnosis of angioimmunoblastic T-cell lymphoma (AITL). Shortly after admission, the patient experienced spontaneous intestinal perforation and hemorrhage caused by multiple intestinal infiltrations of the AITL. Although chemotherapy was administered, the patient died several weeks after admission. A 46,XY,t(8;14)(q24;q11.2) karyotype was identified, and fluorescence in situ hybridization analyses showed split signals for the MYC and T-cell receptor (TCR) alpha genes, by which a TCR::MYC translocation was confirmed. Pathological autopsy analysis revealed systemic infiltration of the AITL and no MALToma lesions. Only a few cases of mature T-cell lymphoma harboring MYC-R have been reported in the literature thus far. To the best of our knowledge, this is the first reported case of AITL with TCR::MYC rearrangement. This condition could be associated with refractoriness to chemotherapy and aggressive clinical course with systemic infiltration that included the intestine.

To investigate the prognostic significance of clinicopathological factors in patients with primary central nervous system lymphoma (PCNSL) in a single center. Patients newly diagnosed with PCNSL at our center were recruited between January 2019 and March 2023. Baseline demographic and clinicopathological data were collected retrospectively. The Kaplan-Meier method and Cox regression analysis were performed for survival analyses. A total of 118 patients were enrolled. The median age was 64 (IQR, 54-68). The median progression-free survival (PFS) and overall survival (OS) were 12.70 (95%CI, 9.73-23.30) months and 36.87 (95%CI, 25.57-NR) months, respectively. KPS < 70 and ECOG ≥ 3 were significantly associated with worse PFS and OS. High International Extranodal Lymphoma Study Group (IELSG) score (IELSG 4-5) and high-risk Memorial Sloan-Kettering Cancer Center (MSKCC) score were also adverse factors for PFS and OS. BTK inhibitors (BTKi) therapy (HR 0.39, 95% CI, 0.18-0.86, p = 0.020) and consolidation therapy (HR 0.19, 95% CI, 0.06-0.64, p = 0.007) were confirmed as independent favorable factors for OS. A high NK lymphocyte proportion was associated with worse OS (p = 0.008). Patients in the high NK lymphocyte group experienced a higher rate of primary tumor resistance (57.14%) than the low NK lymphocyte group (33.33%). KPS < 70, ECOG ≥ 3, IELSG 4-5, and high-risk MSKCC score are adverse factors for PFS and OS. Importantly, BTKi therapy and consolidation therapy are independent favorable factors for OS. Peripheral lymphocyte immunophenotyping could be a potential predictive indicator for prognosis and therapeutic response in PCNSL.

This retrospective study investigated the potential drug-drug interactions between trimethoprim-sulfamethoxazole (TMP-SMZ) and high-dose methotrexate (HD-MTX) in adult patients with primary central nervous system lymphoma (PCNSL). A total of 143 Chinese adult patients with PCNSL who received 498 cycles of MTX were included. Differences in the pharmacokinetics of MTX, including Cmax, clearance (CL) and AUC0-48h with and without co-administration of TMP-SMZ were assessed. The incidence of MTX-related acute kidney injury (AKI), hepatotoxicity, myelosuppression, and delayed MTX elimination at 48 and 72h were also compared. Patients were divided into two cohorts for analysis: 146 cycles with TMP-SMZ exposure and 352 cycles without TMP-SMZ exposure. Patients who received TMP-SMZ concurrently with HD-MTX exhibited a 1.13-fold increase in Cmax, a 1.12-fold increase in AUC0-48h and a reduction in CL by 0.87-fold for MTX. There was no significant difference in the incidence of MTX-related AKI, hepatotoxicity, myelosuppression, or delayed MTX elimination between the two cohorts. Prophylactic TMP-SMZ might lead to increased MTX exposure but has no impact on the incidence of myelosuppression, AKI, and hepatotoxicity. These results suggested that prophylactic TMP-SMZ is safe for adult patients with PCNSL receiving HD-MTX.

We aimed to investigate whether early clinical indicators were associated with eventual disease severity, and to develop a predictive model for severe asparaginase-associated pancreatitis (AAP). Seventy-five acute lymphoblastic leukaemia (ALL) cases with AAP admitted to Shanghai Children's Medical Center from March 2013 to August 2023 were divided into non-severe (n = 44) and severe (n = 31) groups based on Atlanta diagnostic and AAP grading criteria. We compared essential information, asparaginase(ASP) dosage form, cumulative dose, clinical characteristics and laboratory tests between the groups. Statistically significant indicators were analysed with multifactorial logistic regression to identify independent risk factors for severe AAP. Receiver operating characteristic (ROC) curves assessed the early predictive value of age, C-reactive protein (CRP) and fibrinogen (FIB) levels. In the early stages of AAP onset, significant differences in age, CRP, platelet count, red blood cell distribution width, albumin, calcium, FIB, and D-dimer levels were found between the non-severe and severe AAP groups (p < 0.05). Multifactorial logistic regression identified age (odds ratio [OR] = 1.204, p = 0.035), CRP (OR = 1.334, p = 0.003), and FIB (OR = 0.85, p = 0.008) as independent predictors of severe AAP. ROC analysis showed an area under the curves (AUC) for age was 0.681 (95% CI: 0.557-0.805), CRP was 0.766 (95% CI: 0.653-0.880), FIB was 0.735 (95% CI: 0.612-0.857). Optimal cut-off values for age, CRP, and FIB were 9.46 years, 48.5mg/L and 1.265g/L respectively. The combined AUC was 0.916 (95% CI: 0.845-0.986), with 0.903 sensitivity and 0.818 specificity, outperforming individual predictors (p < 0.05). Age, CRP, and FIB levels are good early predictors of severe AAP, and their combination significantly improves predictive accuracy.

Infections are a clinically significant cause of mortality in multiple myeloma (MM) patients. The high number of infections in MM patients is due to the immunosuppressive effects of the disease itself as well as treatment-related immunosuppression. In this real-world evidence (RWE) study, we used several nationwide healthcare registries of Finland to investigate the effect of infection load on mortality in MM patients during 1997-2021. The highest number of infections was recorded during the first year after MM diagnosis. In patients who received allogenic or autologous stem cell transplantation (ASCT), the number of infections during the first two years post diagnosis was significantly higher than in those treated without ASCT. When compared to their age-, sex-, and region-matched controls, MM patients accrued more infections during the year prior to diagnosis. Intriguingly, patients under 70 years old had significantly more infections already 3 years before diagnosis when compared to their matched controls. Prior to MM diagnosis, the relative proportion of streptococcal septicaemia and pneumonia due to Streptococcus pneumoniae increased the most. Of note, even one recorded infection prior to diagnosis was associated with significantly shorter median overall survival. Importantly, Cox proportional hazard models show that recorded infections both before and after diagnosis increase the independent risk of mortality in MM patients.

Recently, germline variants have also been found as contributors of disease etiology in myeloproliferative neoplasms (MPN). The consideration of such inherited traits is crucial for clinical management of patients, particularly with regards to indication for allogeneic hematopoietic cell transplant (allo-HCT) and donor selections. Herein, we describe the very instructive case of a 49-year-old woman diagnosed with JAK2 V617F-positive primary myelofibrosis (PMF) who was found to also carry a germline variant in the SH2B3 gene, detailing clinical management, donor selection process for allo-HCT purposes, and appropriate genetic counseling.