Annals of Hematology最新文献

8p11 myeloproliferative syndrome (EMS) is a rare aggressive hematologic malignancy with a poor prognosis that can rapidly develop into acute leukemia. It is characterized by the translocation of fibroblast growth factor receptor-1 (FGFR1), and there is still a lack of effective and reliable treatment methods at present. This report provides a new therapeutic strategy for EMS patients diagnosed with BCR-FGFR1 fusion. This report describes a case of EMS patient with a positive BCR-FGFR1 fusion gene, whose manifestations are similar to those of chronic myeloid leukemia (CML). After diagnosis by fluorescence in situ hybridization (FISH) and RNA sequencing (RNA-seq), olverembatinib, the third-generation tyrosinase inhibitor (TKI) developed in China, was used for treatment. After monotherapy and follow-up for more than one year, partial molecular response (PR) was achieved. During this period, hematologic remission and cytogenetic remission were achieved. The treatment safety of the entire process was excellent. In summary, olverembatinib provides more treatment options for rare diseases such as 8p11 myeloproliferative syndrome.

Neurolymphomatosis (NL) is a rare manifestation of lymphoma resulting from the infiltration of malignant lymphoma cells into the peripheral nervous system. When evaluating peripheral neuropathy, clinical suspicion of NL is highly necessary because its clinical symptoms vary and pathological diagnosis is often difficult. Imaging modalities carry a high sensitivity to diagnose NL. 18 F-flurodeoxyglucose positron emission tomography-computed tomography (18 F-FDG PET/CT), with a diagnostic sensitivity of over 90%, as well as Magnetic resonance imaging (MRI) neurography, has become the leading diagnostic modalities for NL diagnosis, staging, and treatment response assessment. At present, the prognosis of NL is usually poor, and its treatment is also challenging, with few patients benefiting from the currently available treatment measures. The present report discusses two cases of diffuse large B-cell lymphoma-associated NL. They presented with painful polyneuropathy/polyradiculopathy, and imaging examinations such as MRI and 18 F-FDG PET/CT indicated related neuropathy. Both cases were treated with PR2-based immunotherapy (anti-PD-1 tirelizumab 200 mg d1, rituximab 375 mg/m² d0, and lenalidomide 25 mg d1–14). And clinical efficacy was observed, with improved symptoms. Imaging studies showed a significant reduction in lesions of the cervical plexus nerve roots, lumbosacral nerve, sciatic nerve, and brachial plexus. In this study, the two cases of NL with typical clinical and imaging manifestations discussed in the present report exhibited good clinical efficacy after receiving PR2-based immunotherapy. These results provide insights into the development of a novel, potentially effective treatment option for patients with NL.

Siltuximab is the only approved treatment for idiopathic multicentric Castleman Disease but in many countries the only available treatment is rituximab based. We are performing an indirect comparison of rituximab-based regimens (RBR) and siltuximab by using single arm meta-analysis and the generalized linear mixed model methods comparing outcome in five significant clinical end-points (CR, PR, ORR, 2ysPFS and 2ysOS). Patient’s data were extracted from 14 cohort or phase I and II trials conducted with siltuximab (n = 387 pts) and six cohort studies treating iMCD patients with rituximab (n = 138 pts). Response rates and depth of response is similar between the two arms of the study but 2ys PFS is significantly better with siltuximab monotherapy. Using the generalized linear mixed model in order to provide an indirect comparison of odds to achieve the 2yPFS end-point, the reported OR is 0,358, 95% CI (0,147-0,873) and p = 0,027 favoring siltuximab over rituximab-based regimens (RBR). This is the major finding of our study and to our knowledge is the first time that in a big cohort of patients siltuximab is proved more effective compared to RBR.

Extramedullary disease (EMD), an aggressive form of multiple myeloma (MM), may require a multi-targeted treatment approach rather than standard MM therapies. While precise EMD treatment outcome estimates remain challenging given small clinical trial patient numbers, pooled estimates across studies may increase outcome precision. Meta-regression analyses used Bayesian multilevel, random-effects modeling of patients with and without EMD across nine historical clinical studies of standard treatment regimens, including daratumumab, for relapsed/refractory multiple myeloma (RRMM) from 2013 to 2019. EMD was defined as soft tissue plasmacytomas noncontiguous with bone (“true” EMD). Adjustments were performed to account for differences in baseline age, number of prior lines of therapy (LOT), and International Staging System (ISS) stage. Outcomes included overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). In patients with EMD (n = 158) versus without EMD (n = 2706), pooled ORR (95% credible interval) was 20.7% (11.7–33.9) versus 66.2% (53.0–77.4) with an odds ratio of 0.13 (0.09–0.20), pooled median PFS was 6.3 (4.2–9.5) versus 12.9 (8.8–18.8) months with a hazard ratio of 1.95 (1.63–2.32), and pooled median OS was 21.0 (15.9–27.9) versus 39.0 (31.0–48.5) months with a hazard ratio of 1.87 (1.53–2.26). Poorer outcomes in patients with versus without EMD were consistent following adjustment for age, number of prior LOT, and ISS stage. These results in patients with RRMM treated with standard treatment regimens confirmed notably worse outcomes in patients with versus without EMD, emphasizing continued unmet clinical need in this patient population.

Primary central nervous system lymphoma (PCNSL) is a rare form of lymphoma with a poor prognosis. We used the LOC network database, including 365 patients from 14 voluntary centers. Inclusion criteria were age ≥ 60 years, immunocompetence, confirmed PCNSL diagnosis and treatment with curative intent with MPV-based regimen (Methotrexate, Procarbazine, Vincristine) between 2011 and 2021. We analyzed LOS from first day of chemotherapy to dismissal from hospital. Using the MAXStat method we found the LOS threshold of 15 days, to be one of most statistically significant and most convenient to separate two groups with different OS. The median age of the whole population was 71 years, median Karnofsky performance score (KPS) was 70%. The main differences between short and long LOS groups were median KPS at diagnosis (70% vs 50%) and deep structure involvement status (51% vs 67%). With a median follow up of 22.8 months, the median OS was respectively 62.2 and 20 months for short and long LOS. Median PFS was respectively 18 and 9.3 months. Multivariate analysis found in our cohort that age was associated with OS (P = 0.01) and LOS with OS (P = 0.005) and PFS (P = 0.014). KPS at diagnosis is a cofounder to LOS in the analysis. LOS remains associated with OS (P = 0.016) in a subgroup analysis of patients with baseline KPS < 70%. Altogether, the LOS > 15 days identifies a population of patients with poorer outcome in elderly PCNSL patients. Its underlying drivers require further investigation in larger and prospective cohorts.

Multiple myeloma (MM) is a refractory hematologic malignancy driven by clonal plasma cell proliferation and a complex bone marrow microenvironment. CD81, a tetraspanin protein, has been implicated in immune regulation and cancer progression, but its role in MM remains unclear. This study investigated the prognostic significance of CD81 expression and its relationship with immune cells in 178 newly diagnosed MM patients. CD81 positivity (60.67%) was associated with reduced overall survival (OS) but not progression-free survival (PFS). High CD81 expression correlated with decreased peripheral CD8 + T cell counts and increased M2 macrophage infiltration (CD206+), both linked to poorer outcomes. Conversely, high CD68 expression (pan-macrophage marker) was associated with improved prognosis, potentially reflecting favorable M1 macrophage activity. These findings highlight CD81 as a prognostic marker in MM, influencing immune cell dynamics and clinical outcomes. The interplay between CD81, M2 macrophages, and CD8 + T cells underscores the complexity of the MM immune microenvironment, suggesting novel therapeutic targets. Further studies are needed to elucidate CD81’s mechanistic role in immune modulation.

Hemoglobin Suresnes (Hb Suresnes) is a rare hemoglobin variant caused by a substitution of arginine to histidine at position 141 (p.Arg142His) in the COOH terminus of the α-globin chain. This structural change alters the oxygen affinity of hemoglobin and leads to erythrocytosis. We report the first genetically confirmed case of Hb Suresnes co-inherited with α⁰-thalassemia (--/αα) in an East Asian patient, diagnosed via trio whole exome sequencing (WES). A 33-year-old male presented with asymptomatic erythrocytosis, microcytosis, and a family history of elevated red cell indices. Under genetic analysis with WES, we identified a heterozygous Hb Suresnes variant [NM_000558.3(HBA1): c.425G > A (p.Arg142His)] inherited from his father, alongside α⁰-thalassemia (--/αα) inherited from his mother. The overlapping hematologic phenotype initially mimicked polycythemia vera, prompting empirical therapeutic phlebotomy. This case highlights the diagnostic pitfall of misclassifying hereditary erythrocytosis as polycythemia vera and emphasizes the role of WES in resolving the complexity of coexisting hemoglobinopathies, ensuring accurate diagnosis and appropriate management.

Given the adverse impact of deep vein thrombosis (DVT) on the prognosis of multiple myeloma (MM) patients, identifying biomarkers for DVT is crucial for improving MM patient clinical outcomes. Therefore, this study aimed to evaluate the predictive value of miR-503-5p for DVT in MM, and explored the underlying mechanisms. Serum samples were collected from MM patients with and without DVT to measure miR-503-5p expression levels. ROC and Kaplan-Meier curves were employed to examine the predictive potential of miR-503-5p in MM-related DVT. MM serum-cultured human umbilical vein endothelial cells (HUVECs) were used to investigate the mechanisms of miR-503-5p in influencing the disease. Cell viability, oxidative stress status, and IL-6, TNF-α, TF, and TM levels were evaluated by CCK-8, antioxidant activity assay, and qRT-PCR. MiR-503-5p was upregulated in MM patients with DVT. The upregulation of miR-503-5p was a risk factor that demonstrated a high predictive value for DVT in MM patients. MiR-503-5p upregulation mediated the promotive effect of MM serum on HUVEC viability reduction, IL-6, TNF-α, and TF expression, and oxidative stress, and the inhibitory effect of MM serum on HUVEC TM expression. Moreover, WNT3A was a potential target of miR-503-5p in MM-related DVT. WNT3A downregulation mediated the effect of miR-503-5p on HUVECs. MiR-503-5p might be a promising biomarker for predicting DVT development in MM patients. MiR-503-5p might promote thrombosis in MM by affecting vein endothelial cells (VECs) through targeting WNT3A.

Chronic graft-versus-host disease (cGVHD) is a major complication for long-term survivors after hematopoietic cell transplantation (HCT). Bronchiolitis obliterans syndrome (BOS) is the crucial manifestation of lung cGVHD. Ruxolitinib has been approved by the Food and Drug Administration (FDA) for cGVHD treatment, but the response for BOS has not been sufficiently evaluated. We conducted a multicenter study involving 125 patients diagnosed with BOS post-HCT who received second-line therapies, including 77 patients treated with ruxolitinib (ruxolitinib group) and 48 patients with non-ruxolitinib therapies (control group). The primary endpoint was progression of BOS. By the third month, 18.2% of patients in the ruxolitinib group progressed, versus 43.8% in the control group (p = 0.001). The 2-year overall survival (OS) was 73.2% (95%CI 63.5%-84.5%) for the ruxolitinib group versus 60.2% (95%CI 47.4%-76.6%) for the control group (p = 0.012). The BOS-progression-free survival (BOS-PFS) was 69.0% (95%CI 59.1%-80.5%) versus 51.2% (95%CI 38.7%-67.7%, p = 0.011). Early switch to second-line therapy for BOS independently favored lower progression incidence (OR = 0.203, [95%CI 0.070–0.585], p = 0.003). Additionally, we observed that ruxolitinib was well-tolerated during the treatment of BOS. In conclusion, our findings indicated that ruxolitinib is an effective and safe second-line option for BOS.

Molecular diagnostic methods largely rely on expensive equipment and complex operations, which makes it difficult to achieve rapid and low-cost detection. In recent years, the increasing demand for point-of-care testing has driven the rapid development of isothermal amplification techniques, due to their simplicity and low equipment requirements. However, complex nucleic acid extraction steps are still required before most isothermal amplification. In this study, we propose a nucleic acid extraction-free gene detection method: direct multiplex Recombinase Aided Amplification combined with reverse dot blot hybridization (dmRAA-RDB). This method can detect multiple targets simultaneously and offers advantages such as high sensitivity, high specificity, low cost, no need for expensive instruments, and visual detection. By pre-treating whole blood samples with sodium hydroxide solution, the samples can be directly used for isothermal amplification and combined with commercial reverse dot blot (RDB) technology to rapidly detect 17 types of β-thalassemia mutations. The experimental results demonstrated that the pre-treated whole blood samples allowed for the simultaneous, stable, and efficient enrichment of all three target fragments via direct multiplex isothermal amplification. This single-tube triple amplification strategy demonstrates significant innovation in the field of isothermal amplification. Moreover, the workflow is shortened by nearly half, and a side-by-side comparison of 60 clinical samples showed 100 % agreement with the commercial PCR-RDB kit. The dmRAA-RDB method offers a highly promising, innovative solution for large-scale, rapid, and low-cost β -thalassemia screening in primary-care and resource-limited settings, and opens a new avenue for detecting other mutant genes.