Hematology最新文献

Objectives: The survival and neurological prognosis of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome have been substantially improved by peripheral blood stem cell transplantation and immunomodulating agents since the 2000s. However, some patients with POEMS syndrome are refractory to these treatments. This study aimed to evaluate the efficacy and safety of monoclonal antibody therapy with daratumumab (anti-cluster of differentiation 38) and elotuzumab (anti signaling lymphocytic activation molecule family member 7) for POEMS syndrome.

Methods: We reviewed patients with refractory POEMS syndrome who received daratumumab- or elotuzumab-based treatment between January 2019 and July 2024. We studied the hematologic, vascular endothelial growth factor (VEGF), and clinical responses; time to the next treatment; and adverse events.

Results: Eight patients received 13 regimens of daratumumab, elotuzumab, or both. All patients were recurrent/refractory to immunomodulatory drugs, proteasome inhibitors, and/or autologous stem cell transplantation. After a median of six cycles of treatment (range, 3-32 cycles), one hematologic (8%), seven VEGF (54%), two neurologic (15%) and eight generalized clinical responses (62%) were observed. Six patients received subsequent treatment, and the median time to the next treatment was 11 months (range, 4-33 months). Grade 3 hematologic toxicity occurred in four regimens and grade 2 infusion-related reactions occurred in five. None of the patients died during the median follow-up period of 39 months (range, 3-66 months).

Conclusion: Daratumumab- and elotuzumab-based regimens may be treatment options for refractory POEMS syndrome.

Objectives: MYH9-related disease (MYH9-RD) is a congenital bleeding disorder characterized by thrombocytopenia, platelet macrocytosis, inclusion bodies in neutrophils.The aim of this study was to investigate a Chinese family with MYH9-RD and to identity potential mutations of the MYH9. This investigation will elucidate the molecular mechanisms involved in disease pathogenesis.

Methods: Whole exome sequencing (WES) followed by Sanger sequencing was conducted on all family members. Multiple bioinformatics tools were programmed to predict the conservation of mutations and the effect on the protein structure, including 3D protein model analysis.

Results: Gene sequencing revealed that the patient carried A de novo missense MYH9 mutation (c.4338T > G, p.Phe1446Leu). Bioinformatics and molecular modeling analyses predict the p.Phe1446Leu variant to be deleterious, with probable disruptive effects on protein structure and consequent functional impairment.

Discussion: Our study suggested that a de novo missense mutation in MYH9 may be causative to MYH9-RD. Furthermore, genetic sequencing is expected to soon become a standard component of the diagnostic evaluation for individuals with platelet disorders.

Purpose: To retrospectively evaluate the efficacy and safety of ruxolitinib, with or without intensive chemotherapy, in pediatric patients with hemophagocytic syndrome.Methods: Pediatric patients with newly diagnosed hemophagocytic lymphohistiocytosis treated with ruxolitinib between January 2021 and December 2024 were analyzed.Results: A total of 34 patients were included, with a median age of 45.6 months. The median ruxolitinib treatment duration was 62 days, with a median daily dosage of 0.63 mg/kg. Twenty-four patients received VP-16, while ten did not. Significant differences were observed in hemoglobin, sCD25, LDH, and ALT levels between the groups. The overall response rates at weeks 2, 4, and 8 were 73.5%, 76.4%, and 70.6% respectively. Platelets, ferritin, triglycerides, IL-6, IL-10, TNF-α, and liver function markers also changed significantly. The median follow-up was 502 days. Seven patients died, with a two-year overall survival rate of 78.3%, higher in the non-VP-16 group (90.0%) than the VP-16 group (73.2%). The two-year event-free survival rate was 63.2%, with 80.0% in the non-VP-16 group and 58.3% in the VP-16 group. Poor prognostic factors included high IL-6 levels, lack of response to initial ruxolitinib, and bone marrow hemophagocytic cells. The VP-16 dosage was reduced compared to HLH-1994, and no patients discontinued ruxolitinib due to side effects.Conclusion: Ruxolitinib is effective and safe for pediatric hemophagocytic syndrome, potentially reducing the need for etoposide. Its initial treatment response can serve as an important factor for prognostic analysis.

Background: Autologous hematopoietic stem cell transplantation (auto-HSCT) is standard for eligible multiple myeloma (MM) patients, yet outcomes are heterogeneous. Besides established markers like cytogenetics and ISS, the independent prognostic value of pretreatment hemoglobin (Hb), myeloma subtype, and induction regimen requires clarification. This study aimed to assess these factors to improve risk stratification.

Methods: We retrospectively analyzed 350 MM patients undergoing first auto-HSCT at Beijing Chao-Yang Hospital (2001-2019). The impact of baseline Hb (<10 vs. ≥10 g/dL), subtype (IgG vs. non-IgG), and induction regimen (bortezomib-based vs. others) on progression-free survival (PFS) and overall survival (OS) was evaluated using Kaplan-Meier and Cox regression.

Results: With a median follow-up of 58 months, median PFS and OS were 42 months (95% CI 36-48) and 98 months (95% CI 83-113), respectively. Multivariate analysis identified three independent predictors of superior PFS: Hb ≥10 g/dL (HR = 0.65, P = 0.012), IgG subtype (HR = 0.72, P = 0.018), and bortezomib-based induction (HR = 0.58, P = 0.004). Attaining CR/VGPR post-transplant also significantly prolonged PFS versus PR or less (median 55 vs. 37 months, P = 0.044).

Conclusion: Pretreatment hemoglobin, IgG subtype, and bortezomib-based induction are independent predictors of survival after auto-HSCT. Hb, a simple and widely available marker, adds prognostic value beyond ISS and cytogenetics. Integrating these factors into prognostic models can help tailor therapy and improve patient management.

Background: Primary immune thrombocytopenia (ITP) is an autoimmune disorder characterized by low platelet count (PLT). Bruton tyrosine kinase (BTK) is a therapeutic target in immune-mediated diseases. This study aimed to evaluate the effects of a BTK inhibitor, zanubrutinib (Zan), on refractory ITP.

Methods: Peripheral blood was collected from healthy controls (HC) and refractory ITP patients (n = 15), and peripheral blood mononuclear cell (PBMC) extraction was performed. The proportion of myeloid-derived suppressor cells (MDSCs) in PBMCs and Arg-1, iNOS, Fc gamma receptor (FcγR), GPIIb/IIIa, and GPIb/IX autoantibody levels were measured. ITP monocytes were separated into control (Con), Zan (Zan), dexamethasone (DXM), and combination (Zan + DXM) groups. Detection ophagocytosis and platelet activation by flow cytometry; FcγR expression by qRT-PCR and western blot; and IFN-γ, IL-4, IL-2, and IL-10 levels were determined by ELISA.

Results: PBMCs from the ITP group demonstrated lower MDSCs proportions and Arg-1 levels, but higher iNOS, FcγRIII, FcγRIIb, FcγRI, GPIIb/IIIa, and GPIb/IX autoantibody levels than those in the HC group. Following Zan intervention, ITP monocytes exhibited decreased phagocytosis, FcγRIIa, FcγRI protein, IFN-γ, IL-2, p-mTOR/mTOR levels, and increased FcγRIIb, PLTs, IL-4, PAC-1, and CD62p levels.

Conclusion: Zan may modulate FcγR toward FcγRIIb to inhibit platelet destruction, thereby improving refractory ITP.

Background: With the aging population, there is a growing need for treating multiple myeloma (MM) in elderly patients; however, real-world studies of them are quite limited.

Methods: We retrospectively analyzed 519 patients diagnosed between 1997 and 2020 in the Kansai Myeloma Forum database to evaluate the efficacy and safety of novel agents available for 80 years and older patients with MM. Patients were divided into groups according to the treatment year: up to 2010 (Group 1), 2011-2015 (Group 2), and 2016-2020 (Group 3).

Results: The median age and number of treatment lines were 83 years (range, 80-96) and 2, respectively. The median time to next treatment (TTNT) was 7.8 months. The TTNT for Group 3 was significantly shorter (3.8 months) than in other groups (p < 0.001). Median progression free survival and overall survival (OS) were 24.4 and 43.7 months, respectively, and did not differ significantly between 3 groups based on pairwise comparisons. In Group 3, the 1-year cumulative incidence of adverse events (AEs), progression or death, and planned treatment leading to treatment discontinuation was 37.7%, 29.4%, and 15.6%, respectively. In addition, the median time until discontinuation due to AEs has been shortened in recent years.

Conclusion: Our findings suggest that AEs threaten the continued treatment of very elderly patients receiving novel agents, with careful management needed to extend the TTNT.

Background: Proline-rich transmembrane protein 4 (PRRT4) has been infrequently studied, with limited literature suggesting its potential as a prognostic marker for gastric cancer. This study aims to investigate the prognostic value of the PRRT4 gene in pan-cancer.

Methods: We acquired and analyzed data from several platforms, including The Cancer Genome Atlas (TCGA), Genotype Tissue Expression Project (GTEx), Cancer Cell Line Encyclopedia (CCLE), cBioPortal, HPA, and TIMER 2.0. In addition, we have further analyzed the data using multivariate analyzes and RT-qPCR. In vitro experiments were performed to detect the proliferation and apoptosis of AML cells before and after PRRT4 knockdown.

Results: PRRT4 exhibited low expression in 10 types of cancers and high expression in 3 types, and this expression was significantly correlated with tumor stage, age, and gender across various cancer types. PRRT4, identified as a potential independent prognostic factor for overall survival (OS) in several cancers including LAML, PAAD, SKCM, STAD, THYM, and UVM, and exhibited a high frequency of mutation in UCEC. Moreover, PRRT4 was found to be correlated with DNA methylation and immune infiltration in various cancers. Ultimately, in the multivariate analysis model, PRRT4 was discerned as an independent prognostic biomarker for AML, predicated on the statistics based from our institution. After PRRT4 knockdown, the proliferation ability of THP1 cells was significantly enhanced, and the apoptosis ratio was significantly decreased.

Conclusion: PRRT4 may serve as a potential therapeutic target and prognostic marker for various malignancies.

Objectives: Whether intermediate-dose tertiary prophylaxis can improve quality of life and psychological health in adults with severe/moderate hemophilia A has not been determined. This research aims to explore the impact of intermediate-dose tertiary prophylaxis with recombinant human FVIII (rhFVIII) on quality of life, anxiety and depression in such individuals transitioned from on-demand treatment.

Methods: This retrospective analysis collected data from July 2019 to July 2022. Haemophilia Quality of Life Questionnaire for Adults (HAEMO-QoL-A), Patient Health Questionnaire-9 (PHQ-9), and Generalized Anxiety Disorder-7 (GAD-7) were compared before and after prophylaxis. Additionally, functional independence and joint status were analyzed at the end of the 3-year prophylaxis period, as well as their correlations with HAEMO-QoL-A, PHQ-9, and GAD-7.

Results: The HAEMO-QoL-A total score decreased after prophylaxis (pre-prophylaxis: 88.90 ± 33.38 vs. post-prophylaxis: 79.59 ± 22.89) (P = 0.016). The mean PHQ-9 scores before and after prophylaxis were 4.44 ± 4.63 and 5.56 ± 4.30 (P = 0.058), respectively, while the mean GAD-7 scores were 3.15 ± 3.84 and 4.44 ± 3.99 (P = 0.016). Significant correlations were observed for HAEMO-QoL-A with functional independence (P < 0.001), mood and emotions with age (P = 0.032), PHQ-9 scores with knee joint rehabilitation scores (P = 0.047), and GAD-7 scores with treatment experience and ankle joint rehabilitation scores (P = 0.029, P = 0.039).

Conclusion: Intermediate-dose tertiary prophylaxis with rhFVIII can improve quality of life but not relieve anxiety and depression in adults with severe/moderate hemophilia A. Better functional independence correlates with improved quality of life. Gait and age also influence the quality of life to some extent. We need to undertake anxiety and depression screening and provide psychological treatment when necessary.

Objectives: Immune thrombocytopaenia (ITP) is a rare autoimmune disorder characterized by low platelet count and increased risk of bleeding. This study aimed to be the first publication to characterize the economic burden of bleeding events in patients with ITP in the UK.

Methods: We performed a microcosting analysis to estimate the costs associated with bleeding events in patients with ITP. Healthcare resources utilized in the management of bleeds of different severity were costed using well-established UK cost sources. The results were validated through semi-structured interviews with clinical experts.

Results: The severity of bleeding events was classified into four categories, ranging from bleeding managed at home, through mild bleeding managed in the outpatient or day case setting, to serious and life-threatening bleeding events requiring inpatient admission. Total medical costs per event ranged from £2,930 for managing a mild bleeding event, through £16,711 for a serious bleeding event to £32,461 for a life-threatening event. The major cost driver for mild and serious events were intravenous immunoglobulin (IVIg) costs, amounting to £1,614 and £8,071 for the two severity categories, respectively. For life-threatening events, the costs of intensive care unit stay (£9,089) exceeded those of IVIg (£8,071).

Conclusion: Real-world costs of managing bleeding in patients with ITP in the UK are substantial and greater than costs set only based on the UK NHS Tariff. Mitigating the risk of bleeding in patients with ITP is likely to yield not only clinical advantages for patients but also offer substantial cost savings to the health system.

Objectives: To summarize available data and contribute to a broader understanding of the global incidence and prevalence of acquired factor X deficiency.

Methods: A comprehensive review of English-language publications from PubMed and Embase was conducted. The majority of publications on acquired factor X deficiency were associated with light-chain (AL) amyloidosis. Therefore, this review is structured to assess publications reporting on (1) acquired factor X deficiency associated with AL amyloidosis or (2) acquired factor X deficiency associated with other causes.

Results: The literature includes case reports, case-series, and limited population-based reports of the epidemiology of acquired factor X deficiency. Though no definitive global incidence or prevalence estimates for AL-amyloidosis-associated acquired factor X deficiency were identified, the finding that roughly 6-14% of patients with AL amyloidosis have factor X activity levels below 45-50% of normal highlights the rarity of acquired factor X deficiency associated with AL-amyloidosis. Indeed, AL amyloidosis itself is a rare disorder with an estimated annual incidence of ∼10 cases per million population. Only case reports were available to inform the epidemiology of acquired factor X deficiency not associated with AL amyloidosis. We identified 35 cases from 29 papers published from around the globe. At least 25 of those patients experienced a bleeding event, with factor X activity levels ranging from <1% to 39%.

Conclusion: More population-based data are needed to understand the epidemiology of acquired factor X deficiency; however, the limited data seem to indicate this condition is quite rare. The variation across papers in thresholds used to define deficiency highlights the need for a standardized definition to better inform drug development, resource allocation, and regulatory decision-making.