Annals of Hematology最新文献

The prefibrotic phase of primary myelofibrosis (pre-PMF) represents a distinct subentity within the spectrum of myeloproliferative neoplasms (MPNs), recognized by the World Health Organization (WHO) and the International Consensus Classification (ICC). Pre-PMF is characterized by unique morphological, clinical, and molecular features, distinguishing it from essential thrombocythemia (ET) and overt myelofibrosis (overt-PMF). The diagnostic process for pre-PMF relies on bone marrow histology, identification of molecular mutations and exclusion of other myeloid neoplasms. Misclassification remains a significant challenge due to overlapping phenotypes and the heterogeneity of clinical presentations, which range from asymptomatic cases to severe cytopenias and a high thrombotic risk. Management strategies for pre-PMF focus on mitigating symptom burden, reducing thromboembolic events, and preventing disease progression. Low-risk patients often benefit from observational approaches or low-dose aspirin, while cytoreductive therapies, such as hydroxyurea or interferon-alpha, are utilized in symptomatic or high-risk cases. JAK inhibitors like ruxolitinib have shown promise in addressing splenomegaly and systemic symptoms, although their role in pre-PMF requires further investigation. Advances in artificial intelligence are enhancing diagnostic precision by refining bone marrow histopathological analysis, paving the way for more accurate disease classification and tailored therapeutic strategies. This position paper integrates insights from a German expert panel discussion, underscoring the need for interdisciplinary collaboration, adherence to updated WHO/ICC diagnostic criteria, and personalized treatment approaches. By addressing diagnostic challenges and therapeutic nuances, it seeks to improve outcomes and quality of life for patients navigating the complexities of pre-PMF.

The aberrant function of lymphocytes is considered a significant contributing factor to pure red cell aplasia (PRCA), but the precise mechanism by which T lymphocytes induce erythroid development stagnation remains unclear. In our study, the CD8⁺ T lymphocytes were isolated from bone marrow aspirates of acquired PRCA patients and healthy controls. RNA sequencing (RNA-Seq) was performed to analyze gene expression profiles. Additionally, the expression levels of key molecules and transcription factors were assessed at the transcription and protein levels. The RNA-Seq analysis revealed a significant upregulation of genes associated with the PI3K/AKT/mTOR pathway in CD8⁺ T lymphocytes from patients with PRCA, compared to healthy controls. The mRNA expression of AKT, mTOR and key transcription factors T-bet were significantly upregulated in CD8⁺ T cells from patients with PRCA. Treatment with rapamycin, an mTOR inhibitor, attenuated the activation of CD8⁺ T lymphocytes in PRCA patients. Our findings demonstrate the activation of the PI3K/AKT/mTOR signaling pathway in CD8⁺ T lymphocytes of PRCA patients, suggesting its involvement in PRCA pathogenesis. Targeting this pathway may offer a potential therapeutic strategy for PRCA characterized by CD8⁺ T cell dysregulation.

Treatment of polycythemia vera (PV) aims to maintain hematocrit on target to reduce risk of thrombotic complications, while preventing disease progression to myelofibrosis (MF) and acute myeloid leukemia (AML). This analysis evaluated cost-effectiveness of adding ropeginterferon alfa-2b (ropegIFNα) to phlebotomy in patients with low-risk PV (those younger than 60 years without prior thrombosis), compared to phlebotomy alone. We combined a 12-month decision tree with a semi-Markov cohort model comparing ropegIFNα to the standard treatment from the Austrian healthcare system perspective over 30 years. Outcomes were quality adjusted life years (QALYs), costs, and incremental cost-utility ratio (ICUR). Model inputs were obtained from the phase 2 Low-PV study, additional published literature and from Austrian-specific cost databases. One-way and probabilistic sensitivity analyses (SA) assessed the robustness of findings. RopegIFNα led to 1,43 higher QALYs and 50.960 EUR overall higher costs compared to phlebotomy alone, with an ICUR of 35.525 EUR/QALY. Thrombosis, MF, and AML costs decreased for the ropegIFNα group by 12%, 30% and 16% respectively, due to the delayed complications onset and disease progression. In the one-way SA, ropegIFNα costs and discount rates had the greatest impact on results. The probabilistic SA showed a 100% probability of cost-effectiveness at willingness-to-pay threshold aligned to the Austrian GDP per capita. RopegIFNα is a cost-effective treatment option for patients with low-risk PV. These findings suggest that early treatment with ropegIFNα could ensure optimal resource allocation by preventing costly thrombotic events and progression to MF whilst increasing patient quality of life.

Chronic Graft-versus-host disease (GVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (HSCT), affecting the female genital tract in 25-66% of the patients. This condition, referred to as Genital GVHD is an underdiagnosed gynecologic comorbidity, that can significantly impair quality of life. We aimed to describe the prevalence and management of genital GVHD following HSCT. This retrospective analysis included women who underwent allogeneic HSCT at a single Bone Marrow Transplantation Unit between 2015 and 2020 and were evaluated at a specialized Vulvo-Vaginal Clinic. Diagnosis and severity of genital GVHD were based on the recommendations by the National Institute of Health (NIH), therapeutic options included topical treatments and surgical interventions. Of the thirty-six patients evaluated, 19.4% were diagnosed with genital GVHD. Patients with genital GVHD were older than those with no-genital GVHD (58.42 vs 47.48 years, p = 0.02), and most of them had concurrent multi-organ chronic GVHD (85.71%). Genital GVHD was mostly symptomatic in our cohort (71.42%), clinical findings at the time of diagnosis corresponded with NIH grade 3 (severe disease) in 57.1% of cases. Topical treatments were initiated for all patients with genital GVHD, one required surgical intervention. Genitourinary syndrome of menopause (GSM) was diagnosed among 100% of patients with genital GVHD and among 58.62% of patients without genital GVHD (p = 0.08). In the genital GVHD group, adherence to clinical follow up was limited (43.85%). Genital GVHD should be considered as part of chronic GVHD evaluation after allogeneic HSCT. It is associated with advanced age and the presence of chronic systemic GVHD. Impaired quality of life and limited follow-up within this population emphasize the need for increased awareness and early evaluations.

Aplastic anemia (AA) is a life-threatening bone marrow failure syndrome. The advent of next-generation sequencing (NGS) has shed light on the link between somatic mutations (SM) and the efficacy of immunosuppressive therapy (IST) in AA patients. However, the relationship between SM and hematopoietic stem cell transplantation (HSCT) has not been extensively explored. In this retrospective analysis, we examined 166 AA patients who received HSCT or IST at our institution between May 2019 and December 2023. NGS was conducted on 66 genes within bone marrow cells to investigate the correlation between SM and the prognosis and therapeutic response in AA patients, as well as to assess the impact of mutation types on HSCT outcomes. Clinical data were gathered from 166 AA patients, comprising 84 males and 82 females, with a median age of 32 years (ranging from 9 to 75 years). In our study, a total of 151 somatic mutations were identified across 84 patients (50.6%), with 42 patients (25.3%) presenting a single mutation and 26 patients (15.7%) harboring two mutations. The top five genes with the highest mutation frequency were BCOR/BCORL1 (12.6%), ASXL1 (8.6%), TET2 (6.6%), CEBPA (5.3%), and GATA2 (4.6%). We stratified patients into SM and No-SM groups based on the presence of mutations and further divided them into HSCT and IST groups to assess the influence of mutation types on treatment response and survival within and between these groups. The findings were as follows: 1.Patients in the HSCT group exhibited a higher treatment response (OR 85.9% vs. 68.4%, p < 0.05), although there was no significant difference in survival. 2.Patients with favorable mutations, such as PIGA and BCOR/BCORL1, experienced significantly improved response and survival compared to those with unfavorable mutations like ASXL1, DNMT3A, and TET2 (OR 93.7% vs. 72%, p < 0.05) (3-year OS 93.7% vs. 80%, p > 0.05). 3.The HSCT-Favorable group demonstrated superior response rates (OR 100% vs. 67.7%, p < 0.05) and longer survival (3-year OS 100% vs. 67.7%, p < 0.05) compared to the IST-Favorable group. This study underscores that AA patients carrying favorable mutations, particularly BCOR/BCORL1, tend to have a more robust response and better prognosis than those without mutations or those with unfavorable mutations, such as ASXL1/DNMT3A. These findings are especially pertinent to HSCT, highlighting the importance of NGS prior to initiating treatment.

Renal impairment is reported in 20%-50% of patients with newly diagnosed multiple myeloma and is known as a poor prognostic factor. Although several studies have demonstrated that treatment with novel antimyeloma agents improves renal impairment and myeloma itself, the time-dependent clinical course of recovery of renal function has not been extensively studied. We retrospectively collected the data of characteristics and outcomes in consecutive unselected patients diagnosed with and treated for symptomatic multiple myeloma between January 2015 and December 2022, and extracted and analyzed the cases with renal impairment. Among 234 patients with multiple myeloma, 67 (28.6%) had renal impairment (estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73m²) at the time of diagnosis. The median eGFR at diagnosis was 28 ml/min/1.73m², and the eGFR significantly improved to 41.5 ml/min/1.73m², which corresponds to a 42.9% increase, at 3 months after the initiation of treatment for myeloma (p < 0.0001). Further improvement in renal function was not observed at 6 months (eGFR 46 ml/min/1.73m²) and 1 year (eGFR 43.5 ml/min/1.73m²) after treatment initiation. The primary treatment was a bortezomib-containing regimen in approximately 90% of patients. A post hoc analysis revealed a positive correlation between the serum calcium concentration at diagnosis and improvement in renal function. In conclusion, renal function can partially recover through the treatment of multiple myeloma, and the treatment response during the first 3 months may predict the renal function prognosis. Further accumulation of cases is needed to identify the predictive factors for renal recovery.

Despite the association between aberrant TGFBI expression and tumors development found in various cancer types, the role of TGFBI in diffuse large B-cell lymphoma (DLBCL) progression is not clear. This study attempted to reveal how TGFBI impacts malignant progression and cisplatin sensitivity in DLBCL. Bioinformatics and qRT-PCR were used to analyze expression of TGFBI. To investigate the effect of TGFBI on malignant progression and cisplatin sensitivity in DLBCL cells, cell viability and IC50 values were assessed by CCK-8. Cell proliferation ability was detected by colony formation assay. Cell apoptosis rate was detected by flow cytometry. The degree of DNA damage in cells from different treatment groups was detected by comet assay. Protein expression of TGF-β pathway-related proteins like TGF-β1, Smad2, and p-Smad2 was detected by western blot. Bioinformatics and molecular experiments results revealed substantial upregulation of TGFBI in DCBCL. Cell experiment results indicated that high TGFBI expression expedited DCBCL progression and reduced cisplatin sensitivity. Further rescue experiments revealed that SB525334, a TGF-β pathway inhibitor, could weaken the acceleration of DCBCL progression and restore reduced cisplatin sensitivity both induced by high TGFBI expression. TGFBI could promote malignant progression and inhibit the cisplatin sensitivity of DLBCL cells by regulating the TGF-β pathway. In brief, TGFBI has the potential to be a target in DLBCL treatment.

Mycoplasma pneumoniae (M. pneumoniae), as one of the susceptible pathogens during childhood, may lead to severe mycoplasmal pneumonia and affect platelet fluctuations. We prospectively collected data on persistent/chronic ITP children who were infected with M. pneumoniae infection from August 2023 to December 2023. There were 64 patients (40 males) with a median age of 7.08 years (range 4.30 to 9.76) enrolled in this study. Overall, 33 (51.6%) children received TPO-RAs therapy and 31 (48.4%) received other treatments. The impact of M. pneumoniae infection on platelet count is bidirectional, but thrombocytopenia remains predominant. During M. pneumoniae infection, platelet changes in the TPO-RA group were higher than in the non-TPO-RA group. Thrombocytosis was observed in 6 patients (5 in the TPO-RA group vs. 1 in the non-TPO-RA group). Rescue treatment was implemented in 18 patients (7 in the TPO-RA group vs. 11 in the non-TPO-RA group). Monitoring platelets should be strengthened during M. pneumoniae infection.

Despite advancements in multiple myeloma treatment, prognostic variability persists. We investigated the impact of income and education on treatment and survival in a country with publicly funded healthcare. We analysed data from the Swedish Myeloma Registry (2008-2021) linked to national registers. Cox models assessed survival, adjusting for demographics and comorbidities. Treatment patterns were compared using cumulative incidence functions. Among 8,672 patients, higher education and income correlated with prolonged survival. Adjusted hazard ratios (HRs) for low income were 1.4 (95% CI 1.3-1.5) and for low education were 1.3 (95% CI 1.2-1.4). Higher income patients were more likely to receive lenalidomide (HR 1.5, 95% CI 1.3-1.6) and pomalidomide (HR 1.7, 95% CI 1.4-2.0), and less likely to receive melphalan tablets (HR 0.8, 95% CI 0.7-0.9). Low-income patients were less likely to undergo stem cell transplant (HR 0.8, 95% CI 0.7-0.9). Immigrant status or biological sex did not influence outcomes. Even in a tax-funded system, socioeconomic disparities impact myeloma survival and treatment. Lower socioeconomic status correlates with inferior outcome and more conservative treatment. Attitudinal biases may contribute to these disparities. Better treatment for the less privileged patients could significantly improve myeloma survival, advocating for efforts to overcome the influence of socioeconomic status.