Zhuang J, Shi H, Liu X
… +26 more, Duan M, Du X, Qin L, Hui W, Liang R, Wang M, Chen Y, Li D, Yang W, Tang G, Zhang W, Kuang X, Su W, Han Y, Lan X, Chen L, Xu J, Liu Z, Huang J, Zhao C, Tong H, Hu J, Chen C, Chen X, Xiao Z, Jiang Q
INTRODUCTION: This study was aimed to identify the discrepancies in treatment goals and concerns regarding disease management between patients with myeloproliferative neoplasms (MPNs) and hematologists. METHODS: A study...INTRODUCTION: This study was aimed to identify the discrepancies in treatment goals and concerns regarding disease management between patients with myeloproliferative neoplasms (MPNs) and hematologists. METHODS: A study was conducted among patients with MPNs, including polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF), and hematologists in China. RESULTS: Data from 1,645 respondents with ET, PV, and MF and 715 hematologist respondents were analyzed. Cure of disease and healthy blood counts as treatment goals were reported more by almost half of the respondents with MPNs than by hematologists. However, prevention of thrombotic events, delayed transformation of disease, improvement of symptoms and better quality of life, and reduction in spleen size were less reported by respondents with MPNs than by hematologists. In multivariate analyses, education, comorbidities, symptom burden, disease duration, and annual out-of-pocket expenses for treatment were significantly associated with the treatment goals of respondents with MPNs. However, female physicians and senior professors paid more attention to these goals. Regarding concerns on MPN-related issues, more respondents with MPNs paid more attention to disease knowledge and restrictions in daily life compared to hematologists, whereas the majority of physicians attached importance to medication-related issues. CONCLUSION: The perceptions of patients with MPNs and hematologists differed in terms of treatment goals and concerns of management of MPNs. Sociodemographic and clinical variables were associated with the respondents' perspectives on MPNs. Therefore, sufficient patient-physician communication is suggested to improve treatment satisfaction and compliance.
INTRODUCTION: Research has demonstrated a potential link between lipid metabolites and multiple myeloma (MM); however, the causal relationship remains uncertain. This Mendelian randomization (MR) study aimed to explore t...INTRODUCTION: Research has demonstrated a potential link between lipid metabolites and multiple myeloma (MM); however, the causal relationship remains uncertain. This Mendelian randomization (MR) study aimed to explore the potential causal relationship between lipid metabolites and MM. METHODS: In this study, data on lipid metabolites were obtained from a genome-wide association study of metabolites in blood samples from 7,824 Europeans. Genetic information related to MM came from the UK Biobank database, encompassing 601 patients with MM and 372,016 control samples. In this MR analysis, inverse-variance weighted method was used as the primary analysis method; MR-Egger and weighted median were employed as complementary approaches. Sensitivity analyses were conducted using the Cochran Q test, MR-Egger intercept, MR-PRESSO, and leave-one-out analysis. RESULTS: A total of 121 human lipid metabolites were analyzed in this MR study. The analysis result revealed that 1-docosahexaenoyl-glycerophosphocholine (odds ratio [OR] = 1.0059, 95% confidence interval [CI] 1.0043-1.0076, p < 0.01, FDR = 0.12), tetradecanedioate (OR = 1.0007, 95% CI: 1-1.0013, p = 0.0498, FDR = 0.23), and X-12990-docosapentaenoic acid (OR = 1.0029, 95% CI: 1.0015-1.0044, p < 0.01, FDR = 0.15) were linked to an increased risk of MM. As for palmitoleate (OR = 0.9972, 95% CI: 0.9947-0.9997, p = 0.0299, FDR = 0.19), a nominal inverse association was observed. None of these associations reached statistical significance after FDR correction (all FDR >0.05). Sensitivity analyses verified the robustness of these nominally significant results. CONCLUSION: Genetic evidence demonstrated nominal associations of 1-docosahexaenoyl-sn-glycero-3-phosphocholine, tetradecanedioate, X-12990-eicosapentaenoic acid, and palmitoleate with MM risk, though these did not survive FDR correction. While these findings suggest potential metabolic pathways in MM pathogenesis, further validation is required before considering these compounds as biomarkers for clinical screening or drug target selection.
BACKGROUND: Clinical researchers and laboratory specialists are striving to explore artificial intelligence (AI) to facilitate and optimize haematological diagnostics in response to the growing demand for more efficient...BACKGROUND: Clinical researchers and laboratory specialists are striving to explore artificial intelligence (AI) to facilitate and optimize haematological diagnostics in response to the growing demand for more efficient and accurate diagnoses. SUMMARY: This review summarizes current approaches integrating AI into blood and bone marrow cytomorphology, flow cytometry (FC), genetics, and haemostasis. Efforts include automated cell differentiation in peripheral blood and bone marrow aspirates, algorithms for identifying causes of anaemia, tools for rapid diagnosis of acute leukaemia, and other haematological entities. AI in FC may reduce subjectivity and variability, while in genomics, machine learning is increasingly implemented for processing high-throughput sequencing data and may enable automated detection of karyotypes in the future. In haemostasis, AI allows for automation in quality control, the establishment of personalized reference ranges, and potentially automated result interpretation. AI has, however, limitations such as cross-platform compatibility and often lacks sufficient validation. Ethical concerns include risks of bias and regulations are lagging behind the rapid developments. KEY MESSAGES: AI shows promise for automating and improving many steps in haematological diagnostics, though final interpretation still needs expert haematologists.
INTRODUCTION: The treatment of relapsed or refractory (R/R) Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL) remains challenging after failure to several tyrosine kinase inhibitors. This study eva...INTRODUCTION: The treatment of relapsed or refractory (R/R) Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL) remains challenging after failure to several tyrosine kinase inhibitors. This study evaluated the clinical outcomes of ponatinib in a real-world cohort with R/R Ph-positive ALL, including those treated at the stage of measurable residual disease (MRD) relapse. METHODS: We retrospectively analyzed 79 adults with R/R Ph-positive ALL treated with ponatinib monotherapy. At the start of treatment, 55 patients (69.6%) were in hematologic relapse, while 24 (30.4%) were in MRD relapse. We evaluated complete remission (CR) rate, MRD response, survival outcomes, and predictors of response and survival according to various clinical and genetic parameters. RESULTS: CR was achieved in 48 (60.7%) patients, and 22 of 46 with MRD data (47.8%) achieved complete molecular response. Ponatinib initiation at MRD relapse was associated with higher odds of better molecular response. In multivariate analysis, age under 60 and MRD response better than major molecular response were linked to improved overall survival (OS). However, 2-year OS remained poor at 29.5% (95% CI: 18.9-40.9%). Allo-HCT was performed in 38 patients (48.1%), with a 2-year post-transplant OS of 29.1% (95% CI: 12.9-47.6%). Prior allo-HCT was associated with inferior OS and disease-free survival. CONCLUSION: Ponatinib achieved an acceptable CR rate and MRD response in R/R Ph-positive ALL, but long-term survival remained poor despite allo-HCT. These results support earlier use of ponatinib in the salvage setting and highlight the need for combination strategies to overcome the limited durability of monotherapy in patients with R/R Ph-positive ALL.
INTRODUCTION: Diffuse large B-cell lymphoma (DLBCL) is a common type of non-Hodgkin lymphoma with clinical and genetic heterogeneity, resulting in significant differences in patient prognosis. METHODS: High-throughput se...INTRODUCTION: Diffuse large B-cell lymphoma (DLBCL) is a common type of non-Hodgkin lymphoma with clinical and genetic heterogeneity, resulting in significant differences in patient prognosis. METHODS: High-throughput sequencing was performed on 155 newly diagnosed DLBCL patients, and 12 genes with high mutation rates related to DLBCL were selected. Cox regression analysis was used to determine prognostic factors associated with progression-free survival (PFS) and overall survival (OS) in patients. A new prognostic model was established based on these factors, and its performance was validated using the concordance index (C-index), receiver operating characteristic curve, and calibration curve. Clinical utility was evaluated using decision curve analysis (DCA). RESULTS: Multivariable Cox regression analysis showed that the prognostic factors for PFS and OS in DLBCL patients were IPI, FAT4 mutation, and TP53 mutation, leading to the development of the final prognostic model (FAT4-TP53-IPI model). The FAT4-TP53-IPI model demonstrated better discriminative ability than the IPI model, as indicated by the C-index. The calibration curve showed good discriminatory ability and accuracy, and DCA confirmed the clinical value of the FAT4-TP53-IPI model. Based on the cutoff values obtained from the FAT4-TP53-IPI model, patients were divided into two different risk groups, and survival analysis for PFS and OS demonstrated significantly worse prognosis in the high-risk group compared to the low-risk group (p < 0.01). CONCLUSION: This study demonstrates that integrating genetic mutation status enhances the prognostic value of the IPI scoring system. Our model may serve as a valuable tool for predicting the prognosis of DLBCL patients receiving rituximab-based immunotherapy.
INTRODUCTION: Azacitidine + venetoclax is a new standard of care for acute myeloid leukemia not eligible for intensive chemotherapy. This combination is associated with hematological toxicities and some drug interactions...INTRODUCTION: Azacitidine + venetoclax is a new standard of care for acute myeloid leukemia not eligible for intensive chemotherapy. This combination is associated with hematological toxicities and some drug interactions. Real-world studies have shown a decrease in results and outcomes when compared to the VIALE-A study. METHODS: We report here our single-center experience using AZA + VEN, rigorously following management guidelines from the VIALE-A study, applied to a real-life population. RESULTS: Forty-two AML patients were analyzed. The complete remission (CR)/CR with incomplete recovery (CRi)/MLFS rate was 73.8% after 1 cycle with 51% CR/CRi and 80.9% after 2 cycles. Median overall survival was 18 months (95% CI, 10.3-25.7). Our retrospective study showed that rigorous use of AZA + VEN in a real-world setting was associated with results close to clinical trial observations. CONCLUSION: We showed the need to rigorously follow AZA+VEN dosage but also toxicity guidelines and practice recommendations edited in the clinical trial even in the real world.
INTRODUCTION: The accidental transmission of both malignant and non-malignant haematological diseases through allogeneic haematopoietic stem-cell transplantation (alloSCT) has been documented. Next-generation sequencing...INTRODUCTION: The accidental transmission of both malignant and non-malignant haematological diseases through allogeneic haematopoietic stem-cell transplantation (alloSCT) has been documented. Next-generation sequencing enables the detection of a broad spectrum of mutations associated with myeloid and other disorders. CASE PRESENTATIONS: We report two cases of donor-derived myeloid clonal haematopoiesis (M-CHIP) following alloSCT. In one case, donor-derived CHIP was stabilized through donor-lymphocyte infusions administered in response to declining donor chimerism. CONCLUSION: The transfer of M-CHIP by alloSCT is not uncommon. The long-term relevance of these findings for patients and donors should be the subject of larger prospective trials. Furthermore, the transplantation of CHIP is not uncommon and presents significant medical and ethical challenges.
INTRODUCTION: Nodular lymphocyte-predominant Hodgkin's lymphoma (NLPHL) often follows an indolent course but carries a risk of late recurrence and transformation. Given its rarity, there is significant variability in the...INTRODUCTION: Nodular lymphocyte-predominant Hodgkin's lymphoma (NLPHL) often follows an indolent course but carries a risk of late recurrence and transformation. Given its rarity, there is significant variability in the treatment patterns at various healthcare centers. METHODS: This retrospective chart review aimed to compare the patient characteristics and outcomes of NLPHL patients >18 years of age diagnosed between January 1st, 2007, and December 31st, 2022, at Parkland Health, the safety-net system for uninsured/underinsured patients in Dallas County, with patients treated at the neighboring NCI-designated Harold C. Simmons Comprehensive Cancer Center (SCCC). RESULTS: Our cohort included 53 adult patients (25 at PH vs. 28 at SCCC). PH patients were more likely to belong to racial/ethnic minority groups (black non-Hispanic 84% at PH vs. 32% at SCCC, Hispanic 16% at PH vs. 0% at SCCC, p < 0.01) and to be uninsured (60% at PH vs. 0% at SCCC, p < 0.01). Site of care (PH vs. SCCC) or race/ethnicity did not impact the treatment choice. At a median follow-up of 60 months (IQR 21-83), 3 deaths occurred, resulting in an overall 5-year restricted mean overall survival of 57 months. Overall survival and progression-free survival were not statistically different between the two sites of treatment. CONCLUSION: Despite health inequities that typically impact safety-net patients, we did not observe differences in treatment patterns or outcomes of Nodular lymphocyte-predominant Hodgkin's lymphoma between patients treated at PH compared to SCCC.
Briggeler-Mani J, Häfliger E, Schnegg-Kaufmann AS
… +11 more, Jalowiec KA, Andina N, Agbariah N, De Angelis AD, Grandjean B, Njue L, Ramanjaneyulu A, Bacher U, Banz Y, Porret NA, Rovó A
INTRODUCTION: Paroxysmal nocturnal hemoglobinuria (PNH) clones are frequently found in hypoplastic myelodysplastic syndromes (hMDS), though less commonly than in aplastic anemia. In contrast, the coexistence of hemolytic...INTRODUCTION: Paroxysmal nocturnal hemoglobinuria (PNH) clones are frequently found in hypoplastic myelodysplastic syndromes (hMDS), though less commonly than in aplastic anemia. In contrast, the coexistence of hemolytic PNH with large clones and classical, hypercellular MDS (non-hMDS) is rare and likely underrecognized in clinical practice. Since 2014, 229 MDS patients have been seen at our department. Here, we report two cases with this association and discuss their particular diagnostic and treatment challenges. CASE PRESENTATIONS: The first case is a 68-year-old woman with a hemolytic PNH of 59 years duration. We first saw her in June 2021; she had pancytopenia, with values stable over the past 25 years. After a complete work-up, MDS with low blasts and SF3B1 mutation was diagnosed. She was subsequently diagnosed with symptomatic pulmonary hypertension, and in 2023, she started therapy with ravulizumab, achieving good disease control. The second case concerns a 76-year-old man diagnosed with MDS at age 74. One year later, his anemia worsened, and hemolytic PNH with large clones was diagnosed. The patient showed initial benefit from ravulizumab, and he was later switched to pegcetacoplan, which led to effective disease control. CONCLUSION: We want to emphasize the importance of assessing PNH clones in the diagnosis of non-hMDS, especially in cases with significant anemia. Regarding PNH treatment in such patients, we found that they are underrepresented in studies investigating complement inhibitor. However, standard doses recommended for PNH appear effective and safe regardless of the underlying disease.
INTRODUCTION: Despite adequate pharmacologic treatment and transfusion support for myelodysplastic syndromes (MDS), there is an ongoing need to explore non-pharmacologic approaches for managing MDS symptom burden. Yoga h...INTRODUCTION: Despite adequate pharmacologic treatment and transfusion support for myelodysplastic syndromes (MDS), there is an ongoing need to explore non-pharmacologic approaches for managing MDS symptom burden. Yoga has proved effective in oncologic patients. The aim of this observational study was to explore the feasibility of an 8-week online Kundalini yoga program, including its impact on symptom burden in MDS patients. METHODS: All patients diagnosed with MDS in our medical center were offered an 8-week online program, in which a 1-h weekly kundalini yoga session was held live via Zoom. All segments included postures in the sitting position, specifically planned for this patient population. Symptom burden was assessed before and after each session and at a later timepoint - 8 weeks post-course completion, using the Edmonton Symptom Self-Assessment Scale - global distress score (ESAS-GDS). RESULTS: Fourteen patients participated in the program. The median number of sessions per patient was 4. The questionnaires were reasonably easy for the patients to complete. Mean GDSs significantly improved after yoga sessions. Patients consistently endorsed reduced fatigue (78%), increased alertness (65%), increased general well-being (60%), and reduced anxiety (42%) after practicing yoga. Furthermore, symptom burden remained significantly improved 8 weeks after course completion. CONCLUSION: This Kundalini yoga program for MDS patients was feasible and resulted in significantly better patient-reported health outcomes, ongoing for at least 8 weeks after the last intervention. Longer follow-up within a longer practice program is planned.
INTRODUCTION: Extramedullary involvement in multiple myeloma represents aggressive disease, with clinical stratification of primary extramedullary disease (EMD) remaining a challenge. In this study, we aimed to develop a...INTRODUCTION: Extramedullary involvement in multiple myeloma represents aggressive disease, with clinical stratification of primary extramedullary disease (EMD) remaining a challenge. In this study, we aimed to develop a credible nomogram utilizing routine laboratory variables to predict individual survival for primary EMD patients. METHODS: We retrospectively analyzed a cohort of 60 primary EMD patients, from January 2006 to December 2022. Independent risk factors were identified and subsequently incorporated to generate a nomogram using the Cox proportional hazard regression model. Then, we classified patients into two risk groups based on the nomogram model risk score and compared their survival time using the Kaplan-Meier method. RESULTS: After a median follow-up of 25.4 months, the median progression-free survival (PFS) of primary EMD patients was 29.4 months. Three independent prognostic factors, namely Ki67, endothelial activation stress index (EASIX), and monocyte count, were identified and subsequently incorporated to generate a nomogram using the Cox proportional hazard regression model. Nomogram performance was assessed using various metrics. Then, we classified patients into two risk groups based on the nomogram model risk score, and the Kaplan-Meier curve showed that the median PFS was significantly longer in the low-risk group compared to the high-risk group (37.1 months versus 2.6 months, p < 0.001). CONCLUSION: A predictive nomogram was developed and validated to evaluate the outcome of primary EMD patients.
INTRODUCTION: Primary immune thrombocytopenia (ITP) is an autoimmune condition marked by low platelet counts, leading to symptoms such as bleeding. Avatrombopag (AVA), a second-generation thrombopoietin receptor agonist,...INTRODUCTION: Primary immune thrombocytopenia (ITP) is an autoimmune condition marked by low platelet counts, leading to symptoms such as bleeding. Avatrombopag (AVA), a second-generation thrombopoietin receptor agonist, has shown efficacy in clinical trials but lacks extensive real-world data, particularly in Central and Eastern Europe (CEE). This study aims to evaluate the effectiveness and safety of AVA in routine clinical practice for ITP patients across CEE countries. METHODS: A multicenter, noninterventional, retrospective analysis was conducted in Slovenia, Croatia, and the Czech Republic, involving 41 patients treated with AVA for primary ITP. The primary endpoint was achieving a platelet response at week 8 (W8). RESULTS: AVA treatment resulted in a 68.3% platelet response rate by W8, with a significant increase in median platelet counts. Rescue medication use decreased post-AVA initiation, and many patients reduced or discontinued steroids. AVA was well-tolerated, with only one adverse event reported and no significant bleeding events. CONCLUSION: AVA is effective in improving platelet counts and reducing medication dependency in ITP patients in CEE countries. It offers a viable treatment option with a favorable safety profile, supporting its use across different ITP stages and patient demographics.
BACKGROUND: The practice of allogeneic hematopoietic stem cell transplantation (alloHCT) has evolved from an experimental therapy with high mortality rates to a routine treatment that is increasingly performed worldwide....BACKGROUND: The practice of allogeneic hematopoietic stem cell transplantation (alloHCT) has evolved from an experimental therapy with high mortality rates to a routine treatment that is increasingly performed worldwide. Parallel to this expansion, transplantation has become safer and applicable at higher ages through adapted reduced-intensity protocols and improved supportive care. Advancements in artificial intelligence (AI) methods and computing power over recent decades have driven increasing interest in their application to medicine and, more recently, to hematology. SUMMARY: Concurrently, the expansion of large-scale datasets from transplant registries, hospitals, and national care networks has contributed to the emergence of big data in the field. The implementation of standardized data integration processes across hospitals and networks has created new opportunities to enhance diagnosis, therapy, and patient monitoring while providing decision support for physicians. While the majority of AI models and tools remain at the experimental level and are based on single-center studies, their impact on the medical domain appears sustainable. The current global excitement about these tools reflects the digital transformation in the practice of medicine, but more validation and medical device studies are needed to enable clinical integration. KEY MESSAGES: Here, we review the current state of knowledge and advancements in AI applications within hematology, with a particular focus on alloHCT. We discuss emerging tools for preventing transplant-related complications, including donor selection, reducing non-relapse mortality, managing infection, and controlling graft-versus-host disease.
Acta Haematol
· 2025 Aug · PMID 40759084
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BACKGROUND: Hairy-cell leukemia (HCL) is a rare chronic hematologic malignancy, generally presenting with pancytopenia, relative lymphocytosis, monocytopenia, and splenomegaly. Diagnosis is based on typical bone marrow e...BACKGROUND: Hairy-cell leukemia (HCL) is a rare chronic hematologic malignancy, generally presenting with pancytopenia, relative lymphocytosis, monocytopenia, and splenomegaly. Diagnosis is based on typical bone marrow evaluation with the BRAF-V600E mutation being present in almost 100% of cases of classical HCL. SUMMARY: Treatment usually involves the use of purine analogs (PAs) as first-line therapy. Novel targeting therapies have recently been included in the treatment of therapy-naive HCL such as PA combination with anti-CD20, BRAF inhibitors alone, or combined with anti-CD20. In relapse/refractory disease, other novel agents were studied as BRAF and MEK inhibitors, Bruton tyrosine kinase, or BCL2 inhibitors: all showed encouraging results. Most clinical trials and guidelines do not specify what the optimal approach is for patients with HCL in special situations as elderly population above 80 years old, very young patients below 40 years old, pregnant women, and when leukemia is presented with other comorbidities as active infection or vasculitis. KEY MESSAGES: In this current manuscript, we summarized our approach to HCL in the era of novel agents with special emphasis on age and comorbidities.
UNLABELLED: <p>Introduction: Congenital dyserythropoietic anemia type I (CDA-I) is a rare disorder of erythropoiesis. All CDA-I patients are expected to have iron overload and chronic hemolysis. Patients with severe anem...UNLABELLED: <p>Introduction: Congenital dyserythropoietic anemia type I (CDA-I) is a rare disorder of erythropoiesis. All CDA-I patients are expected to have iron overload and chronic hemolysis. Patients with severe anemia may undergo splenectomy. Hemochromatosis, chronic hemolysis, and splenectomy are all found to increase risk for thromboembolism in thalassemic patients. As CDA-I patients have similar findings, we sought to evaluate prevalence of thromboembolic events (TEEs) in these patients. METHODS: A retrospective case-control study was conducted, including 110 CDA-I patients (study group) and 326 age- and sex-matched iron deficiency anemia patients of the same ethnicity (control group). Patients were risk-stratified using Risk Assessment Models for thromboembolism. RESULTS: We identified 3 cases (2.7%) with TEEs in the CDA group and 1 case (0.3%) in the control group. All patients were females. VTE risk scores were low to moderate for CDA patients and higher for IDA patient. When compared to control group, CDA-I patients were nine times more likely to develop TEE (OR 9.11, 95% CI = 1.15-185.27, p = 0.057). All 3 CDA patients had a history of remarkable hemolysis and iron overload. Two underwent splenectomy. CONCLUSION: These findings show that CDA patients appear to be at increased risk for TEEs. </p>.