Acta Haematologica最新文献

Introduction: Cerebral venous sinus thrombosis (CVST) is a rare but potentially life-threatening condition. Despite advances in diagnostic imaging and therapeutic strategies, data regarding risk factors for CVST progression among patients remain limited.

Methods: The retrospective cohort study aimed to evaluate the yield of neuroimaging and to assess risk factors for CVST progression among patients presenting to the emergency department (ED) after a prior CVST diagnosis. We collected data from the hospital's electronic medical records on patients diagnosed with CVST at our tertiary care center between January 2002 and April 2023. For patients who had subsequent ED visits related to their initial CVST diagnosis, data regarding demographics, clinical presentation, imaging outcomes, and alterations in therapeutic management were retrieved.

Results: Our initial cohort included 251 patients diagnosed with CVST. Of these, 107 (43%) patients returned to the ED with symptoms potentially related to CVST. Headache was the most common presenting symptom (59%), and imaging was performed in 71% of relevant ED visits. Thrombus progression was observed in only 6% of cases. No significant associations were found between demographic factors, clinical presentation, anticoagulation status, and neuroimaging findings. Among patients whose initial CVST diagnosis occurred more than 2 years prior to ED evaluation, only those with thrombophilia experienced thrombus progression.

Conclusions: Thrombus progression is a rare finding among patients with a history of CVST presenting to the ED with neurological complaints. Pediatric patients showed low rates of thrombotic worsening, suggesting a more judicious use of neuroimaging in this population. No significant risk factor was found to predict the risk of CVST progression.

Introduction: Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening condition characterized by excessive immune activation, cytokine storm, and aberrant macrophage function. Although HLH is well studied in children, data on adult HLH remain limited. Our primary goal was to examine in-hospital mortality and its associated risk factors in patients with HLH in a tertiary center.

Methods: This retrospective study at University Hospital Bern queried the hospital database using the i2b2 system to analyze adult HLH patients, assessing clinical, laboratory data, treatments, and outcomes according to the HLH-2004 criteria and Saint-Antoine score.

Results: From 845,846 patients seen in the hospital between 2014 and 2021, a cohort of 54 adult HLH patients was identified. The overall mortality rate was 40.7%. In univariate analysis, we found that deceased patients with HLH were significantly older than surviving patients (median age of 69.6 [range 22-83] vs. 52.5 [24-79] years old [p = 0.002]). Patients with HLH were significantly more likely to have cardiopulmonary and neurological complications, higher alkaline phosphatase levels, lower platelet counts, need platelet transfusions, and lower response rate to the HLH therapy. In multivariate analysis, age (HR 0.94; 95% CI 0.89-0.99; p = 0.024), cardiopulmonary (HR 7.045; 95% CI 1.28-38.66, p = 0.025), neurologic complications (HR 5.55; 95% CI 1.01-30.51; p = 0.04), and the requirement of platelet transfusions (HR 6.22; 95% CI 1.16-33.20; p = 0.032) were all independently associated with in-hospital mortality.

Conclusions: This study identifies risk factors whose early presence can be used to stratify management strategies and improve prognosis in patients with HLH.

Introduction: The significance of autografts' contamination by clonal plasma cells on clinical outcome in newly diagnosed multiple myeloma (NDMM) remains controversial.

Methods: We retrospectively reviewed the clinical and laboratory data of NDMM patients who underwent autologous stem cell transplantation (ASCT) and had received graft minimal residual disease (gMRD) examination by multi-color flow cytometry.

Results: From January 2011 to December 2022, 250 NDMM patients with complete cytogenetic information, gMRD information, and who received ASCT as consolidation were enrolled. Multi-flow cytometry can achieve a median detection sensitivity of 0.004%, and gMRD positivity was 12.4% at a median level of 0.0160% (interquartile range, 0.0049%, 0.05394%). Its presence was correlated with response to induction treatment, with percentages of 2.65%, 12.94%, 28.89%, and 57.14% of patients achieving complete response, very good partial response, partial response, and minimal response/stable disease, respectively. gMRD (+) patients had a higher risk of not achieving bone marrow MRD negativity post-ASCT. After a median follow-up of 33.5 months for the whole cohort, patients in the gMRD (+) group had significantly worse progression-free survival (PFS) than those in the gMRD (-) group did (34.8 vs. 65.0 months, p = 0.001). Multivariable analysis revealed that gMRD (-) was independently predictive of better PFS (hazard ratio 0.464, 95% confidence interval: 0.274-0.785, p = 0.004). We found the significance of gMRD on PFS was in high-risk subgroups and in patients who achieved ≤ partial response prior to ASCT.

Conclusions: In conclusion, gMRD (+) was an independent risk factor for inferior progression-free survival, with the impact primarily affecting high-risk groups and patients who achieved ≤ partial response before ASCT.

Introduction: Acute basophilic leukemia (ABL) is a rare form of acute leukemia, characterized by a high number of immature basophils in the blood. It is clinically associated with skin infiltration, organ enlargement, osteolytic lesions, and symptoms of histamine excess, with rapid progression and poor prognosis. Due to its rarity and the lack of specialized diagnostic tests, there is no universally accepted diagnostic standard.

Case presentations: We report a rare case of ABL, which advances our understanding of the clinical manifestations and pathological mechanisms of the disease. The patient presented with symptoms indicative of hyperhistaminemia, and the diagnosis was confirmed through molecular testing, specifically detecting the FIP1L1::PDGFRA fusion gene. Detailed analysis of this case helped identify early symptoms and highlighted the relevance of hyperhistaminemia in ABL's clinical presentation.

Conclusion: The patient successfully achieved a complete response to treatment and remained relapse-free during an 18-month follow-up. This case underscores the importance of accurate and timely diagnosis and individualized treatment, and it provides valuable insights for managing similar cases of ABL.

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 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 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: 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: 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: 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.