Acta Haematologica最新文献

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.

Background: The entity of Philadelphia (Ph)-like acute lymphoblastic leukemia (ALL) accounts for approximately 20-30% of newly diagnosed adults with B-cell ALL cases in the USA. Compared to other B-cell subtypes, Ph-like ALL is associated with overall poor prognosis and inferior outcomes with high measurable residual disease rates following induction therapy, increased risk of treatment failure and relapse, as well as short event-free and overall survival.

Summary: Here we aim to highlight Ph-like ALL genetic subtypes and methods of genomic profiling for diagnosis and disease prognostication and to summarize current management approaches for frontline treatment including multiagent chemotherapy, immunotherapy, tyrosine kinase and small molecule inhibitors, and the role of allogeneic stem cell transplantation.

Key messages: Despite the improvement in the treatment outcomes of adult patients with newly diagnosed B-cell ALL, patients with Ph-like ALL continue to do poorly with standard therapy. Thus, tailored therapeutic studies are indeed warranted to refine frontline treatment approaches and to improve outcomes for patients with Ph-like ALL.

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.

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 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.