Acta Haematologica最新文献

Introduction: Immunotherapy in DLBCL (diffuse large B-cell lymphoma) disease has become an active research area with great value and potential. However, bibliometric research in this area is still sparse. Through bibliometric analysis, we aimed to visualize the research hot spots and trends of immunotherapy in DLBCL disease to help understand the future development of basic and clinical research.

Methods: The Web of Science Core Collection database was searched for articles and reviews related to the immunotherapy of DLBCL from 2004 to 2024. VOSviewers, CiteSpace, and the R package "bibliometrix" were used to conduct the bibliometric analysis.

Results: A total of 662 articles were included. The number of immunotherapy treatments in DLBCL increased year by year. The publications came from 55 countries, led by the USA and the People's Republic of China, and 1,349 institutions, with the leading research institutions being The University of Texas MD Anderson Cancer Center and Memorial Sloan Kettering Cancer Center. Leukemia & Lymphoma is the journal with the most research, and Blood is the journal with the most co-citations. We identified 4,833 authors, among which Young and Ken H. had the most significant articles, while Neelapu S.S. had the largest number of co-citations. After analysis, the most common keyword is CAR T (CAR T cells: chimeric antigen receptor T-cell immunotherapy, a current and developing area of research.

Conclusions: This is the first bibliometric study to comprehensively summarize research trends and advances in immunotherapy in DLBCL disease. This information will provide a reference for researchers and healthcare providers in immunotherapy research by clarifying recent research frontiers and hot spots such as CAR T cells, bispecific antibodies, and so on.

Introduction: High-dose therapy with melphalan followed by autologous stem cell transplant in the upfront setting (upfront ASCT) has significantly improved clinical outcomes of myeloma patients and become the standard of care for the past 30 years. However, with the advent of modern induction therapy, the role of upfront ASCT approach has been called into question. Several prospective studies have examined whether continuing with triplet therapy as consolidation with optional ASCT at relapse (triplet-alone) could result in comparable outcomes.

Methods: This was a systematic review and meta-analysis of randomized controlled trials comparing upfront ASCT versus triplet-alone approach among myeloma patients treated with triplet therapy, which included two novel agents and a corticosteroid, as induction. Cochrane Library, PubMed and conference proceedings were searched. Primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), safety, and second primary malignancies (SPM). Subgroup analysis was conducted for high-risk cytogenetics.

Results: Our search yielded three trials, conducted between 2010-2018, including 1,737 patients. Two trials evaluated bortezomib plus lenalidomide (VRd) induction and the third study tested carfilzomib plus lenalidomide (KRd) induction. Maintenance was given in all trials to both arms. There was no difference in OS between the arms; the pooled OS in all patients and those with high-risk cytogenetics was hazard ratio (HR) 1.03 (95% CI, 0.85-1.26; I2 = 0%; 1,737 patients, 3 trials) and 0.85 (95% CI, 0.59-1.23; I2 = 0%; 222 patients, 2 trials), respectively. The pooled PFS for upfront ASCT versus triplet-alone was significantly improved in all the patients and in the high-risk cytogenetics subgroup, HR 0.67 (95% CI 0.59-0.76; I2 = 0%; 1,737 patients, 3 trials) and HR 0.59 (95% CI: 0.44-0.7; I2 = 0%; 306 patients, 3 trials), respectively. The risk of any grade 3-4 adverse events was higher in the upfront ASCT arm versus triplet-alone approach (relative risk = 1.17 [95% CI, 1.12-1.23; 1,737 patients]). The risk of secondary malignancies was reported in all three trials and was comparable between both arms. Two trials reported on secondary myeloid neoplasms, which were significantly higher among upfront ASCT arm versus triplet-alone approach, OR 9.7 (1.8-52.25, I2 = 0%, 1,422 patients).

Conclusion: Although upfront ASCT approach, in the era of triplet therapy, resulted in a significantly longer PFS among all patients, this did not translate into a survival benefit, regardless of cytogenetic risk. Upfront ASCT was associated with an increased rate of secondary myeloid neoplasms. In the current plethora of innovative therapies, the role of upfront ASCT is debatable.

Introduction: Acute myeloid leukemia (AML) represents a significant burden for patients and their families, and to the healthcare system. This study estimated the total cost of illness associated with newly diagnosed AML patients in Canada.

Methods: The economic burden of AML was estimated using an incidence-based model, analyzing different types of AML cases in Canada. Direct and indirect costs were calculated using scientific literature and Canadian clinical experts' inputs. Patients were categorized depending on their eligibility for intensive chemotherapy (fit and unfit patients) as well as according to age and cytogenetic markers.

Results: The total average cost of AML per patient is estimated to be CAD 178,073 with a cost of CAD 210,983 and CAD 145,163 for fit and unfit patients, respectively. The costs related to treatment represent half of the total average cost (52%), followed by hematopoietic stem cell transplant (23%), best supportive care (16%), productivity loss (6%), and wastage (4%).

Conclusion: For patients with AML, the costs associated with fit patients are higher than unfit patients. Hospitalization and best supportive care costs are key cost drivers for the total costs of fit and unfit patients, respectively. This study highlights that AML is associated with a significant economic burden in Canada.

Background: Lymphomas are a diverse group of disorders characterized by clonal proliferation of lymphocytes. While definitive diagnosis relies on histopathology, immunohistochemical, molecular and genomic analyses, imaging modalities including positron emission tomography/computed tomography (PET/CT), computed tomography (CT), and magnetic resonance imaging (MRI) are essential in diagnostic processes and management. Imaging aids in detecting suitable biopsy sites, assessing disease extent, evaluating treatment response, and detecting recurrence. However, accurate diagnosis and staging remain challenging due to tumor heterogeneity, inter-observer variability, and technical imaging issues.

Summary: Artificial intelligence (AI), particularly deep learning (DL) models, is transforming lymphoma imaging by enabling automated detection, segmentation, and classification across PET/CT, CT, and MRI modalities. Key applications include automated metabolic response assessment and total metabolic tumor volume quantification in PET/CT, lymph node segmentation and classification in CT, and improved detection of central nervous system involvement in MRI. Despite promising results, significant challenges limit widespread clinical adoption, including variability in imaging protocols affecting model generalizability, reliance on small retrospective datasets, lack of model interpretability, and difficulties integrating AI tools into existing clinical workflows.

Key messages: (1) DL applications can automate detection, segmentation, and classification in lymphoma imaging, improving diagnostic accuracy and reducing inter-observer variability across PET/CT, CT, and MRI modalities. (2) Challenges in DL adoption include validating model performance across diverse imaging protocols, addressing data biases, and ensuring generalizability to real-world clinical settings. (3) Integrating AI into clinical workflows requires careful validation to ensure safety, consistency, and alignment with existing diagnostic and treatment standards.

Introduction: ETV6::JAK2 is a fusion known to drive acute lymphoblastic leukaemia (ALL) in the presence of other genomic lesions which define the JAK/STAT class of Philadelphia chromosome-like acute lymphoblastic leukaemia (Ph-like ALL). Ph-like ALL comprises approximately 15% of ALL. Patients with mutations or gene fusions signalling through the JAK/STAT pathway have particularly poor prognosis. Emerging treatments targeting JAK2 fusions and mutations are promising, and phase 3 clinical trials are in progress. However, with widespread use of JAK2 inhibitors, it is important to anticipate and manage resistance mechanisms. The JAK2 p.G993A mutation confers resistance in vitro, even to high-dose JAK2 inhibitors such as ruxolitinib. We postulated that direct inhibition of STAT3 and STAT5, downstream from JAK2, may overcome resistance.

Methods: Murine-derived IL-3-dependent Ba/F3 cells were transfected with ETV6::JAK2 containing a p.G993A mutation for this study. These cells were confirmed to demonstrate IL-3 independence and ruxolitinib resistance prior to use in experiments. An inhibitor-response assay was conducted using differing concentrations of SH-4-54 and pimozide (STAT3/5 inhibitors) applied to ETV6::JAK2 p.G993A cells and two control cell lines.

Result: SH-4-54 and pimozide were effective against ETV6::JAK2 p.G993A cells with median lethal doses (LD50) of 296 nM for SH-4-54 and 455 nM for pimozide. Both drugs demonstrated a lesser effect on empty vector Ba/F3 cells, with an LD50 of 371 nM for SH-4-54 and 596 nM for pimozide. Neither drug demonstrated significant effect on non-JAK/STAT-activated KG-1a myeloid cells at doses near the LD50.

Conclusion: SH-4-54 and pimozide both overcame treatment resistance in our in vitro model of JAK/STAT-driven Ph-like ALL with a mutation conferring JAK2 inhibitor resistance. While SH-4-54 demonstrates greater potency than pimozide, pimozide may be a more promising option given its demonstrated safety profile in humans. Direct STAT3 and STAT5 inhibition may be an effective approach for overcoming inevitable JAK2 inhibitor resistance-conferring mutations in patients with the poor prognostic subtype of JAK/STAT class Ph-like ALL.

Introduction: Major histocompatibility complex II (MHC-II)-mediated antigen presentation contributes to the pathogenesis of immune thrombocytopenia (ITP). Human leukocyte antigen (HLA)-DRB5 is an MHC-II molecule and this study aims to investigate its role and mechanisms in ITP development.

Methods: Guinea pig anti-mouse platelet (PLT) serum-induced ITP mice received tail vein injection of HLA-DRB5 overexpressing adenoviral vector/immune receptor expressed on myeloid cells-1 (IREM-1) monoclonal antibody (mAb). PLT count changes in mice blood were assessed by a hematology analyzer. MHC-II/CD80/CD86 expression in mice blood was measured by quantitative real-time-PCR and immunofluorescence assay. CD8+ T-cell proportion in mice blood was detected by flow cytometry.

Results: HLA-DRB5 overexpression exacerbated PLT reduction since the 5th day of the establishment of ITP mice model and enhanced MHC-II/CD80/CD86 expression upregulation as well as CD8+ T-cell ratio elevation in the blood of ITP mice, while its effects were reversed by IREM-1 mAb.

Conclusion: HLA-DRB5 overexpression upregulates MHC-II-mediated antigen presentation to CD8+ T cells, thus lowering PLT count in the ITP mice model.

Introduction: Aplastic anemia (AA) is characterized by bone marrow failure and cytopenia. Eltrombopag (ELT) is effective and safe for treating refractory/relapsed AA; however, reports on the long-term outcomes of transfusion-dependent non-severe AA (TD-NSAA) are limited.

Methods: Patients with TD-NSAA refractory to immunosuppressive therapy (IST) or relapsed after IST, treated with ELT alone, and followed up for at least 12 months were retrospectively enrolled. The baseline characteristics of patients, efficacy and adverse effects of ELT, and relapse and clone evolution rates after ELT were documented.

Results: Of the 55 patients with TD-NSAA included, 24 (43.6%) were men. Median age at diagnosis was 46 (19-80) years. Twenty-four patients had relapsed TD-NSAA, and 31 patients had refractory TD-NSAA. During the median follow-up period of 28 (12-48) months, the overall and complete response rates at 3, 6, and 12 months of ELT treatment were 38.2, 60.0, and 52.7 and 9.1, 14.6, and 9.1%, respectively. After a median follow-up of 28 (12-48) months, 21.2% (7/33) of patients experienced relapse, with a median duration from ELT treatment to relapse of 14 (6-45) months.

Conclusion: ELT was effective in patients with relapsed/refractory TD-NSAA, with tolerable adverse effects.

Introduction: The combination of venetoclax (VEN) and azacytidine (AZA) has demonstrated potential in achieving rapid and effective remissions in elderly patients with acute myeloid leukemia (AML). Allogeneic hematopoietic stem cell transplantation is a promising potential cure for high-risk AML, as VEN-based therapies have a worse prognosis in elderly patients. This study aimed to assess the efficacy of sequential haploidentical HSCT following two courses of VEN and AZA therapy in patients with AML aged 55 years and older.

Methods: We conducted a retrospective study on AML patients aged 55-70 years who received intensive chemotherapy or two courses of VEN/AZA therapy, followed by haploidentical allo-HSCT (haplo-HSCT) based on disease risk degree, measurable residual disease status, and patient's preference.

Results: Between January 2019 and December 2023, 141 newly diagnosed AML patients received initial treatment with intensive chemotherapy or VEN/AZA therapy. Among them, 64 patients received haplo-HSCT, while 77 did not. The 1-year overall survival (OS) and relapse-free survival (RFS) of patients who received haplo-HSCT were significantly higher than those who did not receive haplo-HSCT (p < 0.05). Among patients who received transplantation, there was no significant difference in 1-year OS and RFS between the VEN/AZA and intensive chemotherapy groups: 76.3% versus 69.3% (p = 0.367) for OS, and 74.5% versus 69.7% (p = 0.473) for RFS. High-risk ELN stratification and the presence of ≥4 gene mutations were associated with lower OS and RFS in both univariate and multivariate analyses.

Conclusions: AML patients over 55 years of age who received haplo-HSCT after two courses of VEN/AZA therapy had outcomes similar to those who received haplo-HSCT after intensive chemotherapy, suggesting that two courses of VEN/AZA therapy as a bridge to haplo-HSCT are feasible for patients over 55 years old.

Introduction: The prevalence of preexisting obstructive coronary artery disease (CAD) and the occurrence of anginal chest pain as a presenting symptom in patients with light-chain (AL) and transthyretin (ATTR) cardiac amyloidosis (CA) are undetermined.

Methods: A single-center analysis of clinical, laboratory, imaging, and angiographic characteristics of CA cohort was performed.

Results: Included were 98 CA patients (43 AL, 47 wtATTR, 8 mutant ATTR). Eighteen patients (18%) had preexisting obstructive CAD at the time of CA diagnosis. These patients were older and had worse left ventricular ejection fraction, yet revealed similar cardiac biomarkers' levels. The 3-year survival rate was comparable between patients with versus without preexisting CAD (p = 0.974). Anginal chest pain was a presenting symptom of newly diagnosed CA in 24% of patients (n = 19) with no preexisting CAD, 53% (n = 10) of which had AL-CA. Two patients had an acute myocardial infarction. The prevalence of diabetes mellitus, dyslipidemia, hypertension, and smoking was similar among CA patients presenting with versus without chest pain. Of the newly diagnosed CA patients with no preexisting CAD who underwent symptoms evaluation (n = 37), 99mTc-Sestamibi myocardial perfusion scintigraphy demonstrated stress-induced perfusion defects in 45% (9/20) and normal study in 45% (9/20) of patients. Coronary evaluation revealed nonobstructive coronary artery lesions or normal coronaries in 75% of patients (18/24).

Conclusion: CA patients may initially present with anginal chest pain and myocardial perfusion defects which may reflect coronary microvascular ischemia. CA should be considered in the differential diagnosis of patients presenting with chest pain, nonobstructive CAD, and elevated cardiac biomarkers.

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.