Acta Haematologica最新文献

Introduction: Newly diagnosed autoimmune hemolytic anemia (AIHA) develops in 1-3 individuals per 100,000 people per year. Warm autoimmune hemolytic anemia (WAIHA) is the most common type of AIHA, accounting for approximately 70-80% of cases. This report outlines complex presentation of DTA-negative, anti-e-mimicking autoantibody mediated WAIHA following a transient viral infection in an adult male patient with no prior transfusions.

Case presentation: A 55-year-old male patient presented with several weeks of flu-like symptoms followed by jaundice, dyspnea, and fatigue with lab work up notable initially for an anti-C antibody mediated WAIHA but later determined to be an anti-e mimicking pan-agglutinating autoantibody.

Conclusion: This report highlights a complex case of a patient with an autoantibody mimicking anti-e associated WAIHA and the challenge of identifying suitable transfusion options.

Chronic myeloid leukemia (CML) was the first leukemia to be described in medical literature and remains one of the most well-studied hematologic malignancies. This review traces the historical evolution of CML research, from its first clinical recognition in the mid-19th century to modern molecular diagnostics and targeted therapy. Key milestones include the discovery of the Philadelphia chromosome in 1960, identification of the BCR::ABL1 fusion gene in the 1980s, and the subsequent development of tyrosine kinase inhibitors (TKIs). The introduction of imatinib in the early 2000s revolutionized CML treatment, transforming a fatal disease into a chronic condition with near-normal life expectancy for most patients. Second- and third-generation TKIs have since been introduced to overcome drug resistance and target specific BCR::ABL1 mutations, such as T315I. Recently, research has focused on mechanisms of TKI resistance, novel signaling pathways, and strategies to achieve treatment-free remission (TFR). Emerging therapies such as vamotinib, KF1601, and combination regimens are being explored. Furthermore, new insights into non-kinase functions of BCR::ABL1 and the role of microRNAs in resistance open additional therapeutic avenues. This review provides a concise overview of CML from a historical and molecular perspective, highlighting diagnostic advances, evolving response criteria, and future directions in treatment.

Acute myeloid leukemia (AML) is a clinically and genetically heterogeneous malignancy marked by a differentiation block in myeloid progenitors. Despite advances in molecular-targeted therapies, long-term outcomes remain poor, underscoring the need for novel treatment strategies. Differentiation therapy, exemplified by the success of all-trans retinoic acid in acute promyelocytic leukemia, offers a compelling alternative to cytotoxic approaches. This review highlights recent advances in phenotypic screening strategies-including high-throughput compound libraries, computational tools, and CRISPR-based functional genomics-which have revealed novel differentiation inducers, genes, and regulatory pathways. Notably, recent phenotypic screening studies identified Triciribine (TCN), an AKT inhibitor, as a differentiation inducer in AML cells. In addition, CRISPR loss- and gain-of-function screens have uncovered key regulators of differentiation, such as transcriptional (KAT6A), metabolic (NMNAT1, GLUT1), and post-transcriptional (ZFP36L2, YTHDC1) effectors. Emerging computational methods, such as the Lineage Maturation Index and single-cell data integration, further enhance target prioritization and translational relevance. However, differentiation therapy outside APL has shown variable and often incomplete clinical success, frequently limited by partial maturation and context-dependent responses. Together, these approaches reveal novel therapeutic vulnerabilities in AML and support the development of differentiation-based strategies for a broader range of patients.

The prognosis and management of pregnancy-associated aplastic anemia (PAA) following allogeneic hematopoietic stem cell transplantation (allo-HSCT) remain uncertain. This study evaluated the safety and feasibility of allo-HSCT in 18 patients with PAA who were treated between January 2013 and November 2023. The donor types included 8 matched sibling donors, 1 matched unrelated donor, 3 mismatched unrelated donors, and 6 haploidentical donors. Median neutrophil engraftment occurred at 11.5 days (range: 6-15), and platelet engraftment occurred at 11.5 days (range: 7-28). The cumulative incidence (CI) of both neutrophil and platelet engraftments was 100%. The CI rates were 22.96%±10.10% for grade II acute graft-versus-host disease (aGVHD) and 12.61%±8.37% for chronic GVHD (cGVHD). No cases of grade III-IV aGVHD, extensive cGVHD, or relapse were observed. The CI of transplantation-related mortality was 19.87%±10.49%. Among the 15 surviving patients, the median follow-up was 1,409 days (range: 228-3,666). The overall survival (OS) and relapse/rejection-free (GRFS) rates were both 80.14%±10.49%. These findings suggest that allo-HSCT is a viable and effective treatment option for PAA.

High-dose chemotherapy (HDT) followed by autologous stem cell transplant (ASCT) has been standard of care in the treatment of relapsed and refractory lymphoma. Some severe toxicities are associated with this treatment modality. Pulmonary toxicity is one of these significant adverse effects and a potential cause of treatment related mortality. In this retrospective study we report the incidence, risk factors and outcome of treatment-induced pneumonitis in 286 lymphoma patients receiving HDT followed by ASCT. The cumulative incidence of treatment-induced pneumonitis was 4,6 % and occurred in 11/286 patients. 3 months incidence rate was 2,6 %. Most of the patients diagnosed with treatment-induced pneumonitis had received BEAC as HDT regimen. The risk of treatment-induced pneumonitis was higher if HDT-ASCT was given in later treatment lines. Also, a prior thoracic radiotherapy as part of first line treatment was associated with higher risk for pneumonitis after HDT-ASCT. In two patients the pneumonitis did not response to high dose steroid treatment. This study is providing new information about the incidence of pneumonitis associated with HDT-ASCT and its risk factors, which might be useful to take into consideration during and after treatment with HDT-ASCT.

Background: Lymphoma has recovery rates above 60%, but many survivors experience impaired quality-of-life (QoL) requiring survivorship care. This study evaluated the role of an integrative oncology (IO) clinic in managing lymphoma survivors.

Methods: In this exploratory preference-based controlled trial, adults in remission after lymphoma treatment were allocated to two groups: those attending the IO survivorship clinic (intervention) and those declining (control). The intervention included complementary medicine, spiritual, and social support, delivered weekly for up to 6 months in addition to standard follow-up. The primary outcome was QoL improvement (EQ-5D-5L index). Secondary outcomes included symptom relief (MYCAW), cognitive function, and perceived control.

Results: Twenty-nine patients were enrolled: 15 in the intervention and 14 in the control group. Over the first 3 months, a significant Time×Group interaction in EQ-5D-5L scores favored the intervention (p=0.005), reflecting superior QoL trajectory. MYCAW concerns also improved significantly in the intervention group across 6 months (p=0.005 and p=0.03). At 3 months, FACT Cog-Oth scores were significantly higher in the intervention arm (p=0.01), indicating better "other" cognitive functions (e.g., memory, clarity, confusion). To note, adherence to IO mainly decreased after 3 months.

Conclusion: In this exploratory preference-based study, an IO survivorship clinic for lymphoma survivors was associated with improvements in QoL, especially for adherent patients. Given the preference-based design, these findings should be interpreted cautiously and viewed as hypothesis-generating rather than confirmatory. Further studies are warranted to evaluate long-term benefits and sustainability of this approach.

Background: Lip lymphoma is an exceptionally rare extranodal lymphoma with limited data to guide clinical management. We conducted the first large-scale population-based analysis to characterize its epidemiology, treatment patterns, and outcomes.

Methods: We identified all lip lymphoma cases (2000-2022) from the SEER database (17 registries). Patients were categorized as localized primary lip lymphoma (LPLL, stage I) or lymphoma involving the lip area (LIL, stages II-IV).

Results: Among 82 patients (median age 62 years, 54.9% female), age-adjusted incidence was 0.0459 per million per year. MALT lymphoma predominated (46.3%). With median follow-up of 74.5 months, 21 deaths (25.6%) occurred, only 5 (6.1%) lymphoma-related. Ten-year overall and cancer-specific survival rates were 72.7% and 92.6%, respectively. In multivariate analysis, age (HR 1.115/year, p<0.001) and non-low-grade histology (HR 3.251, p=0.043) independently predicted survival. All lymphoma-related deaths occurred in patients with aggressive or unknown histologies; none in confirmed low-grade B-cell lymphomas. No treatment strategy (surgery, radiotherapy, or systemic treatment) showed a significant superiority in terms of survival.

Conclusion: Lip lymphoma demonstrates excellent prognosis, particularly for low-grade B-cell histologies. Age and histological grade represent principal prognostic factors guiding treatment strategies.

Introduction: This study evaluated the prognostic role of circular RNAs (circRNAs) in individuals diagnosed with mantle cell lymphoma (MCL), using the framework of the competing endogenous RNA (ceRNA) network model.

Methods: Differentially expressed circRNAs were identified from the GSE159808 dataset, and differentially expressed messenger RNAs (mRNAs) were extracted from GSE32018. Corresponding microRNAs (miRNAs) were retrieved to construct a ceRNA regulatory network relevant to MCL. Functional enrichment analysis and survival analysis were performed on 35 mRNAs incorporated in the ceRNA network to identify transcripts associated with survival outcomes in MCL. A prognostically relevant ceRNA subnetwork was then constructed based on these results.

Results: Thirteen circRNAs (9 upregulated, 4 downregulated) and 457 differentially expressed mRNAs were identified. The initial ceRNA network included 11 circRNAs, 40 miRNAs, and 35 mRNAs. Gene Ontology analysis indicated enrichment in pathways related to dentin-containing tooth development, the plasma membrane signaling receptor complex, and growth factor receptor binding. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis demonstrated significant involvement in the B-cell receptor signaling pathway, Fc gamma (Fcγ) receptor-mediated phagocytosis, and the Wnt signaling pathway. Survival analysis identified six mRNAs significantly associated with overall survival in individuals with MCL. These results were used to derive a refined prognostic ceRNA network consisting of 6 mRNAs, 7 miRNAs, and 6 circRNAs.

Conclusion: CircRNAs may regulate MCL prognosis by modulating miRNA-mRNA interactions within the ceRNA network. These findings suggest a regulatory mechanism by which circRNAs contribute to molecular pathways influencing disease progression and survival in MCL.