Hematological Oncology最新文献

Primary lymphoma of the female genital tract (PLFGT) is a rare disease. The incidence is gradually increasing each year. There have been few reports about PLFGT, and most of them have involved individual cases and small-sample retrospective analyses. The pathogenesis of PLFGT is still under exploration and may be associated with hormones, inflammation/infection, and immunodeficiency. Diffuse large B-cell lymphoma (DLBCL) is the most common pathological type. The majority of the patients presented with vaginal bleeding, abdominal pain, an abdominal mass, and other nonspecific symptoms. Lymphoma-associated B symptoms are quite rare. These patients initially visited gynecological departments, possibly leading to misdiagnosis due to nonspecific features. The treatment strategies for and prognosis of PLFGT differ substantially from those of other gynecologic malignancies. Thus, interdisciplinary cooperation among gynecologists, pathologists, and hematologists is essential.

This study, including 412 patients newly diagnosed with myelodysplastic neoplasm (MDS), investigated the clinical, molecular, and prognostic features of MDS with moderate-to-severe bone marrow fibrosis (MF). Among the patients with MDS, 347 (84%) had MF grade 0–1 (MF0–1), and 65 (16%) had MF grade 2–3 (MF2–3). Patients with MDS with MF2–3 showed similar overall survival (OS) (16.6 vs. 21.3 months; p = 0.34) but demonstrated inferior progression-free survival (PFS) (6.6 vs. 15.2 months; p = 0.02) and a higher risk of leukemia transformation (35.4 vs. 16.4%; p < 0.001) compared to those with MF0–1. In the MDS with excess blast (MDS-EB) subtypes, individuals with MF2-3 exhibited shorter OS (4.8 vs. 11.7 months; p = 0.01) and PFS (3.1 vs. 7.9 months; p = 0.006) than those in patients with MF0-1. However, individuals with MF0-1 and MF2-3 showed similar OS and PFS rates among the patients with the MDS non-excess blast (MDS-nonEB) subtypes. Additionally, we reclassified the patients with MDS according to the 2022 World Health Organization (WHO) classification. Patients with MDS with fibrosis (MDS-f) had a shorter OS (5.6 vs. 13.8 months; p = 0.01) and PFS (3.1 vs. 7.9 months; p = 0.006) than MDS with increased blasts (MDS-IB) subtypes. Our study reveals the unique features of patients with MDS-MF2-3 and validates the refinements made in the 5th edition of the WHO proposal.

This study compares the safety profiles of two Bruton's tyrosine kinase (BTK) inhibitors, Ibrutinib and Zanubrutinib, in patients with chronic lymphocytic leukemia (CLL). While Ibrutinib has transformed CLL treatment, it is associated with significant adverse events (AEs). Zanubrutinib, a second-generation BTK inhibitor, offers potential for improved safety. In this prospective study, 200 CLL patients were enrolled, with 100 receiving Ibrutinib and 100 receiving Zanubrutinib. Baseline characteristics such as age, sex, body mass index (BMI), Eastern Cooperative Oncology Group (ECOG) performance status, and genetic factors were evaluated. AEs and serious AEs (SAEs) were tracked and graded using the Common Terminology Criteria for Adverse Events (CTCAE). Multivariate logistic regression models were conducted to determine predictors of SAE and AEs grade ≥ 3. Adjusted odds ratio (aOR) and 95% confidence interval (CI) were reported. The mean ages of the Ibrutinib and Zanubrutinib groups were 49.65 and 49.16 years, respectively (p = 0.285). The Zanubrutinib group had a higher percentage of patients with worse ECOG status (71% vs. 57%, p = 0.039). Fewer Zanubrutinib patients experienced severe AEs (4% vs. 9%, p = 0.152) or SAEs (8% vs. 17%, p = 0.054). Neutropenia occurred only in the Ibrutinib group (3%). Subgroup analysis showed a higher complication rate with Zanubrutinib in non-refractory patients (11.40% vs. 5.26%, p = 0.065). Stage III CLL was a protective factor of grade ≥ 3 AEs (aOR = 0.007; 95% CI: 0.0003–0.1829) and SAE (aOR = 0.015; 95% CI: 0.001–0.177). While ECOS status (2 vs. 3) resulted in reduced risk of SAE, chromosome 17p deletion emerged as the main risk factor of SAE (aOR = 6.40; 95% CI: 1.33–30.79). Zanubrutinib demonstrated a more favorable safety profile than Ibrutinib, with fewer severe adverse events. It may be a safer alternative for CLL patients, particularly those at higher risk for complications from BTK inhibitors. However, these differences stemmed from variability in baseline clinical characteristics rather than the interventions themselves.

Various prognostic scoring systems in myelofibrosis (MF) have been developed to guide clinical decision-making in MF. However, discrepancies between different scoring systems for individual patients remain poorly understood, which can result in conflicting treatment recommendations. Moreover, data regarding there applicability in Asian populations remain scarce. We conducted a retrospective analysis of patients with overt MF at National Taiwan University Hospital from November 1, 2006, to November 30, 2023. This study evaluates the distribution, concordance, and prognostic value of various scoring systems (IPSS, DIPSS, DIPSS+, MYSEC-PM, MIPSS70, MIPSS70+v2, GIPSS), focusing on the mutational landscape, particularly TP53 mutations, and cytopenic phenotypes in an Asian MF cohort. All prognostic systems effectively stratified patients by risk (p < 0.005); however, concordance between systems was low (Cohen's κ < 0.4, except for IPSS vs. DIPSS+). GIPSS demonstrated superior performance with a comparable C-index but lower Akaike and Bayesian information criterion values. Besides high-molecular risk mutations, TP53 mutations (5.2%) were associated with worse overall survival (OS) (5-year: 30% vs. 68%, p < 0.001) and a trend toward higher leukemic transformation (5-year: 22% vs. 10%, p = 0.055). Cytopenic phenotype (59%) was associated with a higher incidence of ASXL1 mutations (44% vs. 28%, p = 0.04). In multivariable analysis, elderly patients, higher-risk GIPSS, TP53 mutation and cytopenic phenotype were associated with a poorer OS. This study validated multiple prognostic scoring systems in an Asian MF cohort, with GIPSS showing superior risk stratification. Further, cytopenic phenotype and TP53 mutations were identified as independent factors linked to poorer survival.

Despite the study of BCR::ABL1-positive and -negative myeloproliferative neoplasms (MPNs) providing seminal insights into cancer biology, tumor evolution and precision oncology over the past half century, significant challenges remain. MPNs are clonal hematopoietic stem cell-derived neoplasms with heterogenous clinical phenotypes and a clonal architecture which impacts the often-complex underlying genetics and microenvironment. The major driving molecular abnormalities have been well characterized, but debate on their role as disease-initiating molecular lesions continues. The introduction of the ABL1 tyrosine kinase inhibitors have been extremely successful in the treatment of chronic myeloid leukemia with most patients having a near-normal life expectancy. Similar success has, however, not been achieved for BCR::ABL1-negative MPNs in terms of disease course modification and most patients remain incurable. In both disease categories, genomic instability seems to increase the risk of disease progression to accelerated/blast phase, which is resistant/refractory to conventional treatment and associated with a poor prognosis. To address some of these issues, the late John Goldman and Tariq Mughal founded a scientific and clinical platform in 2006, the Post-American Society of Hematology (ASH) MPN workshop, to appraise novel cancer biology, candidate therapeutic targets, treatments and other clinical challenges and pay tribute to all the many scientists and clinicians around the world instrumental to the progress made and continuing advances being made. This paper summarizes some of the recent data discussed at the 18^th edition of the workshop and includes reference to some data presented or published after the workshop, including the 26^th John Goldman CML conference.