Hematological Oncology最新文献

The 2022 WHO and ICC classifications introduced conflicting definitions for myelodysplasia-related acute myeloid leukemia (AML-MR) and myelodysplastic syndrome/AML (MDS/AML), leading to diagnostic uncertainty. This study compared the molecular and clinical characteristics of these entities to clarify their relationship. We conducted a multicenter retrospective study of 568 AML and 75 MDS/AML patients from a Chinese cohort, with findings validated in two independent public cohorts (n = 524). Molecular features, treatment responses, and overall survival (OS) were compared across subgroups defined by WHO and ICC criteria. AML-MR and MDS/AML patients exhibited overlapping molecular features, including frequent ASXL1 (25.0% vs. 22.7%) and TP53 mutations (19.4% vs. 12.0%), as well as a high incidence of complex karyotypes (24.4% vs. 21.3%). Non-AML-MR cases had significantly lower frequencies of these alterations but were enriched for NPM1 and FLT3 mutations (all p < 0.05). AML-MR patients had significantly shorter OS than Non-AML-MR patients across both classification systems (median OS: 10.3 vs. > 22 months, p < 0.001), but comparable remission rates (p = 0.514) and OS (10.3 vs. 13.3 months, p = 0.425) to MDS/AML. IPSS-R and IPSS-M showed no prognostic discrimination in either group (p > 0.05), while ELN 2022 showed limited predictive performance. In response, we developed a modified risk stratification model that categorized patients into three risk groups with distinct survival outcomes (median OS: 21.7, 8.5, and 5.7 months; p < 0.0001). This model remained discriminatory within the AML-MR (13.7 vs. 8.5 vs. 5.6 months, p = 0.001) and MDS/AML (31.2 vs. 11.7 vs. 6.3 months, p = 0.0044) subgroups and was validated in external cohorts (p < 0.01). AML-MR and MDS/AML form a biological continuum with shared molecular and clinical features, supporting the ICC classification update. Our integrated model may improve prognostic stratification and guide clinical decision-making for these high-risk patients.

Despite significant advances in novel therapies, multiple myeloma (MM) remains incurable due to inevitable relapse. Chimeric antigen receptor (CAR) T-cell therapy is an innovative immunotherapy that has demonstrated remarkable efficacy in patients with relapsed/refractory (R/R) MM. To date, four B-cell maturation antigen (BCMA)-targeting CAR T-cell therapies have been approved in the United States and China for the treatment of R/R MM: idecabtagene vicleucel, ciltacabtagene autoleucel, equecabtagene autoleucel, and zevorcabtagene autoleucel. Although these four CAR T-cell therapies have achieved encouraging response rates in R/R MM, a comprehensive comparative analysis of their efficacy and toxicity profiles is still lacking. In this review, we compare the efficacy and safety of these four approved BCMA-directed CAR T-cell therapies. We also discuss potential factors underlying the observed differences and highlight strategies that may further improve the clinical outcomes of this revolutionary therapy.

CD20-negative large B-cell lymphomas exhibit aggressive behavior and are ineligible for rituximab-containing therapy. To identify antigens targeted by treatment, we analyzed CD79B and CD19 expression in 108 samples from 75 patients with CD20-negative large B-cell lymphomas using H-score. Diffuse-strong (H-score 300) CD79B and CD19 expression was observed in 51% and 57% of samples, and low/negative (H-score ≤ 100) in 35% and 30%, respectively. CD79B expression was significantly lower in de novo CD20-negative diffuse large B-cell lymphoma (DLBCL) than in CD20-negative DLBCL changed from CD20-positive DLBCL after rituximab-containing therapy and in CD20-negative DLBCL transformed from CD20-positive low-grade B-cell lymphoma after rituximab-containing therapy (H-score ≤ 100 in 79% vs. 27% vs. 10%, p < 0.001). CD19 expression was lower in de novo CD20-negative DLBCL than in transformed DLBCL (H-score ≤ 100 in 43% vs. 3%, p = 0.006). Of 12 patients with plasmablastic lymphoma, CD79B and CD19 were negative in 83% and 66% of cases, respectively. Among 46 CD20-negative large B-cell lymphomas with low CD79B and/or CD19 expression, the tumor proportion score for programmed death-ligand 1 was positive (≥ 1%) in 33% of cases. The combined positive score for programmed death-ligand 1 was positive in 52% of programmed death-ligand 1 tumor proportion score-negative samples. In conclusion, CD79B and CD19 were variably expressed in CD20-negative large B-cell lymphomas, but lower in de novo DLBCL, and especially in plasmablastic lymphoma. Programmed cell death protein 1/programmed death-ligand one inhibitors may represent a treatment option.

Measurable residual disease (MRD) status in chronic lymphocytic leukemia (CLL) patients treated with venetoclax is a predictive factor of outcome in clinical trials. This multicenter prospective study was aimed to show the feasibility of MRD assessment in the real-life setting and to confirm the results of clinical trials. Forty-four patients were enrolled: 43% had 17p deleted and/or TP53 mutated (del17p/TP53mut), 62% had complex karyotype, and 65% of patients were previously treated with B-cell receptor inhibitor (BCRi). MRD was evaluated by 8-color flow cytometry (FC) on peripheral blood (PB) every 3 months from therapy start and samples with 10⁻⁴ CLL cells were considered as undetectable (uMRD). PB-uMRD patients were evaluated on bone marrow (BM). In 23 patients venetoclax was combined with Rituximab (VR). Median follow-up was 39.47 months (range 31.02–43.32). Median number of PB samples for each patients was 5 (IQR 4–7). Undetectable MRD on PB at any timepoint was obtained in 34/40 patients (85%): 82% in venetoclax monotherapy (Vmono) and 86.9% in VR group. Concordance of PB/BM samples was 92% at 24 months. No significant difference in uMRD rates was detected based on del17p/TP53mut and number of previous therapies. Three-year progression-free survival (PFS) for Vmono and VR was 53.5% and 55%. Median PFS in del17pl/TP53mut was 29.8 and 34 months in Vmono and VR respectively. Landmark analysis based on 9-month MRD showed a trend towards a better PFS in uMRD patients. Median PFS was 21.7 and 13.04 months in 24-month uMRD and detectable MRD patients after VR, respectively (log rank p = 0.0309). In conclusion, in these high-risk relapsed/refractory CLL patients who were MRD-monitored in the context of a real-life study the results were similar compared to published data in more selected patients.

Multiple myeloma (MM) is recognized as a malignancy shaped by its complex tumor microenvironment (TME), which fuels disease progression and therapeutic resistance. Recent advances in single-cell omics, spatial transcriptomics, mass cytometry, and advanced imaging have enabled high-resolution mapping of tumor and immune cell interactions within their native context, also revealing spatial heterogeneity that influences clinical outcomes. These tools, complemented by scalable computational frameworks and artificial intelligence, provide cost-effective alternatives to dissect immune landscapes and derive prognostic biomarkers from both bulk and single-cell data. However, technical complexity, resource demands, and the need for robust standardization limit their immediate clinical application. On the other hand, machine learning techniques enhance integration and predictive power of existing datasets, supporting the development of personalized, immune-informed therapeutic strategies. This review highlights recent advances, discusses the strengths and limitations of emerging technologies with a particular focus on their integration to decipher TME biology and pave the way toward precision medicine in MM.