Abstract Purpose The sensitivity of real-time quantitative reverse-transcription polymerase chain reaction (RT-qPCR) for detecting measurable residual disease (MRD) in patients with chronic myeloid leukemia (CML) who have achieved a deep molecular response is limited. We validated a digital PCR (dPCR) assay (LQ Check BCR::ABL1 Major %IS Kit) for MRD quantification. Methods Validation was performed according to CLSI guidelines EP17-A2, EP06, EP05-A3, and EP07 using BCR::ABL1 -positive and -negative materials and the World Health Organization (WHO) 1st International Standard. A nonparametric analysis of the limit of blank was used to establish a positivity cutoff of ≥ 2 droplets. The limit of detection (LoD) was verified using a detection criterion of ≥ 95%, and the limit of quantitation (LoQ) was defined as the lowest level meeting ≥ 95% detection and a study-defined %CV of ≤ 76%. Clinical validation included 72 CML specimens for molecular response (MR) category comparisons and 67 specimens for paired quantitative comparisons. Results The LoD and LoQ were both 0.0025% on the International Scale (IS) with a detection rate of 95.8%. The assay showed linearity over 5 logs (R 2 = 0.9916–0.9972), within-run %CV ≤ 1.52%, cross-condition %CV ≤ 2.76%, and WHO-traceable accuracy. In 67 paired specimens, the correlation coefficient was r = 0.9740, with a Passing–Bablok slope of 1.0189, intercept of −0.2552, and Bland–Altman mean bias of 0.2266. Among the 72 specimens, dPCR classified 20 as having a deeper MR than RT-qPCR. Reproducibility was characterized by r = 0.99 and a mean bias of 0.0967. Whole blood was preferably processed within 48 h, with processing at 72 h considered acceptable only when BCR QC criteria were met. Conclusion The LQ Check BCR::ABL1 Major %IS Kit enabled sensitive, precise, and reproducible BCR::ABL1 quantification at MR4.6. The clinical significance of a deeper MR classification using dPCR, particularly for treatment-free remission, requires longitudinal validation.
Bone marrow (BM) examinations are intrinsically multimodal: hematopathologists integrate peripheral blood, aspirate cytomorphology, trephine histology, flow cytometry, cytogenetics, and molecular genetics data into a single interpretation. Because WHO-HAEM5 and ICC 2022 define entities through integrated morphological, immunophenotypic, cytogenetic, and molecular criteria, multimodal diagnostic reasoning embedded in a procedural workflow, not isolated image classification, represents the appropriate target for the use of artificial intelligence (AI). We review the existing research on integrated multimodal AI systems for BM examination by classifying these systems into three categories: mature single-modality tools; systems that perform cross-modal prediction, in which one modality is estimated from another; and genuine multimodal fusion systems, in which several modalities are jointly ingested by a single model. Evidence is stronger at the single-modality level, where deep learning approaches expert performance in aspirate cytology, trephine histology, and flow cytometry assessments, and the first Food and Drug Administration (FDA) De Novo–authorized all-digital bone marrow aspirate (BMA) application has defined a new device category. On the other hand, while cross-modal prediction is rapidly expanding, genuine multimodal fused systems that jointly ingest matched morphology, flow, molecular, and clinical data to yield unified guideline-aligned recommendations remain unrealized. Direct head-to-head evidence is sparse and endpoint-dependent; nevertheless, the lack of demonstrated superiority over the strongest single-modality comparator does not automatically imply the absence of benefits. The dominant obstacles are fusion of heterogeneous modalities with missing data, absence of large paired multi-institutional datasets and harmonized nomenclature, class imbalances, batch-effect-driven generalization failures, immature explainability, uncertainty quantification, and regulatory pathways. Nevertheless, integrated multimodal AI systems for BM examinations have entered a promising early translational phase, and the field should aim to pursue integration using paired datasets, explicit fusion architectures, calibrated abstention-aware models, and staged prospective validation.
Mixed-phenotype acute leukemia (MPAL) is a rare hematological malignancy with poor prognosis, for which there are currently no standardized therapeutic guidelines. Preclinical and clinical studies have shown that venetoclax and BCR::ABL1 tyrosine kinase inhibitors have synergistic effects on Philadelphia chromosome–positive (Ph +) leukemias. We retrospectively analyzed five patients with de novo Ph + MPAL who received venetoclax, olverembatinib, and prednisone (VOP) therapy. All patients achieved complete remission after the initial induction therapy and tested negative for measurable residual disease. During consolidation therapy, two patients developed severe myelosuppression and died of respiratory failure due to pulmonary infections. The remaining three patients underwent allogeneic hematopoietic stem cell transplantation and maintained durable complete molecular remission. These findings suggest that the VOP regimen may be effective in patients with Ph + MPAL. However, they also underscore the need to optimize venetoclax dosing during consolidation to reduce the risk of life-threatening myelosuppression and infectious complications.
Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) is a distinct biological subtype of T-cell acute lymphoblastic leukemia (T-ALL) that was first described in 2009 based on a gene expression profile resembling that of early T-cell precursors in the thymus. ETP-ALL is characterized by an immature immunophenotype featuring positivity for CD7 and cytoplasmic CD3, with co-expression of myeloid/stem cell markers, and absence of CD1a, CD8, with weak or absent CD5 expression. ETP-ALL accounts for 5.5
Myelodysplastic syndromes (MDS) are heterogeneous clonal hematological disorders characterized by ineffective hematopoiesis resulting in peripheral cytopenias. Luspatercept, an erythroid maturation agent, represents a novel therapeutic option for the management of anemia associated with low-risk MDS, particularly in patients with ring sideroblasts and/or SF3B1 mutations. We retrospectively studied 26 adults with low- or intermediate-risk MDS who were treated with luspatercept from 2021 to 2024 at the Nice University Hospital. Data were collected from ORBIS and CLINICOM and analyzed using Microsoft Excel. Treatment was initiated at 1 mg/kg, depending on the patient. The median age was 74 years, and 38.5
