Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive leukemia for which we developed a nationwide network to collect data from new cases diagnosed in France. In a retrospective, observational study of 86 patients (2000-2013), we described clinical and biological data focusing on morphologies and immunophenotype. We found expression of markers associated with plasmacytoid dendritic cell origin (HLA-DRhigh, CD303+, CD304+, and cTCL1+) plus CD4 and CD56 and frequent expression of isolated markers from the myeloid, B-, and T-lymphoid lineages, whereas specific markers (myeloperoxidase, CD14, cCD3, CD19, and cCD22) were not expressed. Fifty-one percent of cytogenetic abnormalities impact chromosomes 13, 12, 9, and 15. Myelemia was associated with an adverse prognosis. We categorized chemotherapeutic regimens into 5 groups: acute myeloid leukemia (AML)–like, acute lymphoid leukemia (ALL)–like, lymphoma (cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP])–like, high-dose methotrexate with asparaginase (Aspa-MTX) chemotherapies, and not otherwise specified (NOS) treatments. Thirty patients received allogeneic hematopoietic cell transplantation (allo-HCT), and 4 patients received autologous hematopoietic cell transplantation. There was no difference in survival between patients receiving AML-like, ALL-like, or Aspa-MTX regimens; survival was longer in patients who received AML-like, ALL-like, or Aspa-MTX regimens than in those who received CHOP-like regimens or NOS. Eleven patients are in persistent complete remission after allo-HCT with a median survival of 49 months vs 8 for other patients. Our series confirms a high response rate with a lower toxicity profile with the Aspa-MTX regimen, offering the best chance of access to hematopoietic cell transplantation and a possible cure.
Multiparameter flow cytometry (MFC) is a powerful and versatile tool to accurately analyze cell subsets, notably to explore normal and pathological hematopoiesis. Yet, mostly supervised subjective strategies are used to identify cell subsets in this complex tissue. In the past few years, the implementation of mass cytometry and the big data generated have led to a blossoming of new software solutions. Their application to classical MFC in hematology is however still seldom reported. Here, we show how one of these new tools, the FlowSOM R solution, can be applied, together with the Kaluza ® software, to a new delineation of hematopoietic subsets in normal human bone marrow (BM). We thus combined the unsupervised discrimination of cell subsets provided by FlowSOM and their expert-driven node-by-node assignment to known or new hematopoietic subsets. We also show how this new tool could modify the MFC exploration of hematological malignancies both at diagnosis (Dg) and follow-up (FU). This can be achieved by direct comparison of merged listmodes of reference normal BM, Dg, and FU samples of a representative acute myeloblastic case tested with the same immunophenotyping panel. This provides an immediate unsupervised evaluation of minimal residual disease.
Supplemental Digital Content is available in the text
The assessment of minimal residual disease (MRD) is increasingly considered to monitor response to therapy in hematological malignancies. In acute myeloblastic leukemia (AML), molecular MRD (mMRD) is possible for about half the patients while multiparameter flow cytometry (MFC) is more broadly available. However, MFC analysis strategies are highly operator-dependent. Recently, new tools have been designed for unsupervised MFC analysis, segregating cell-clusters with the same immunophenotypic characteristics. Here, the Flow-Self-Organizing-Maps (FlowSOM) tool was applied to assess MFC-MRD in 96 bone marrow (BM) follow-up (FU) time-points from 40 AML patients with available mMRD. A reference FlowSOM display was built from 19 healthy/normal BM samples (NBM), then simultaneously compared to the patient’s diagnosis and FU samples at each time-point. MRD clusters were characterized individually in terms of cell numbers and immunophenotype. This strategy disclosed subclones with varying immunophenotype within single diagnosis and FU samples including populations absent from NBM. Detectable MRD was as low as 0.09% in MFC and 0.051% for mMRD. The concordance between mMRD and MFC-MRD was 80.2%. MFC yielded 85% specificity and 69% sensitivity compared to mMRD. Unsupervised MFC is shown here to allow for an easy and robust assessment of MRD, applicable also to AML patients without molecular markers.
Postremission treatment is crucial to prevent relapse in acute myeloid leukemia (AML). High-dose cytarabine delivered every 12 hours on days 1, 3, and 5 (HDAC-135) is the standard of care for younger adult patients with AML. Although this standard has been unsuccessfully challenged by other treatment regimens, including multiagent chemotherapy, the timing of HDAC administration has attracted little attention. Here, we retrospectively compared the safety, efficacy, and health care resource consumption associated with HDAC-135 and another standard, condensed HDAC-123 regimen, as consolidation treatment in younger AML patients in first complete response. This study included 221 patients (median age, 46.6 years; range, 18-60 years). HDAC-123 and HDAC-135 were used in 92 and 129 patients, respectively. Both regimens were associated with similar rates of relapse-free survival, cumulative incidence of relapse, nonrelapse mortality, and overall survival, including in core binding factor AML subgroup in which levels of minimal residual disease reduction were similar in both schedules. Hematological recovery times regarding neutrophils and platelets were significantly shorter in patients receiving HDAC-123, with an average difference of 3 to 4 days for each consolidation cycle. The total duration of hospitalization for the whole postremission program was shorter with HDAC-123 (32 days; interquartile ratio [IQR], 22.0,36.5) compared with HDAC-135 (41 days; IQR, 30.5, 50.0) (P < .0001). In conclusion, the condensed HDAC-123 regimen induced faster hematological recovery and therefore significantly reduced the length of hospital stay without affecting treatment response or outcome in younger AML patients.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.