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.
ABSTRACTlabile group of amino acids to a diphtheria toxin (DT) payload that has been truncated at its receptor binding region. 20 Since IL-3, the natural ligand for IL-3R, binds with very high specificity and avidity, 21 SL-401 is able to transport DT efficiently and preferentially to cells that overexpress IL-3R, leading to internalization followed by receptor-mediated endocytosis and localization of SL-401 to early endosomes. After cleavage of the SL-401 DT constituent in the acidic medium of endosomes, DT translocates into the cytosol and binds to ADP-ribosylated elongation factor 2, leading to blockade of protein synthesis and cell death. 22 Given the ubiquitous and high expression of IL-3R by BPDCN and the lack of therapies available to treat BPDCN, SL-401 is a potential therapeutic for BPDCN. The present study evaluated the cytotoxicity of SL-401 against patient-derived BPDCN cell lines (CAL-1 and GEN2.2) and primary BPDCN cells isolated directly from 12 patients. The investigations were performed in vitro, as well as in vivo in a murine model of BPDCN. The aim of the study was to provide further support for the use of SL-401 in patients suffering from BPDCN. Methods Patients' cells and cell linesPeripheral blood or bone marrow cells were obtained for diagnostic purposes from 12 BPDCN patients (Table 1) from our national network that collects data and cells from cases diagnosed in France since (authorization number #DC-2008. BPDCN was diagnosed from the results of histopathology and immunostaining of cutaneous lesions, blood or bone marrow. 2,8 Two established cell lines derived from BPDCN patients were used (GEN 2.2, patent #0215927, Dr. Plumas, EFS Rhone-Alpes, Grenoble, France and CAL-1, Dr. Maeda, Nagasaki University, Japan) as well as TF/H-Ras (Prof. Frankel) and CD123 neg (MFI<800) Daudi cell lines (ACC78, DSMZ Braunschweig, Germany) as positive and negative controls, respectively. Other lymphoid and myeloid leukemic cells used to compare sensitivity to SL-401 are described in the Online Supplementary Appendix. Drug and cultureThe SL-401 drug (Stemline Therapeutics, New York, NY, USA) was stored at -80°C and tested at eight concentrations ranging from 365 pM to 0.08 fM (21 ng/mL to 0.4 ng/mL) in order to cover (including myeloperoxidase, CD13, CD33, CD117, CD15, CD65, CD14, CD64); T : T lymphoid markers (including membrane CD3, intracytoplasmic CD3, CD7, CD5, CD2, CD8) Cytotoxicity evaluation by flow cytometryFlow cytometry was performed using a CANTO II cytometer (BD Biosciences, San Jose, CA, USA) and DIVA 6.2 software (BD Biosciences). The cytotoxic effects of SL-401 and the various drugs were evaluated using annexin-V and 7-amino actinomycin D (AV/7AAD) and a panel of different monoclonal antibodies to gate the blastic population described in the Online Supplementary Appendix. In the mouse model, anti-mouse and anti-human CD45 plus anti-human CD123, CD4, CD56, CD304 were used to identify BPDCN human cells (Online Supplementary Appendix). A defined number of calibrated 3-mm latex beads (Flowco...
Schistocytes were thus frequently observed in DIC patients, usually with low percentage, within or close to the reference range (<0.5%). Schistocytes measurement is not a clue test for the initial diagnosis of DIC, but might be of clinical value to suggest an associated or underlying thrombotic microangiopathy if ≥ 1%.
Isolated trisomy 8 (+8) is a frequent cytogenetic abnormality in the myelodysplastic syndromes (MDS), but its characteristics are poorly reported. We performed a retrospective study of 138 MDS patients with isolated +8, classified or reclassified as MDS (excluding MDS/myeloproliferative neoplasm). Myeloproliferative (MP) features were defined by the repeated presence of one of the following: white blood cell count >10 × 10 /l, myelemia (presence of circulating immature granulocytes with a predominance of more mature forms) >2%, palpable splenomegaly. Fifty-four patients (39·1%) had MP features: 28 at diagnosis, 26 were acquired during evolution. MP forms had more EZH2 (33·3% vs. 12·0% in non-MP, P = 0·047), ASXL1 (66·7% vs. 42·3%, P = 0·048) and STAG2 mutations (77·8% vs. 21·7%, P = 0·006). Median event-free survival (EFS) and overall survival (OS) were 25 and 27 months for patients with MP features at diagnosis, versus 28 (P = 0·15) and 39 months (P = 0·085) for those without MP features, respectively. Among the 57 patients who received hypomethylating agent (HMA), OS was lower in MP cases (13 months vs. 23 months in non-MP cases, P = 0.02). In conclusion, MP features are frequent in MDS with isolated +8. MP forms had more EZH2, ASXL1 and STAG2 mutations, responded poorly to HMA, and tended to have poorer survival than non-MP forms.
During the summer 1999, four clustered cases of airport malaria were observed in France. The cases ’ analysis revealed that airport malaria, which is a rare disease whose diagnosis is difficult, can be observed outside occupations at risk, in people livin
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.