Édouard Cornet

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.

DISEASE OVERVIEW: Hairy cell leukemia (HCL) and HCL-like disorders, including HCL variant (HCL-V) and splenic diffuse red pulp lymphoma (SDRPL), are a very heterogeneous group of mature lymphoid B-cell disorders. They are characterized by the identification of hairy cells, a specific genetic profile, a different clinical course and the need for appropriate treatment. DIAGNOSIS: Diagnosis of HCL is based on morphological evidence of hairy cells, an HCL immunologic score of three or four based on the CD11C, CD103, CD123, and CD25 expression. Also, the trephine biopsy which makes it possible to specify the degree of tumoral medullary infiltration and the presence of BRAF V600E somatic mutation. RISK STRATIFICATION: Progression of patients with HCL is based on a large splenomegaly, leukocytosis, a high number of hairy cells in the peripheral blood and the immunoglobulin heavy chain variable region gene mutational status. The VH4-34 positive HCL cases are associated with poor prognosis. TREATMENT: Risk adapted therapy with purine nucleoside analogs (PNA) are indicated in symptomatic first line HCL patients. The use of PNA followed by rituximab represents an alternative option. Management of progressive or refractory disease is based on the use of BRAF inhibitors associated or not with MEK inhibitors, recombinant immunoconjugates targeting CD22 or BCR inhibitors.

AIMS: To determine full blood count (FBC) normal reference values for adults. METHODS: FBC normal values for healthy adults were defined, after establishing preanalytical conditions, in a population of 33 258 subjects, 19 612 men and 13 646 women. The values were established after excluding from this population all people having conditions liable to modify, directly or indirectly, FBC parameters. RESULTS: Results for values of standard parameters are provided in detail for each parameter, by sex and by age group from 16 to 69 years of age. In addition, we present FBC values from a population of 339 subjects aged over 69 years with no comorbidities. CONCLUSIONS: These normal values are proposed for use in everyday practice. They make it possible to distinguish, without ambiguity, a normal situation from a pathological situation. Moreover, they might be used over all mainland France.

The CellaVisiontrade mark DM96 is an automated image analysis system dedicated to locating and preclassifying the various types of white blood cells in peripheral blood smears. The system also partially characterizes of the red blood cell morphology and is able to perform platelet counts. We routinely analyzed the blood samples from 440 patients with quantitative and/or qualitative abnormalities detected by the XE-2100 Sysmextrade mark. Only 2.6% of cells are not identified by DM96trade mark. After classification of the unidentified cells very good correlation coefficients are observed between DM96trade mark and manual microscopy for most hematological parameters and accuracy is judged excellent up to 98%. For most common parameters, false positive and false negative ratios are also very good. Whatever the pathology and the number of blasts on smear, all patients were positive for blast detection on DM96trade mark. The system is a useful tool for assisting in the diagnosis and classification of most acute or chronic leukemia. Automatic cell location and preclassification, along with unique cell views on the computer screen, could reduce the time spent performing differentials and make real-time collaboration between colleagues a natural part of the classification process. The workstation also provides an ergonomically correct and relaxed working environment. We suggest its use in routine analysis; the system could be very helpful for the accurate morphological diagnosis of samples from patients with malignant hematological disease.

A large, multicentre, retrospective survey of patients with hairy cell leukaemia (HCL) was conducted in France to determine the frequency of second malignancies and to analyse the long-term effects of the established purine nucleoside analogues (PNAs), cladribine and pentostatin. The survey retrospectively reviewed the medical history of patients and their immediate family, clinical and biological presentation at the time of HCL diagnosis, treatment choice, response to treatment, time to relapse and cause of death. Data were collected for 487 patients with HCL. Of the patients included in the survey, 18% (88/487) had a familial history of cancers, 8% (41/487) presented with malignancies before HCL diagnosis and 10% (48/487) developed second malignancies after HCL was diagnosed. An excess incidence of second malignancies was observed, with a standardized incidence ratio (SIR) of 1·86 (95% confidence interval (CI): 1·34-2·51), with no significant difference between PNAs. For second haematological malignancies alone, the SIR was markedly increased at 5·32 (95% CI: 2·90-8·92). This study highlights the high frequency of cancers in HCL patients and their family members. The frequency of second malignancies is notably increased, particularly for haematological malignancies. The respective role of pentostatin and cladribine in the development of second malignancies is debatable.