Pierre Lemaire

Blastic Plasmacytoid Dendritic Cell Neoplasm: From Origin of the Cell to Targeted Therapies

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological malignancy with an aggressive clinical course. It is grouped with acute myeloid leukemia-related precursor neoplasms in the 2008 World Health Organization classification. Most patients with BPDCN have skin lesions at diagnosis and subsequent or simultaneous involvement of the bone marrow, peripheral blood, and lymph nodes. Patients usually respond to initial chemotherapy but often relapse. Stem cell transplantation may improve survival. This neoplasm is derived from precursors of plasmacytoid dendritic cells and is characterized by the coexpression of the immunophenotypic markers CD4, CD56, CD123, blood dendritic cell antigen-2, blood dendritic cell antigen-4, CD2AP, and lineage(-). Atypical immunophenotype expression may be present, making diagnosis difficult. BPDCN is often associated with a complex karyotype, frequent deletions of tumor suppressor genes, and mutations affecting either the DNA methylation or chromatin remodeling pathways. A better understanding of the etiology and pathophysiology of this neoplasm could open the way to new therapies targeting specific signaling pathways or involving epigenetics.

The bendamustine plus rituximab regimen is active against primary nodal marginal zone B-cell lymphoma.

Primary nodal marginal zone lymphoma (NMZL) is a rare disease. There is no current consensus on how to treat it. The bendamustine plus rituximab (BR) regimen is effective for the treatment of follicular and other indolent lymphomas, but its efficacy in NMZL is not known. We analyzed the outcome of 14 patients diagnosed with NMZL (median age 67 years) who were treated with 375 mg/m2 of rituximab on day 1 and 90 mg/m2 of bendamustine on days 1 and 2. The overall and complete response rates were 93% and 71%, respectively. Major toxicity (grade 3/4 neutropenia) occurred in 5% of treatment courses. After a median follow‐up of 22 months (range: 18‐55), the overall survival and the free survival rates were 100% and 93%, respectively. None of the patients showing a complete or partial response developed secondary myelodysplastic syndrome/acute myeloid leukemia. Bendamustine plus rituximab was found to be an active and well‐tolerated regimen leading to the rapid control of disease.

IgM k multiple myeloma with monoclonal surface immunoglobulin expression

IgM myeloma is a very rare disorder. Surface antigen expression has been reported in only one previous case of IgM myeloma. Differential diagnosis must be made to rule out Waldenström’s macroglobulinemia. A 63-year-old woman was diagnosed with stage II (International Staging System) multiple myeloma and standard-risk cytogenetics. She was admitted to our department because of severe lumbar pain. X-ray imaging revealed multiple bone lesions in the skull. Laboratory studies indicated anemia (hemoglobin: 9.5 g/dl), hypoalbuminemia (25 g/l) and increased beta2 microglobulin (5 mg/l). Serum protein electrophoresis and immunofixation showed hypergammaglobulinemia (16.5 g/L) and IgM Kappa monoclonal gammapathy at 11.6 g/L. Bone-marrow aspirate showed infiltration of 29% of myeloma cells with a mixture of small-sized cells (Fig. 1a), lymphoplasmacytic cells (Fig. 1b), and classical plasma cells (Fig. 1c). Cytogenetics revealed a finding of 46, XX. Fluorescent in situ hybridization (FISH) showed an IgH/CCND1 rearrangement in 80% of the plasma cells. MYD88L265P and CXCR4 mutations were negative. A flow cytometric analysis of the bone marrow (Cytomic FC500; Beckman-Coulter, FL) showed that the cells were positive for CD38 and CD138, CD20, CD56, CD200, CD45 low, intracytoplasmic (Fig. 2a), and surface immunoglobulin kappa (Fig. 2b), but negative for CD19. The patient underwent four cycles of chemotherapy with thalidomide, bortezomib, and dexamethasone

Advances in the understanding and management of T-cell prolymphocytic leukemia

T-prolymphocytic leukemia (T-PLL) is a rare T-cell neoplasm with an aggressive clinical course. Leukemic T-cells exhibit a post-thymic T-cell phenotype (Tdt−, CD1a−, CD5+, CD2+ and CD7+) and are generally CD4+/CD8−, but CD4+/CD8+ or CD8+/CD4− T-PLL have also been reported. The hallmark of T-PLL is the rearrangement of chromosome 14 involving genes for the subunits of the T-cell receptor (TCR) complex, leading to overexpression of the proto-oncogene TCL1. In addition, molecular analysis shows that T-PLL exhibits substantial mutational activation of the IL2RG-JAK1-JAK3-, STAT5B axis. T-PLL patients have a poor prognosis, due to a poor response to conventional chemotherapy. Monoclonal antibody therapy with antiCD52-alemtuzumab has considerably improved outcomes, but the responses to treatment are transient; hence, patients who achieve a response to therapy are considered for stem cell transplantation (SCT). This combined approach has extended the median survival to four years or more. Nevertheless, new approaches using well-tolerated therapies that target growth and survival signals are needed for most patients unable to receive intensive chemotherapy.

IgD κ multiple myeloma and myelodysplastic syndrome

![Figure][1] An 82-year-old woman presented with left-hip pain. Radiographs revealed multiple bone lesions in the skull and left acetabulum. Laboratory tests showed a peak of monoclonal immunoglobulin D (IgD) κ at 5.1 g/L; albumin, 23 g/L; and hemoglobin, 9 g/dL. Other parameters were normal

Un cas de dégranulation plaquettaire in vitro induite par l’EDTA

A 71 year-old woman is admitted to Le Mans hospital center for management of a chronic skin lesion. She has no personal nor familial bleeding history and does not take any medication. In peripheral blood collected with EDTA (ethylene diamine tetra-acetate), the platelet count is elevated and the blood film shows uniformly grey platelets. In sodium citrate-collected blood, platelets show no abnormality. We describe an EDTA-related artifact that is not to be mistaken for grey platelet syndrome.

[Blastic plasmacytoid dendritic cell neoplasm: two case reports].

Blastic plasmacytoid dendritic cell neoplasm (LPDC) is a rare and aggressive leukemia entity with cutaneous and extracutaneous involvement, reaching most often lymph, blood and bone marrow. Two cases of LPDC diagnosed in Hospital Center of Le Mans are reported, a 78 year old woman (case 1) and a 82 year old man (case 2), and have been clinically, biologically and histologically documented. The clinical presentation, diagnostic difficulties are reminded, as well as the pathogenesis and therapeutic aspect.

Vérification de méthode en vue de l’accréditation : exemple de l’hémogramme automatisé sur deux analyseurs LH750 Beckman-Coulter à l’Hôpital européen Georges Pompidou

Preliminary evaluation of quantitative clinical laboratory measurements is a prerequisite for the accreditation of clinical laboratories, according to the French Committee of Accreditation guidelines following the European reference Standard EN ISO 15189. Numerous papers have been published regarding biochemistry and immunology. However, data are lacking for automated complete blood count accreditation. We report here our experience at Hôpital européen Georges Pompidou hematology laboratory and present the performance characteristics of two mirrored LH750 Beckman-Coulter analysers, including precision, accuracy and uncertainty of measurement.