Françoise Tassin

Clonal chromosome aberrations in Philadelphia-negative cells from chronic myelocytic leukemia patients treated with imatinib mesylate: report of two cases

Imatinib mesylate (tested as STI571), an abl kinase inhibitor, induces sustained, complete hematologic and cytogenetic responses in chronic myelocytic leukemia (CML) patients; however, emergence of clonal chromosomal aberrations in Philadelphia-negative (Ph-) cells during treatment has been reported. We describe two CML patients in chronic phase who presented with complete cytogenetic responses during imatinib mesylate therapy but developed new clonal chromosomal rearrangements in Ph- cells. The first patient presented with a duplication of chromosome 1, dup(1)(q21q42), and the second showed two new clonal aberrations consisting of inv(1)(q12q32) and del(7)(q22) in the same clone.

A Four-Parameter Index of Marrow Dysplasia Has Predictive Value for Survival in Myelodysplastic Syndromes

Marrow dysplasia is a major characteristic of patients with myelodysplastic syndrome (MDS), along with marrow blastosis, cytopenia and cytogenetic anomalies. However, the impact of the degree of marrow dysplasia on survival has not been fully assessed. In this retrospective analysis of 111 patients selected according to the IPSS criteria of MDS diagnosis, the presence or absence of 21 dysplasia characteristics recognizable in bone marrow smears stained by the May-Griinwald-Giemsa method was correlated with patient survival. Using Cox proportional hazards regression analysis, megaloblastosis (MEGALO), neutrophil agran-ularity (AGRAN) and hypogranularity (HYPOGRAN) were highly significant predictors (p < 0.005), and Pelger-Huët anomaly (PELGHUET) a significant predictor (p = 0.05), of patient survival. The regression analysis yielded a dysplasia-based risk index (D1) where DI = 1.26 MEGALO + 0.82 AGRAN - 1.08 HYPOGRAN + 0.45 PELGHUET. The two subgroups of 60 and 47 patients with DI ≤ 0 and > 0 showed highly significant differences in median survivals (2.6 vs 1.1 yrs; p <0.0001). Multivariate analysis further showed that DI offered additional predictive power that was independent of that provided by the IPSS (p=0.002 and 0.001 respectively). Analysis of survival curves stratified for IPSS and DI showed that the additional predictive power offered by inclusion of the DI essentially concerned the IPSS low/INT-1 risk categories. Further stratification for age did not improve survival prediction. The data indicate that a set of 4 dysplasia parameters can offer some prediction for survival of MDS patients in addition to that provided by the IPSS. Further mul-ticenter studies should aim at including some form of evaluation of the degree of dysplasia in prognostic systems.

Cessation of intensive treatment with recombinant human erythropoietin (rHuEpo) Is followed by secondary anemia

Abstract Little information is available on the evolution of hematological parameters after cessation of intensive treatment with rHuEpo. Groups of 3–5 rats were iron overloaded to avoid functional iron deficiency and received daily IV injections of 150 U rHuEpo for 20 days. During treatment, reticulocytes, soluble transferrin receptor (sTfR, a quantitative measure of total erythropoiesis) and Hct increased progressively (p

Translocation (2;3)(p21;q26) as the Sole Anomaly in a Case of Primary Myelofibrosis

Translocation t(2p;3q) is a rare but recurrent finding in myeloid disorders. We present the first case of primary myelofibrosis with t(2;3)(p21;q26) as the sole chromosomal anomaly. The comparison with the 11 other previously published myeloid-associated t(2p;3q) cases confirms that this nonrandom translocation involves a pluripotent stem cell and is associated with a poor prognosis.

Inositide-specific phospholipase c beta1 gene deletion is a rare event in myelodysplastic syndromes.

Inositide-specific phospholipase c β 1 gene deletion is a rare event in myelodysplastic syndromes

Lymphocytoses B monoclonales : de la revue de la littérature à la pratique de laboratoire.

Monoclonal B-cell lymphocytosis (MBL) is defined as an asymptomatic condition characterized by the presence of less than 5,000 monoclonal B-cells per microliter and the absence of clinical signs or symptoms of a B-cell lymphoproliferative disorder. Most MBL cases involve B cells presenting an identical phenotype to CLL (CLL-like MBL) with a Catovsky-Matutes score of 3 to 5 and share the same chromosomal abnormalities than CLL. Depending on the absolute B cell count, one may distinguish low-count CLL-like MBL (<500 B cells/μL) which have no evidence of progression, no reduction in overall survival, no increase in infection risk and do not require any specific follow-up. Patients with clinical CLL-like MBL (>500 B cells/μL) have a 1% to 2% per year risk of progression to CLL requiring therapy, a higher risk of infectious complications and mortality implicating an annual follow-up by hematologist. MBL may also express other less common phenotypes and are named atypical MBL in case of CD5 antigen expression (Catovsky-Matutes score: 1-2) and non-CLL-like MBL for CD5 negative cases (Catovsky-Matutes score: 0-2). Their poorer prognosis implicates imaging studies, bone marrow biopsy and cytogenetic analysis in addition to physical examination in order to rule out non-hodgkinien lymphoma, and require a more frequent follow-up. This review focuses on key concepts in the classification, diagnosis, monitoring and biology of MBL in laboratory practice.

Atypical plasma cells with coexpression of myeloid markers and bundles of Auer rod-like inclusions.

Sir, Although variable morphological and immunophenotypic features of plasma cells are described [1], plasma cells with bundles of Auer rod-like inclusions and myeloid markers coexpression have never been reported. A 76-year-old patient complaining of a long-lasting bone pain in the lumbar region was admitted in the hospital. Physical examination revealed a patient in poor condition. Laboratory tests showed a mild anemia (hemoglobin 9.8 g/dL) with normal leukocyte and platelet counts, elevated LDH, and renal failure. Serum protein electrophoresis revealed a severe hypogammaglobulinemia (0.36 g/dL) and quantitative evaluation of immunoglobulins showed normal IgA but decreased IgG and IgM. The urinary protein level was increased at 1073 mg/L with predominant monoclonal kappa light chains. A scintigraphy showed multiple nonspecific hyperfixation sites. X-ray skeleton examination and magnetic resonance imaging had not been performed when bone marrow cytology was carried out. The bone marrow (BM) aspirate smear revealed a hypercellular marrow with 15% infiltration by two atypical cell populations. The first population corresponded to plasma cells containing intracytoplasmic azurophilic granules, termed Buhot plasma cells. The second population contained bundles of Auer rod-like inclusions and a fragmenting cytoplasm. We also detected extracellular Auer rod-like depositions (Figure 1). Even if Auer rods are indicative of the myeloid lineage of blasts [2], Auer rod-like inclusions have seldom been reported in B-cell neoplasms, including chronic lymphocytic leukemia and

Haematological and molecular responses in refractory anaemia with ring sideroblasts and thrombocytosis treated with lenalidomide

To the Editor: Refractory anaemia with ring sideroblasts and thrombocytosis (RARS-T) is a rare entity and is defined as an overlap syndrome with clinical and morphologic features of both myelodysplastic syndrome (MDS) and BCR-ABL-negative myeloproliferative neoplasm, including marked thrombocytosis associated with abnormal megakaryocytes (1). Mutations in the Janus Kinase 2 gene (JAK2) and/or Splicing Factor 3B subunit 1 (SF3B1) gene have been detected in 50–70% of patients with RARS-T (2–4). The presence of such a mutation in either JAK2 or SF3B1 was associated with a better overall survival in a recent European study (5). Because of its activity in lower-risk MDS with or without the 5qcytogenetic abnormality (6) and in myelofibrosis (7), lenalidomide treatment has been given with success in two patients with RARS-T. In this letter, we would like to report a case of RARS-T that was successfully treated by lenalidomide. An 84-years-old woman was referred for unexplained normocytic anaemia (Hb 7.7 g/dL) with marked thrombocytosis (1515 9 10/L). Peripheral blood smear showed a left shift in neutrophils. Bone marrow cytology disclosed hypercellularity (illustrated in Fig. 1A) with 15.6% erythroid cells, 77.6% granulopoietic cells, 3.2% monocytes, 4.0% lymphocytes, 1% blasts and numerous megakaryocytes. Ring sideroblasts constituted 90% of erythroid precursors (Fig. 1B). Erythropoiesis and granulopoiesis were both hyperplasic with evidence of dysplasia. The most prominent feature was the presence of numerous atypical megakaryocytes of different sizes and shapes, many with hypolobated nuclei (Fig. 1C). Metaphase cytogenetics revealed the presence of 5qin one mitosis, which could not be confirmed by FISH using a specific EGR1(5q31) probe, or Array-CGH analysis (SurePrint G3 Human CGH Microarray). We could not detect any mutation in the SF3B1 gene, but the JAK2V617F mutation was retrieved and estimated at 12.5–31% of JAK2 alleles. Based on these findings, RARS-T with a JAK2-V617F mutation was diagnosed. Because of her anaemia, cytoreductive treatment was not an attractive option. After transfusion of 4 units of red blood

CHIC cells: a novel ALK+ cell line derived from a relapsed anaplastic large cell lymphoma.

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Reply to Lo Vasco et al.

In their letter,1 commenting to our paper,2 Lo Vasco et al. precise the prognostic data of the MDS patients included in their original paper3 on cryptic deletions of the inositide-specific phospholipase c 1 gene (PI-PLC 1). All the patients with MDS and a normal karyotype at diagnosis were at high risk as evaluated by clinical meanings (French-American-British classification (FAB), International Prognostic Scoring System (IPSS)). In our series,2 selection of the patients was done according to the unique criteria given by Lo Vasco et al. in their original paper,3 that is, the evidence of a normal karyotype at diagnosis. The IPSS score in our cases was low (12 patients), intermediate (10) or high (1). The discrepancies between the results of both studies probably can be explained by differences in the selection of the MDS populations. The data of Lo Vasco,1, 3 strictly related to high-risk IPSS categories, show that, respectively, 4/9 and 4/13 cases bear the PI-PLC 1 deletion. On the contrary, in our series where only one patient was at high risk, none of the 23 patients showed a cryptic deletion of band 20p12.3.2 Similar observations were recently done by Verburgh et al.4 who failed to detect a deletion of the PI-PLC 1 gene in a series of 33 MDS patients with normal karyotype, of which two belonged to the high-risk group as defined by the IPSS. In the same way, no deletion was observed in the 10 low-risk MDS patients reported in the comment of Lo Vasco et al.1 All these data indicate that the deletion of the PI-PLC 1 gene probably will not be detected in MDS patients with normal karyotype and low or intermediate IPSS risks. Conversely, in the high-risk group, the deletion could be frequent (about one-third of the reported cases till now) and associated with alterations of the signalling pathways and short survivals.