[Haematopoietic stem cell transplantation in the treatment of autoimmune diseases]. / Intensification thérapeutique dans les maladies auto-immunes.

PURPOSE: During the past ten years, more than 1000 patients suffering from severe autoimmune disease have received an autologous haematopoietic stem cell transplant. These new therapeutic have been used in systemic sclerosis (scleroderma), multiple sclerosis, rheumatoid arthritis, juvenile idiopathic arthritis and systemic lupus erythematosus. CURRENT KNOWLEDGE AND KEY POINTS: Autologous haematopoietic stem cell transplantation has become a curative option for condition with very poor prognosis as severe systemic sclerosis, lupus erythematosus or other systemic diseases. This review summarizes the current experience in the phase I and II clinical trials in Europe and North America. We describe the main results and the limits of stem cell transplantation in systemic diseases. FUTURE PROSPECTS AND PROJECTS: Autologous haematopoietic stem cell transplant in the treatment of autoimmune disease has evolved from a experimental concept to a clinically feasible and powerful therapy for selected patients with severe disease.

Evaluation of residual disease in B-cell chronic lymphocytic leukemia patients in clinical and bone-marrow remission using CD5-CD19 markers and PCR study of gene rearrangements.

We evaluated minimal residual disease (MRD) in 23 CD5 + B-chronic lymphocytic leukemia (CLL) patients who achieved clinico-hematological remission confirmed by bone-marrow biopsy. MRD was evaluated by dual marker analysis flow-cytometry using CD5 and CD19 markers, and by the study of Ig heavy chain gene rearrangements using the fast polymerase chain reaction (PCR). According to our laboratory conditions patients were considered to be in complete phenotypic remission when total CD19+ cells were < 25% and the ratio of CD5 + CD19 + /CD19 + cells was < 25%. According to these strict criteria only 9 of the 23 patients were in complete phenotypic remission. In order to evaluate the sensitivity of the above method, PCR analysis of the configuration of the Ig heavy chain gene region was performed in 12 of these patients. Five of 7 patients in complete phenotypic remission retained a detectable monoclonal rearrangement of the Ig heavy chain gene. For the remaining 5 patients in partial phenotypic remission, only one failed to show a monoclonal band and this is probably explained by the presence of an unusual gene rearrangement. In conclusion, this study suggests that PCR is more sensitive than dual marker flow-cytometry for evaluation of residual disease and that it is indeed possible to achieve complete remission at the molecular level, in B-CLL. Nevertheless, we suggest a word of caution as this was a retrospective study, and samples were not assessed before treatment. Thus the possibility that apparent molecular remission might correspond to unusual gene rearrangements cannot be completely excluded in these cases.

Activated Stat related transcription factors in acute leukemia.

Cell proliferation and differentiation are under the control of cytokines and growth factors. Different signaling pathways are involved in the transmission of a specific signal through successive phosphorylation and dephosphorylation of proteins leading to gene transcription necessary for growth and differentiation. The cytokines and growth factors activate the Stat family of transcription factors. The Jak-Stat pathway is essential for cytokine signal transduction. Dysregulation of this cascade might lead to uncontrolled hematopoiesis. Studies have been carried out to examine the functionality of this pathway in cells from patients with acute leukemia. Members of the Stat protein family (Stat1, Stat3 and Stat5) are constitutively activated in cells collected from some acute leukemias suggesting dysregulation of the Jak-Stat pathway. Evidence of the existence of constitutively activated spliced variants of Stat3 and Stat5 proteins are described. The mechanisms of such activation remain to be clarified.

[Severe pulmonary embolism and recurrent thrombophlebitis caused by hereditary antithrombin III deficiency]. / Embolie pulmonaire sévère et thrombophlébite récidivante en rapport avec un déficit héréditaire en antithrombine III.

Severe pulmonary embolism with thrombosis of the inferior vena cava was observed in a 16 year old girl with no risk factors and treated successfully by fibrinolytic therapy. Secondarily, despite heparino-therapy, upper limb venous thrombosis occurred. Investigation of the clotting factors in the patient and her family revealed a hereditary deficit of antithrombin III. The features of the haemotological diagnosis of this rare condition and the therapeutic implications are discussed.

Filterability in children.

The filterability of total blood and erythrocytes has been investigated in 36 children from 2 to 14 years old by the filtration method developed by Reid. Red blood cells being obtained by centrifugation, were washed three times and resuspended in saline. Filterability was recorded as the filtration time of 1 ml of total blood or red cells suspension. The filtration time of total blood was: 49.10 +/- 14.5 s/ml; that of resuspended cells was: 18.19 +/- 6.16 s/ml. These results have been correlated with age, fibrinogen, white blood cells, glycaemia, haematocrit, and compared with the results obtained in 42 adults whose filtration times were: 33.04 +/- 7.40; and red cells' time: 13.99 +/- 2.95. Statistical analysis shows that the difference is very significant and not correlated with the investigated factors. Erythrocyte filterability may be influenced by still unknown factor.

[Relevance of cytological and immunophenotypical analysis for the diagnosis of B-cell chronic lymphocytic leukaemia]. / Pertinence des analyses cytologiques et immunophénotypiques dans le diagnostic de la leucémie lymphoïde chronique B.

The objective of this study was to describe the cytological and immunophenotypical parameters evocative of B-cell Chronic Lymphocytic Leukaemia (B-CLL) and their ability to participate to the differential diagnosis of other B-chronic lymphoproliferatives disorders with blood dissemination (B-CLD). Two groups of pathology included 92 patients, 79 patients had a B-CLL and the 13 other had a B-CLD (1 Prolymphocytic Leukaemia, 12 non- Hodgkin's Lymphoma in which 4 Splenic Lymphoma with Villous Lymphocytes or SLVL). The lymphoid morphology was studied on blood smear stained with May Gr nwald Giemsa and the immunophenotypical analysis was performed by flow cytometry. The 72 patients with B-CLL were characterized by a predominance of small mature lymphocytes with a Matutes's CLL score 3 (generally CD5+, CD23+, SmIg poor expression). 4 out of B-CLL with cleaved lymphocytes 5 % showed the same immunological characteristics than the typical B-CLL cases. 3 cases of B-CLL with prolymphocytes between 5 and 55 % showed in 2 cases an immunophenotyping compatible with the diagnosis of B-CLD. The presence of shadow cells of Gumprecht was highly evocative of B-CLL. In conclusion, the cytological analysis remains at the root of any diagnosis and can be sufficient in most cases of typical CLL with the presence of shadow cells of Gumprecht on the blood smear. In case of presence of cleaved lymphocytes, the immunophenotyping becomes essential to confirme the diagnosis of B-CLL. In prolymphocytic cases, the differential diagnosis between mixed CLL and B-CLD (especially Mantle Cell Lymphoma and Marginal Zone B-Cell Lymphoma without villous lymphocytes) needs a multidisciplinary approach (clinical, cytogenetical and histological).

[Disappearance of auto-antibody-induced haemolysis after resection of a gastric stromal tumor. Case report and review of the literature]. / Disparition des autoanticorps induisant une hémolyse après résection d'une tumeur stromale gastrique. Description d'un cas et revue de la littérature.

INTRODUCTION: There are two types of autoimmune haemolytic anemia, idiopathic or associated to other disorders (infections, thyroidal diseases, cancer.). The treatment of this particular anemia depends on the primary or secondary feature. EXEGESIS: We report the case of a 76-year old woman, presenting an autoimmune haemolytic anemia with a positive direct Coombs test in IgG. The corticodependance of this anemia after 6 months of treatment had indicated a splenectomy. During surgery, a gastric stromal tumor was discovered. After removal of the tumor and splenectomy, the haematological symptomatology quickely disappeared and induced the negativation of the Coombs test within a post operative period going from 7 to 14 months, without any immunosuppressor treatment. CONCLUSION: Splenectomy does not induce the negativation of a Coombs test in an autoimmune haemolytic anemia, someaning that there is a link between the anemia and the tumor. This observation is completed by a review the literature.

CD66c expression in B-cell acute lymphoblastic leukemia: strength and weakness.

INTRODUCTION: In B-cell acute lymphoblastic leukemia (B-ALL), testing at diagnosis for BCR/ABL1 gene rearrangements is mandatory for prognostic stratification and treatment decisions. Several diagnostic methods have been proposed using flow cytometry to identify BCR/ABL1(+) B-ALL. METHODS: We evaluated expression of the myeloid antigen CD66c by flow cytometry in B-ALL. We studied 94 patients with B-ALL. The t(9;22)(q34;q11) or BCR/ABL1 rearrangement was detected by cytogenetic analysis or RT/PCR. Myeloid antigens CD66c, CD13, CD33, CD117, Myeloperoxidase, CD15 and CD65 were determined by flow cytometry. RESULTS: Of these 94 cases, 17 (18%) cases displayed BCR/ABL1 gene rearrangements and 38 (40%) cases were CD66c positive. CD66c was the most common myeloid antigen expressed on malignant lymphoblasts. Its expression was correlated with BCR/ABL1 rearrangements (P = 0.0001): sensitivity 82%, specificity 69%, positive predictive value 37% and negative predictive value 95%. Co-expression of CD66c(+) CD13(+) was more frequent in BCR/ABL1(+) B-ALL (29%) than BCR/ABL1(-) cases (4%) (P = 0.0044). Some BCR/ABL1(-) B-ALL cases (including hyperdiploid or cases with normal karyotype) were CD66c positive (31%). CONCLUSION: CD66c expression is correlated, but not specifically, with BCR/ABL1 rearrangement. It would seem better to interpret the absence of CD66c expression with a lack of BCR/ABL1 rearrangement. This myeloid antigen could be interesting in the detection of minimal residual disease.

[Hereditary thrombocytopenia-thrombocytopathy with myelofibrosis (author's transl)]. / Thrombopénie-Thrombopathie héréditaire avec myélofibrose.

A case of hereditary autosomal recessive thrombocytopenia is reported. Thrombocytopathy is associated with the thrombocytopenia. There is a contrast between the cytologic aspect of poor bone-marrow without any megakaryocyte and the histologic aspect of dense bone-marrow with a normal number of megakaryocytes. Myelofibrosis can explain this discrepancy. The life time of platelets being just a little shortened, the disease is probably due to a lack of bone-marrow production.

[Erythroblastopenia caused by parvovirus in siblings, revealing a hereditary spherocytosis. Apropos of a case]. / Erythroblastopénies à parvovirus dans une fratrie, révélatrices d'une sphérocytose héréditaire. A propos d'un cas.

Following the occurrence in two siblings of parvovirus B19-related acute transient erythroblastopenia with specific IgMs, hereditary spherocytosis (HS) was diagnosed for the first time in the two patients as well as in three other members of the family.