[Hematological aspects of Gaucher disease]. / Aspects hématologiques de la maladie de Gaucher.

PURPOSE: Gaucher disease is the most frequent lysosomal storage disease, and corresponds to an inherited deficiency of glucocerebrosidase. Due to excessive accumulation of glucocerebroside in bone marrow, cytopenia and bone lesions occur. KEY POINTS: The clinical signs at diagnosis include frequently anaemia, thrombopenia and splenomegaly. The hematologist is often in first line of the diagnosis, but it must avoid certain diagnostic traps (pseudo-Gaucher cells or even pseudo-pseudo-Gaucher cells in certain crystal storage diseases). The treatment of substitution when adequately carried out generally makes it possible to quickly improve the hematologic parameters. Another hematologic aspect must be evoked in Gaucher disease, i.e. the incidence of associated malignant pathologies and more particularly of multiple myeloma. Many cases of association between multiple myeloma and Gaucher disease have been reported in the literature. Recently two important series demonstrated the nonfortuitous character of this association. PROJECTS: The physiopathological links which could connect myeloma and Gaucher disease are not known to date. Immune network imbalance could be an interesting hypothesis that should require further investigations.

[Necrotic myocarditis in acute eosinophilic lymphoblastic leukaemia]. / Myocardite nécrosante révélant une leucémie aiguë lymphoblastique hyperéosinophilique.

INTRODUCTION: Hypereosinophilia can cause severe cardiac complications. The association between an acute lymphoblastic leukemia and hypereosinophilia was rare. We report a case of a 29-year-old man who presented a heart failure secondary to necrotic myocarditis related to an acute eosinophilic lymphoblastic leukaemia. EXEGESIS: The patient developed a heart failure and secondary a cardio-embolic stroke, due to a large mobile left ventricle thrombosis. His peripheral blood showed a total white count of 28,500 leucocytes/mm3 with 18,800 eosinophils/mm3. The myelogram cytology showed precursor B-cell acute lymphoblastic leukaemia with hypereosinophilia. CONCLUSION: The possibility of the rapid emergence of cardiac lesions in hypereosinophilic syndromes warrants very close physician vigilance. An Echocardiography and MRI performed at the early stage and in the follow-up allow to detect and to manage these cardiac disorders.

[Treatment of essential thrombocythemia]. / Traitement de la thrombocythémie essentielle.

PURPOSE: Essential thrombocythemia (ET) is a myeloproliferative syndrome that rises many therapeutic problems. This affection is rarely life threatening, but hemorrhagic and thrombotic complications must be prevented when possible. The rarity of these complications makes difficult the assessment of treatment efficiency. Few randomised clinical trials were done, and treatment often rests on retrospective studies. The potential toxicity of treatments, their leukemogenicity in particular, rises a decisional problem for young patients. We propose to review available data in order to propose the most rational treatment for each patient. CURRENT KNOWLEDGE AND KEY POINTS: After numerous years when we only disposed of retrospective studies, non-randomised prospective studies or isolated case-reports, two randomised trials allows us to more precisely define ET treatment. The first trial proved the efficiency of the hydroxyurea-aspirin association in the prevention of thrombotic events in high-risk patients. The second trial signalled to our attention the increased risk of bleeding of the association anagrelide-aspirin, with also the possibility of increased appearance of myelofibrosis. FUTURE PROSPECTS AND PROJECTS: New perspectives in the treatment of ET will require to get more insights in the role of hydroxyurea and anagrelide in particular by longer follow-up. But not less important is a better definition of the thrombosis risks (who has to be treated?) and also of the diagnostic groups since ET can, in some particular cases, be misdiagnosed with polycythemia vera or idiopathic myelofibrosis.

[Eosinophils and antitumour response]. / Eosinophiles et réponse antitumorale.

PURPOSE: Immune response probably plays a role in the tumour control. Cytotoxic T-lymphocyte response is antigen-specific and requires previous encounter with the antigen to develop an efficient immune response. Regarding the innate immunity, natural killer (NK) cells can destroy neoplastic cells lacking HLA class I molecules. In addition to these effector cells, eosinophils are granulocytes usually involved in allergic diseases or response to parasitic infections. Many types of cancer, however, are associated with eosinophilia, either in the tumour itself and/or in peripheral blood. We will focus our attention on the putative involvement of eosinophils in the antitumour response. CURRENT KNOWLEDGE AND KEY POINTS: Recent studies on the relationship between tumour and eosinophils have mainly focused on the << tumour-associated tissue eosinophilia >> (TATE), which seems to be more relevant than peripheral blood eosinophilia. Most studies show that TATE is a favourable prognostic marker, except in Hodgkin's disease, since eosinophils probably deliver in this case an antiapoptotic and proliferative signal for Reed-Sternberg cells via the release of soluble CD30L. FUTURE PROSPECTS AND PROJECTS: The putative anti-tumour effect of eosinophils relies on their tight contact with tumour cells. As a consequence, future immunotherapy studies aiming at an anti-tumour eosinophilic reaction might attract and activate eosinophils within the tumour itself. This could be obtained via direct injection of cytokines (IL-3, IL-5, GM-CSF...) at tumour site or by the use of expression vectors encoding for these molecules.

[Gelatinous bone marrow transformation in anorexia nervosa]. / Transformation gélatineuse de la moelle osseuse au cours de l'anorexie mentale.

Moderate hematologic abnormalities, like anemia or leukopenia, are frequently seen in anorexia nervosa, whereas pancytopenia and bone marrow abnormalities are uncommon. We report a case of tricytopenia with gelatinous bone marrow transformation in anorexia nervosa. Marrow gelatinous transformation (also called serous fat atrophy or starvation marrow) is characterized by the association of marrow hypoplasia and interstitial infiltration of a ground gelatinous substance (acidic mucopolysaccharides). Changes in peripheral blood cell counts are various and moderate, and do not always reflect the severity of bone marrow damage. The pathogenesis is not yet well elucidated but is certainly related to the nutritional status because gelatinous bone marrow transformation is found in anorexia nervosa and in other clinical situations with cachexia. Gelatinous transformation of the marrow is reversible with feeding.

Modulation of normal human erythropoietic progenitor cells in long-term liquid cultures after HIV-1 infection.

Long-term bone marrow cultures (LTBMC) have been infected by two isolates of human immunodeficiency virus type 1 (HIV-1) (HIV-1 LAV and HIV-1 NDK) at multiplicities of infection ranging from 10(2) to 2.10(6) tissue culture infectious units (TCIU) per 10(6) bone marrow mononuclear cells (BMMNC). These infected cells are nonproducer cells and the viruses can be rescued by coculture with peripheral blood lymphocytes, cord blood lymphocytes, or BMMNC and not by the CEM cell line. HIV-1 clearly is not cytopathic for these cells. Following production and growth of erythroid burst-forming units (BFU-E) and erythroid colony-forming units (CFU-E) for at least 6 weeks after infection with HIV-1 NDK, colony assays displayed a 50% inhibition of BFU-E production during 3 weeks of LTBMC. This was followed by a stimulation phase. On the contrary, HIV-1 LAV induces a 150% stimulation of BFU-E production, followed by 50% inhibition. Production of CFU-E was inhibited by 80-100% with the two isolates of HIV-1 after four weeks of LTBMC. Stimulatory and inhibitory activities were recovered from supernatants of infected LTBMC and lymphoid CEM cell lines, suggesting that HIV-1 induces release of a humoral factor responsible for disruption of hemopoietic progenitor cell production in vitro and consequently for hematologic abnormalities in AIDS patients.

Ribosome lamella complex in neoplastic cells of a Sézary's syndrome.

The first case of ribosome lamella complex (RLC) is reported in abnormal cells of a Sézary's syndrome, a T cell malignancy. Until now this ultrastructural cytoplasmic inclusion has usually been described in hairy cell leukaemia and other lymphoproliferative syndromes of B cell origin. Since RLC are also observed in abnormal lymphoid T cells, in non lymphoid cells, and moreover in non haematopoietic cells, they lack diagnostic specificity.

Histamine release reaction of basophils in chronic granulocytic leukaemia. Induction by heterologous anti-immunoglobulin E, concanavaline A, and phytohaemagglutinin; effect of heavy water.

Basophils possess membrane bound IgE molecules, and immunological activation leads to a secretory process with cell degranulation and histamine release. Heterologous anti IgE, concanavaline A, and phytohaemagglutinin are potent non-cytotoxic releasing agents. They operate by a mechanism similar to that of immunological activation. Heavy water is not a histamine releasing inducer but it increases histamine release of the cells. We studied the histamine release reaction of leukaemic basophils in 10 patients and found a physiological response such as that previously reported with normal human basophils.

Phase-I-II study of high-dose melphalan and autologous marrow transplantation in adult patients with poor-risk non-Hodgkin's lymphomas.

Eleven adult patients with poor-risk non-Hodgkin's lymphoma were treated with high-dose melphalan (140 mg/m2) or high-dose combination chemotherapy (BCNU, Ara-C, vindesine and melphalan) followed by autologous bone marrow transplantation. Six of the eight patients evaluable for response achieved complete remission and one achieved partial remission. Response duration ranged from 1.5 to 12 months (median 2 months). Prompt hematological recovery occurred in all patients. The duration of aplasia and the extrahematological toxicity were similar in both groups. High-dose melphalan alone or associated with other drugs followed by marrow infusion appears to produce a high response rate and demonstrates the potential for salvaging patients with refractory lymphoma.

High-dose melphalan and autologous bone marrow transplant for relapsed acute leukaemia.

Seven patients with relapsed acute leukaemia were treated with high-dose melphalan (HDM) followed by the infusion of autologous cryopreserved remission marrow. Toxicity was minimal and all seven patients had a complete response. Four patients are still in unmaintained remission at 14, 13, 10, and 3 months, the first two having received a second course of HDM to consolidate the result. The role of HDM as a form of intensification therapy for patients with acute myeloid leukaemia in first remission should be investigated.

Etoposide and cisplatinum in resistant lymphomas.

Etoposide and cisplatinum have used separately to treat refractory lymphomas. This report describes 22 patients in whom these two agents were used in conjunction. All had been extensively treated with standard therapies previously. The combination of etoposide and cisplatinum was chosen on the basis of preclinical evidence for synergy and because these agents do not cross-react. Cisplatinum was continuously infused for 5 days at a dose of 15 mg/m2/d. As a push a 100 mg/m2/d dose of etoposide was injected on days 1 and 2 of treatment. This schedule produced good responses in 18 patients, i.e. 15 partial remissions and three complete remissions. The side effects were acceptable.

Maintenance chemoimmunotherapy of nonlymphoblastic acute leukemias.

A trial of maintenance chemotherapy of nonlymphoblastic acute leukemia led to a comparison of two groups of patients in complete remission. Group 1 (14 patients) received only monthly reinduction chemotherapy. Group 2 (17 patients) received identical chemotherapy together with weekly immunotherapy combining BCG and irradiated leukemic cells. While the duration of the first complete remission was unmodified, the overall survival time and, above all, survival after the first relapse were prolonged in group 2 chemoimmunotherapy. These results were all the more marked when a homogeneous group of patients having received the same induction chemotherapy were considered.

[Recommended algorithms of prescription in the diagnosis of iron deficiency and overload]. / Algorithmes de prescription recommandés pour le diagnostic d'un déficit et d'une surcharge en fer.

In view of the recent development of new tests of biochemistry and molecular biology the assessment of iron status should be reconsidered and updated. The French Society of Clinical Biology (SFBC) and the French Society of Hematology (Cellular Hematology Group) recommend algorithms in the diagnosis of iron deficiency and iron overload bearing in mind the best efficiency and health economy. These recommendations are based on the known sensibility and specificity of each test. The analytical requirements for the determination of the tests as well as the clinical and biological signs evoking an iron deficiency or overload are recalled.

[Hairy cell leukemia: study of the development of 211 cases]. / Leucémie à tricholeucocytes: étude de l'évolution de 211 cas.

Large series of patients with hairy cell leukaemia have only recently been published. The 211 cases reported here provide useful information on the clinical presentation, prognostic factors, evolution and management of this uncommon disease. At presentation, 28% of the patients had no spleen enlargement, and only 20% had severe pancytopenia. However, severe neutropenia (less than 0.5 X 10(9)/l) was present in 32% of the cases. Prognosis was primarily related to the degree of peripheral cytopenia, usually corrected by splenectomy, but it was poor in both non-splenomegalic and splenectomized patients with persistent anaemia and neutropenia, and it is in these patients that other treatments should be tested.