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In a compatible clinico-radiological setting, the diagnosis of Erdheim-Chester disease (ECD) involves the analysis of histiocytes in tissue biopsies: they are typically foamy and CD68+ CD1a, whereas in Langerhans cell histiocytosis (LCH) they are CD68+ CD1a+. Overlap forms of histiocytoses are frequent. Technetium bone scintigraphy showing nearly constant tracer uptake by the long bones is highly suggestive of ECD and a 'hairy kidney' appearance on abdominal CT scan is observed in more than half ECD cases. CNS involvement is a strong prognostic factor and an independent predictor of death in cases of ECD. Optimal initial therapy for ECD appears to be administration of IFN-α (and/or pegylated IFN-α) and prolonged treatment significantly improves survival; however, tolerance may be poor. Best alternative therapies are anakinra, mainly effective for mild forms of the disease, infliximab, and sirolimus. Cases of ECD present with strong systemic immune activation, involving IFN-α, IL-1/IL1-RA, IL-6, IL-12, and MCP-1, consistent with the systemic immune Th-1-oriented disturbance associated with the disease. Between 57 and 75 % of ECD patients carry the BRAF

Secondary acute myeloid leukaemia (AML) occurring after breast cancer is a rare long-term complication of the chemo- and/or radiation therapy required to treat breast cancer. The usually recognized curative option of these secondary AML includes courses of anthracycline-based chemotherapy followed by haematopoietic stem cell transplantation (HSCT). Cardiac dysfunction during AML treatment of these patients previously treated with anthracyclines for breast cancer has not been reported to date. We evaluated the evolution of cardiac function in seven patients treated with anthracyclines and/or autologous or allogeneic bone marrow transplantation for secondary AML occurring after breast cancer. All of the patients who received a cumulative anthracycline dose above the cardiac toxicity threshold developed cardiac symptoms during AML chemotherapy courses. Moreover, four of the five transplanted patients developed severe heart failure among which two were fatal. Thus, the risk of severe cardiac dysfunction after treatment of secondary AML following breast cancer must be taken in account as part of the therapeutic strategy of those patients. As discussed here, an accurate evaluation of risk factors, the use of sensitive detection tests and of cardioprotective drugs as well as that of non-cardiotoxic chemotherapy might decrease the occurrence and severity of this life-threatening complication.

Congenital cutaneous leukaemia is rare.A two-month-old girl presented bluish cutaneous macules of the trunk, histological examination of which suggested acute myeloid leukaemia (LAM B 5). The blood picture was negative for circulating tumour cells and the outcome under chemotherapy was favourable at one year of follow-up.The prognosis of congenital leukaemia is serious. Aleukaemic congenital leukaemia is seen occasionally but is rare. The existence of multiple cutaneous tumours in newborn infants raises the possibility of TORCH infection and of other malignant tumours such as nephroblastoma or neuroblastoma.

A complete blood analysis with a careful morphologic examination of peripheral blood and bone morrow smears completed by cytochemical reaction will help to classify the most acute myeloid leukaemia (AML). Actually, the study of other cytogenetis and immunophenotypic markers are now necessary to confirm diagnosis. The World Health Organisation WHO classification (2001) incorporates theses approaches. The purpose of this study is a bio-clinical review according to the WHO recommendations in 153 cases of LAM diagnosed between January 1998 and December 2003. The patients were aged 2 months to 90 years with sex ratio (M/F) of 1,22. The morphologic conclusion was difficult in 12% cases. Presence of dysplasia is noted in 50% of cases with multilineage dysplasia in 42% of cases. Our results showed cloned chromosomal abnormalities in 57% of cases (t(8;21): 12%, t(15;17) : 10%, Inv16: 1,3%, 11q23: 2,6% et complex karyotype: 14,3%). In 69% of cases with multilineage dysplasia, the karyotype was normal. 3 cases of LAM were noted at patients treated for breast cancer with chirurgic chemotherapy and radiotherapy 3, 4 et 5 years after treatment (LAM3 with t(15;17), LAM4 with genetic abnormalities of chromosomes 3, 5, 7, 8, 9, 14 et 16 et LAM 6 with genetic abnormalities of chromosomes 4, 7, 12, 14, 19 et 21). In WHO classification, cytology is essential in diagnosis of LAM even if the karytype have an important prognostic value. Research of signs of dysplasia lineage after lineage constitutes an important microscopic work and it is difficult to quantify dysplasia when the lineage is poor.

Despite important progress in the therapy of acute myeloid leukaemia (AML) most patients relapse and die from the disease, underlying the need for potent and more specific drugs for the treatment of this pathology. Recently, we demonstrated that the PI3-kinase-Akt-mTOR (mammalian target of rapamycin) pathway is constitutively activated in about 60% of AML patients cells. In vitro, low doses of the specific inhibitor of mTOR, rapamycin, block the phosphorylation of the classical targets of this kinase and inhibit the proliferation of leukemic progenitors without affecting the growth of normal haematopoietic progenitors. The results of this preclinical study led us to investigate the activity of rapamycin in relapsed, refractory, or poor-risk AML patients. The results of this study will be discussed in the review.

Myeloid sarcoma is a malignant neoplasia composed of abnormal myeloid or monocytic cells, often localized in bones, but also rarely in extra-medullary sites such as lymph nodes, skin and soft tissue. We report a case of caecal myeloid sarcoma, diagnosed in a 60 year old woman who complained from abdominal pain and weight loss, in absence of any medullary disorder. Initially misdiagnosed as a B lymphoma because of a weak positivity for CD79a, the diagnosis of primitive caecal myeloid sarcoma was eventually established after further investigations showing a positivity for lysozyme and myeloperoxidase. This report of such a rare clinical and pathological presentation of a myeloid sarcoma underlines a difficult differential diagnosis for which adequate immunohistochemistry, including lysozyme and myeloperoxydase is mandatory.

We report the case of a 8-year-old girl diagnosed with myelodysplastic syndrome. This case was morphologically characterized by the presence of bundle of Auer rods in the neutrophils. The evolution of the disease was marked by a quick transformation in a acute myeloid leukaemia with t(8;21) refractory to treatment. We reviewed the literature for clinical, biological and therapeutic features of this rare childhood hemopathy.

Although the French-American-British (FAB) morphologic classification of myeloid malignancies has been accepted for many years, the important advances in cytogenetic, immunophenotype and genetic fields needed to be integrated in an updated approach using all the available informations. Thus, the World Health Organization (WHO) Classification of haematopoietic malignancies not only incorporates morphology, immunophenotype, cytogenetic and molecular features, but also ensures to be clinically useful. This collaborative project has begun in 1995 and has been published in 2001. The proposed WHO classification is less a disruption with regard to the FAB classification than an updated revision where morphology is always important. These review emphasises the modifications proposed in the new WHO classification concerning the myeloid disorders.

Fifty percents of cancer arise in people older than 65-year-old. Most clinical trials in cancer treatment are limited in patients younger than 65-year-old. We review literature-describing particularity of cancer treatment in elderly patients.Therapeutic decisions should be based on an estimation of the patient's life expectancy, and risks and benefits should be weighted up accordingly. Geriatric oncology is made of a geriatric evaluation of patient and of knowledge of clinical trial about elderly patients.We present in this issue the principle of geriatric evaluation and the results of recent clinical trial on elderly cancer patients.

Disseminated fusariosis in children is a rare and serious fungal infection, that occurs especially in neutropenic immunosuppressed patients, treated for malignant hemopathy, or bone marrow transplant recipient. Treatment is difficult and mortality is estimated between 50 and 70% in adult patients. CASE REPORT 1: A ten-year-old boy, treated for an acute lymphoblastic leukemia in second relapse, presented a disseminated fusarium spp infection, that occurred during neutropenia. He died due to fusariosis infection in spite of amphotericin B treatment. CASE REPORT 2: A ten-year-old neutropenic girl, treated for an acute myeloïd leukemia, presented disseminated fusariosis, uncontrolled by amphotericin B. Recovery was observed after voriconazole introduction and resolution of neutropenia. Ten months later, she presented a leukemia's relapse, treated by new intensive chemotherapy with secondary prophylaxis by voriconazole, without fusariosis's recurrence.Voriconazole, a new triazole agent, seems to be an alternative antifungal agent to amphotericin B for disseminated fusarium infection, either at the acute phase or for secondary prophylaxis.

A group of 139 patients with de novo acute myeloid leukemia were investigated to determine the prognostic significance of karyotype on early death, complete remission, continuous complete remission and survival. There were 27 children and 112 adults. Mean age was 32 years. t(15;17) was found associated with a high rate of early death and a diploid karyotype with long continuous complete remission. The presence of a structural change was predictive of shorter survivals. The study of the prognostic impact of recurrent anomalies reveals a good prognostic impact for normal karyotype (1 year survival probability: 40%), followed by t(8;21) (1 year survival probability: 24%), and by t(15;17) (1 year survival probability: 9%).

Main chemotherapy regimens used to treat adult patients with acute myeloid leukemia (AML) in first or further relapse were reviewed. In retrospective study, second complete remission rates ranged from 30% to 64%, while they ranged from 8% to 89% in prospective trials. The second complete remission rates were closely associated with age and duration of first complete remission. Combination therapies resulted in higher complete remission rates but were associated with higher toxicity. Median duration of second complete remission was14 months and overall median survival was12 months. The probability of 3-year survival ranged from 8% to 29%. The inhomogeneity of these studies, the differences in dosages and schedules, and the frequent absence of randomisation make it difficult to select the best salvage therapy. No reinduction regimen has so far clearly proven superior. Only stem cell transplantation provided durable remissions for the majority of AML patients after a first relapse. Considering the poor outcomes of patients with AML in first relapse, improved therapies need to be developed. A number of novel agents that include several differentiation agents, enzyme inhibitors, and monoclonal antibodies have been studied to provide improved outcomes for patients with AML who have relapsed. This is the same for acute promyelocytic leukaemia (APL). Arsenic trioxide has shown great promise for the induction, consolidation, and maintenance of complete remission in relapsed patients with APL. Within this context autologous and allogeneic bone marrow transplantations are also considered in second or subsequent relapse. Molecular monitoring for the PML-RARalpha fusion protein permits prompt intervention for early molecular relapse ultimately improving chances of prolonged remission.

The beginning of this century was marked, in our specialty as in other, by two revolutions: the routine use of molecular biology tools for a better prognosis of the disease (flt3 receptor duplication in AML, mutational profile of Ig genes in CLL, gene expression profile with ARN chips in aggressive lymphomas.), and the discovery of "intelligent" molecules, targeting the tumoral cell. In this category, the most appealing is the STI571 (Gleevec , Novartis), targeting the molecular abnormality of the cells expressing bcr-abl protein: CML, ALL Ph1(+). Other molecules targeting signal transduction proteins (ras farnesylation inhibitors for example) are already in clinical trials. The increasing therapeutic use of monoclonal antibodies is also to be cited, with a special mention concerning the rituximab, used in several B lymphoid pathologies, from lymphoma to autoimmune diseases. His very good tolerance permits his use in ambulatory patients, and his combination with chemotherapy or his linkage with radioactive elements render this molecule indispensable. The other side of these molecules is their incredibly high cost, explaining the uncontrolled expenses in 2001 of hospitals hosting hematology as well as oncology activities.

The diagnosis and management of acute myeloid leukemia (AML) in the elderly is reviewed, including the basic aspects of epidemiology, cytogenetics, and prognostic factors. AML at higher ages is associated with several unique biologic and clinical characteristics. It generally arise from an early level of hematopoietic stem cells, and has a particularly high incidence of poor prognostic karyotypes. Effective treatment of the elderly patient with AML remains a challenging task. The importance of therapeutic approaches and promising new drugs is summarized. Prospective randomized studies clearly demonstrate that elderly patients benefit from intensive induction therapy. Hematopoietic growth factors accelerate the recovery from treatment-induced neutropenia and may improve the outcome. In patients not eligible for intensive chemotherapy, prospective studies testing different palliative or moderately intensive treatments are needed to improve quality of life and survival. New treatment strategies need to be developed to further improve on the therapeutic perspectives for elderly patients with AML.

Two distinct clinical syndromes have been associated with the p11.12 region of the short arm of chromosome 8: stem-cell myeloproliferative disorder (B-or T-cell lymphoblastic leukemia/lymphoma with myeloid hyperplasia and peripheral blood eosinophilia) and acute myeloid leukemia (myelomonocytic or monocytic with erythrophagocytosis). The FGFR1 and MOZ genes are rearranged in these diseases and encode one of the four fibroblast growth factor receptors and a member of a novel histone acetyltransferase family, respectively. The predicted fusion proteins that are putatively oncogenic - FOP-FGFR1, CEP110-FGFR1, and FIM-FGFR1 - and - MOZ-CBP, MOZ-p300, and MOZ-TIF2 - lead to tumorigenesis through distinct pathways. The constitutive kinase activity triggered by dimerization mediated by the protein-protein interaction motifs of the FGFR1 protein partner regardless of external stimuli and the delocalization of the fusion proteins compared to their normal counterparts may lead to tumorigenesis presumably by inducing inappropriate recruitment in the cytoplasm of signaling substrates. Currently, little is known about the precise role of MOZ in the regulation of gene transcription. However, all the aberrant proteins described to date retain the MOZ histone acetyltransferase domain fused to that of the transcription coactivators CBP, p300, and TIF2. The fusion of two acetyltransferases whose activity may be mistargetted or misregulated could be a critical event in leukemogenesis. The increasing number of translocations affecting FGFR1 and MOZ strongly suggest their involvement in oncogenic processes and point to these proteins as potential therapeutical targets.

Engraftment in relation to infused CD34+ cell number was retrospectively analysed in 66 patients with hematological diseases: non-Hodgkin's lymphoma (n = 33), multiple myeloma (n = 21), acute myelogenous leukemia (n = 7), Hodgkin's disease (n = 4) and myelodysplastic syndrome (n = 1). Progenitor cells were mobilized with rhG-CSF, alone or in association with chemotherapy. The cells were harvested by leukapheresis until at least 2 x 10(6) CD34+/kg body weight were obtained. A total of 194 leukaphereses were performed (median = 3 per patient, range 1-9). A median of 3.40 x 10(8) nucleated cells/kg (range 0.31-27.59) and a median of 7.15 x 10(6) CD34+ cell/kg (range 1.31-115.70) were transplanted. Regardless of transfusional support or patient diagnosis, engraftment was rapid in patients who had receivedor = 5 x 10(6) CD34+ cell/kg. In this case, absolute neutrophil blood countor = 0.5 x 10(9)/l was obtained on day 12 post graft (range 7-19) and platelet countor = 20 x 10(9)/l was also reached after the same median time interval (range 8-121). From the present results, a minimal threshold of 5 x 10(6) CD34+ cell/kg appears to be suitable for providing rapid and complete hematopoieitc reconstitution in patients exposed to high doses of chemotherapy with or without total body irradiation. Furthermore, administration of rhG-CSF during post-graft period significantly decreased the neutrophil time recovery (P = 0.002) but not that of platelets (P0.05).

Inflammatory response involves complex signalling pathways at cellular and molecular levels. During the cellular activation, intracellular substrates are subsequently phosphorylated for inducing transcription and synthesis of various inflammatory and/or anti-inflammatory mediators. This review focuses on the description of the main mechanisms involved in the activation signalling pathways that occur during inflammatory processes.

P glycoprotein (Pgp) expression is associated with failure of anticancer chemotherapy in acute myeloid leukemia (AML). However, a consensus has been difficult to reach, due to the variable results obtained by different methods. Samples of 27 patients with AML were studied here according to international recommendations (Beck, et al. , Cancer Research 1996; 56: 3010-20). Pgp expression was performed by immunocytochemistry (ICC) using the avidin-biotin peroxidase technique with JSB1 and UIC2 monoclonal antibodies. Flow cytometry (FCM) analysis of Pgp was investigated using UIC2 in an indirect immunofluorescent assay. UIC2 staining was measured by the Kolmogorov-Smirnov statistical test and fluorescence intensity ratio. Finally, the rhodamine 123 test (Rh 123) with or without verapamil was performed to detect functional activity.by ICC, results of JSB1 and UIC2 were consistent in 94% of the cases. In 74% of the cases, concordant conclusions were observed by ICC and FCM. Overall, Pgp expression was detected in 67% of the cases (ICC/JSB1+ and ICC/UIC2+ or FCM/UIC2+). Functional activity of Pgp was shown in 59% of the patients. Rh 123 efflux was correlated with Pgp expression in 70% of the 27 studied cases but 3 cases were Pgp-/Rh 123+ and 5 Pgp+/Rh 123-. In conclusion, assessment of Pgp expression by ICC and FCM using two different monoclonal antibodies coupled with functional efflux test is required to identify discordant expression/function cases suggesting a non functional Pgp or another alteration of drug transport.

Adhesion molecules play a major role in the regulation of normal hematopoiesis. Precursor/cell matrix/endothelial interactions determine retainment or release of hematopoietic cells from the bone marrow microenvironment. Consequently, changes in the affinity or quantitative expression of adhesion molecules on either the bone marrow stroma or the cell precursor component during a malignant process will affect cell attachment. Adhesion molecules, therefore, are modulator molecules which alter the biological behavior of leukemic cells in terms of migration and localization properties. Several membrane-bound adhesion molecules and, in some instances, their soluble counterparts which may be biologically active, have been described in acute myeloid leukemia. The panel of receptors expressed demonstrates heterogeneity between various cases of acute myeloid leukemia. There is generally no correlation between the adhesion receptor phenotype and the morphologic or clinical features of acute leukemia. These receptors function in interactions of leukemic blasts with the cellular and matrix components of the marrow microenvironment. Adhesive interactions may influence the proliferation and survival of leukemic cells. However, the precise role that these molecules play in the generation and sustenance of the leukemic state remains undetermined.

The treatment of cancer with alkylating drugs or topoisomerase II inhibitors can be responsible for the development of myelodysplastic syndromes and acute myelogenous leukemia. Alkylating agents such as melphalan and cisplatinum mainly produce damages at chromosomes 5 and 7 whereas topoisomerase II inhibitors-induced lesions essentially affect chromosomes 11 and 21. Rearrangements of the MLL gene at band 11q23 are frequently observed in human de novo myeloid and lymphoid leukemia as well as in leukemia or myelodysplasia secondary to therapy with drugs targetting topoisomerase II such as the epipodophyllotoxins. A relationship between the treatment with etoposide on teniposide and the development of translocations of the MLL gene has been clearly evidenced. The potential molecular basis of the chromosomal rearrangements implicating topoisomerase II and its inhibitors are discussed. The chemical structure of the inhibitors, their mechanism of action and the genes targetted by these drugs are presented. DNA cleavages induced directly by topoisomerase II inhibitors or by the drug induced apoptotic cellular response are responsible for nonrandom chromosomal aberrations and contribute to leukemogenesis.

A case of pre-leukemic granulocytic sarcoma (GS) of the uterus was found in a 73-year old woman. The diagnosis was suggested by vaginal cytology and the green color of the gross lesions, then confirmed by naphthol AS-D chloro acetate esterase stain and immunohistochemistry on fixed tissue with the anti-lysozyme, anti-myeloperoxidase, CD 43 and CD15 antibodies. At the time of GS discovery, the patient presented no evident leukemia but myelogram contained 20% of blast cells. She developed acute myeloid leukemia 2 months later. Cytogenetic study of the bone marrow revealed chromosome 21 trisomy. GS is frequently mistaken for malignant lymphoma since it expresses some of the leukocytic antigens (leukocyte common antigen, CD 45 RO (UCHL1), MB2). Therefore, the use of a large panel of antibodies, including anti-myeloperoxidase, anti-lysozyme and CD15, is recommended. Precise diagnosis is essential because all GS must be treated as acute myeloid leukemias.

The granulocytic sarcoma is a rare and extramedullary tumor, which is composed of granulocytic precursor cells. The diagnosis remains difficult. Infectious disease are often associated with leukemic processes. Combination of clinical, radiological and pathological findings are useful for diagnosis. On gross examination, the tumor appears green. The detection of myeloperoxidases and the presence of immature eosinophils can help histological analysis. Granulocytic sarcoma occurs before or during an acute leukemia. It is treated like an acute leukemia. Prognostic is greatly improved by early diagnosis and treatment. The lack of cytogenetic abnormalities is associated with a prolonged survival. We describe a new case of rapidly growing pleural granulocytic sarcoma. The uncommon modifications of chromosome 5 long arm in this case could explain the immature eosinophil reaction in that tumor.

Specific epidemiologic data on myelodysplastic syndromes are rare. Analysis of data is in fact affected by problems of terminology and classification. The link between the exposure to ionizing radiation or alkylating agents and MDS is well established. Etiologic factors of acute leukemia, or new factors such as non ionizing radiation, solvent, ethylene oxide, glycol eters, tobacco smoke, exhaust gases, agricultural work have been hypothesized but should be confirmed by other studies on MDS.

A 30-year-old man with a testicular tumor ressembling a "round cell sarcoma" was treated for rhabdomyosarcoma. Complete remission was achieved but the patient relapsed and died of the disease. A retrospective diagnosis of granulocytic sarcoma was established using an anti-myeloperoxidase antibody, unfortunately not available at the time of the initial diagnosis. No hematological disorders were observed during the course of the disease. Four cases of granulocytic sarcoma of the testis have been reported in the literature. All these cases where accompanied or followed by leukemia. The present case seems to be the first case of granulocytic sarcoma of the testis not accompanied by hematological disorders.

This is a retrospective study on the use of cytarabine at low doses in acute myeloid leukemias in 41 patients. Four groups of AML are included: group A: 19 cases of de novo AML in elderly patients; group B: ten cases of AML in relapse; group C: five cases of AML refractory to previous treatment and group D: seven cases of secondary AML. Cytarabine was given subcutaneously at the dose of 10 mg/m2 of body surface, for 21 days per month for the first course; then 15 days per month for the following courses. The response rates were 42, 20, 0, and 43% respectively for the A, B, C, and D groups. A complete remission was attained in only 15% (six patients). Extra haematological tolerance was excellent. Infection complications were noted in 66%, whereas a severe neutropenia was observed in 34% of patients. Hemorrhagic complications were more rare (20% of patients). The mean duration of complete remission was 10 months. The median survival was 10.5 months (2 to 31 months) for the responder patients, and 2.4 months (1 to 7 months) for the non-responders. Cytarabine at low doses seems to be a good indication for first intention treatment of AML in elderly patients. It does not give a bone marrow aplasia, the infection and hemorrhagic episodes are less numerous than with conventional dose chemotherapy, the life quality is improved, and treatment at home is often possible.

Every year in Canada, approximately one thousand cancer cases are reported in children from birth to age 14. Leukemia accounts for approximately 30 per cent of these cases. Leukemia and its treatment are likely to cause to children more oral complications than all other types of cancer. Both the leukemic condition itself and the therapy cause oral signs and symptoms with significant morbidity. Since life expectancy for a patient with leukemia has been greatly improved, dentists have an increasing role to play before, during and after a treatment against leukemia. A review of the oral manifestations related to leukemia and its treatment is presented.

Cytogenetic study reveals non random chromosomal abnormalities in 50-80% of patients with acute leukemia. These changes are correlated with morphological [t(15;17) closely connected with FAB M3] and (or) immunological findings [t(1;19) with pre-B/early pre-B ALL]. Karyotype in ALL is an independent prognostic factor. Patients with ALL and hyperdiploidy50 chromosomes fared the best as well as patients with AML and inv(16). Conversely the Philadelphia chromosome or t(4;11) in ALL, del5q or trisomy 8 in AML have shown an adverse predictive value. Cytogenetic study is a useful tool to detect relapse and residual disease. Cytogenetic abnormalities have also provided focus for molecular studies of leukemogenesis.

The treatment of acute myeloid leukaemia in adults is based on chemotherapy which is divided in two phases: induction (to achieve a complete remission) and post-induction treatment (to maintain the complete remission). Induction chemotherapy usually combines cytosine arabinoside and one anthracycline. The complete remission rate which varies from 50 to 90% is mainly influenced by the age of patients, the presence of certain cytogenetic abnormalities or the presence of a preleukaemic phase. The efficacy of post-induction treatments remains controversial. Maintenance treatment (with low-dose chemotherapy) has probably a marginal efficacy. More intensive (as intensive as induction chemotherapy) chemotherapies seems capable to prolong survival but can only be applied to the youngest patients. The rate of 5-years survivors is about 30-45% and influenced by a very low numbers of factors. The treatment of relapses is very difficult and seems to prolong survival only when the duration of the first remission has been longer than 18 months. In other cases, it can be justified to restrict the treatment to transfusions and oral chemotherapy.

Confocal microspectrofluorometry allows the analysis of fluorescent molecules such as anthracylines in isolated living cells. An optical microscope fitted with a phase-contrast 100 X water-immersion objective enables simultaneous observation of the sample, focusing of the laser beam on the selected cell fraction (nucleus) and collection of the fluorescence emitted from the sample. The resulting intranuclear spectra are interpreted according to a quantitative model of the fluorescence spectra of both free and DNA-bound anthracycline. The intranuclear drug concentration can thus be determined. This technique has been applied to blast cells collected in patients with acute leukemia. Leukemic cells are aspirated from bone marrow, separated by Ficoll sedimentation and resuspended in RPMI-1640 containing 10% fetal calf serum and 200 nM tetrahydropyranyl-doxorubicin (THP-DOX). After one hour, 20 cells are analyzed and the mean nuclear drug content is determined (C1). Cells are then resuspended in the same medium but without anthracycline for 3 hours and the mean intranuclear drug concentration is then also determined (C3). From C1 and C3 the retention rate (RR) is calculated. Firstly, the accuracy of the method was checked. In 4 AML patients, two different samples aspirated on the same day were divided into two portions. Thus, two measurements were made on each one (4 values per patient). Coefficients of variation were satisfactory (4, 6, 12, and 12%). Secondly, blast cells collected in patients with AML and ALL at diagnosis or in relapse were studied. P-glycoprotein (P-gp) and CD34 expression was also studied using respectively immunohistochemistry land flow cytometry. Results obtained from the first 21 patients showed that there was no correlation between RR and either P-gp or CD34 expression. This could result from the efflux of THP-DOX by other mechanisms and/or low sensitivity of the staining technique.

Multidrug resistance (MDR) phenotype expression was evaluated retrospectively in 87 patients with acute myeloid leukemia (AML), 69 with de novo AML, ten with relapsed AML and eight with AML secondary to myelodysplastic syndrome (MDS). MDR phenotype, characterized by P-glycoprotein expression (MRK16 monoclonal antibody) and decrease in intracellular daunorubicin (DNR) accumulation was determined using flow cytometry. All patients received chemotherapy including cytosine-arabinoside and anthracycline (daunorubicin, zorubicin, idarubicin) or mitoxantrone, and quinine in ten cases. The predictive value of the MDR phenotype for clinical responsiveness was studied using uni- and multivariate analyses. Univariate analysis showed that DNR accumulation (p10(-4)), P-glycoprotein expression (p = 10(-4)) and disease status (de novo versus recurrent AML and acute MDS) (p = 10(-4)) were predictive of clinical responsiveness. The significance of these three parameters was maintained in multivariate analysis. When de novo AML was considered, only DNR accumulation was of predictive value (p10(-4)) for complete response to chemotherapy.

A complex translocation involving chromosome 6, 8 and 9 [t(6;9;8)(p23;q34;q22)] associated with other structural and numerical abnormalities was observed on bone marrow karyotype of a woman suffering with acute myeloblastic leukemia (AML2). Fluorescence in situ hybridization agreed with the conventional cytogenetic interpretation by showing that a part of chromosome 6 short arm was inserted on the rearranged chromosome 9 resulting in the t (6;9) usually encountered in AML.

Granulocytic sarcoma of the larynx. Case report and review of the literature. Granulocytic sarcoma is a rare extramedullary tumor. It occurs either as an isolated tumor or associated with acute or chronic myelogenous leukemia. It has also been reported in patients with myelodysplastic syndromes when the granulocytic sarcoma is a harbinger of imminent disease progression. Granulocytic sarcoma can occur anywhere in the body. The larynx is a rare site of this lesion. A first case of glottic localisation is presented. The treatment of granulocytic sarcoma must include surgery, radiation and chemotherapy.

Three rare cases of tumours of the cervix are reported: embryonal rhabdomyosarcoma, granulocyte sarcoma and lymphoma. There were particular problems with diagnosis in each case requiring histochemistry, immunohistochemistry and ultrastructure examinations. Embryonal rhabdomyosarcoma is a uncommon tumour in the adult. Clinically, there is a vegetative formation but no botryoid aspect. Striated muscle cell proliferation, suggested by the morphology of the malignant cells was confirmed by immunohistochemistry which demonstrated desmine and vimentine and by the ultrastructural study which demonstrated Z lines in the cytoplasm of the malignant cells. Granulocyte sarcoma is characterized by a non-tumoural non-destructive infiltration of inflammatory-like cells. Their granulocyte nature is confirmed by histochemistry, the Leder's reaction on frozen samples, immunohistochemistry (expression of NP57). Electron microscopy can also be used. The diagnosis of lymphoma is difficult due to the non-tumoural nature of the lymphomatous infiltration which can simulate inflammatory reaction. In our case, the diagnosis was made on the tumoural aspect of the biopsy made in the deep infiltration zone of an adjacent organ (bladder). Immunohistochemistry demonstrated the lymphoid nature of the tumour and identified a B phenotype. The ultrastructural study gave little information.

Infections caused by fungi of the genus Aspergillus have become a major and dangerous problem in the modern treatments of blood diseases using cytotoxic drugs. Invasive pulmonary aspergillosis is the usual clinical manifestation of the disease. The clinical signs, not very suggestive, are those of an infective pneumonia and localized radiological forms are initially more frequent in most cases. The extra pulmonary forms are frequent: nose and sinus, skin, bone, digestive, central nervous system are principal localisations; but all organs may be affected by the processus of dissemination. The proximal tracheobronchial localisations may be seen by fibroscopy in 20% of cases, associated to invasive pulmonary aspergillosis. Diagnosis rests on pathological data, but in many cases the only possible examinations are broncho-alveolar lavage and bronchial brushing. The positive results are a major test of diagnosis.

Granulocytic sarcoma is more frequent in adults; it can be a tumoral localization of acute non-lymphoblastic leukemia. This report describes an infantile case revealing an acute myeloid leukemia.A 14 month-old girl was admitted because of enlarged bilateral cervical lymph nodes. They had increased in volume over the past month and were accompanied by fever and anorexia. The liver and spleen were moderately enlarged. Hematologic data were: Hb = 7.5 g%; leucocytes = 14,900/mm3; platelets = 614,000/mm3. There were no abnormal cells. X-rays and MRI showed a mediastinal mass. Bone scintigraphy was normal but the myelogram showed a few atypical cells that were also seen in a biopsy of the cervical lymph node. Electron microscopic examination of these cells showed that they were myeloid in origin. This was confirmed by immunohistochemistry. The cytogenetic examination showed many chromosomal abnormalities in the lymph node and myelogram. The child is now recovered after nine months of chemotherapy.Diagnosis of acute myeloblastic leukemia in children is difficult when it is revealed by granulocytic sarcoma without major infiltration of bone marrow. The clinical presentation as a mediastinal mass is rare. The cytogenetic study was determinant for diagnosis.

Human natural interferon gamma (IFN-gamma) exerts differentiating and cytocidal effects in vitro on the human myeloblastic leukemia cell line ML-2. The anti-leukemic effects of the crude preparation of IFN-gamma are more intensive than those of the mixture of purified IFN-gamma, IFN-alpha, tumor necrosis factor alpha and lipopolysaccharide, suggesting existence of an unknown anti-leukemic factor in the crude IFN-gamma sample.