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SASE1 is the first beamline of the European XFEL that became operational in 2017. It consists of the SASE1 undulator system, the beam transport system, and the two scientific experiment stations: Single Particles, Clusters, and Biomolecules and Serial Femtosecond Crystallography (SPB/SFX), and Femtosecond X-ray Experiments (FXE). The beam transport system comprises mirrors to offset and guide the beam to the instruments and a set of X-ray optical components to align, manipulate and diagnose the beam. The SASE1 beam transport system is described here in its initial configuration, and results and experiences from the first year of user operation are reported.

Resume Introduction Le lymphome a grandes cellules B intravasculaire est une proliferation de cellules tumorales aboutissant a l’occlusion de la lumiere des petits vaisseaux. Il s’agit d’une hemopathie maligne rare et de diagnostic difficile en raison d’une presentation clinique polymorphe. Observation Nous rapportons ici l’observation d’un patient atteint d’un lymphome intravasculaire revele par un syndrome d’activation macrophagique. Cette association est tres souvent marquee par une plus grande severite clinique et impose une prise en charge therapeutique precoce et adaptee. Conclusion En raison du caractere polymorphe et de la presentation systemique du lymphome a grandes cellules B intravasculaire, l’interniste peut etre confronte a cette pathologie, plus grave encore lorsqu’elle s’associe a un syndrome d’activation macrophagique. Il faut donc savoir l’evoquer d’autant que le pronostic depend de la rapidite de la prise en charge avec notamment la mise en route precoce d’une polychimiotherapie associee au rituximab.

Resume Nous abordons la complexite de la decision medicale de proposer – ou non – l’allogreffe de cellules souches hematopoietiques – seul traitement susceptible de guerir certaines hemopathies malignes. Les risques importants de morbi-mortalite inherents a cette procedure therapeutique et son impact sur la qualite de vie des patients suscite des questionnements ethiques que nous nous efforcons de traiter en croisant les regards des soignants impliques dans le processus de l’allogreffe cellules souches hematopoietiques.

Alors que l’indication de greffe de moelle osseuse se base sur des criteres biomedicaux, nous interrogeons l’influence des facteurs psychosociaux sur la decision medicale de proposer — ou non — une greffe de moelle. Face au caractere pejoratif a court terme des pathologies susceptibles d’etre traitees par l’allogreffe, les hematologues se montrent reticents a la prise en compte de ces facteurs comme criteres decisionnels.

Resume Les complications humerales dans les protheses d’epaule sont loin d’etre rares. La difficulte a reproduire l’anatomie de l’humerus est liee a l’existence d’un offset entre la tete et la diaphyse humerale. Nous avons concu un implant sans tige avec centrage automatique epiphysaire. Les auteurs rapportent les resultats de 63 implants poses pour omarthrose centree ou necrose, avec un recul moyen de 35 mois. L’âge moyen lors de l’intervention etait de 64 ans, le score de Constant preoperatoire de 29,8. Le score de Constant etait de 75, le gain en elevation anterieure active de 50°, pour 20° en rotation externe. L’analyse radiographique finale ne montrait aucun lisere, aucune migration de l’implant. Il s’agit donc d’une prothese simple a poser avec une reproduction fidele de l’anatomie. Les resultats cliniques en sont superposables a ceux de la litterature avec une excellente tenue a moyen terme.

Resume La survie des patients ayant un lymphome de Hodgkin s’est nettement amelioree ces dernieres annees, avec cependant une augmentation des complications tardives, en particulier neoplasiques. Nous rapportons l’observation d’un patient ayant presente une rechute d’un lymphome de Hodgkin classique concomitante a la decouverte d’un adenocarcinome bronchique, 20 ans apres la prise en charge initiale par chimiotherapie de type Mopp et radiotherapie en mantelet. Les mecanismes physiopathologiques de ces complications sont discutes. Une surveillance prolongee est necessaire chez tous les patients ayant un lymphome de Hodgkin.

Lead is known to induce hematological disturbances resulting from abnormalities in cell differentiation and hemoglobin synthesis during hematopoiesis. The aim of the present work was to study human erythropoiesis in vitro in the presence of lead. Human erythroblastic progenitors, burst-forming units-erythroid (BFU-E), were exposed to lead acetate at increasing concentrations during 14 days of culture. Hematotoxicity was evaluated in vitro according to proliferation and differentiation of cell colonies arising from BFU-E development. The ability of cells to synthesize proteins, porphyrins, and hemoglobin was measured by spectrophotometric tests and by high-pressure liquid chromatography (HPLC). Results showed that in the presence of 10(-3) mol/L lead acetate, no hemoglobinized cells were observed in culture and no fluorescent porphyrins were detected in cells. Up to 10(-3) mol/L, lead acetate is not cytotoxic, i.e., it does not induce cell destruction. The present work demonstrates that lead acetate interferes with the porphyrin synthesis of human erythroblastic progenitors in vitro. The decrease of porphyrin content with 10(-5) mol/L lead acetate suggest that delta-aminolevulinic acid dehydratase can be inhibited by lead acetate during in vitro erythropoiesis. In vivo erythropoiesis occurs in the bone marrow. As about 95% of the body burden of lead in adults is located in the bones with a biological half-life of some years, the concentration of lead acetate found to block porphyrin synthesis in vitro has to be compared with in situ bone marrow lead concentrations.

Deoxynivalenol (DON) is a trichothecene mycotoxin produced by various species of fungi. Trichothecenes are known as major contaminants of cereals and cereal-containing foods. DON has been detected in agricultural products worldwide and persists in products after processing. In humans as well as in animals, DON has been shown to induce both alimentary and hematological toxicities. Granulo-monocytic progenitors (CFU-GM) from human umbilical cord blood from rat bone marrow were cultured in the presence of DON (from 10(-6) to 10(-8) mol/L) for 14 days. DON rapidly inhibits human and rat CFU-GM in a concentration-dependent manner between 10(-6) and 2.5 x 10(-7) mol/L. IC50 values on days 7, 10, and 14 were, respectively, 3 x 10(-8), 2.9 x 10(-8), 3.9 x 10(-8) mol/L for human CFU-GM and 2.6 x 10(-7), 1.5 x 10(-7), and 1.6 x 10(-7) mol/L for rat CFU-GM. The present study defines the cytotoxic and inhibitory DON concentrations for rat and human CFU-GM and provides a system for further investigation of cellular DON targets and elucidation of the mechanism of trichothecene hematotoxicity. Moreover, we propose one of the trichothecenes tested in our studies as a reference molecule for in vitro studies, since one mycotoxin seems to be the most potent myelotoxic inhibitor of CFU-GM detected to date.

The rapid rate of blood cell renewal makes the hematopoietic system a susceptible target for xenobiotic toxicity, and xenobiotics could interfere with cell proliferation and differentiation. Hematotoxic molecules can affect one or more hematopoietic lineages, leading to blood disorders (neutropenia, agranulocytosis, thrombopenia, anemia, and pancytopenia). Erythropoiesis is the part of hematopoiesis responsible for red blood cell production by proliferation and differentiation of specific erythroblastic progenitors, the BFU-E/ CFU-E (Burst and Colony-Forming Unit-Erythroid). Some drugs and chemicals (antituberculosis drugs, chloramphenicol, penicillamines, ethanol, and lead) are able to cause dysfunction in heme biosynthesis and are responsible for hematological diseases such as porphyrias. The aim of this work was to obtain a useful tool to predict the toxic effect of xenobiotics in the proliferation or erythroblastic progenitors and on their differentiation. Optimal growth conditions for erythroblastic ...

T-2 toxin is a trichothecene mycotoxin produced by vari ous species of fungi. Trichothecenes are known as major contaminants of cereals and their derivatives. In man as well as in animals, T-2 toxin has been shown to induce ali mentary intoxication and, among others, haematological symptoms. Granulo-monocytic progenitors from human umbilical cord blood on the one hand and granulo-mono cytic progenitors from rat bone marrow on the other, were cultured in the presence of T-2 toxin (from 10-7to 10-10M) for 14 days. A study of concentration and effect relation ships showed a strong and rapid effect of T-2 toxin on rat colony forming unit-granulocyte and macrophage (CFU-GM) between 5.10-9M and 10-9M. On the other hand, human CFU-GM were able to grow in the presence of the same T-2 toxin concentrations. IC50were determined on day 7, 10 and 14. They were, respectively, 1.6.10-9 M; 3.6.10-9M; 1.4.10-9M for human cells, and 2.2.10-9M; 3.3.10-9M; 2.6.10-9M for rat cells. The present study was prompted by the need to define precisely the cytotoxic and inhibitory T-2 toxin concentrations for rat and human CFU-GM. It is particularly relevant for the investigation of cellular T-2 toxin targets and in order to elucidate the mechanism of trichothecene haematotoxicity.

Intravascular large B cell lymphoma is a neoplastic cell proliferation leading to the occlusion of the lumen of small vessels. This is a rare haematological malignancy, which is difficult to diagnose because of a heterogeneous clinical presentation.We report a 62-year-old man who presented a macrophage activation syndrome as the presenting manifestation of an intravascular lymphoma. This association is frequently marked by a greater severity and clinical care requires an early and appropriate treatment.Due to the polymorphism and the systemic presentation of intravascular large B cell lymphoma, the internist may be confronted with this disease, which is considered to be more severe if associated with a macrophage activation syndrome. Awareness of the intravascular large B cell lymphoma is important because the prognosis depends on the rapidity of the initiation of chemotherapy associated with rituximab.

Studying exoplanet host stars is of the utmost importance to establish the link between the presence of exoplanets around various types of stars and to understand the respective evolution of stars and exoplanets. Using the limb-darkened diameter (LDD) obtained from interferometric data, we determine the fundamental parameters of four exoplanet host stars. We are particularly interested in the F4 main-sequence star, �� Cyg, for which Kepler has recently revealed solar-like oscillations that are unexpected for this type of star. Furthermore, recent photometric and spectroscopic measurements with SOPHIE and ELODIE (OHP) show evidence of a quasi-periodic radial velocity of \sim150 days. Models of this periodic change in radial velocity predict either a complex planetary system orbiting the star, or a new and unidentified stellar pulsation mode. We performed interferometric observations of �� Cyg, 14 Andromedae, {\upsilon} Andromedae and 42 Draconis for two years with VEGA/CHARA (Mount Wilson, California) in several three-telescope configurations. We measured accurate limb darkened diameters and derived their radius, mass and temperature using empirical laws. We obtain new accurate fundamental parameters for stars 14 And, {\upsilon} And and 42 Dra. We also obtained limb darkened diameters with a minimum precision of \sim 1.3%, leading to minimum planet masses of Msini=5.33\pm 0.57, 0.62 \pm 0.09 and 3.79\pm0.29 MJup for 14 And b, {\upsilon} And b and 42 Dra b, respectively. The interferometric measurements of �� Cyg show a significant diameter variability that remains unexplained up to now. We propose that the presence of these discrepancies in the interferometric data is caused by either an intrinsic variation of the star or an unknown close companion orbiting around it., 10 pages + 2 pages appendix, 16 figures, accepted for publication in A&A

Les leucemies aigues sont caracterisees par un dysfonctionnement acquis portant sur la maturation et la proliferation des cellules hematopoietiques normales. On distingue les leucemies aigues myeloides et les lymphoides, en fonction de l’origine du precurseur hematopoietique atteint. La classification FAB (franco-americano-britannique) a ete remplacee par une nouvelle classification (OMS ou WHO) qui repose sur les differentes entites representees par les anomalies cytogenetiques recurrentes. Cette classification prend en compte les outils de l’immunophenotypage, de la cytogenetique et de la biologie moleculaire.

Overall survival of patients with Hodgkin lymphoma has dramatically increased in recent years, with an increased rate of malignant complications. We report here a 54-year-old man who presented with concomitant relapse of classical Hodgkin's lymphoma and lung adenocarcinoma 20 years after initial treatment with chemotherapy and mantle radiotherapy. Pathogenic mechanisms of these malignant complications are discussed. A prolonged follow-up of patients with Hodgkin's lymphoma is required.

Physical processes working in the stellar interiors as well as the evolution of stars depend on some fundamental stellar properties, such as mass, radius, luminosity, and chemical abundances. A classical way to test stellar interior models is to compare the predicted and observed location of a star on theoretical evolutionary tracks in a H-R diagram. This requires the best possible determinations of stellar mass, radius, luminosity and abundances. To derive its fundamental parameters, we observed the well-known rapidly oscillating Ap star, $��$ Equ, using the visible spectro-interferometer VEGA installed on the optical CHARA array. We computed the calibrated squared visibility and derived the limb-darkened diameter. We used the whole energy flux distribution, the parallax and this angular diameter to determine the luminosity and the effective temperature of the star. We obtained a limb-darkened angular diameter of 0.564~$\pm$~0.017~mas and deduced a radius of $R$~=~2.20~$\pm$~0.12~${\rm R_{\odot}}$. Without considering the multiple nature of the system, we derived a bolometric flux of $(3.12\pm 0.21)\times 10^{-7}$ erg~cm$^{-2}$~s$^{-1}$ and an effective temperature of 7364~$\pm$~235~K, which is below the effective temperature that has been previously determined. Under the same conditions we found a luminosity of $L$~=~12.8~$\pm$~1.4~${\rm L_{\odot}}$. When the contribution of the closest companion to the bolometric flux is considered, we found that the effective temperature and luminosity of the primary star can be, respectively, up to $\sim$~100~K and up to $\sim$~0.8~L$_\odot$ smaller than the values mentioned above.These new values of the radius and effective temperature should bring further constraints on the asteroseismic modelling of the star., Accepted by A&A

Phloem Necrosis of the trunk of the rubber tree in Ivory Coast. 2. Etiology of the disease. Numerous experiments were performed in order to identify the causal pathogen of rubber tree Phloem Necrosis. Trials of control by fungicides and bactericides, of identification of the microorganisms isolated from decayed tissues, of transmission from diseased to healthy trees and also, microscopic observations of necrotic phloem samples, all failed in practice. However, symptomatology and epidemic spread in plantation suggest a pathological cause of this disease.

Phloem necrosis of rubber tree (Hevea brasiliensis) is characterized by cell wall degradation, alteration of the middle lamella, the vesiculation of endomembranes, the formation of tylosoids and the internal coagulation of rubber

In patients with hematological malignancy (HM) developing acute respiratory failure (ARF) bronchoalveolar lavage (BAL) is considered as a major diagnostic tool. However, the benefit/risk ratio of this invasive procedure is probably lower in the subset of patients with acute myeloid leukemia (AML). The study was to analyze the yield of BAL performed in HM patients (n=175) with AML or lymphoid malignancies (LM) admitted in intensive care unit (ICU) for ARF and pulmonary infiltrates. BAL was performed in 121 patients (53/73 AML patients (73%) and 68/102 LM patients (67%)) without a definite diagnosis at admission or contraindication for fiberoptic bronchoscopy. Life-threatening complications were noticed in 12/121 patients (10%). The overall diagnostic yield of BAL was 47% (25/53) in AML patients and 50% (34/68) in LM patients. A microorganism was recovered from BAL in 23% (12/53) of AML patients and 41% (28/68) of LM patients (P

To determine the maximum-tolerated dose (MTD), dose-limiting toxicities and pharmacokinetic of semisynthetic homoharringtonine (ssHHT), given as a twice daily subcutaneous (s.c.) injections for 9 days, in patients with advanced acute leukaemia, 18 patients with advanced acute myeloid leukaemia were included in this sequential Bayesian phase I dose-finding trial. A starting dose of 0.5 mg m(-2) day(-1) was explored with subsequent dose escalations of 1, 3, 5 and 6 mg m(-2) day(-1). Myelosuppression was constant. The MTD was estimated as the dose level of 5 mg m(-2) day(-1) for 9 consecutive days by s.c. route. Dose-limiting toxicities were hyperglycaemia with hyperosmolar coma at 3 mg m(-2), and (i) one anasarque and haematemesis, (ii) one life-threatening pulmonary aspergillosis, (iii) one skin rash and (iv) one scalp pain at dose level of 5 mg m(-2) day(-1). The mean half-life of ssHHT was 11.01+/-3.4 h, the volume of distribution at steady state was 2+/-1.4 l kg(-1) and the plasma clearance was 11.6+/-10.4 l h(-1). Eleven of the 12 patients with circulating leukaemic cells had blood blast clearance, two achieved complete remission and one with blast crisis of CMML returned in chronic phase. The recommended daily dose of ssHHT on the 9-day schedule is 5 mg m(-2) day(-1).

The 26 km of vacuum chambers where circulates the beam of the Large Hadron Collider (LHC) must be maintained under Ultra High Vacuum (UHV) to minimize the beam interactions with residual gases, and allow the operation of specific systems. The vacuum level is measured by several thousands of gauges along the accelerator. Bad vacuum quality may trigger a beam dump and close the associated sector valves. The effects of radiation or Electromagnetic Interferences (EMI) on components that may stop the machine must be evaluated and minimized. We report on the actions implemented to mitigate their impact on the vacuum control system.

Lead is known to induce hematological disturbances resulting from abnormalities in cell differentiation and hemoglobin synthesis during hematopoiesis. The aim of the present work was to study human erythropoiesis in vitro in the presence of lead. Human erythroblastic progenitors, burst-forming units-erythroid (BFU-E), were exposed to lead acetate at increasing concentrations during 14 days of culture. Hematotoxicity was evaluated in vitro according to proliferation and differentiation of cell colonies arising from BFU-E development. The ability of cells to synthesize proteins, porphyrins, and hemoglobin was measured by spectrophotometric tests and by high-pressure liquid chromatography (HPLC). Results showed that in the presence of 10(-3) mol/L lead acetate, no hemoglobinized cells were observed in culture and no fluorescent porphyrins were detected in cells. Up to 10(-3) mol/L, lead acetate is not cytotoxic, i.e., it does not induce cell destruction. The present work demonstrates that lead acetate interferes with the porphyrin synthesis of human erythroblastic progenitors in vitro. The decrease of porphyrin content with 10(-5) mol/L lead acetate suggest that delta-aminolevulinic acid dehydratase can be inhibited by lead acetate during in vitro erythropoiesis. In vivo erythropoiesis occurs in the bone marrow. As about 95% of the body burden of lead in adults is located in the bones with a biological half-life of some years, the concentration of lead acetate found to block porphyrin synthesis in vitro has to be compared with in situ bone marrow lead concentrations.

Summary Background Some patients treated by transplantation of haemopoietic stem cells (peripheral blood or bone marrow) become permanently infertile, but others retain or recover fertility. We assessed the outcome of conception in women, and partners of men previously treated by autologous or allogeneic stem cell transplantation (SCT). Method We sent questionnaires to 229 centres of the European Group for Blood and Marrow Transplantation. We sought details about the original disease, transplant procedure, and outcome of conception for both male and female patients. Findings 199 centres gave information relating to 19 412 allogeneic and 17 950 autologous transplant patients. 232 (0·6%) patients conceived after SCT. Crude annual birth rate for 4-month survivors of SCT was lower than the national average for England and Wales at 1·7 per 1000 patients. 312 conceptions were reported in 113 patients (74 allograft) and partners of 119 patients (93 allograft). Most pregnancies were uncomplicated and resulted in 271 livebirths. 28 (42%) of 67 allograft recipients had caesarean section compared with 16% in the normal population (difference=26% [95% CI 15–38]), 12 (20%) of 59 had preterm delivery compared with a normal rate of 6% (14% [4–24]), and 12 (23%) of 52 had low birthweight singleton offspring compared with a normal rate of 6% (17% [6–29]). Interpretation Pregnancy after SCT is likely to have a successful outcome. Pregnancies in allograft patients who have received total body irradiation should be treated as high risk for maternal and fetal complications.

The epidemiology and clinical outcome of acute myeloid leukaemia in human immunodeficiency virus (HIV)-infected adults is poorly documented. We retrospectively surveyed all French haematology centres for adult acute myeloid leukaemia (AML) cases diagnosed between January 1990 and July 1996 who were found to be HIV-seropositive before or at the time of AML diagnosis. Medical charts were reviewed to determine the stage of HIV infection, the characteristics of AML and the response of AML to chemotherapy. Sixteen cases of AML (13 men, three women) were reported by 12 haematology units. Based on assumptions on the size, age and sex distribution of the HIV-infected population in France, the estimated risk of AML in 1990 to 1996 among HIV-infected adults was twice that of the general population (standardized incidence ratio = 2.05; 95% confidence interval, 1.17-3.34). Two other cases occurring before 1990 were spontaneously notified to the authors and were included in the clinical analysis. At AML diagnosis, the median CD4+ cell count was 275 x 106/l and nine patients had acquired immune deficiency syndrome (AIDS). Fifteen patients were scheduled for remission-induction therapy of AML. No deaths were related to AML treatment. Complete remission was obtained in 11 out of 15 patients. Three patients were long-term survivors: two remain alive in complete remission at 8 years and 9 years, respectively, and the third died of AIDS at 8 years. A CD4+ cell count above 200 x 106/l at AML diagnosis was predictive of longer survival (log-rank test: P = 0.004). Like many other malignancies, the incidence of AML appears to be increased in HIV-infected patients. Our results show a twofold higher incidence, although this needs to be confirmed in a specifically designed prospective epidemiological study. Such patients, especially those with CD4+ cell counts above 200 x 106/l at AML diagnosis, should receive remission-induction therapy, which can confer long-term survival.

Die vordere untere Schulterluxation ist die haufigste Luxation beim Menschen. Ihre Inzidenz schwankt zwischen 8,2-12,3 Luxationen jahrlich pro 100.000 Personen [17, 22, 35], sinkt jedoch rasch mit zunehmendem Alter: von 20 pro 100.000 Personen zwischen dem 15. und 20. Lebensjahr auf 5 nach dem 30. Lebensjahr [29].

To report two cases of an unusual form of intravascular lymphoma, characterized by bone marrow involvement at presentation with haemophagocytic syndrome.We describe the clinicopathological features of two patients with intravascular lymphoma primarily involving bone marrow. Both patients complained only of fever with pancytopenia and reactive haemophagocytic syndrome. Diagnosis was made on bone marrow examination, which showed large tumour cells of B-cell lineage confined within the lumen of sinuses.These two cases and five previous reports could represent a variant of intravascular lymphoma, characterized by early involvement of bone marrow without dissemination to other organs. This form of intravascular lymphoma, called IVL-HS, seems to be an 'Asian' variant with a high prevalence in Asian people and a very low prevalence in Western countries. At a practical level, bone marrow biopsy may be useful in the diagnosis of intravascular lymphoma when the clinical presentation is restricted to fever of unknown origin with a reactive haemophagocytic syndrome.

A total of 193 patients with acute myelocytic leukaemia (AML) [147 in first complete remission (CR1)], ranging from 60 years to 75 years of age (median 63 years), were autografted between January 1984 and December 1998. The source of stem cells was peripheral blood (PB) in 128 patients, bone marrow in 51 patients and a combination of both in 14 patients. Total body irradiation (TBI) was used in 34 cases. Ninety-seven per cent of patients had successful engraftment of neutrophils on day 15 (range days 7-71) and of platelets on day 30 (range days 9-894). In patients autografted in CR1, the transplant-related mortality (TRM) was 15 +/- 4%, the relapse incidence (RI) was 58 +/- 5%, the leukaemia-free survival (LFS) was 36 +/- 5% and the overall survival was 47 +/- 5% at 3 years. The source and dose of stem cells were studied in particular; in patients transplanted in CR1, the RI was 44 +/- 11% in those receiving marrow compared with 63 +/- 6% in those receiving PB (P = 0.04). Patients autografted in CR1 who received higher granulocyte-macrophage colony-forming units (CFU-GM) doses (above the median) had a lower RI (47 +/- 11% vs. 79 +/- 9%, P = 0.009). There was a significant improvement in patients transplanted after March 1996; for those in CR1, the RI was 41 +/- 8% vs. 65 +/- 6% (P = 0.01), the LFS was 53 +/- 8% vs. 28 +/- 5% (P = 0.01) and the overall survival was 72 +/- 7% vs. 36 +/- 6% (P = 0.02). By multivariate analyses, significant factors for the outcome were the date of transplant with recent improvement and the source of stem cells, with a lower RI for marrow. Autologous stem cell transplantation (ASCT) is a potential therapeutic approach in patients with AML over 60 years of age; results have improved recently.

Micro-organisms are unique « cell factories » able to valorize agricultural by-products instead of only degrading or mineralizing them for depollution or methanisation processes. The difficulties encountered in treating such compounds often result from high concentration of pollutants and/or high toxicity to the microflora. Liquid effluents with high chemical oxygen demand (COD) (> 100 g COD/litre) are often rich in aromatic compounds.

The place of allogeneic bone marrow transplantation (BMT) in the treatment of aggressive non-Hodgkin's lymphoma (NHL) remains controversial. We conducted a retrospective study of French experience in allografting NHL between 1984 and 1994. To improve the homogeneity of the study population, cases of low-grade, Burkitt and lymphoblastic NHL were excluded. 73 patients were included in the analysis. Median age at transplantation was 35 years (range 9-61 years); 64 patients were in stage IV and 45 had bone marrow involvement at diagnosis. At the time of transplantation, 46 patients had sensitive disease (25 in complete remission; CR). The overall survival (OS) and progression-free survival (PFS) rates were 41% and 40% respectively at 5 years (median follow-up of survivors 90 months). The probability of disease progression was 30% at 5 years, and only one relapse occurred after 15 months. 32 patients died of transplantation-related complications. In multivariate analysis, pretransplant complete remission was the main factor associated with longer survival (OS at 60 months of 76% among the 25 patients in CR at transplant and of 23% among the 48 patients not in CR at transplant). Neither acute nor chronic graft-versus-host disease (GvHD) influenced the relapse rate. In conclusion, in this high-risk population the overall results of allogeneic BMT were encouraging, despite a high transplant-related mortality rate. We believe this procedure should be studied further in prospective controlled trials.

Total-body irradiation (TBI) has an established role in many preparative regimens used before bone marrow transplantation (BMT) in the treatment of hematological malignancies in children and adults. Better choice in TBI techniques and dosimetry have permitted better homogeneity of dose, and therefore a significant sparing of critical tissues. Advances in treatments over the past 20 years have greatly improved survival; therefore, the evaluation of early and late complications, with a sufficient follow-up, according to different conditioning regimens is important. In this article, we review and compare different TBI techniques and dosimetry, and their influence on the distribution and homogeneity of dose, and the possible relationship to the risk of complications. We also describe the acute and late effects of TBI in children and adults appearing in the first month post-BMT as veno-occlusive disease, interstitial pneumonitis, or after 3 months, i.e., endocrinal late effects and growth in children, cataracts, neurological and bone or other complications, secondary tumors and alteration in the quality of life. The responsibility of TBI in the increased rate of certain complications is difficult to assess from chemotherapy or allograft side effects (chronic graft vs. host disease) or from other associated medical treatments, such as long term steroid therapy.

Aim In order to assess the influence of total-body irradiation (TBI) on the outcome and incidence of complication after bone marrow transplantation (BMT), we retrospectively analyzed our patients treated for acute leukemia and conditioned with TBI prior to BMT. Patients and Methods Between 1980 and 1993, 326 patients referred to our department with acute non-lymphoblastic leukemia (ANLL, n=182) and acute lymphoblastic leukemia (ALL, n=144) in complete remission underwent TBI either in single dose (190 patients: 10 Gy administered to the midplane, and 8 Gy to the lungs [STBI]) or in 6 fractions (136 patients: 12 Gy on 3 consecutive days, and 9 Gy to the lungs [FTBI]) before BMT. The male-to-female ratio was 204/122 (1.67), and the median age was 30 years (mean: 30 ± 11, range: 3 to 63). The patients were analyzed according to 3 instantaneous dose rate groups: 118 patients in the LOW group (≤0.048 Gy/min), 188 in the MEDIUM group (> 0.048 and ≤ 0.09 Gy/min), and 20 in the HIGH group (> 0.09 cGy/min). Conditioning chemotherapy consisted of cyclophosphamide (CY) alone in 250 patients, CY and other drugs in 54, and 22 patients were conditioned using combinations without CY. Following TBI, allogeneic and autologous BMT were realized respectively in 118 and 208 patients. Median follow-up period was 68 months (mean: 67 ± 29, range: 24 to 130 months). Results Five-year survival, LFS, RI and TRM rates were 42%, 40%, 47%, and 24%, respectively. Five-year LFS was 36% in the STBI and 45% in the FTBI group (p = 0.17). It was 36% in the LOW group, 42% in the MEDIUM group, and 30% in the HIGH group (p > 0.05). Five-year RI was 50% in STBI, 43% in FTBI, 55% in LOW, 41% in MEDIUM, and 44% in HIGH groups (STBI vs. FTBI, p = 0.48; LOW vs. MEDIUM, p = 0.03: MEDIUM vs. HIGH, p = 0.68). TRM was not influenced significantly by the different TBI techniques. When analyzing separately the influence of fractionation and the instantaneous dose rate either in ANLL or ALL patients, no difference in terms of survival and LFS was observed. Fractionation did not influence the 5-year RI both in ANLL and ALL patients. However, among the patients with ANLL, 5-year RI was significantly higher (58%) in the LOW group than the MEDIUM group (31%, p = 0.001), whereas instantaneous dose rate did not significantly influence the RI in ALL patients. The 5-year TRM rate was significantly higher in allogeneic BMT group both in ANLL (37%) and ALL (37%) patients than those treated by autologous BMT (ANLL: 15%, ALL: 18%: p = 0.002 and 0.02, respectively). The 5-year estimated interstitial pneumonitis (IP) and cataract incidence rates were 22% and 19%, respectively, in all patients. IP incidence seemed to be higher in the HIGH group (46%) than the MEDIUM (19%, p = 0.05) or LOW (25%, p = 0.15) groups. Furthermore, cataract incidence was significantly influenced by fractionation (STBI vs. FTBI, 29% vs. 9%; p = 0.003) and instantaneous dose rate (LOW vs. MEDIUM vs. HIGH, 0% vs. 27% vs. 33%; p < 0.0001). Multivariate analyses revealed that the best factors influencing the survival were 1st CR (p = 0.0007), age ≤ 40 years (p = 0.003), and BMT after 1985 (p = 0.008). The RI was influenced independently only by the remission status (p = 0.0002). On the other hand, the TRM rate was lower in patients who did not experience graft-vs.-host disease (GvHD, p < 0.0001), and in those treated after 1985 (p = 0.0005). GvHD was the only independent factor involved in the development of IP (p = 0.01). When considering the cataract incidence, the only independent factor was the instantaneous dose rate (p = 0.0008). Conclusion The outcome of BMT patients conditioned with TBI for acute leukemia was not significantly influenced by the TBI technique, and TRM seemed to be lower in patients treated after 1985. On the other hand, cataract incidence was significantly influenced by the instantaneous dose rate.

Trichothecenes are mycotoxins produced by various species of fungi which can occur on various agricultural products. Among these compounds, T-2 toxin, HT-2 toxin, diacetoxyscirpenol (DAS) and deoxynivalenol (DON) are the most naturally encountered and potent trichothe cenes. Consumption of trichothecene contaminated foods by farm animals and humans leads to mycotoxicoses. Trichothecenes are known to induce haematologic dis orders such as neutropenia, thrombopenia, and aplastic anemia in human and animals. The aim of our investigations is to explore the effects of trichothecenes on the haematopoietic progenitors. The four trichothecenes previously demonstrated to be strongly cytotoxic for human CFU-GM have been tested on human BFU-E. For this purpose, a culture model of human erythroblastic progenitors (BFU-E) optimized for toxicological studies was used to determine the effects of T-2, HT-2, diacetoxyscirpenol (DAS) and deoxynivalenol (DON) on red blood cell precursor proliferation and differentiation. Results showed that human BFU-E are as sensitive to trichothecenes as human CFU-GM, except for DON, in the range of concentrations tested. Differentiation of erythroblastic progenitors could be perturbed by these mycotoxins. Human erythroblastic progenitors are also a target of trichothecenes.

Two successive studies comparing tazocilline (12 g piperacillin + 1.5 g tazobactam/ day) + aminoside (15 mg/k/day amikacin in the first trial, 3 mg/kg/d tobramycin in the second) to ceftazidime (3 g/day) + aminoside included 466 febrile episodes in profoundly neutropenic patients after chemotherapy (or chemo-radiotherapy) for hematological malignancies. Patients were treated for acute leukemia (72%), or autografted for non-Hodgkin lymphoma or myeloma (25%), few patients for solid tumors. The mean duration of neutropenia was 21 days ± 11 (92% > 7 days); 466 febrile episodes were analysed for intention-to-treat, and were attributed to bacteremia in 119 cases, to local infection in 178 cases, and were of unknown origin (FUO) in 169 cases. A majority of Gram positive strains (55.5%) was isolated at day 0. The 72 h apyrexia was obtained more often (51.6% of the cases) with Tazocillin + aminoside than with ceftazidime + aminoside (33.6%, p < 0.0001). This results was due to a better control of bacteremia (p = 0.03) and local infection (p = 0.006) with tazocillin + aminoside, but not FUO (p = 0.19). Identical results of both antibiotic associations were observed during the first course of antitumoral chemotherapy, but tazocillin was significantly superior for 72 h apyrexia when fever occurred during consolidation therapy (p < 0.0001) or relapse treatment (p = 0.006). Superinfections due to Gram positive strains and major infectious events (infectious deaths and retardations of underlying disease treatment due to infection) were less frequent when patients received tazocillin + aminoside (respectively p = 0.002 and p = 0.02). The initial empirical antibiotic association remained unchanged and lead to a persisting apyrexia in only 20.3% of the cases treated with tazocillin + aminoside, but this was significantly better than with the other association (9.5%, p = 0.02).

Allogeneic BMT for patients with acute myeloid leukemia (AML) is presently a reference therapy. The indications for this therapy mainly rely upon prognostic factors, and their importance is constantly reassessed. To examine the impact of time from diagnosis to transplant on survival and leukemia-free survival (LFS), we analyzed 109 patients from the database of the SFGM comprising patients who had all received an HLA-identical allogeneic BMT for a diagnosis of AML in first complete remission (CR1) between January 1987 and December 1992. All patients were conditioned with cyclophosphamide (CY) and total body irradiation (TBI) (CYTBI), and methotrexate (MTX) + cyclosporin A (CsA) were used as graft-versus-host disease (GVHD) prophylaxis. Patient characteristics were: age = 33 +/- 9, M/F = 64/45, white blood cell count (WBC) at diagnosis = 27 +/- 42 x 10(9)/l, FAB distribution: M1 and M2 = 55; M3 = 15, M4 and M5 = 33, M0, M6 and M7 = 6. Karyotyping was carried out for 64 patients: 32 had a normal karyotype, 16 had good prognosis abnormalities (t(8;21), t(15;17), inv 16) and 16 patients had other abnormalities. Eleven patients needed two courses of induction to achieve CR. Time between diagnosis and BMT was 120 (64-287) days. Forty-nine patients developed gradeor = 2 acute GVHD (actuarial probability = 46%). With a median follow-up of 50 months (27-100), the 5-year probabilities for transplant-related mortality (TRM), relapse, overall survival and LFS are respectively 25%, 26%, 59% and 55%. A multivariate analysis showed that survival is adversely influenced by three independent factors: time to transplant (120 days vsor = 120 days), acute GVHD (grade 2-4 vs grade 0-1) and age (33 vsor = 33). LFS is only influenced by the first two of these factors. The favorable impact of a shorter time from diagnosis to transplant should lead to performing the transplant as early as possible. Practically speaking, this means that when such therapy is chosen for a patient with CR1 AML, the search for an allogeneic donor should begin immediately and transplant be performed as soon as possible.

Deoxynivalenol (DON) is a trichothecene mycotoxin produced by various species of fungi. Trichothecenes are known as major contaminants of cereals and cereal-containing foods. DON has been detected in agricultural products worldwide and persists in products after processing. In humans as well as in animals, DON has been shown to induce both alimentary and hematological toxicities. Granulo-monocytic progenitors (CFU-GM) from human umbilical cord blood from rat bone marrow were cultured in the presence of DON (from 10(-6) to 10(-8) mol/L) for 14 days. DON rapidly inhibits human and rat CFU-GM in a concentration-dependent manner between 10(-6) and 2.5 x 10(-7) mol/L. IC50 values on days 7, 10, and 14 were, respectively, 3 x 10(-8), 2.9 x 10(-8), 3.9 x 10(-8) mol/L for human CFU-GM and 2.6 x 10(-7), 1.5 x 10(-7), and 1.6 x 10(-7) mol/L for rat CFU-GM. The present study defines the cytotoxic and inhibitory DON concentrations for rat and human CFU-GM and provides a system for further investigation of cellular DON targets and elucidation of the mechanism of trichothecene hematotoxicity. Moreover, we propose one of the trichothecenes tested in our studies as a reference molecule for in vitro studies, since one mycotoxin seems to be the most potent myelotoxic inhibitor of CFU-GM detected to date.

The diphenyl-ether herbicides exert their phytotoxic activity by preventing chlorophyll formation in plants as a result of inhibition of protoporphyrinogen oxidase. This enzyme is the last step of the common pathway for chlorophyll and haem biosynthesis. The aim of this work is to determine whether herbicide inhibitors of plant protoporphyrinogen oxidase could act on the human protoporphyrinogen oxidase involved in haemoglobin synthesis and cause heamatologic diseases. Human erythroblastic progenitors (BFU-E/CFU-E: Burst Forming Unit-Erythroid and Colony Forming Unit-Ery throid) were exposed to oxyfluorfen, a diphenyl-ether herbicide in the presence of erythropoietin, and the haematoxicity evaluated in vitro by scoring the develop ment of BFU-E/CFU-E colonies after 7 and 14 days of culture. The toxic effect on differentiation has been evaluated using four criteria: morphology, total protein, total porphyrin, and haemoglobin content. The study of BFU-E/CFU-E proliferation and differentia tion showed a cytotoxic effect of oxyfluorfen only at very high concentrations. In contrast, haemoglobin synthesis can be inhibited by concentration of oxyfluorfen (10-4 M) that have no adverse effect on cellular proliferation.

International audience; Diacetoxyscirpenol (DAS) is a trichothecene mycotoxin produced by various species of fungi. Trichothecenes are known as major contaminants of cereals and cereal-containing foods. DAS has been detected in agricultural products worldwide and persists in products after processing. In human as well as in animals, DAS consumption has been shown to induce haematological disorders (neutropenia, aplastic anemia). Granulo-monocytic progenitors (CFU-GM) from human umbilical cord blood and rat bone marrow have been cultured in the presence of DAS (from 10(-8) M to 5 x 10(-10) M) for 14 days. Study of concentration and effect relationships have shown a sharp effect of DAS on rat CFU-GM between 10(-7) M and 10(-8) M, while human CFU-GM are able to grow in the presence of 10(-8) M of the toxin. IC50 values on day 14 are respectively, 7.6 x 10(-9) M for human CFU-GM and 6.2 x 10(-9) M for rat CFU-GM.

Paroxysmal nocturnal haemoglobinuria (PNH) is a rare acquired disorder of haematopoietic stem cells. Although knowledge about the pathophysiology of the disease is increasing, no multivariate analysis of factors influencing survival has been undertaken, mainly because the disease is rare. We undertook such an investigation.Data were collected on 220 patients with PNH diagnosed over a 46-year period (1950-1995) from participating French centres. Diagnosis of the disease required, at least, an unequivocally positive Ham's test.The Kaplan-Meier survival estimate was 65% (SE 4) at 10 years and 48% (6) at 15 years after diagnosis. 8-year cumulative incidence rates of the main complications (pancytopenia, thrombosis, and myelodysplastic syndrome) were 15% (3), 28% (4), and 5% (2), respectively. Demographic data, presenting features, initial treatment, complications, and causes of death were similar to those previously reported. In multivariate analysis, seven factors were significantly associated with survival in patients with PNH. Poor survival was associated with the occurrence of thrombosis as a complication (relative risk 10.2 [95% CI 6-17], p0.0001), evolution to pancytopenia (5.5 [2.8-11], p0.0001), myelodysplastic syndrome or acute leukaemia (19.1 [7.3-50], p0.001), age over 55 years at diagnosis (4 [2.4-6.9], p0.0001), need for additional treatment (2.1 [1.3-3.6], p0.003), and thrombocytopenia at diagnosis (2.2 [1.3-3.8, p0.003). Better survival was shown for patients in whom aplastic anaemia antedated PNH (0.32 [0.14-0.72], p0.02). Factors associated in multivariate analysis with a high risk of thrombosis during the disease course were thrombosis at diagnosis (5.1 [2.5-10.6], p = 0.0002), age over 54 years (2.6 [1.5-4.6, p = 0.0014), and infection at diagnosis (2.6 [1.3-5.2], p = 0.0099). The risk factors for progression to pancytopenia were absence at diagnosis of anaemia (4.03 [1.3-12.2], p = 0.03) and neutropenia (2.45 [1.1-5.7], p = 0.03). The risk factors for development of myelodysplastic syndrome or acute leukaemia were abdominal pain crisis at presentation (10.5 [2.5-44.0], p = 0.004) and year of diagnosis after 1983 (8.45 [1.8-40.7], p = 0.004).This large number of cases permitted a detailed analysis of prognostic factors for the first time, in this rare disease. Estimates of PNH prognostic factors may serve as baseline data in the assessment of current and future treatments for this disease.

The study analysed the financial benefits of transplantation with peripheral blood stem-cells primed after chemotherapy and growth factor in comparison with bone marrow transplantation. Twenty-three consecutive transplantations were performed during one year: 14 peripheral blood stem-cell (CSC group) and 9 bone marrow transplantations (MO group). No differences in patients characteristics were seen between the two groups except for higher number of "BEAM" conditioning in CSC group. Were analyzed delay in neutrophil and platelet recovery, numbers of days in hospital, with fever, under antibiotics, costs of supportive therapy, stem-cell collection and cryopreservation. Difference was significant for duration of neutropenia with advantages in CSC group, but the number on days in hospital, with fever or under antibiotics were similar. Number of platelet transfusions was reduced in CFC group: this economical advantage was lost with the cost of growth factor used for priming stem-cells stem-cell collections and cryopreservations. In our retrospective study, financial advantages associated to peripheral blood stem-cell transplantation was not verified.

In order to assess the influence of total-body irradiation technique on veno-occlusive disease (VOD) incidence, we retrospectively analyzed our leukemia patients treated with bone-marrow transplantation conditioned using total-body irradiation and high-dose chemotherapy.Between 1980 and 1992, 305 patients with acute non-lymphoblastic leukemia (ANLL; n = 170) and acute lymphoblastic leukemia (ALL; n = 135) were treated with bone-marrow transplantation in their first complete remission (CR; n = 223) or in second CR (n = 82). All patients underwent total-body irradiation either in single dose (n = 176; 10 Gy to L4, 8 Gy to the lungs) or in 6 fractions (n = 129; 12 Gy in 3 consecutive days to L4, 9 Gy to the lungs) before bone-marrow transplantation. Patients were analyzed in 2 instantaneous dose rate groups: 104 (34%) patients received an instantaneous dose rateor = 4.80 cGy/min (mean: 3.07 +/- 0.60 cGy/min), and 201 (66%)4.80 cGy/min (mean: 6.60 cGy/min +/- 0.30). Conditioning chemotherapy consisted of cyclophosphamide alone in 231 patients, cyclophosphamide and etoposide or melphalan in 53 patients, and 21 patients were conditioned with cytosine arabinoside and melphalan. Bone-marrow transplantation was autologous in 197 patients, and allogeneic in 108 patients.Thirty (10%) of the 305 patients experienced VOD. In univariate analyses, its incidence was not influenced by instantaneous dose rate (9.6% [10/104] inor = 4.80 cGy/min group vs. 10% [20/201] in4.80 cGy/min group; p = 0.91), fractionation (11% [19/176] in single-dose total-body irradiation vs. 8.5% [11/129] in fractionated total-body irradiation, p = 0.64), age (9% [21/241] inor = 40-year old-patients vs. 14% [9/64] in40-year-old patients, p = 0.29), sex (6% [7/113] in male patients vs. 12% [23/192] in female patients, p = 0.15), type of VOD prevention (16% [16/101] in patients using heparin vs. 10% [14/142] in those receiving dinoprostone and pentoxifylline combination, p = 0.23), type of bone-marrow transplantation (9% [10/108] in allogeneic bone-marrow transplantation group vs. 10% [20/197] in autologous bone-marrow transplantation group, p = 0.96), or type of acute leukemia (9.6% [13/135] in ALL vs. 10% [17/170] in ANLL, p = 0.93). However, VOD incidence was significantly lower in patients whose conditioning chemotherapy consisted of cyclophosphamide alone (6.5% [15/231] vs. 20% [15/74] by other drugs +/- cyclophosphamide, p0.0001), and in patients treated after 1985 (7% [16/226] vs. 18% [14/79] in those treated before 1985, p = 0.01). Multivariate logistic regression analysis revealed that the best independent factors influencing the occurrence of VOD were the male sex (p = 0.03), conditioning chemotherapy consisting of cyclophosphamide alone (p = 0.01), and bone-marrow transplantation after 1985 (p = 0.008).In our series of 305 acute leukemia patients treated with allogenic or autologous bone-marrow transplantation, total-body irradiation technique (fractionation or instantaneous dose rate) did not seem to influence the incidence of VOD.

Allogeneic BMT is presently recognized as one of the reference anti-leukemic treatments for AML patients. It could be a very useful therapy in CR1 AML if it is efficient as an early form of consolidation after induction therapy. Later procedures may be of lesser importance since they concern a population which may have already been cured by chemotherapy. Alternatively it is not solved if very early BMT gives patients sufficient therapy and provides lower toxicity. To answer this question we analyzed data from the Société Française de Greffe de Moelle (SFGM) on a sub-group of patients according to the following criteria: (1) Allogeneic BMT carried out on patients with AML in CR1; (2) after January 1985; (3) conditioning with CyTBI; (4) GVHD prophylaxis with MTX-CsA; (5) interval between diagnosis and BMT100 days. Forty-two fulfilled all criteria. Age was 31 +/- 8 years and M/F ratio was 19/23. WBC at diagnosis were 36 +/- 49 x 10(9)/l and four patients needed two induction courses to achieve CR1. Median follow-up is now 51 (24-116) months. Twenty-two patients developed a gradeor = 2 acute GVHD. Early transplant mortality at 1 year is no higher than 14%. Two patients died of secondary malignancies at 3.5 and 6.5 years after BMT. Finally 5-year (and 7-year) probabilities for relapse, survival, leukemia and event-free survival are respectively 17% (17%), 71% (62%), and 71% (71%) and 68% (59%). These data indicate the feasibility of such an approach with low mortality and low relapse rates providing a good long-term outcome. This should prompt an invitation to initiate the search for an HLA-identical sibling when AML is diagnosed in a young patient eligible for allo-BMT.

To evaluate the importance of fractionating total body irradiation (TBI) in patients receiving an allogenic bone marrow transplant (BMT) for an acute myeloblastic leukemia (AML) in first complete remission (CR1).Between 1983 and 1990, 171 consecutive patients received either single dose TBI (STBI) (n = 65) or fractionated TBI (FTBI) (n = 106) after being conditioned with cyclophosphamide and before receiving a non-T-depleted Human Leucocyte Antigen (HLA)-identical marrow. Both groups were comparable except for date of BMT and diagnosis-to-BMT interval (D-BMT).After 63 months median follow-up, transplant-related mortality (TRM), probability of relapse, and 5-year disease-free survival (DFS) were 0.38 and 0.27 (p = 0.04), 0.29 and 0.26 (p = 0.22), 0.43 and 0.56 (p = 0.06), respectively, for STBI and FTBI. The supposed influence of the schedule of TBI disappeared in the multivariate analysis: TRM was enhanced by severe acute graft vs. host disease (p = 0.0002), early years of transplant (before January 1, 1987) (p = 0.0003), and longer D-BMT intervals (p = 0.038). Relapse was linked to early years of transplant (p0.00001), and the absence of chronic GVHD (p = 0.007). Longer DFSs were observed for later years of transplant (after January 1, 1987 and later) (p = 0.001), milder acute GVHD (p = 0.005), and shorter D-BMT intervals (p = 0.045). Important improvements of the results were made during the 7-year observation period: TRM, probability of relapse, and DFS were, respectively, 0.36, 0.28, and 0.46 for patients transplanted before January 1, 1987 vs. 0.21, 0.15, and 0.67 after that date.Our data strongly suggest that allogenic BMT is the best postremission treatment for AML in CR1, and the results are better when BMT shortly follows the achievement of remission. The schedule of TBI was of little importance compared with the improvements made in the management of patients undergoing BMT during the 1980s, and, therefore, reports concerning data prior to 1985 should be interpreted cautiously.

Thirteen patients (pts) with highly refractory acute myeloid leukemia (AML) 10 pts with de novo AML and 3 with blast crisis of chronic myeloid leukemia were treated with carboplatin (CP) 150 mg/m2/day through continuous IV infusion for 7 consecutive days. Seven of them received CP at least as third or more line therapy after a median duration of the disease of 26 weeks. None achieved a complete remission but a good hematologic response, with disappearance of circulating blast cells along with correction of bone marrow failure, persisting for 3 months was obtained in one patient and correction of hyperbasophilemia was observed in another with blast crisis of chronic myelogenous. Myelosuppression was the most consistent toxic effect. Two deaths occurred, one from renal acute failure and the other from sepsis. Median survival after CP was 8 weeks (range 4 days-11 months) and the majority of patients were able to return home. When used as a single agent and with the dose-schedule used in this study, CP does not appear effective in refractory AML. Other studies are necessary to assess its role at an higher dose or in combination with other agents in earlier phases of the disease.

Hepatic veno-occlusive disease is a frequent complication after high-dose chemo- or radiotherapy after bone marrow transplantation and is a major cause of mortality. During the 3 weeks following transplantation, acute major hepatic vascularization is observed together with portal hypertension and weight gain, ascitis and oedema of the lower limbs due to non-thrombotic obstruction of the centrilobular hepatic veins. This report summarizes the observations presented at a French symposium of France Autogreffe and Groupe d'Etude de la Greffe de Moelle osseuse. Different pathogenic processes are implicated including endothelial mechanisms due to toxic factor related to graft preparations and immunosuppressor treatments (methotrexate, cyclosporin), physical factors related to irradiation, immunological factors related to the expression of class II antigens on endothelial cells and viral factors, in particular cytomegalovirus infection. The incidence of veno-occlusive disease varies greatly from one series to another. Two French groups reported 5 and 3 cases among 1991 and 253 autologous grafts respectively (1.2 and 2.3%) while the Seattle group observed 53% among 355 consecutive grafts, although the same clinical criteria were used. Histological criteria include fibrosis around a non-thrombotic occlusion of the centrilobular veins, cytolysis and congestion of the sinuses. Other methods for diagnosis include transjugular biopsy, the suprahepatic pressure and imaging techniques. Prophylactic continuous infusion of low-dose heparin has been associated with a lower incidence. Trials using anti-tumour necrosis drugs and prostaglandin E1 have also been undertaken and show possible effects towards decreasing prevalence.(ABSTRACT TRUNCATED AT 250 WORDS)

We report the first case of full-term pregnancy arising from donated oocytes in a 36-year-old woman with chronic myeloid leukemia (CML), 6 years after allogeneic bone marrow transplantation (BMT) following total body irradiation (TBI) (12 Gy) and cyclophosphamide 120 mg/kg. The first attempt at implantation with her own cryopreserved ovocytes was unsuccessful. Thereafter, she became pregnant after donated oocyte implantation using estradiol and progesterone support replacing the defective ovarian function. The baby was normal. Unfortunately, 6 months later, she relapsed in chronic phase of CML.