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L’enquete « Regards croises 2009 » a ete realisee a l’issue du premier Plan cancer aupres de 300 patients cancereux presentant une anemie chimioinduite et de 359 professionnels de sante (medecins et infirmieres) pour evaluer et comparer leur perception de la prise en charge de la fatigue et de l’anemie chimio-induite. Les patients presentaient un cancer du sein, du poumon, colorectal ou une hemopathie maligne non myeloide, l’anemie pouvait etre traitee ou non, le seuil d’anemie etant fixe a 11 g/dl en accord avec les recommandations europeennes de 2007. Apres l’analyse principale des populations et les analyses secondaires des sous-populations par type de tumeur et de specialite medicale, une analyse exploratoire des souspopulations de patients par groupes d’âges (< 70 ans et ≥ 70 ans) et une analyse typologique prevue au protocole ont ete effectuees, afin d’identifier des profils de patients ayant des attitudes et/ou des comportements similaires a l’egard de la fatigue. L’analyse des souspopulations par groupes d’âge n’a montre aucune difference notable liee a l’âge concernant la perception de la fatigue et les attentes de prise en charge. Ainsi, ces resultats montrent que la fatigue du patient âge doit etre prise en charge au meme titre que celle du sujet jeune. L’analyse typologique des patients a permis d’identifier quatre profils dont la perception de la fatigue et les attentes en matiere de prise en charge different: les patients « astheniques insoumis » (33 %), les patients « astheniques domines » (30 %), les patients « qui relativisent » face a la fatigue (26 %) et les patients « non concernes » par celle-ci (11 %). L’identification du profil des patients en consultation pourrait permettre de proposer une prise en charge de la fatigue adaptee a leurs attentes. Enfin, une analyse typologique des medecins a ete brievement rapportee ici. Elle souligne, malgre l’implication globale des professionnels de sante dans la prise en charge de la fatigue, la diversite des attitudes medicales a cet egard. L’enquete « Regards croises 2009 » a donc apporte des enseignements sur la perception de la fatigue a l’aube du nouveau Plan cancer et les progres qui restent encore a effectuer.

Pour la premiere fois, une enquete a ete menee pour evaluer la perception des patients et des professionnels de sante sur la fatigue et l’anemie chimioinduite, en etablissant d’emblee un protocole qui devait permettre des comparaisons statistiques des sous-groupes de patients en fonction du type de cancer et des medecins en fonction de leur specialite. L’enquete « Regards croises 2009 » a ete realisee aupres de 300 patients atteints de cancer, de 250 medecins (oncologues, pneumologues, gastroenterologues et hematologues) et de 109 infirmieres. Les patients inclus presentaient une tumeur solide (cancer du sein, du poumon ou colorectal) ou une hemopathie maligne non myeloide, ils etaient traites par chimiotherapie et presentaient ou avaient presente une anemie (hemoglobine [Hb] < 11 g/dl). Les comparaisons des sous-groupes ont montre une relative homogeneite des resultats, confirmant les resultats globaux de l’enquete publies precedemment, en faveur d’une amelioration de la prise en charge de la fatigue, avec des particularites liees aux types de cancer et a la specialite medicale concernee. Ces specificites pourraient etre prises en compte pour adapter la prise en charge.

L’enquete « Regards croises 2009 » a ete realisee aupres de 300 patients atteints de cancer, de 250 medecins (oncologues, hematologues, pneumologues et gastroenterologues) et de 109 infirmieres afin d’evaluer et de comparer leur perception de la prise en charge de la fatigue et de l’anemie chimio-induite. Les patients inclus presentaient une tumeur solide (cancer du sein, du poumon ou colorectal) ou une hemopathie maligne non myeloide, etaient traites par chimiotherapie et presentaient ou avaient presente une anemie (hemoglobine [Hb] < 11 g/dl). Trois patients sur quatre (77 %) se plaignaient de fatigue, donnees qui sont en accord avec celles de la litterature. Des donnees nouvelles ont ete apportees par l’enquete: les patients ont exprime une grande satisfaction a l’egard de leurs relations avec les professionnels de sante, notamment dans la prise en charge du cancer (notes de 7,5 a 9,1/10), mais aussi avec des notes un peu moins elevees, dans le suivi de leur fatigue (notes de 6,6 a 8,4/10). La perception des professionnels de sante interroges etait en accord avec celle des patients, meme s’ils sous-evaluaient la qualite de leur relation avec les patients. Cela montre l’evolution positive de la prise en charge des patients atteints de cancer en France, depuis les etats generaux des malades du cancer publies en 1999 et qui avaient conduit a l’instauration du premier Plan cancer. La place du medecin traitant a aussi ete exploree aupres des patients: elle apparaissait essentielle, meme si les informations fournies sur la maladie cancereuse et sur la fatigue semblaient plus satisfaisantes lorsqu’elles provenaient des oncologues et des medecins specialistes. Ces resultats invitent a poursuivre les efforts d’ecoute et de dialogue aupres des patients en accord avec le Plan cancer 2009–2013.

L’enquete « Regards croises 2009 » a ete realisee aupres de 300 patients atteints de cancer, de 250 medecins (oncologues, hematologues, pneumologues et gastro-enterologues) et de 109 infirmieres pour evaluer et comparer leur perception de la prise en charge de la fatigue et de l’anemie chimio-induite. Les patients inclus presentaient une tumeur solide (cancer du sein, du poumon ou colorectal) ou une hemopathie maligne non myeloide, etaient traites par chimiotherapie et presentaient ou avaient presente une anemie (Hb < 11 g/dl). Trois patients sur quatre (77 %) se plaignaient de fatigue. Les patients et les professionnels de sante avaient une opinion consensuelle concernant l’impact de la fatigue sur la vie quotidienne des patients. Les professionnels de sante etaient unanimes sur la priorite que represente la prise en charge de la fatigue et sur la difficulte a la realiser. Leur perception a donc evolue depuis les precedentes enquetes qui montraient les insuffisances de la prise en charge de la fatigue des patients atteints de cancer. Les resultats montrent aussi que les patients interroges n’avaient pas conscience de la relation entre fatigue, chimiotherapie et anemie. Ainsi, un effort d’information des patients sur les traitements disponibles reste necessaire. C’est une des priorites exprimees de facon unanime par les trois populations interrogees, tout comme ameliorer la prise de conscience des professionnels de sante concernant la necessite de prendre en charge la fatigue et le recours a des traitements efficaces, qui s’integrent facilement avec les cycles de chimiotherapie et la vie quotidienne des patients.

L’enquete ≪ Regards croises ≫ a ete realisee en 2009, aupres de patients atteints de cancer et de professionnels de sante, pour evaluer et comparer leur perception de la prise en charge de la fatigue et de l’anemie chimioinduite. Les 300 patients inclus presentaient une tumeur solide (cancer du sein, du poumon ou colorectal) ou une hemopathie maligne non myeloide. Ils etaient traites par chimiotherapie et presentaient ou avaient presente une anemie (Hb < 11 g/dl). Tous les patients ont complete un auto-questionnaire remis par leur medecin. Les 359 professionnels de sante inclus etaient en charge de patients cancereux (250 medecins: oncologues, hematologues, gastroenterologues, pneumologues; 109 infirmieres) et ont repondu a un entretien telephonique. La fatigue est l’effet indesirable de la chimiotherapie le plus souvent cite par les patients (77 %). Comme decrit dans les enquetes precedentes, la fatigue reste en tete des complications qui affectent le plus la vie quotidienne des patients (37 %). La perception des professionnels de sante sur la fatigue et sa necessaire prise en charge est proche de celle des patients, ce qui montre une evolution des mentalites. Les professionnels de sante ont aujourd’hui conscience que la fatigue et les causes de cette fatigue doivent etre prises en compte dans le suivi des patients traites par chimiotherapie. L’integralite des resultats de l’enquete sera detaillee dans les publications suivantes.

Resume Propos. – L'agranulocytose medicamenteuse idiosyncrasique est un accident hematologique relativement peu frequent, mais susceptible de mettre rapidement en jeu le pronostic vital. Actualites et points forts. – L'agranulocytose medicamenteuse est caracterisee classiquement par un nombre de neutrophiles inferieur a 0,5 × 109/l, dans les formes les plus graves inferieur a 0,1 × 109/l, lie a la prise de divers medicaments, parmi lesquels on retrouve actuellement surtout des antibiotiques, des antithyroidiens de synthese et la ticlopidine (> 60 % des medicaments incrimines). Son incidence est estimee entre 2,4 et 15,4 cas par million d'habitants. Sur le plan clinique, l'agranulocytose medicamenteuse peut etre asymptomatique (50 % des cas), decouverte sur un hemogramme systematique ou se manifester par un tableau infectieux plus ou moins severe : fievre « nue », septicemie, choc septique, et infections localisees type angine, infections cutanees variees et pneumonie. De nos jours, avec une prise en charge « optimisee » sa mortalite est neanmoins inferieure a 5 %. Perspectives. – Les progres attendus concernent la mise en place, en routine clinique, de protocoles standardises incluant une antibiotherapie probabiliste a la moindre infection et des facteurs de croissance hematopoietique (G-CSF) en cas de marqueur de mauvais pronostic.

PURPOSE The purpose of this study was to evaluate the efficacy and tolerance of recombinant human interferon gamma (rIFN-gamma) as second-line treatment in patients with persistent disease at second-look laparotomy. PATIENTS AND METHODS One hundred eight patients with residual disease at second-look laparotomy were treated with rIFN-gamma (20 x 10(6) IU/m2) administered intraperitoneally (IP) twice a week for 3 to 4 months. In the absence of clinically assessable disease, response to rIFN-gamma was assessed with a third-look laparotomy. RESULTS Of 98 assessable patients, 31 (32%) achieved a surgically documented response, including 23 patients (23%) with a complete response (CR). The age and size of residual tumor were significant prognostic factors for the response to rIFN-gamma. A 41% CR rate was observed in 41 patients younger than 60 years and with residual tumor less than 2 cm. The probability of response was independent of previous response to first-line chemotherapy. The median duration of response was 20 months and the 3-year survival rate in responders was 62%. Response to rIFN-gamma was the most significant prognostic factor for survival of patients with residual disease. Adverse events included fever, flu-like syndrome, neutropenia, and liver enzyme disturbances. No significant peritoneal fibrosis was noted. CONCLUSION These results support the potential interest of IP rIFN-gamma as adjuvant treatment in ovarian cancer. Controlled prospective trials are required to determine its place in the therapeutic strategy of this malignancy.

Resume Un malade presente une aplasie medullaire idiopathique, rebelle a tout traitement, et developpe, sous triple association d'antibiotiques, une pneumopathie infectieuse febrile non etiquetee. Un lavage broncho-alveolaire (LBA) est effectue et le patient est mis sous antifongiques. La culture du LBA permet le diagnostic de Cunninghamella bertholletiae des la 24eme heure. Malgre le diagnostic precoce et un traitement approprie le malade decede. L'examen histologique post-mortem confirmera l'envahissement mycosique de la trachee, des poumons, de la rate, de l'estomac et du pancreas. Cette observation est a notre connaissance la premiere dissemination generalisee consecutive a une primoinvasion pulmonaire par C. bertholletiae decrite en Europe. Le cas est compare aux 14 autres cas decrits dans le monde.

Photodynamic therapy is a new treatment for early carcinomas. Although undergoing phase 1/2 clinical assays, clinical indications for this therapy remain rare mainly because of the approximate dosimetry of HPD uptake by tumour tissues in human beings.

The aim of this study is to report personal experience of pancytopenia related to low-dose methotrexate and to review the literature.We included retrospectively all cases of pancytopenia related to low-dose methotrexate (25 mg/week), followed between January 1997 and December 2006, in the university hospital of Strasbourg, France.Five women, mean age 75.6 years, were included in the present study. Clinical manifestations included: symptomatic anemia (n=4), infection (n=3) and hemorrhagic manifestations (n=2); one patient had no feature. Mean hemoglobin concentration was 8,8 g/dl; mean white cell and platelet counts were 1,500 /mm(3) and 16,000 /mm(3), respectively. Potential risk factors were identified in all patients: renal failure and low serum albumin levels (n=5), anti-inflammatory drug intake (n=2), folate deficiency (n=4) and cobalamin deficiency (n=1). One patient died of septic and hemorrhagic cerebral complications.Pancytopenia related to tow-dose methotrexate is a rare but life-threatening disorder. Search and prevention of potential risk factors are required in all patients; determination of MTHFR genotype may be of several interests as folate supplementation.

During last decades, several progresses have been made in the diagnosis of cobalamin (vitamin B12) deficiency. Routine used of cobalamin standardized assays have potentially modified the frequency and the type of hematologic abnormalities.Current studies on cobalamin deficiency, including more precise definitions and the description of new etiologies of cobalamin deficiency in adults, as the food-cobalamin malabsorption syndrome, show that hematological abnormalities are generally incomplete compared to historical descriptions of megaloblastic anemia. Nevertheless, they include severe manifestations in 10% of the patients: pancytopenia, severe anemia (hemoglobin6 g/dl) or hemolytic anemia and pseudo thrombotic microangiopathy related to cobalamin deficiency. These studies also show the efficacy of new treatment modalities including oral cobalamin administration.Future studies will confirm these data with the routine use of the new cobalamin assay: holotranscobalamin and validate the usefulness of oral cobalamin therapy.

Agranulocytosis is a life-threatening disorder that frequently occurs as an adverse reaction to drugs.Idiosyncratic drug-induced agranulocytosis is characterized by a neutrophil count0.5x10(9)/l, in serious forms0,1x10(9)/l that currently occurs especially in association with antibiotics, antithyroid drugs ant ticlopidine (60% of the incriminated drugs). The overall incidence of idiosyncratic agranulocytosis ranges from 2.4 to 15.4 cases per million patients exposed to drugs per year. Although patients experiencing idiosyncratic agranulocytosis may be asymptomatic (50%), the severity of the neutropenia usually leads to severe sepsis: fever of unknown origin, septicemia, septic shock or localized documented infections such as sore throat, various cutaneous infections or pneumonia. Nevertheless, the mortality rate of idiosyncratic agranulocytosis is now around 5% with appropriate management.In the future, management of drug-induced agranulocytosis may include pre-established procedures using in critically situations, broad-spectrum antibiotic therapy and hematopoietic growth factors (G-CSF).

To define usefulness and response to therapy and outcome in adults with idiopathic thrombocytopenic purpura (ITP) in clinical practice. We retrospectively reviewed a cohort of 201 consecutive patients with ITP, diagnosed between 1985 and 1994. In particular, we analyzed the therapies used, their response rates, prognostic indicators of response and outcome. In 62 patients, with minor bleeding episodes and a mean (+/- SD) platelet count of 88 +/- 23 x 10(9)/l, no treatment was used and chronic ITP was diagnosed in 59%. A total of 139 patients, with bleeding episodes in 71.2% cases and a mean platelet count of 20 +/- 13 x 10(9)/l, received at least one treatment. Three patients died (1.5% of the series). Corticosteroids were used in 118 patients, with an initial response rate of 82.2% and a long-term complete response (CR) of only 22.9%. Intravenous immunoglobulin was used in 26 patients, with an initial transient response in more than 60%. A splenectomy was performed in 55 patients, with an initial response rate of 92.5% and a long-term CR in 60%. Young age and prior response to corticosteroids were significant predictors of a durable response to splenectomy. Danazol was given in 37 patients, with a favorable response in 73% of cases. Our results illustrate the guidelines of the American Society of Hematology. Patients with moderate thrombocytopenia do not require treatment. In severe cases, splenectomy is the only treatment giving durable cures in a significant proportion of patients. Despite frequent chronicity, ITP is life-threatening only in a minor subset of patients.

We report here a case of primary hepatic anaplastic large cell Ki-1 non-Hodgkin's lymphoma in a 60 year old patient followed for hereditary hemochromatosis.

To report on an uncommon association of agranulocytosis in primary Sjögren's syndrome (SS).The clinical, haematological, and immunological features of seven patients with primary SS associated with a chronic (6 months) agranulocytosis, and the outcome of the patients, were analysed.Patients were white women with an unexplained agranulocytosis. They all had non-erosive arthritis and three had a thrombocytopenia or Evan's syndrome. In three patients, transient or durable expansion of T lymphocytes was present in the peripheral blood or in the bone marrow, but evolved independently from neutrophil counts. There was no paroxysmal nocturnal haemoglobinuria clone or antibodies to neutrophil surface antigens. In vitro bone marrow culture was normal (four patients) or showed a decrease in colony forming unit-granulocyte monocyte (CFU-GM) and colony forming unit-erythroblast (CFU-E) (one patient). Serum levels of soluble Fas ligand (sFasL) were normal, and granulocyte-colony stimulating factor (G-CSF) concentrations were either normal or raised. One patient was treated with steroids associated with intravenous immunoglobulins and achieved a lasting response. Two other patients were treated with steroids and methotrexate, with poor efficacy. Short courses of subcutaneous G-CSF produced a transient and mild response in all three patients. Complete recovery of the neutrophils occurred temporarily during pregnancy in two patients. After a mean follow up of 34.8 months (range 6-139) all patients were alive and none developed serious infections.A subset of patients with primary SS and non-destructive arthritis may develop a chronic but well tolerated agranulocytosis that is usually poorly responsive to steroids and oral methotrexate.

Agranulocytosis is a life-threatening disorder that frequently occurs as an adverse reaction to drugs. The overall incidence of nonchemotherapy drug-induced agranulocytosis (DIA) ranges from 2.6 to 10 cases per million patients exposed to drugs per year. Although patients experiencing DIA may initially be asymptomatic, the severity of the neutropenia usually leads to severe sepsis, requiring intravenous broad-spectrum antibiotic therapy. In this setting, old age, septicaemia, shock, and the metabolic complications of infection, such as renal failure, are poor prognostic variables. The severity of neutropenia (0.1 x 10(9))/l) and its duration (10 days) may also impact negatively on the outcome. With appropriate management using pre-established procedures, the mortality rate is now around 5%. Haematopoietic growth factors have been shown to shorten the duration of neutropenia in DIA. However, it has yet to be determined whether their use translates into a better outcome in DIA patients experiencing sepsis. DIA still remains a rare event. However, given the increased life expectancy and subsequent longer exposure to drugs, as well as the development of new agents, physicians should be aware of this complication and its management.

In young subjects, the discovery of a cobalamine deficiency (Biermer's disease) at the time of neuropsychiatric disorders even of isolated MRI anomalies is a rare event (less than 0.01%).We report two observations of cobalamine deficiency, in patients 30 and 37 years old, revealed by acroparesthesia and spontaneous hypersignal in the T2 sequence of MRI and by a peripheral sensitive neuropathy respectively.The neuropsychiatric demonstrations of pernicious anemia are polymorphic with, sometimes, isolated spinothalamic attacks. The MRI can contribute to the diagnosis but more often leads to an erroneous diagnosis. Our observations are of special interest because symptoms occurred apart from supplementation of folates and recovered ad integrum with an early treatment by vitamin B12.

Otological manifestations exceptionally reveal acute leukaemia, whereas leukaemic infiltration of any tissue is frequent at postmortem examination. We present two cases of acute myeloblastic leukaemia revealed by a loss of hearing due to a middle-ear leukaemic infiltration. The characteristics of such a clinical and radiological finding are emphasized. It is suggested that middle and inner ear can be a 'sanctuary' localization, which might sometimes require radiation therapy to achieve durable and complete remission.

Our study was aimed at determining the role of hematopoietic growth factor in drug-induced agranulocytosis.Fifty-five cases of drug-induced agranulocytosis were reviewed and subdivided retrospectively into a G-CSF group (n = 15) and an untreated group (n = 40). Mortality and hematological recovery (number of days required for neutrophil counts to exceed 1.5 x 10(9)/L) were studied in the two groups.The mean granulocyte count was 0.09 x 10(9)/L. All patients presented infection. In the G-CSF group, no mortality (0% versus 5%, P = 0.85) and a shorter recovery time (8.1 versus 9.5 days P = 0.39) were observed. No significant difference between the two groups was observed in either the duration of antibiotic therapy (9.3 days in the G-CSF group versus 10.1 days in the untreated group, P = 0.51) or duration of hospitalization (10 days in the treated group versus 11 days in the G-CSF group, P = 0.46).Our results as well as a literature review indicate that G-CSF could decrease the time to hematological recovery and perhaps reduce mortality. However, the exact role of hematopoietic growth factors requires further investigations.

First results of a randomized trial (APL91 trial) and other randomized or non-randomized studies have shown that ATRA followed by chemotherapy significantly increased event-free survival (EFS) and survival, and decreased the incidence of relapse by comparison to chemotherapy alone in newly diagnosed APL. We present here long-term follow-up of the APL91 trial. In this trial, 101 patients had been randomized between ATRA followed by three courses of daunorubicin-AraC chemotherapy (ATRA group) and the same chemotherapy alone (chemotherapy group). Results were reanalyzed 73 months after closing of patient entry. Updated results of APL 91 trial found a Kaplan-Meier estimate of EFS and relapse rate at 4 years of 63% and 31% in the ATRA group, as compared to 17% and 78% in the chemotherapy group (P= 10(-4) and relative risk 2.95, P= 10(-4) and relative risk 3.68, respectively). Kaplan-Meier survival at 4 years was 76% in the ATRA group and 49% in the chemotherapy group (P= 0.026, relative risk 2.7). In the chemotherapy group, seven of the 27 relapses occurred after 18 months, but no relapse was seen after 43 months. In the ATRA group, four of the 17 relapses occurred after 18 months, including two late relapses (at 58 and 74 months). In the chemotherapy group, 23 of the 25 patients who relapsed achieved a second CR with ATRA, and the Kaplan-Meier estimate of second relapse was 40% at 30 months. In the ATRA group, the 10 patients who relapsed and were retreated with ATRA achieved a second CR. In conclusion, long-term results of APL91 trial confirm the superiority of the combination of ATRA and chemotherapy over chemotherapy alone in newly diagnosed APL, and that ATRA should be incorporated in the front-line treatment of APL.

Castleman's disease is an unusual condition of unknown cause, consisting of massive proliferation of lymphoid tissue. Two forms (localized and multicentric) have been described. Interleukin-6 (IL-6) is at the core of the disease, being responsible for most of the clinical and biological signs that may be observed. Despite the benignancy of this pre-lymphoma condition, its course is usually aggressive and of poor prognosis in regard to the multicentric form. No consensus regarding treatment has been defined. Available data on the multicentric form of the disease are to scarce to allow any conclusion about the treatment timing and type of chemotherapy best suited to this condition. We report the case of a patient in whom interferon alpha (IFN-alpha) was used as first line treatment.The case of a 52-year-old man with multicentric Castleman's disease combined with high IL-6, in whom, however, testing for human herpes virus-8 proved to be negative, is described. Interferon alpha (4.5 MU/m2 three times per week during 18 months) administered as first line treatment induced dramatic improvement in the patient's general condition and normalization of the tumoral syndrome. Moreover, biological parameters and IL-6 returned to normal. Two years after interferon disruption, complete remission is still present.On the basis of the present data and those of two previous observations, anti-IL-6 and anti-infective properties of IFN-alpha are discussed. Treatment of multicentric Castleman's disease is based on corticosteroids and drugs derived from those pertaining to treatment of malignant lymphomas. Our results indicate that IFN-alpha is truly directed against Castleman's disease and has less toxicity than drugs usually prescribed. This argues for early use of IFN-alpha in Castleman's disease, in association or not with corticosteroids.

The purpose of this study was to assess the safety and efficacy of stem cell transplantation (SCT) mainly autologous SCT as consolidation therapy in APL patients who relapsed and achieved a second complete remission (CR2). Fifty adult patients with a first relapsed APL, of whom 39 had been previously treated with ATRA, entered a multicenter trial of oral ATRA until complete remission (CR) achievement followed by timed sequential chemotherapy (EMA combining etoposide 200 mg/m2/day for 3 days, mitoxantrone 12 mg/m2/day for 3 days, and cytarabine 500 mg/m2/day for two sequences of 3 days). EMA was started either after CR achievement, or on day 1 of ATRA because of initial white blood cell (WBC) counts5 x 10(9)/l, or rapidly added to ATRA in order to prevent ATRA syndrome because WBC count increased under ATRA. Forty-five patients (90%, 95% CI 78%-97%) were in CR after induction therapy. Five patients died from infection during aplasia following EMA chemotherapy. Eleven patients who achieved CR had a familial HLA-identical donor and were allografted. The median disease-free survival (DFS) of allografted patients was 8.2 months. The 34 other CR patients were scheduled for autologous peripheral blood (PB) SCT (intent-to-treat group). Actually, autologous transplantation was only carried out in 22 patients (65%) (17 PBSCT and five autologous bone marrow transplantation (BMT)). Reasons for not autografting were early relapse (three patients), severe toxicity of EMA chemotherapy (six patients), and refusal or failure of stem cell harvest (three patients). The 3-year DFS rate of patients actually autografted was 77%. Among the 17 autografted patients still in CR2, nine patients have already reached a longer CR2 than first CR (CR1). Results of detection of PML/RARalpha by RT-PCR after autologous transplantation show negative findings in eight of the nine patients tested. We conclude that (1) ATRA combined to EMA chemotherapy is effective in the treatment of relapsed APL; (2) allogeneic BMT may be too toxic after salvage treatment including EMA intensive chemotherapy; (3) clinical outcome of autografted patients and preliminary molecular results regarding detection of PML/RARalpha after autologous PBSCT are encouraging.

All transretinoic acid (ATRA) followed by daunorubicin (DNR)-AraC chemotherapy (CT) has improved the outcome of acute promyelocytic leukemia (APL) by comparison to CT alone. In a randomized trial, (1) we compared 2 induction schedules (ATRA followed by CT [ATRA--CT] and ATRA plus CT [ATRA+CT, with CT added on day 3 of ATRA treatment]) and (2) we assessed the role of maintenance treatment. Four hundred thirteen patients/=75 years of age and with newly diagnosed APL were included. Induction treatment was stratified on white blood cell (WBC) count and age: patients/=65 years of age and with an initial WBC count of/=5,000/microL (n = 208) were randomized between ATRA--CT and ATRA+CT (initially randomized patients); patients with a WBC count greater than (high WBC count group, n = 163) and patients 66 to 75 years of age with a WBC count greater than 5,000/microL (elderly group, n = 42) were not initially randomized and received ATRA+CT from day 1 and ATRA --CT, respectively. All patients achieving CR received 2 additional DNR-AraC courses (only 1 in patients 66 to 75 years of age) and were then randomized for maintenance between no treatment, intermittent ATRA (15 days every 3 months) for 2 years, continuous low-dose CT (6 mercaptopurine + methotrexate) for 2 years, or both, using a 2-by-2 factorial design. Overall, 381 (92%) of the patients achieved complete remission (CR), 31 (7%) suffered an early death, and only 1 patient had leukemic resistance. ATRA syndrome occurred in 64 patients (15%) and was fatal in 5 cases. The CR rate was similar in all induction treatment groups. Event-free survival (EFS) was significantly lower in the high WBC group (P =.0002) and close to significance in the elderly group (P =.086) as compared with initially randomized patients. Relapse at 2 years was estimated at 6% in the ATRA+CT group, versus 16% in the ATRA--CT group (P =.04, relative risk [RR] =.41). EFS at 2 years was estimated at 84% in the ATRA+CT group, versus 77% in the ATRA--CT group (P =.1, RR =.62). Two hundred eighty-nine patients were randomized for maintenance. The 2-year relapse rate was 11% in patients randomized to continuous maintenance CT and 27% in patients randomized to no CT (P =.0002) and 13% in patients randomized to intermittent ATRA and 25% in patients randomized to no ATRA (P =.02). An additive effect of continuous maintenance CT and intermittent ATRA was seen, and only 6 of the 74 patients who received both maintenance treatments had relapsed. Overall survival was improved in patients who received maintenance CT (P =.01), and there was a trend for better survival in patients who received maintenance ATRA (P =.22). Our findings strongly suggest that early addition of chemotherapy to ATRA and maintenance therapy combining continuous CT and intermittent ATRA can reduce the incidence of relapse in APL. This effect already translates into significantly better survival for maintenance treatment with continuous CT.

To discuss the potentially fortuitous occurrence of both renal carcinoma and B-cell malignant proliferation and its physiopathology.We describe a series of eight patients presenting with both diseases.In these patients renal carcinoma was associated with either malignant non-Hodgkin lymphoma (seven cases) or multiple myeloma (one case). Of the eight patients three had both malignancies within the same renal tumor.Though this association is unusual, it may not be fortuitous. Its physiopathology is discussed in regard to either growth factor synthesis within the renal tumor or mutations in tumor-suppressor genes.

We prospectively assessed autologous stem cell transplantation for consolidation treatment in a trial of intensive chemotherapy in high risk myelodysplastic syndromes (MDS). In this trial, patients aged 55 years or less with no HLA-identical sibling and achieving CR were scheduled to receive unmanipulated autologous bone marrow transplantation (ABMT) preceded by a consolidation chemotherapy course. Forty-two of the 83 patients aged 55 years or less included in the trial (51%) achieved CR. Three were allografted in CR. Twenty-four of the remaining 39 patients who achieved CR (62%) received ABMT (16 patients) or autologous peripheral blood stem cell transplantation (APSCT) (eight patients). Indeed, as bone marrow harvest was often insufficient, APSCT was subsequently proposed after mobilization by consolidation chemotherapy followed by G-CSF. The conditioning regimen combined cyclophosphamide and busulfan. ABMT and APSCT were performed 1-7 months (median 3) after CR achievement. Hematological reconstitution occurred in all patients and tended to be faster after APSCT than ABMT although not significantly. Three patients died from the procedure, nine relapsed after 2-26 months and 12 (50%) were still in CR after 8-55 months. In autografted patients, median Kaplan-Meier disease-free survival and survival were 29 and 33 months from the autograft, respectively. Thus, ABMT or APSCT can be performed in almost two-thirds of MDS patients who achieve CR with intensive chemotherapy. PBSC collection may yield higher numbers of stem cells than marrow collection in some cases, and could improve the percentage of MDS patients autografted in CR. Longer follow-up is required to determine if autograft will prolong CR duration in at least some patients.

Abnormalities involving the 14q32 region are recurrent chromosomal changes in plasma cell malignancies. Recent preliminary molecular analyses found IGH rearrangements in almost 100% of human myeloma cell lines and in 75% of patients. However, no systematic study analyzing the nature of the partner chromosomal regions have been reported thus far. To define the exact incidence of illegitimate IGH rearrangements and the respective incidence of partner genes cloned to date, we analyzed 141 patients with either multiple myeloma (MM, n = 127) or primary plasma cell leukemia (PCL, n = 14) using fluorescence in situ hybridization. The overall incidence of illegitimate recombinations was 57% (80 of 141 patients). Analysis of this incidence according to Durie and Salmon stage, patients' status, i.e., MM versus primary PCL and diagnosis versus relapse, immunoglobulin type and subtype, and beta2-microglobulin value, did not show any correlation. To analyze the nature of the partner chromosomal region, we selected probes specific for the following genes: FGFR3 (4p16), MYC (8q24), CCND1 (11q13), MAF (16q23), and BCL2 (18q21). These probes, combined with differentially labeled 14q32 probes, were used for dual-color fluorescence in situ hybridization on interphase plasma cells. Among the 80 patients with illegitimate IGH rearrangement, we identified 23 IGH-CCND1 fusion cases [i.e., t(11;14)], 17 IGH-FGFR3 fusion cases [i.e., t(4;14)], 3 IGH-MYC fusion cases [i.e., t(8;14)], and only one IGH-MAF fusion case. No IGH-BCL2 fusion case was detected. In 37 of 80 patients, none of these partner genes was involved. Analysis of cases with specific translocations according to their bioclinical features at diagnosis did not show any correlation. This study demonstrated that CCND1 and FGFR3 genes are involved together in about 50% of MM and primary PCL patients with illegitimate IGH rearrangements.

To evaluate the results, prognostic factors and especially side-effects of the treatment for subdiaphragmatic Hodgkin's disease (SHD) a retrospective study was conducted in the Haematology Departments and in the Cancer Centres of Nancy and Strasbourg between 1976 and 1990; 55 patients corresponding to the IA to IIB SHD stages were analysed. The median age was 45 years. In accordance with Ann Arbor classification, we observed 12 CS IA (21.3%), 2 CS IB (3.5%), 14 CS IIA (25.4%) and 27 CS IIB (49.7%). Twenty-five patients (45.4%) underwent laparotomy with spleen involvement in 10 cases. Fifteen patients (27.3%) had exclusive radiotherapy, 10 by inverted-Y field with or without splenic field, 5 by limited field to inguinal and homolateral iliac nodes. Forty patients had prior chemotherapy, 18 by MOPP protocol, 18 by hybrid MOPP/ABVD protocol and 4 by other schemes. The total dose delivered ranged from 26 to 45 Gy. With a median follow-up of 8 years, the overall and disease specific survival rates are respectively 61% and 83% at 10 years. Nine patients relapsed (16.4%), 4 among the 15 (26.6%) treated by exclusive irradiation and 5 among the 40 (12.5%) treated by combined therapy. We observed 8.3%, 21.4% and 18.5% of relapses respectively among the clinical stages IA, IIA and IIB. Eleven patients (20%) developed a second cancer. Twenty-six long-term complications were noted, nine of which concerned the digestive system. The only significant prognostic factor is age, with 10-year specific survival rates of 96% and 66% respectively for patients younger and older than 50 years (p=0.0003). Our data confirm that the most appropriate treatment for stage IA is exclusive radiotherapy and combined therapy for all other cases. With the use of CT-scan and eventually lymphography, the laparotomy is reserved only for cases with an uncertain diagnosis. Tobacco use is also clearly a risk factor in our series for late vascular complications and second cancers.

Hairy cell leukemia represent 2% of all the leukemias. The etiology is unknown. The diagnosis is based on the peripheral blood examination, showing characteristic lymphoid B cells, with loose lacy chromatin and unconstant cytoplasmic projections. The abnormal lymphoid cells express CD19, CD20, CD22, CD79a, CD25 and CD103. The tumor cells are Sig + with clonal light chain restriction. The treatment is based on recombinant IFN: we discuss the interest and the risks of second malignancy related to the prescription of the purine analogues.

The effectivness of interferon alpha (IFN) for the treatment of chronic myelogenous leukemia (CML) during the chronic phase is now well established. Several studies have shown that IFN produces hematologic remission in 60% to 80% of patients [1]. In some studies the achievement of complete hematologic response within 3 months seems to represent a significant factor which correlates with a cytogenetic response [2]. Also, the treatment with IFN resulted in suppression of the Ph-positive cells population which was complete in 7% to 25% of the patients [3, 4]. A major cytogenetic response (i.e., less than 35% Ph-positive cells) was noted in 35 to 45% of the patients. Such cytogenetic response was not only complete but also prolonged for periods ranging between 2 and 8 years [5].

Treatment with interferon prolongs survival in chronic myelogenous leukemia. We conducted a clinical trial to assess the efficacy of treatment with a combination of interferon and cytarabine.Previously untreated patients with chronic myelogenous leukemia were randomly assigned to receive either hydroxyurea (50 mg per kilogram of body weight per day) and interferon alfa-2b (5 million units per square meter of body-surface area per day), or hydroxyurea and interferon in the same dosages plus monthly courses of cytarabine (20 mg per square meter per day, for 10 days). The end points were overall survival, complete hematologic remission at 6 months, and major cytogenetic response (less than 35 percent Philadelphia chromosome-positive cells in the bone marrow) at 12 months.The trial was stopped when a sequential analysis showed a benefit of interferon and cytarabine. A significant improvement in survival was observed in the interferon-cytarabine group (360 patients) as compared with the interferon group (361 patients) (P=0.02; relative risk of death, 0.64; 95 percent confidence interval, 0.44 to 0.93). After three years, the survival rate was 85.7 percent with interferon and cytarabine and 79.1 percent with interferon alone. The rate of hematologic response was higher in the interferon-cytarabine group than in the interferon group (P=0.003). Major cytogenetic responses were observed 12 months after randomization in 126 of 311 patients treated with interferon and cytarabine (41 percent) and in 75 of 314 patients treated with interferon only (24 percent, P0.001).The combination of interferon and cytarabine, as compared with interferon alone, increases the rate of major cytogenetic response and prolongs survival in patients with the chronic phase of chronic myelogenous leukemia.

Mycosis fungoides can mimic pigmented purpuric dermatitis. We report such a case which progressed to peripheral T-cell lymphoma; progression was revealed by reactive hemophagocytic syndrome (RHS).A 65-year old male patient was hospitalized for a pigmented and purpuric eruption. The skin lesions appeared 2 years earlier and at that time biopsy had shown pigmented and purpuric dermatitis. One month before hospitalization, general signs appeared. On admission, he had papular and purpuric rash, mainly on the trunk, hepatosplenomegaly, enlarged axillar and inguinal lymph nodes, and fever at 38.2 degrees. A skin biopsy showed histologic changes typical of mycosis fungoides. He also had bicytopenia, hepatitis, and increased triglyceride and ferritin levels suggesting RHS which was proved by means of bone marrow biopsy. These tests also evidenced peripheral T-cell lymphoma. The patient was treated with two courses of chemotherapy (CHOP) but the disease progressed and he deceased.Mycosis fungoides can occasionally begin with an eruption very closely resembling pigmented purpuric dermatitis. Therefore, repeated biopsies should be done in case of widespread permanent pigmented purpuric dermatitis of no apparent origin. RHS is a life-threatening disease. The diagnosis should be suspected in any cytopenic patient with fever, increased triglyceride levels and abnormal liver tests. A search for an etiology must then be undertaken a prompt treatment is needed.

We report our experience of CBDCA-CPM combination chemotherapy as first line therapy in 101 ovarian cancers. The therapeutic scheme was: initial cytoreductive surgery followed by six chemotherapy cycles (CBDCA 400 mg/m2/d IV dl, CPM 600 mg/m2/d IV dl, dl = d21) and second-look laparotomy. The initial stages were four Ic, three IIa, four IIb, four IIc, 15 IIIa, 28 IIIb, 23 IIIc and 20 IV. After initial surgery, there were 39 macroscopic residual diseases superior to 2 cm, 26 macroscopic residual diseases inferior or equal to 2 cm, four microscopic diseases and no residual disease in 30 cases (unknown in two cases). The overall response rate to chemotherapy was 83% with 56% histologic complete response rate. The main toxicity was haematological with 60% of leucopenia grade III-IV, 52% of thrombopenia grade III-IV. Age at diagnosis, residual disease after first look surgery and length of CA 125 normalization were significant prognostic factors for survival in this series.

Hodgkin's disease, non-Hodgkin lymphoma or leukemia occurring in a pregnant patient is a rare event. Diagnosis of hematologic malignancies in a pregnant woman usually poses a quandrum of psychological, ethical and medical considerations. All of these situations require a multidisciplinary team. Adequate staging and treatment of hematologic malignancies are complicated by the pregnancy. In the first trimester, termination of the pregnancy should be considered in order to provide the best outcome for the woman and fetus. In this review we have focused on the use of chemotherapy for the pregnant patient. This review reveals that the use of chemotherapy resulted in both objective disease remissions and the subsequent delivery of normal infant.

Fetal and neonatal immune thrombocytopenias with platelet count less than 150.10(9)/l, result from transplacental passage of maternal platelet-specific antibodies. The main risk of these diseases is severe brain damage or death due to intracranial hemorrhage. Prevention and screening are difficult because of the lack of predicting factors. Only some women are at high risk of fetal thrombocytopenia (HLA DRW 52a HPA-la negative women or women with a previous history of immune thrombocytopenic purpura and having platelet-specific autoantibodies). Antenatal diagnosis and therapy have altered the natural course of fetal alloimmune thrombocytopenia. No prenatal treatment has proved to be effective in autoimmune thrombocytopenia and prenatal diagnosis by fetal blood sampling is controversial. A better knowledge of the pathogenesis of gestational incidental thrombocytopenia in otherwise healthy pregnancies, could define a group at high risk of fetal thrombocytopenia.

Mesenteric ischemic process can lead to bowel infarction or indolent low-grade ischemia. Inherited thrombophilia represents about 30 to 40% of mesenteric vein thrombosis. Analysis of thromboembolism sites occurring during genetic defect of coagulant factors showed that mesenteric thrombosis is the third localization after lung and legs, in equal incidence with cerebral thrombosis. The genetic defects known to be associated with thrombophilia, as deficiencies of protein C, protein S, antithrombin III, and dysfibrinogenemia, are discussed. A special interest is devoted to resistance to activated protein C. Acquired diseases, as myeloproliferative disease or paroxysmal nocturnal hemoglobinemia, inducing thrombosis are also discussed. Recent advances in both basic and clinical research have provided new insights that may be integrated into diagnostic and therapeutic practices.

True non parasitary splenic cysts are uncommon. They are characterized histological by an epithelium on the inner surface of the cyst wall. This study presents, about 5 new cases of splenic cysts, the clinical presentation, the difficulties of the diagnosis based on the ultrasound exploration and computed tomography scan investigation, and the different possibilities of management of these cysts. The principal of the treatment is the resection of the totality of a cyst with a diameter higher than 5 cm. A partial splenectomy seems to be the best treatment, whenever possible, especially in children.

The efficacy of gastrointestinal decontamination in reducing the incidence of severe bacterial or fungal infections and of moderate to severe acute graft-versus-host disease (GVHD) has been suggested. We report here a retrospective study of 71 patients grafted consecutively in our institution with bone marrow from HLA genotypically identical siblings. Complete decontamination (plastic isolator or laminar airflow room, sterile nursing and oral antimicrobial drugs) was carried out in all patients. Sixty eight patients were evaluable. Only six patients had aerobic Gram negative rods or anaerobic bacteria in their faeces and 44 of 68 (65%) had yeasts in their faeces. Most patients had oropharyngeal and/or nasal colonisation with bacteria (Gram positive cocci: 39 patients (57%); Gram negative rods: 13 patients (19%)) or yeasts (29 patients (43%)). Thirty nine patients (57%) experienced severe gradeor = II acute GVHD (grade II-IV). A significant relation was found between bacterial oropharyngeal or nasal colonisation and GVHD (P0.01) but not between gastrointestinal microflora and GVHD, whatever microorganisms were considered (bacteria, yeasts).

PTL after solid organ transplantation are a serious complication occuring in 1–18% of patients. Between 1978 and february 1994, 1000 transplantations were performed and eleven secondary lymphoproliferative disorders were observed (1.1%). Seven of them were high-grade lymphoma and required chemotherapy.

Forty-three children with malignant diseases who received 48 totally implanted venous accesses (TIVA) were retrospectively analyzed. More than half the patients had acute leukemia. Mean age was 6 years 10 months. Mean duration of use of the TIVA was 473 +/- 50 days (range 28 to 1,285 da; median 424 days). Removal of the TIVA was required because of an adverse event in 33% of cases. Main reasons for removal included infection (22.9%), thrombosis (6.25%), and catheter dysfunction (4.16%). Catheter-related infections were most often due to staphylococci (90%), especially S. epidermidis (63%). Infection rate was 0.48 per 1,000 patient-days. Flushing with a vancomycin-heparin solution can be expected to decrease this rate. Selection of the implantation site is discussed. In children under 6 years of age, the cephalic vein and external jugular vein are often frail or absent and are therefore less appropriate than the internal jugular vein or subclavian vein.

e19653 Background: Despite the frequency of fatigue related-anemia in patients, and its repercussions on the quality of life, patient management remains inadequate. Moreover, few data are available...

We assessed the efficacy and tolerability of VIM (etoposide/ifosfamide/methotrexate) combination therapy in 24 patients who were failing the treatment protocol of the Lymphomes Non Hodgkiniens (LNH) 84 study. Eight patients were refractory to the LNH 84 induction cycles, but ten achieved a partial response (PR). The six remaining patients attained complete response (CR) after LNH 84 induction, but relapsed either during consolidation therapy or after completing the whole program. Twenty-three patients are evaluable for response. The VIM regimen provided a CR rate of 43% and a PR rate of 17%. Treatment failed in nine cases (39%). The CR rate was particularly high (67%) in the group of patients who had PR with LNH 84 induction treatment. Of the ten who had attained CR, five relapsed after 4 to 42 months and five are still alive with no evidence of disease after 29 to 62 months. VIM therapy was well tolerated. A total of 101 VIM courses were given. Myelotoxicity was the most common side effect. Grade 3 or 4 cytopenia was recorded after 11% of the cycles. Among eight infectious episodes recorded, one was fatal. This study demonstrates that CR and long disease-free survival are obtainable with the VIM regimen in a small number of patients failing a high-dose doxorubicin-containing first-line treatment.

Invasive Trichosporon capitatum infections are seldom reported. We present here five cases of septicemia. All patients had an acute myeloblastic leukemia and were severely neutropenic. They have also been treated before the onset of the fungal infection with broad-spectrum antibiotherapy and also with an oral azole antifungal agent. The role of this antifungal therapy in the development of T. capitatum infection is discussed. The prognosis of T. capitatum infections is severe. Eight of the 10 published cases had a fatal outcome and one of our patients died of the fungal infection in spite of the treatment.