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La Leucémie Aigüe Myéloïde (LAM), est une hémopathie maligne caractérisée par une prolifération de cellules myéloïdes immatures présentant une différenciation variable. Les LAM représentent un groupe de maladies biologiques hétérogènes impliquant le plus souvent la moelle osseuse et le sang périphérique. Elles peuvent toutefois se manifester dans les tissus extra-médullaires.Aujourd’hui et ce, depuis plusieurs décennies, la Cytarabine est un des deux piliers dans le traitement de la LAM en association avec des Anthracyclines selon un schéma « 7+3 » lors de la cure d’induction et le plus souvent en monothérapie durant les cures de consolidation. La Cytarabine et les Anthracyclines se présentent sous forme de solutions et sont administrées par voie intra-veineuse (IV). Leur activité n’est pas ciblée, par conséquent, celle-ci peut s’accompagner d’effets secondaires généraux comme des pancytopénies ou encore des toxicités cardiaques décrites pour les Anthracyclines. Ces toxicités pouvant conduire parfois jusqu’au décès toxique du patient, d’où l’intérêt des recherches qui ont conduit à une nouvelle formulation : le Vyxeos®.En effet, en août 2017, la Food and Drug Administration (FDA), a approuvé le Vyxeos® (Jazz Pharmaceutical), une formulation liposomale caractérisée par une co-encapsulation de Daunorubicine et Cytarabine (44mg/100 mg, respectivement) avec un ratio molaire fixe de 5 : 1), indiquée dans le traitement des patients adultes présentant une LAM nouvellement diagnostiquée, secondaire à un traitement (LAM-t) ou avec des anomalies associées aux myélodysplasies (LAM-MRC). Le Vyxeos® a obtenu une autorisation temporaire d’utilisation (ATU) de cohorte en France en juillet 2018, puis l’AMM pour cette même indication en août 2018.

Introduction: although the majority of adult acute myeloid leukemia (AML) patients achieve complete remission (CR), a relapse still occurs in 35-80% and long-term survival rates remain extremely low after relapse (10-20%). At relapse, the common admitted strategy is to reach a second CR (CR2) and to bridge eligible patients to allogeneic hematopoietic stem cell transplantation (HSCT). We assessed the efficacy and safety of gemtuzumab ozogamycin (GO, anti-CD33 linked to calicheamicin) combined with cytarabine (GO+AraC) in relapsed AML. Methods: a retrospective study was conducted among relapsed AML patients in Saint-Louis Hospital (Paris, France) from January 2008 to December 2018, all consecutive patients with AML in first relapse treated with GO+AraC were included. Results: 71 patients with a median age of 45,6 (17-77,2) were included. ELN-2010 classification was favorable in 42 patients (59%), intermediate in 19 (27%), and unfavorable in 10 (14%). Median follow-up was 1.5 years. Overall response rate after salvage was 77% (N=55) with 52 patients (74%) achieving CR. Thirty patients (54%) were bridged to HSCT in CR2. During salvage 6 sinusoidal obstruction syndromes. were found. Non-relapse mortality at 3 years was 12% (95% CI, [6- 23]). The 3-year cumulative incidence of relapse was 55% (95% CI [40-71]). The 3-year overall survival (OS) was 43% (95% CI, 30-56). Factors associated with decreased OS were a shorter time to relapse and unfavorable ELN status. Conclusion: in patients with AML in first relapse, GO+Arac is an efficient salvage regimen, especially in patients with ELN favorable/intermediate profile and time to relapse of more than 12 months.; Introduction : bien que la rémission complète (RC) soit obtenue dans la majorité des cas de leucémie aiguë myéloïde (LAM), des rechutes surviennent dans 35 à 80% des cas, et la survie à long terme de ces patients est extrêmement faible (20-10%). La stratégie thérapeutique actuelle constitue à atteindre une deuxième RC afin de pouvoir proposer une allogreffe de cellules souches. Notre essai a pour objectif d’évaluer l’efficacité et la tolérance du Gemtuzumab Ozogamycin (GO), un antiCD33 conjugué à la calichéamycine, associé à la cytarabine (GO+AraC) en rechute de LAM. Méthodes : nous avons conduit un essai rétrospectif monocentrique entre janvier 2008 et décembre 2018. Les patients consécutifs présentant une première rechute de LAM traités par GO+AraC étaient inclus. Résultats : 71 patients d’un âge médian de 45,6 ans [17-17,2] ont été inclus. La classification ELN 2010 était favorable chez 42 (59%) des patients, intermédiaire chez 19 (27%) et défavorable chez 10 (14%). Le suivi médian était de 1,5 an. 77% patients obtenaient une réponse, dont 52 (74%) une RC. 30 patients (54%) ont été allogreffés en RC2. 6 syndromes d’obstruction sinusoïdale ont été notés durant le rattrapage. La mortalité sans rechute à 3 ans était de 12% (IC95% [6-23]). L’incidence cumulée de rechute à 3 ans était de 55% (IC95% 40-71). La survie globale à 3 ans était de 43% (IC95% [30-56]). Les facteurs associés à une diminution de la survie étaient un délai de rechute court et le statut ELN défavorable. Conclusion : GO+AraC est un traitement de rattrapage efficace chez les patients en première rechute de LAM, en particulier pour les groupes ELN favorable/intermédiaire, et en cas de rechute tardive (>12mois).

Sinusoidal obstruction syndrome is a rare complication of autologous hematopoietic stem cell transplantation. This syndrome is mainly described following conditioning regiment with busulfan, cyclophosphamide and/or total body irradiation.We report for the first time two cases of sinusoidal obstruction syndrome occurring lately after BeAM conditioning regiment (bendamustine, etoposide, aracytine, melphalan) for autologous stem cell transplantation in patients treated for malignant lymphoma.Our observations highlight the difficulty to diagnose this complication with often non-specific clinical presentation and possible delayed occurrence after to transplantation, but also the therapeutic challenges, defibrotide being the only agent currently efficient. Physiopathology and potential responsibility of bendamustine in the sinusoidal obstruction syndrome occurrence will be discussed.

Our home care unit (HCU) developed the administration of IV chemotherapy at home for some pediatric oncologic patients.We conducted a retrospective monocentric analysis, leading to identify patients with at least one sequence of chemotherapy at home in 2015.Two hundred and forty four sequences of home chemotherapy have been administered in 2015. We identified two situations for home IV chemotherapy. Pediatric oncologist of day hospital prescribes the sequence. The chemotherapy is delivered at hospital for the first day. HCU takes over for the next days at home. For a sequence replacing a conventional hospitalization, the attending physician examines the patient, and confirm the clinical validation. The pediatric oncologist of HCU checks lab exams, and prescribes the chemotherapy. For both situations, IV chemotherapy is prepared by our hospital pharmacy, delivers at home or at day hospital, and HCU team manages home material and organizes hospitalization.This kind of organization allows setting up home IV CT for more and more patients. It allows to limit daily hospitalization for some patients living far from the hospital, and whose therapies lead to several hospitalizations.

L’utilisation de médicaments cytotoxiques comme agent anticancéreux ou immunosuppresseur est aujourd’hui une pratique courante dans le traitement de nombreuses pathologies. Beaucoup sont encore administrés par voie injectable. Des services très différents sont amenés à les utiliser quotidiennement, ce qui expose les personnels travaillant à la pharmacie de l’hôpital, dans les services de soins hospitaliers ou à domicile. Le projet "CYTOPRO" visait à évaluer l’exposition aux cytotoxiques dans divers services de soins et à la pharmacie du CHU de Lille.

Herein, we report the first case of kaposiform haemangioendothelioma (KHE) associated with acute B-lymphoblastic leukemia (B-ALL).A five-month-old infant presented a plaque of angiomatous appearance on the forearm that had increased in volume since birth, as well as pallor and cutaneous haematomas. Kasabach-Merritt syndrome (KMS) was evoked despite hepatomegaly and considerable splenomegaly. Laboratory tests revealed severe anaemia and thrombocytopenia as well as major hyperleukocytosis with 90% blasts. Skin biopsy revealed vast vascular lobules containing cohesive fusiform endothelial cells not expressing Glut1, bound up in a dense infiltrate of B-lymphoblast cells. It was in fact KHE associated with B-ALL confirmed by the myelogram. The child was treated with the INTERFANT 2006 protocol followed by allograft of haematopoietic stem cells, which resulted in complete haematological remission. At the same time, almost total regression of KHE was noted.In this infant, KHE had an inflammatory appearance and was associated with thrombocytopenia, evocative of KMS. Analysis of blood and marrow samples resulted in a diagnosis of B-ALL. Histopathological examination of the angioma revealed a typical appearance of KHE associated with dense lymphoblastic proliferation. This appearance could have resulted either from passive contamination by circulating blast cells or from active recruitment of tumor cells at the KHE site.HK mimicking KMS may reveal B-ALL.

We report the case of 20-year-old patient who presented in emergency with bilateral massive, spontaneous subconjunctival hemorrhage. Clinical findings suggested a blood dyscrasia, which was confirmed by blood cell count. The patient was urgently referred to hematology where the diagnosis of acute lymphoblastic leukemia was made. This case highlights the importance of working up any unusual subconjunctival hemorrhage, as it may reveal, in certain cases, a severe life-threatening disease.

International audience; Pulmonary Langerhans histiocytosis (PLH) is a rare disease due to the accumulation of Langerhans cells at the level of the bronchioles. These dendritic immunocytes form granulomata and destroy the wall of the airway. We report a case of PLH developing at the same time as Hodgkin's lymphoma in a young woman who smoked tobacco and cannabis. We observed a complete remission of the PLH lesions parallel to the remission of the Hodgkin's lymphoma after chemotherapy, in the absence of any change in the consumption of tobacco and cannabis. This observation leads us to discuss the potential relationships between PLH on one hand, and smoking, the lymphoma and its treatment on the other.

Pulmonary Langerhans histiocytosis (PLH) is a rare disease due to the accumulation of Langerhans cells at the level of the bronchioles. These dendritic immunocytes form granulomata and destroy the wall of the airway. We report a case of PLH developing at the same time as Hodgkin's lymphoma in a young woman who smoked tobacco and cannabis. We observed a complete remission of the PLH lesions parallel to the remission of the Hodgkin's lymphoma after chemotherapy, in the absence of any change in the consumption of tobacco and cannabis. This observation leads us to discuss the potential relationships between PLH on one hand, and smoking, the lymphoma and its treatment on the other.

We report the results of the protocol CMA (cyclophosphamide, methotrexate, Aracytine) reinforced of 26 patients affected by Burkitt lymphoma in facial-maxillary localisation, in a retrospective study from January 2000 till December 2007 and prospective from January till September 2008. Their average age was 7.89 years, with a sex ratio of 2.71. The global response to the treatment was 92.3% with 57.7% of complete remission and 34.6% of incomplete remission. The morbidity related to treatment was essentially a haematological complication (84.6%) and hydroelectrolytic complication (84.6%). Evolution was made towards death in 30.8 and 15.4% were lost of view. The median monitoring was 18.2 months. Treatment response was linked to the therapeutic compliance (P0.001), and the delay of consultation (P = 0.01).

Nucleoside analogues (NA) are important agents in the treatment of haematological malignancies and solid tumours. Their rapid catabolism, cell resistance and overdistribution in the body jeopardize the NA chemotherapy. Our objective is to design a vector for these molecules targeting cancerous tissue and ensuring its cellular internalization and protection in the biological media. Micro-sized, nano-sized and molecular vectors were developed and characterized: polymeric microparticles of poly (ε-caprolactone) (PCL), multilamellar liposomes and inclusion complexes of the prodrug of cytarabine (Ara-C), which is active on some cell types resistant to treatment, the AraC-SATE (bis(tbutyl-S-acyl-2-thioethyl)-cytidine monophosphate).The microparticles were prepared by the "double emulsion - solvent evaporation" method using as surfactants, amphiphilic copolymers consisting of biodegradable blocks (PCL) and bio-removable blocks (polyethylene glycol, PEG). A series of copolymers mPEG-PCL with PCL blocks of different molecular weights was synthesized and the effect of PCL chain length on the particle physico-chemical properties was studied. Satisfactory encapsulation efficiency could be obtained, which was 10 times greater than that of microparticles prepared with PCL alone. Liposomes were prepared by the ethanol injection method. A formulation study was conducted in order to select the formula having the optimal encapsulation efficiency. Investigations about the cell internalization and the aerodynamic behaviour of the nebulized liposomes showed the relevance of developed liposomes for targeting lung cells that could be of great interest for the treatment of metastases in the lungs. The molecular encapsulation of the AraC-SATE in the hydroxyporpyl-β-cyclodextrin was carried out in order to increase the apparent solubility of the prodrug. The evaluation of inclusion complexes on murine leukemic cell cultures showed a cytotoxic activity comparable to that of the prodrug indicating that the molecular inclusion does not alter the biological activity of the prodrug.; Les analogues de nucléosides (AN), sont des agents importants dans le traitement d’hémopathies malignes et de certaines tumeurs solides. Le catabolisme rapide, la résistance cellulaire au traitement et le grand volume de distribution dans le corps limitent potentiellement l’efficacité thérapeutique des AN. Notre objectif est de concevoir un vecteur permettant un ciblage de ces molécules vers les tissus cancéreux, assurant son internalisation cellulaire et sa protection dans les milieux biologiques. Trois types de vecteurs de taille micronique, submicronique et moléculaire ont été élaborés et caractérisés : microparticules polymériques à base de poly(ε-caprolactone) (PCL), liposomes multilamellaires et complexes d’inclusion de la prodrogue de la cytarabine (Ara-C), qui est active sur certaines lignées cellulaires résistantes à l’Ara-C, l’AraC-SATE (bis(tbutyl-S-acyl-2-thioethyl)-cytidine monophosphate).Les microparticules ont été préparées par la méthode de « double émulsion - évaporation de solvant » en utilisant comme surfactants des copolymères amphiphiles composés de blocs biodégradables de PCL et de blocs bio-éliminables de polyéthylène glycol (PEG). Une série de copolymères mPEG-PCL avec des blocs PCL de différents poids moléculaires a été synthétisée et l’effet de la longueur de chaînes de PCL sur les caractéristiques physico-chimiques des particules a été étudié. Une efficacité d’encapsulation satisfaisante a pu être obtenue, qui a été dix fois plus importante que celle des microparticules à base de PCL seul. Les liposomes ont été préparés par la méthode d’injection d’éthanol. Une étude de formulation a été réalisée afin de sélectionner la formule permettant d’obtenir la meilleure efficacité d’encapsulation. Le test d’internalisation cellulaire et du comportement aérodynamique des liposomes nébulisés ont montré la pertinence des liposomes élaborés pour le ciblage des cellules pulmonaires qui pourrait être d'un grand intérêt pour le traitement des métastases au niveau des poumons.L’encapsulation moléculaire de l’AraC-SATE dans l’hydroxyporpyl-β-cyclodextrine a été réalisée pour augmenter la solubilité apparente de la prodrogue. L’évaluation des complexes sur des cultures de cellules leucémiques murines a montré une activité cytotoxique comparable à celle de la prodrogue indiquant que l’inclusion moléculaire ne modifie pas l’activité biologique de la prodrogue.

Large vessel thrombosis is a very rare clinical presentation of acute leukemia which is usually revealed by hemorrhagic complications or thrombosis of small vessels. We present here the case of a patient with previously undiagnosed acute myeloid leukemia who was referred to our hospital with symptoms of acute ischemia of the left lower limb. Occlusion of the left popliteal artery due to a leucostasis was noted and successfully treated with emergency surgical thromboembolectomy and chemotherapy.

At the time of diagnosis, central nervous system (CNS) involvement is identified in less than 10% of adult acute lymphoblastic leukemia (ALL). Long-term disease-free survival can be achieved in these patients. CNS disease at presentation does not appear to be an independent poor prognostic factor. In CNS leukemia, innovative treatments and alternative delivery techniques are, however, warranted. Outcome in such patients is a reflection of an aggressive systemic and CNS-directed therapy. However, CNS toxicity represents the dose-limiting side effect of treatment. With effective CNS prophylaxis including intrathecal chemotherapy, high-dose systemic administration of certain agents and cranial irradiation, most adults with ALL without CNS disease at diagnosis may remain free of CNS leukemia. CNS involvement at the time of relapse occurs in 1 to 15% of cases. Leukemic relapse remains a major therapeutic challenge. Adult ALL with CNS recurrence remains of poor prognosis and is generally associated with a systemic and medullary relapse.

Gemcitabine or Gemzar forms part of the class of the anti-cancer drugs antimetabolites. Gemcitabine is a structural analogue of the deoxycytidine with 2 fluorine atoms. There is a strong analogy between gemcitabine and cytosine arabinoside (Aracytine or Depocyt), at the same time structural, mechanistic and metabolic. However, if the intracellular derivatives triphosphate of gemcitabine seem more stable than those of the cytarabine, the two molecules move away from share their therapeutic activity. Indeed, if the cytosine arabinoside finds its place in the treatment of hematologic diseases, myeloblastic or lymphoblastic acute leukaemia and in acute myeloid leukaemias and myelodysplasy, gemcitabine sees its indications in the treatment of solid tumours such as non small cell lung cancer, adenocarcinoma of the pancreas, cancer of the bladder and metastatic breast cancer.

We reviewed the most recent systemic drugs used in Belgium causing toxic corneal side effects. These adverse reactions are rarely specific and often ignored or unknown. This description can help the physician's evaluation for a better interdisciplinary approach.

Progressive multifocal leukoencephalopathy (PML) is an opportunistic infection of the central nervous system, occurring in immunocompromised patients. Treatment, not codified to date, is more often inefficient with a rapid and fatal deterioration.A 48-year-old woman, treated with immunosuppressant agents for systemic lupus, presented with PML mimicking neurolupus flare. A complete remission was obtained with cytarabine and cidofovir.Combined cytarabine and cidofovir appears a promising therapeutic option in PML associated with autoimmune systemic disorders.

International audience; Primary malignant lymphoma of the ovary is a rare tumor (1,5% of ovarian tumors). Clinically, it occurs as an abdominal mass with pain which can be confused with an epithelial ovary tumor. Most tumors are observed during the fourth decade. Burkitt lymphoma, is sporadic in western countries, usually with abdominal involvement. Diagnosis is guided by biological analysis and imaging. Prognosis depends on medullary and neuromeningeal involvement. Polychemotherapy is required. We report a case of a young woman who developed abdominal Burkitt Lymphoma mimicking advanced-stage bilateral ovarian cancer.

Acute airway obstruction caused by mucoid impaction can cause sometimes life-threatening respiratory distress. Bronchial plugging is usually observed in subjects with chronic diseases such as asthma, allergic bronchopulmonary aspergillosis, or cystic fibrosis. In children, it can be related to heart failure. Acute airway obstruction in a patient without a chronic respiratory disease is exceptional. We report the case of a patient who developed bronchial plugs obstructing the bronchi during a period of agranulocytosis induced by chemotherapy. The patient experienced acute respiratory distress with asphyxia. The plugs were composed of fibrin and required several fibroscopic procedures for clearance. To our knowledge, this is the first case report of acute airway obstruction by plugging during a period of agranulocytosis.

A 23 year-old girl was admitted for a facial tumefaction, fixed to the mandible. The X-rays showed a fuzzy osteolytic lesion of the mandibular angle. The CT-scan confirmed the rupture of the cortical bone and the extension to the soft tissue. Biopsy provided the diagnosis of granulocytic monoblastic sarcoma (chloroma). Chemotherapy was efficient.Mandibular localizations of chloroma are rare. Granulocytic monoblastic sarcoma is a localized tumor made of extramedullar immature granulocytes, in general associated (or more rarely preceded by) with leukemia. Early diagnosis is important because high dose chemotherapy induction may completely cure leukemia.

The hyalohyphomycetes, Fusarium spp, are very common in our environment. Some of them have been recognized as being opportunistic agents responsible for localized as well as generalized infections, especially in the case of malignant blood diseases. Their poor sensitivity to standard antifungal therapeutics makes them very dangerous. We report a case of cutaneous and systemic fusariosis due to Fusarium moniliforme in a patient with acute lymphoblastic leukemia.A 20 year-old male student was suffering from acute type 6 myeloblastic leukemia. During the second consolidation schedule with a combined therapy of aracytine and amsacrine, this patient whose food diet was exclusively based on cereals, showed evidence of febrile aplasia, associated with myalgia, abdominal pain and diarrhoea. Microbiological samples were sterile. Ten days later, we noted the appearance of painful, diffuse and purple dermohypodermal cutaneous nodules surrounded by an erythematous ring. Histological and microbiological examination of the hypodermis biopsies of the skin nodules revealed invasion by Fusarium moniliforme. Treatment with voriconazole in association with transfusions of leukocytes led to clinical and microbiological cure.In our case report, the clinical pattern starting with digestive symptoms suggested dissemination from a digestive site, which is very unusual in Europe. In our patient, the malnutrition, together with a diet exclusively based on contaminated cereals in a context of malignant hemopathy, resulted in the colonization of the digestive tract by these moulds and the aplasia-inducing chemotherapy schedules enhanced their pathogen potential.

Cytotoxic nucleoside analogues are widely used in treatment of patients with hematological malignancies as well as for some solid tumors. Resistance developed against these molecules limit their clinical use. Many studies on cell models and clinical samples have identified cellular mechanisms involved in this phenomenon. Here, we describe the available data concerning the proteins involved in the metabolism and the mechanism of action of nucleoside analogues, as well as the clinical studies showing their implication in the resistance to these drugs.

Rescue therapies for relapsing/refractory primary central nervous system lymphoma (PCNSL) and intraocular lymphoma (IOL) remain a challenging problem for clinicians. In 2001, we published encouraging results for 22 patients treated at relapse with a CYVE regimen combining high doses of Ara-C (50 mg/m(2)/d in 12 hours infusion dl through d5; 2 g/m(2)/d d2 through d5) and VP16 (200 mg/m(2)/d d2 through d5), followed by intensive chemotherapy based on high doses of thiotepa (250 mg/m(2)/d d-9 through d-7), busulfan (10 mg/kg total dose d-6 through d-4) and cyclophosphamide (60 mg/kg/d, d-3 and d-2 with hematopoietic cell rescue at d0. Patients were enrolled onto the study for a relapse (n = 10; 2 IOL, 3 CSF, 5 brain lesion) or for a refractory disease (n = 12; 9 IOL, 3 brain lesion). CYVE rescue was not administered to patients with refractory IOL who had previously received high doses of methotrexate and Ara-C as part of their first-line treatment. Twenty patients received the intensive chemotherapy and hematopoietic cells rescue. We updated our results in March 2003. Seven patients had neurologic adverse events during the entire procedure. With a median follow up of 6.2 years, the median overall survival is 91 months, and the median survival after intensive chemotherapy has not been reached.

During the two last decades, the prognosis of children with Burkitt lymphoma has improved dramatically. Treating patients with Bukitt lymphoma in countries with limited resources is a challenge. We report our results in a serie of 95 children with Burkitt lymphoma treated between September 1990 and December 2000 according to SFOP LMB89 protocol. The median age was 45 months (range 8 months, 18 years). Seventy three percent of patients had abdominal tumor and 10% had maxillary tumor. According to Murphy classification, one patient had stage I, 17 patients stage II, 60 patients stage III and 17 patients stage IV. When considering the LMB prognosis groups, 1 patient was in group A, 83 were in group B and 11 were in group C. 73 patients were evaluables for treatment results. Complete remission was achieved in 50 patients, of whom 6 relapsed. 18 patients died from early treatment toxicity. The 5 years relapse free survival rate was 56%. It was at 100%, 84%, 52% and 38% for stage I, II, III and IV respectively. These results are below what is expected with this protocol. Improvement of supportive-care is the main condition to reach western results.

The treatment of acute myeloid leukemia (AML) permits in a population of 25 to 60 years, a complete remission (CR) about 60 to 85% with relapse free survival at 5 years from 45 to 60%. We report our therapeutic results during two years, from june 1996 to december 1998. 104 patients with the novo AML treated according to AML 06/96 protocol, the mean age was 32.5 years old, from 16 to 55 years old. The hyperleucocytar form (GB50,000 elts/mm3) represented the third of the cases, only 98 patients received the induction. 6 patients died before treatment. The whole rate of CR was 55%. The rate of failure was 16%, the deaths was about 15.5%, the relapse represented 30.6% with mean delay about 14.1 months, from 4 to 35 months. The CR has been maintained in 9 patients with mean recession of 53 months, from 36 months to 62 months. The overall survival at 5 years was 9%. Our results are still unsufficient in comparison with the literature and could be improved by recess of ARA-C and donorubicin doses in induction and consolidation, as well as a good knowledge about the cytogenetical aspect of the treated population.

Systemic mastocytosis is a rare disease, characterized by mast cells proliferation in various organs. Two types of clinical manifestations can be distinguished: those related to mast cells mediators release and those related to tumoral proliferation involving different organs, these later defining aggressive systemic mastocytosis. Until recently, treatment was mainly symptomatic, without anti tumoral effect.These last years, advances have been made in the understanding of the disease with the discovery of the c-kit oncogene mutation and the approach of the disease as a myeloproliferative disorder.Based on experiences acquired in the treatment of this kind of disorders, evaluation of new therapeutics, such as cladribine or combination of interferon-alpha and cytarabine is in progress. At least, tyrosine kinase inhibitors, a new family of molecules, are able of inhibiting some types of the mutated c-kit protein and one of them, imatinib mesylate, has shown a great efficacy in the treatment of gastro intestinal stromal tumors (GIST) which also involves the c-kit mutation. By analogy, treatment of patients with c-kit susceptible mutation might be treated with this molecule.

Burkitt Lymphoma is the most frequent lymphoma of childhood in West Africa. The main localisations are facial and abdominal. In this study, the authors describe the case of a sub-cutaneous localisation of a Burkitt to a seven years old boy. He was admitted at the hospital because of an abdominal tumefaction. Nowadays such a case has seldom been published. After using cyclophosphamide, methotrexate and aracytine, all the tumefactions disappeared. This case was interesting because of the exceptional localisation of the lymphoma, which may induce a wrong diagnosis.

This review article describes the identification of the tyrosine kinase BCR/ABL as the hallmark of chronic myeloid leukemias (CML) as well as the development of a specific inhibitor of this tyrosine kinase, the STI571 (Glivec, imatinib mesylate). The authors discuss the results of a phase I and three phase II trials reporting the efficacy of STI571 as treatment for CML patients and propose two simplified algorithms that may help to guide decision-making for the individual patient.

A bilateral leukemic hypopyon can be inaugural in the child's leukemia or reveal a relapse. A five years old child with acute lymphoblastic leukemia presented after 30 months of treatment a bilateral hypopyon. Anterior chamber paracentesis with cytological survey revealed leukemic cells and confirmed the ocular relapse. The treatment included the association of topical corticosteroids, chemotherapy and radiotherapy. This child died unfortunately 16 months later following a medullar relapse. We remind the different clinical aspects of leukemic invasion of the anterior segment and the therapeutic methods for this relapse.

The drugs concerned by this review are cytarabine (ara-C), gemcitabine and fludarabine. Seventy-eighty per cent of a dose of ara-C are excreted under the form of ara-U (main metabolite). Plasma concentrations of ara-C are not related to drug pharmacodynamics (response to treatment) in contrast to intracellular levels of ara-CTP (active metabolite) which are associated with cytotoxic activity. Gemcitabine is able to autoactivate its own mechanism of action. Gemcitabine is characterized by a short half-life of elimination (15-20 min) and plasma pharmacokinetics of the drug are not linked to pharmacodynamics. Prolonged administration of gemcitabine is pharmacokinetically and pharmacologically justified and should deserve more intense clinical investigations. Total body clearance of F-ara-A (main circulating metabolite of fludarabine) is linked to creatinine clearance and drug-related neutropenia are more frequent in patients with creatinine clearance below 50 mL/min. So far there are no relationships between intracellular levels of F-ara-CTP and response to treatment.

Histiocytic sarcoma, proliferation arising from immunoregulatory effector system cells, is a very rare and recently recognized tumor. Diagnosis is based on immunohistochemical and molecular genetic study, which allows to distinguish histiocytic sarcoma from lymphocytic proliferation, such as non-Hodgkin's lymphoma. We report the case of a gastric interdigitating reticulum cell sarcoma, treated by resection and chemotherapy. We review here clinical, histological, immunohistochemical and genotypic features of histiocytic tumors of the digestive tract.

Between 1989 and 1996, 21 cases with acute non lymphoblastic leukemia (11 males and 10 females) were diagnosed in our institution. Median age was 9 years (range, 2-15 years). Leukocyte count was more than 50,109/l in 47% of cases. According to the French-American-British (FAB) criteria, 7 cases were classified M1, 10 cases were classified M2, 1 classified M4Eo and 3 classified M5. All patients were treated with "7 + 3" protocol and complete remission was achieved in 17 cases (80%), 2 cases (10%) failed to respond and 2 (10%) died during induction. Relapse was observed in 15 cases. The 3-year survival rate was 20% and the relapse-free-survival rate was 12% confirming the worse prognosis of this leukemia when treated with standard chemotherapy.

Pilonidal sinus is a frequent, benign disease with either an acute or a chronic course. The treatment of this common disease is essentially surgical. Necrotizing fasciitis is a rare complication of this disease that can be life-threatening, especially in immunocompromised subjects. The authors report the case of a 35-year-old woman with bone marrow aplasia following chemotherapy for type 2 acute myeloblastic leukaemia, who developed necrotizing fasciitis of a pre-existing sacrococcygeal pilonidal sinus and present a review of the literature.

Effective treatment in primary central nervous system lymphoma remains elusive. Usually high dose methotrexate and/or cytosine arabinoside may improve survival. We report the results of multimodality therapy in 248 patients (SFNC series). The addition of chemotherapy to radiation therapy and high dose methotrexate increased the duration of survival. We demonstrate that the use of anthracyclines in addition to radiation therapy had a significantly favorable impact on survival which is not reported in the literature. Survival was not longer in patients receiving intrathecal chemotherapy. The efficacy of chemotherapy alone has not been clearly defined.

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

Cytosine arabinoside (Ara-C) is one of the most active drugs in the treatment of adult acute myeloid leukemia and is widely applied at all phases of therapy. In spite of its extensive clinical use, controversies exist about the most appropriate way and dose of intravenous administration: continuous or bolus infusion and standard-, intermediate- or high-dose. The present review focuses on the role and place of each modality of administration of Ara-C and on the potential interest on hematopoietic growth factors recently given concomitantly to Ara-C therapy. Based on available clinical and experimental data, the following conclusions can be drawn: conventional continuous infusion Ara-C-based regimens remain the standard therapy regarding first remission induction. The use of high-dose Ara-C has been followed by improved results in patients with slow initial cytoreduction after a first course of treatment and is an interesting approach for consolidation protocols. In relapsed and refractory adult acute myeloid leukemia, higher than conventional doses undoubtedly enhance the efficacy of Ara-C salvage therapy. Encouraging results emerge from the association of hematopoietic growth factors administered concomitantly to Ara-C based regimens, which need confirmation in prospective randomized placebo controlled comparative trials.

Haematopoietic colony-stimulating factors are a group of molecules that can stimulate haemopoiesis. With the advent of recombinant DNA technology and the cloning of their genes, they can be utilized against malignant blood diseases. They might be useful in therapy of acute myelogenous leukaemia either by increasing the efficacy of antileukaemic drugs or by shortening the duration of granulocytopoenia following chemotherapy or bone marrow transplantation. Encouraging results have been obtained, but stimulation of leukaemic cells is not ruled out. Further clinical and biological investigations are required to provide insight into the role of cytokines in treatment of acute myelogenous leukaemia.

Ara-C is currently used in the treatment of adult acute myeloid leukemia (AML). The cytotoxicity of Ara-C derives from an inhibition of DNA synthesis which can be determined using flow cytometry from the amount of bromodeoxyuridine (BrdUrd) incorporated into cells after a short exposure to BrdUrd. We developed a computer program to quantify inhibition of the rate of DNA synthesis by analysis of the distribution of BrdUrd/DNA. A resistance index (RI) was expressed as the ratio of the amount of BrdUrd incorporated into S phase cells incubated with Ara-C to that incorporated in the absence of Ara-C. In Ara-C sensitive and resistant HL60 cell lines, a linear relationship between RI and log Ara-C concentration was observed. This technique was applied to 96 bone marrow samples from patients with de novo AML treated by a regimen containing Ara-C. A first group of nine patients with high RI values included only drug resistant (DR) patients; a second group of 63 patients with low RI values included 62 patients who achieved a complete remission (CR); a third group of 24 patients with intermediate RI values included 19 CR and five DR patients. In view of these results, we think that it is possible to detect a majority of DR patients treated by Ara-C.

Acral erythema (AE) is a painful, erythematous bullous eruption of the palms and soles which is chemotherapy-induced. To the numerous chemotherapies which induce AE we must add, perhaps, a new drug, Vépéside. AE is followed by graft-versus-host-disease in all patients receiving bone marrow transplantation. AE and early GVH disease being very similar, we discuss the differential diagnosis which can be very difficult.

the association of acute febrile neutrophilic dermatosis (Sweet's syndrome) with malignant haemopathies is well known and characterized by an usual lack of hyperleukocytosis: indeed, moderate neutropenia is often reported. However, cases of Sweet's syndrome in the agranulocytosis stage are exceptional (7 in the literature).We report the case of a woman with acute myeloblastic leukaemia who had presented with Sweet's syndrome in the phase of therapeutic aplasia during induction of treatment, in the absence of white blood cells transfusion or treatment with haematopoietic growth factor (GM CSF, GCSF).the physiopathology of Sweet's syndrome is unknown. Various mechanisms have been suggested, including immune reaction type III, increased interleukin-1 synthesis, increased chemotaxis of neutrophils, action of haematopoietic growth factors, iatrogenic effect of some drugs (e.g. cotrimoxazole, furosemide or minocycline). Yet none of these mechanisms involving circulating polymorphonuclears or their bone marrow precursors can explain the occurrence of Sweet's syndrome in the phase of agranulocytosis.the diagnosis of Sweet's syndrome must be considered in patients with agranulocytosis in order to avoid ineffective antibiotics and to initiate a corticosteroid therapy that will accelerate the cure of this benign dermatosis.