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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.

Introduction Analyse de l’efficacite et de la tolerance des implants de carmustine (Gliadel ® ) deposes lors d’une exerese en association avec le protocole Stupp pour le traitement de premiere intention des glioblastomes supratentoriels de l’adulte nouvellement diagnostiques.’ Materiel/methode Etude cas-temoin et etude appariee en score de propension chez 787 glioblastomes avec (groupe Implantation) et sans (groupe Standard) implantation de Gliadel ® en association avec le protocole Stupp. Resultats La survie sans progression mediane etait de 12,0 mois (95 % CI 10,7–12,6) dans le groupe implantation et de 10,0 mois (95 % CI : 9,0–10,0) dans le groupe standard. Le hazard ratio de progression tumorale dans le groupe implantation en comparaison du groupe standard etait de 0,81 (95 % CI 0,69–0,94 ; p = 0,004) dans l’etude cas-temoin et de 0,78 (95 % CI 0,63–0,95 ; p = 0,016) dans l’etude appariee. La survie globable mediane etait de 21,0 mois (95 % CI 19,7–23,4) chez les patients ayant eu du Gliadel ® au cours de l’evolution de la maladie (en premiere intention et/ou en recidive) et de 17,6 mois (95 % CI 16,0–19,0) chez les patients n’en ayant jamais eu. Le hazard ratio de deces dans le groupe ayant eu du Gliadel ® au cours de l’evolution de leur maladie en comparaison du groupe n’en ayant jamais etait de 0,76 (95 % CI 0,65–0,90 ; p = 0,001) dans l’etude cas-temoin et de 0,73 (95 % CI 0,62–0,86 ; p p Conclusion L’implantation peroperatoire de Gliadel ® au cours d’une chirurgie de resection large associee au protocole Stupp pour le traitement de premiere intention des glioblastomes offre un gain de survie significatif avec une tolerance acceptable.

Objectives: To study the therapeutic efficiency of a local chemotherapy in the management of glioblastomas, comparison with literature datas. Materials and methods : this is a retrospective, monocentric study including all the patients with a carmustine wafer (Gliadel®) implantation an histologic diagnosis of WHO grade 4 glioma xere required. The inclusion period is from 2006 to 2008, 46 patients were concerned. Primary endpoints are progression-free survival and overall survival. Adverse events reliable to this therapeutic strategy were also assessed. Our results are compared to historical series. Results: Median progression free survival is 34 weeks and overall survival median is 70 weeks. Historical studies analysis of populations with similar prognosis factor cannot provides significant differences concerning patients survival when carmustine wafers are implanted. Adverse events are acceptable in their frequency, (around 10% in our study). Theses complications are miscellaneous : brain oedema (2,12%), CSF leakage (2,12%), resection cavity haematoma (4,24%). Literature review and conclusions: Prospective and randomized studies conclusions about efficacy of carmustine wafers implantation in the high-grade glioma treatment are not evidence-based, due to important methodological bias and clear disclosures. Adverse events linked to carmustine wafers are preventable, when guidelines of use are respected, especially the fact that a macroscopic removal is required before the implantation. An analysis of the pharmacokinetics properties of carmustine wafers and local parameters of mass transfer, gives us an explanation to the lack of therapeutic efficiency.; Matériels et méthodes : Il s'agit d'une étude rétrospective monocentrique incluant les patients ayant bénéficié d'une implantation de pastilles de carmustine (Gliadel®) au niveau du foyer d'exérèse et dont l'examen anatomopathologique concluait à un gliome de grade 4 selon l'OMS. La période d'inclusion est de 2006 à 2008, soit 46 patients. Les critères de jugements sont la survie sans récidive et la survie globale. Les critères secondaires sont les complications en rapport avec cette approche thérapeutique. Ces résultats sont comparés aux séries historiques. Résultats : La médiane de survie sans récidive est de 34 semaines, la médiane de survie globale de 70 semaines. La comparaison aux séries historiques avec des facteurs pronostics comparables ne met pas en évidence de différence de survie lors de la mise en place des implants de carmustine dans le foyer opératoire. Les complications liées à ce traitement sont peu fréquentes. Revue de la littérature et conclusions : Les études prospectives randomisées concluant à une efficacité de la mise en place de pastilles de carmustine dans le traitement des gliomes de haut-grades sont marquées par d'importants biais méthodologiques et des conflits d'intérêts manifestes. Ces éléments remettent en cause les conclusions proposées par les auteurs. Les complications en rapport avec cette stratégie thérapeutique sont en grande partie liées au non respect des précautions d'usage. Une analyse des propriétés pharmacocinétiques des implants de carmustine et des conditions locales de transport massique dans lesquelles sont utilisées les pastilles, fournit une explication rationnelle à ce manque d'efficacité thérapeutique.

Despite progress in the initial management of glioblastoma (GB), the vast majority of patients will experience recurrence within 2-3 years. The medical treatment of these recurrences is being modified by the use of antiangiogenic therapies. Twenty-four patients, who relapsed from GB after chemoradiation followed by adjuvant temozolomide in Rennes, were treated by conventional chemotherapy (nitrosourea) or by the combination of irinotecan and bevacizumab. In this retrospective analysis, overall survival from diagnosis of recurrence was significantly longer in patients treated with the combination of bevacizumab and irinotecan than with nitrosourea (5 months versus 11.5 months). The combination of irinotecan and bevacizumab appeared to provide clinical benefit to patients with recurrent GB.

Cutaneous syringotropic T-cell lymphoma is a rare form of lymphoma. We report a case involving a misleading cutaneous presentation on the sole of the foot.A 55-year-old woman presented discrete coalescent papules on her left foot, having an anhidrotic appearance, for which a number of antifungal treatments had been given without success. The skin biopsy revealed CD4+ T lymphocytic dermal infiltrate, mainly near the sweat glands, with syringotropism. The diagnosis of syringotropic T-cell lymphoma was reinforced by the presence of dominant cutaneous T-lymphocyte clone in the skin biopsy. Staging tests were negative. Treatment was initiated with an extremely potent (class IV) dermal corticosteroid.Syringotropic T-cell lymphoma is an extremely rare form of cutaneous lymphoma similar in presentation to mycosis fungoides, characterised by the mainly perisudoral and syringotropic nature of the lymphocytic infiltrate. The value of this case report lies in the extremely mild nature of the misleading skin lesions, which could only be diagnosed through biopsy. Treatment for this condition is not as yet codified due to the extremely low number of cases reported in the literature.

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.

The idea of intraoperative adjuvant treatment is not new. This review describes only the strategies studied in phase III clinical trials. Among these strategies, only Gliadel® obtained marketing authorization. Some immunotoxins, administered by convection-enhanced delivery, and a gene therapy approach using an adenovirus went through a phase II trial and are currently being studied in a phase III trial. Brachytherapy has never been validated by a clinical trial.

Clostridium perfringens is rare in neurosurgery. The source of clostridial brain abscess is usually a penetrating head injury. We report the case of a 57-year-old man who had parietal glioblastoma resection with local carmustine chemotherapy and who presented a clostridial brain abscess three weeks later. Progression was especially brutal, leading to patient's death in few hours. We discuss the etiology and progression of this case compared to the data reported in the literature.

To assess waiting time effect in patient with multiform glioblastoma (GBM) treated with 3D conformal planned postoperative radiotherapy and to investigate the impact of chemotherapy as first adjuvant treatment.We retrospectively analyzed 94 consecutive patients with histologically proven GBM. Surgery was considered as macroscopically complete in 33 cases (35%). Median irradiation dose was 60 Gy (8-63, mean 56 Gy). Dose per fractions was 1.8 Gy (five patients), 2 Gy (76 patients) and 2.7 Gy (13 patients). Forty patients received adjuvant pre-radiotherapy chemotherapy as intra-operative carmustine (nine patients) and adjuvant five-day protocol temozolomide alone (31 patients) or with cisplatinum (two patients). All patients received only one chemotherapy cycle.There were 56 males and 38 females. Median age was 62.1 years old (7-82, mean: 59.2 year). Median follow-up was nine months (1-49). For overall patients, median waiting time between fist clinical sign and start of the non surgical treatment was 68 days ((3-274, mean: 81.9 days). For those who received chemotherapy as first treatment, this waiting time was 54 days (3-221, mean 68.3 days). For overall patients, median waiting time between surgery and beginning of radiotherapy was 46 days (8-401, mean 59.3 days). For patients who did not receive chemotherapy as first adjuvant treatment this waiting time was 46 days (-278, mean 55.4 days). Median local control was 14.5 months. Six, 12-, 18-, and 24-month local control rates were 75.6+/-4.6%, 57.6+/-6.2%, and 36.7+/-8% and 27.6+/-8.2%, respectively. According to multivariate analysis, we retrieved two independent prognostic factors of local control, macroscopically total removal of the tumor [RR=2.85, IC 95% (1.3-6.5), p=0.012] and irradiation dose above 60 Gy, [RR=3.14, IC 95% (1.5-6.6), p=0.002]. Median overall survival was 14.3 months. Six-, 12-, 18, and 24-month overall survival rates were 84+/-3.9%, 55.1+/-5.9%, 34.2+/-6.3% and 30.4+/-6.7%, respectively. There was no independent prognostic factor.In our series neither waiting times nor adjuvant immediate chemotherapy were prognosticator of local control and overall survival outcome of patients with glioblastoma.

The visual cortex may be involved in adverse drug reactions, leading to three different clinical presentations: cortical blindness, visual hallucinations and visual aura without headache. The drugs with potential visual cortex toxicity are described.

Carmustine wafers (Gliadel) and temozolomide (Temodal) were recently approved for initial management of glioblastoma. Gliadel) is a polymer wafer containing carmustine. These wafers are designed to be placed in the surgical cavity after glioblastoma resection to deliver local chemotherapy. This treatment is intended for tumors for which gross total resection is possible. Temozolomide is administered concomitantly with radiotherapy for six weeks followed by six cycles of adjuvant temozolomide (EORTC 26981, also known as "Stupp's protocol"). Temozolomide administered according to this protocol produced a median survival benefit of 2 months in glioblastomas, and carmustine a similar benefit in high-grade gliomas. The two-year survival rate was 26.5% with radiotherapy plus temozolomide compared with 10.4% with radiotherapy alone. In patients with complete resection, two-year survival reached 38%. These two new treatments are essentially intended for patients younger than 70 years and with a Karnofsky index70. Ongoing studies are evaluating the possible value of combining these two treatments.

Antineoplastic drugs used in the treatment of cancers present with variable renal tolerance profiles. Among drugs with a potential for renal toxicity, platinum salts, methotrexate, and gemcitabine are well-known. The mechanisms of their renal toxicity and the means of its prevention are presented in this article. Anti-angiogenic drugs, recently marketed or still under clinical development, may also interact with the kidneys. In general, optimising the renal tolerance of anticancer drugs requires an appropriate evaluation of patients'renal function, before and during treatment, at each course. Serum creatinine alone is not a reliable index of renal function. Its evaluation must be performed with the use of Cockcroft-Gault or aMDRD formulae. In patients with abnormal renal function, dosage adjustment is often required to improve the renal tolerance, and also to limit the risk of extra-renal toxicities (such as haematological toxicities) induced by a drug overdosage, in those patients with reduced drug-elimination.

This article summarizes the different clinical results of the IFM trials: high dose therapy supported with autologous stem cells improves survival, melphalan 200 mg/m2 is the best preparative regimen, unpurged peripheral blood stem cells are the recommended source of stem-cells to support high dose therapy, tandem transplants significantly improve survival. However, despite these encouraging results, long term survival needs inovative strategies evaluated with the current IFM 99 protocol.

Despite surgery, post-operative irradiation and adjuvant conventional chemotherapy, prognosis of high-grade gliomas remains poor. Carmustine (BCNU) has been shown to have limited activity at conventional dosage but is still the standard chemotherapy. Activity of chemotherapy is limited by the blood-brain barrier impermeability and high levels of expression of multidrug resistance proteins on tumor and/or endothelial cells. Despite high response rates, development of intra-arterial chemotherapy remains limited because of frequent acute brain toxicity related to drug administration. High-dose intravenous chemotherapy rescued by autologous hemopoietic stem cell transplantation is an alternative that might increase drug delivery through the blood-brain barrier and tumor control. Several phase I-II trials using high-dose BCNU were published. The maximum tolerated dose seems to be 800 mg/m2 and interstitial pneumonitis and hepatitis are dose-limiting toxicities. Few phase I-II trials of high-dose therapy were published using drug combinations. High response rates in patients with progressive tumor were observed and in adjuvant setting, encouraging results in terms of median survival time and long survivors were published. No phase III trial was reported to date. Future investigations should include randomized trials comparing high-dose and conventional-dose chemotherapy and development of new high-dose regimens that incorporate new drugs such as temozolomide.

We report two cases of leptomeningeal metastatic dissemination to the spinal cord of a grade B oligodendroglioma. Diagnosis was suspected on MRI but imaging findings were nonspecific. The pathways by which the intramedullary part of the spinal is reached by metastatic cells remains controversial. In the reported cases, both frontal and cystic primary intracerebral lesions were observed. Chemotherapy after radiotherapy appears to improve outcome. Nevertheless, prognosis remains very poor.

Treatment of patients with small-cell lung cancer (SCLC) remains disappointing despite high initial complete response rate. The dramatic initial chemosensitivity of tumor cells is frustrated by the early emergence of drug resistant clonogenic cells, regardless of front line treatments. Enhancement of dose-intensity (DI) can be achieved by various strategies: initial or late intensive chemotherapy with the use of hematological supports, moderate increase in the initial dose of chemotherapy or intensive weekly chemotherapy. Although the dose relationship is fairly well established regarding the response rate, the effect of DI on survival is not clearly shown in most of the different trials. But the effect of a moderate increase in the initial dose of cisplatinum and cyclophosphamide on survival, opens new directions in the therapeutic strategy of SCLC. The contribution of hematopoietic growth factors and reinfusion of hematopoietic progenitors may be of great interest in the management of this disease.

The clinical course of unilesional plaques with a histological diagnosis of mycosis fungoides is generally benign. This uncommon situation raises the question of nosology among epidermotropic T-cell proliferations.Two women (age 65 and 70 years, cases 1 and 2) and one man (age 66 years, case 3) each had a well-limited unique oval-shaped plaque measuring 1 to 3 cm in diameter for several months. The localization of the erythematous, squamous plaques with minimal infiltration and little or no pruritus remained unchanged in the dorsal area. Histology reported mycosis fungoides: dense superficial dermal infiltration in band attached to the epidermis with a clear lower limit, formed by small and medium-sized atypical lymphocytes, sometimes with cerebriform nuclei. Epidermotropism on isolated cells or theques was noted. There was no spongiosis. Immunolabeling demonstrated predominance of CD4+ cells and tumoral infiltration uptake of anti-V beta 8 monoclonal antibodies in the two cases examined. The lesion totally regressed in case 1 after local application of carmustine with no recurrence after 5 years. Patient 2 declined treatment and no change was observed 5 years later. Surgical exeresis was performed in case 3 without recurrence 3 years later.No histological feature or T-cell immunophenotype distinguishes this clinical entity from classical mycosis fungoides. As no other long-term lesions developed, our three cases would argue for a benign course of what is probably a variety of mycosis fungoides. Unilesional plaque mycosis fungoides must be lymphomatoid contact dermatitis. Woringer-Kolopp disease differs by its nearly exclusive epidermotropic distribution.

Nitrosoureas belong to the group of alkylating agents, and are increasingly used in the treatment of brain malignancies, due to their excellent penetration through the hemo-meningeal barrier. Since 1976, pulmonary toxicity from nitrosoureas has emerged as a significant problem, especially with BCNU, and 72 cases are available in the literature for review. While it is difficult to ascertain the exact prevalence of nitrosourea lung (estimate range between 1 and 20%), it is now clear that a direct relationship exists between cumulated exposure to the nitrosourea, and the likelihood of developing pulmonary toxicity. The clinical picture is that of a diffuse, severe fibrosis with hypoxemia. Histopathology, available in 55 reports, showed diffuse bland fibrosis. The outcome is poor with 67% of the patients dead by the time of publication. While we feel that corticosteroids should be tried for any possible beneficial effect, they seem to be of limited help.

Treatment of disseminated Hodgkin's disease still fails in about 50 percent of the cases. The prognosis is poorer in case of early relapse or when the disease is refractory to first-line therapy from the start. Second- or third-line chemotherapy regimens have given rather disappointing results with a complete remission rate usually around 30 percent and a small number of cures. The indications for radiotherapy in localized lymph node relapses remain to be precisely determined. Based on the theoretical dose-effect concept, high-dose chemotherapy followed by autologous bone marrow transplantation increases the number of prolonged complete remissions in patients who respond to salvage chemotherapy. A wider use of haematopoietic growth factors should reduce the toxicity of this treatment.

Cerebral metastases of malignant melanoma are correlated with a very poor prognosis. Surgery of an isolated metastase can lead to a long survival but the brain lesions are frequently numerous and associated with an extracerebral diffusion. Dacarbazine (DTIC) gives a mean response rate of 21% on visceral localisations but doesn't cross the blood brain barrier (BBB). Neither do the biological response modifiers like Interleukin 2 (Il2) that leads to 25% response rate in disseminated melanoma. Nitrosoureas like carmustine (BCNU) and semustine (CCNU) have been investigated in different non randomised studies and the clinical results didn't illustrate their theorical ability to cross the BBB. Radiotherapy is also used as a palliative therapy with 7 to 16 weeks survival. Fotemustine (muphoran), a new amino acid linked nitrosourea, can give a response rate up to 28.2% in patients with cerebral metastases and the increased survival of responding patients is significant. The availability of this new drug may suggest associations with surgery and radiotherapy in the future to improve the survival of such patients.

The results obtained with protracted intra-arterial chemotherapy infusions in 60 case of primary or secondary liver tumor are discussed. The treatment should if possible be associated with surgical excision of the dominant tumor mass. Subjective improvement is obtainable in 75% of cases and objective improvement (including longer survival) in 50%. In some exceptionally favourable cases complete histologic disappearance of the metastases has also been achieved. Carcinoembryonic antigen determination appears to be the most reliable follow-up test.

The authors reviewed the recent data about prognostic factors, criteria of response and chemotherapy in multiple myeloma of bone. They insist on the new staging of durie and salmon anf on the interest of poly chemotherapy.

Among 62 children over 1 year of age at diagnosis who were treated for stage IV neuroblastoma, 33 entered remission after conventional therapy. They received high-dose chemotherapy and in vitro purged bone marrow transplantation as consolidation therapy. Fifteen patients received one course and 18 two courses. At present, 16/33 grafted patients are alive in CR with a median follow-up of 28 months. Toxicity of this regimen was tolerable. Under this treatment, actuarial disease free survival is improved compared with that observed under conventional therapy.

In order to study the response of patients with multiple myeloma of the bones (MM) to various anti-cancer drugs (Melphalan M, Cyclophosphamide Cy, Nitrosourea NU, Vincristine V, Adriamycine A and Prednisone P), 70 MM received the following treatment : 1) Induction therapy : a) M and P or b) M and Cy and P ; 2) Levelling with partial or complete response : V Cy P (in case a) or V M Cy P (in case b) ; 3) Relapse : A and NU. The following results were obtained : 1) Only 42.6% of patients respond to induction therapy ; 2) Fewer than 10% of patients showing a response reach a second levelling with Vincristine ; 3) 50% of those not showing a response reach a levelling between --20 and --50 and have prolonged survival ; 4) Only 20% of non responders are improved by Cy P or A and NU. The median actuarial survival is 42 months. Among the responders two poor prognosis factors must be underlined : hypercalcemia and the speed of response.

Nineteen patients were treated with high dose chemotherapy followed by an autologous bone marrow transplantation. The chemotherapy regimen was an association of BCNU, procarbazine, etoposide, melphalan. Six patients had a progressive disease; 4 short-term complete remissions were observed. In 13 responding patients, 6 maintained complete remissions were noted.