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Summary Introduction Patients with liver metastasis from uveal melanoma have a poor prognosis. Efficacy and safety of hepatic transarterial chemoembolization (TACE) using melphalan and microspheres was evaluated. Materials and methods Monocentric retrospective study of all consecutive patients treated by TACE using melphalan and 250μm calibrated microspheres between 2004 and 2016. Radiological response was assessed according to RECIST 1.1, modified (m)-RECIST and EASL on contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI). The primary endpoint was overall survival (OS). Liver metastasis response, hepatic, extrahepatic and global progression free survival (PFS) complications were evaluated with the common terminology criteria for adverse events version 4.0 (CTCAE 4.0) and survival factors were secondary endpoints. Results Thirty-four patients underwent 138 TACE (4; 4.1 sessions; range 1–9). Median OS was 16.5 months (mean 21.6 months). Liver metastasis response combining partial and complete response was 42.4%, 97%, 97% with RECIST 1.1, mRECIST, EASL, respectively. There were 58 severe (CTCAE ≥ 3) but manageable complications in 28 patients, except for 1 toxic death. Conclusion For patients with liver metastases from uveal melanoma ineligible for local treatments, TACE using melphalan may be performed as first line therapy in metastatic miliary disease from uveal melanomas with careful supportive care.

PURPOSE To determine the efficacy and toxicity of chemoimmunotherapy followed by either whole-brain radiotherapy (WBRT) or intensive chemotherapy and autologous stem-cell transplantation (ASCT) as a first-line treatment of primary CNS lymphoma (PCNSL). PATIENTS AND METHODS Immunocompetent patients (18 to 60 years of age) with untreated PCNSL were randomly assigned to receive WBRT or ASCT as consolidation treatment after induction chemotherapy consisting of two cycles of R-MBVP (rituximab 375 mg/m2 day (D) 1, methotrexate 3 g/m2 D1; D15, VP16 100 mg/m2 D2, BCNU 100 mg/m2 D3, prednisone 60 mg/m2/d D1-D5) followed by two cycles of R-AraC (rituximab 375 mg/m2 D1, cytarabine 3 g/m2/D, D1, and D2). Intensive chemotherapy consisted of thiotepa (250 mg/m2/d D9; D8; D7), busulfan (8 mg/kg D6 through D4), and cyclophosphamide (60 mg/kg/d D3; D2). WBRT delivered 40 Gy (2 Gy/fraction). The primary end point was 2-year progression-free survival. Cognitive outcome was the main secondary end point. Analysis was intention to treat in a noncomparative phase II trial. RESULTS Between October 2008 and February 2014, 140 patients were recruited from 23 French centers. Both WBRT and ASCT met the predetermined threshold (among the first 38 patients in each group, at least 24 patients were alive and disease free at 2 years). The 2-year progression-free survival rates were 63% (95% CI, 49% to 81%) and 87% (95% CI, 77% to 98%) in the WBRT and ASCT arms, respectively. Toxicity deaths were recorded in one and five patients after WBRT and ASCT, respectively. Cognitive impairment was observed after WBRT, whereas cognitive functions were preserved or improved after ASCT. CONCLUSION WBRT and ASCT are effective consolidation treatments for patients with PCNSL who are 60 years of age and younger. The efficacy end points tended to favor the ASCT arm. The specific risk of each procedure should be considered.

Background To evaluate the effectiveness and feasibility of high-intensity focused ultrasound (HIFU) for the treatment of bone metastases. Methods A single-center prospective study was made involving 17 consecutive patients with symptomatic bone metastases. Patients were treated by Focused Ultrasound (FUs) performed with magnetic resonance (MR) guidance. Surgical treatment or radiotherapy treatment was not indicated for patients who underwent FUs. Lesions were located in the appendicular and axial skeleton and consisted of secondary symptomatic lesions. The clinical course of pain was evaluated using the Visual Analog Scale (VAS) before treatment, at 1 week, and at 1 month after treatment and the Oral Morphine Equivalent Daily Dose (OMEDD) was also recorded. We used Wilcoxon signed rank test to assess change in patient pain (R CRAN software V 3.1.1). Results We observed a significant decrease in the pain felt by patients between pre- procedure and 1 week post-procedure (p = 2.9.10–4), and pre-procedure and 1 month post-procedure (p = 3.10–4). The proportion of responders according to the International Bone Metastases Consensus Working Party was: Partial Response 50% (8/16) and Complete Response 37.5% (6/16). Conclusions HIFU under MR-guidance seems to be an effective and safe procedure in the treatment of symptomatic bone lesions for patients suffering from metastatic disease. A significant decrease of patient pain was observed. Trial registration NCT01091883. Registered 24 March 2010. Level of evidence: Level 3.

Bendamustine (B) associated with rituximab (R) is widely described in literature for the management of patients with chronic lymphoid leukaemia (CLL) and indolent non-Hodgkin lymphoma. Safety data regarding late hematotoxicity such as late onset neutropenia (LON) are scarce. The aim of our study was to assess the incidence and to identify risk factors for LON in patients with indolent non-Hodgkin lymphoma and CLL treated with B and R (B-R). One hundred forty five patients were treated with B-R as first or second line. Patients with neutropenia prior induction treatment, treated beyond second line and relapsing within 3 months after the end of induction treatment, were excluded. Patients receiving at least 1 cycle of B-R and having LON during follow-up period were included and considered as eligible for toxicity assessment. A complete blood count was performed 4 weeks after the last cycle of induction treatment and thereafter every 3 months for 1 year. Thirty six patients were identified in our cohort (incidence of 25%), mostly affected by CLL (n = 11) and follicular lymphoma (FL) (n = 15). During follow-up, 84 events of LON were recorded, 61% and 39% were of grades 1/2 and 3/4, respectively. No episode of febrile neutropenia was documented. Amongst 13 of the 15 patients with FL undergoing R maintenance, 8 had treatment discontinuation because of LON. Median time for LON (grade 2) and time to recovery (grade 3) were of 11.2 and 17.3 weeks, respectively. One year after B-R induction, LON persisted in 4 patients. The risk of LON was increased both in patients with FL or CLL and performance status1. The LON in B-R treated patients is clinically relevant. Close clinical and biological follow-up and treatment prophylaxis (eg, valaciclovir and cotrimoxazole) especially for FL patients undergoing maintenance with R monotherapy seems relevant.

Introduction Distant metastases of papillary thyroid cancers are rare. Most common metastatic sites include bone and lung, whereas metastases to brain, eye, breast, liver, kidney, muscle, and skin are infrequent and almost always appear in advanced-stage tumor disease. Metastases to ovary and/or uterus are even scarcer. We report herein a very exceptional case of asymptomatic malignant-to-benign tumor-to-tumor metastasis of thyroid origin into a uterine leiomyoma. Case presentation We present the case of a 53-year-old female patient who had a previous history of pT1b N0 M0 R0 papillary carcinoma of the lower left thyroid lobe, treated by total thyroidectomy and central lymph node dissection and two successive administrations of radioactive treatment with iodine-131. Six years later, follow-up imaging disclosed an asymptomatic slow-growing 40-mm-long pedicled subserous heterogeneous uterine myoma including a 12-mm hypervascular nodule, which was suspicious for thyroid malignancy on MRI. Discussion Histopathology of a hysterectomy specimen disclosed a hypervascular well-limited poorly differentiated trabecular carcinomatous infiltration within the uterine leiomyoma. The immunohistochemical profile of the suspicious nodule was compatible with a thyroid origin. Conclusion A hypervascular "hot spot" intramyoma nodule was the diagnostic clue in a clinical context of hematogenous tumor spread of thyroid origin (increased thyroglobulin level).

Resume La tomographie par emission de positons au 18-fluorodesoxyglucose couplee a la tomodensitometrie ( 18 F-FDG TEP-TDM ou TEP-TDM) est devenue incontournable dans certains domaines de l’imagerie oncologique. Elle est parfois realisee, hors standard, au diagnostic ou dans le suivi des sarcomes. Materiels et methodes Nous avons evalue la pratique et l’impact de la TEP-TDM dans la prise en charge quotidienne des sarcomes de l’adulte a partir des dossiers consecutivement presentes en Reunion de concertation pluridisciplinaire « sarcome » pendant 10 mois. Resultats Sur 232 patients, 50 (21 %) avaient eu une TEP-TDM. La sensibilite et la specificite de la TEP-TDM etaient de 94,7 %, et 57,1 %, respectivement. La valeur de la SUV etait tres variable, y compris pour un sous-type histologique ou un grade donne. La TEP-TDM modifiait la strategie therapeutique dans 14 % des cas. Dans les cas ou des localisations extrapulmonaires sont suspectees pour certains sous-types particuliers de sarcomes, la TEP-TDM peut apporter des informations complementaires en raison de sa bonne sensibilite malgre sa faible specificite. Conclusion Compte tenu de la large predominance de la localisation pulmonaire comme site metastatique, un scanner thoracique en coupes fines est suffisant dans la plupart des cas pour le bilan d’extension. L’utilisation de la TEP-TDM dans le bilan des sarcomes de l’adulte doit etre discutee au cas par cas et sa place reste a preciser par des etudes complementaires.

8029 Background: Hodgkin Lymphoma (HL) treatment in the elderly is a challenge, as standard ABVD is able to cure no more than 60% of the patients (p.). Bendamustine (Be), and Brentuximab Vedotin (BV), are well-tolerated and effective drugs in relapsing HL, but only preliminary data exist in 1st line treatment of the elderly (Evens AM 2018). Methods: HALO is a prospective international multicenter open-label phase I/II study (NCT02467946) to assess the safety and efficacy of Be-BV in advanced-stage elderly HL p. Briefly, BV 1.2 mg/kg on D1, and Be 90 mg/m2 on D1-2 were administered Q3W for 6 cycles. The primary endpoint was the feasibility and the efficacy of Be-BV. Results: Between July 2015 and February 2019, 59/60 p. consecutive enrolled received at least 1 Be-BV cycle, and are valuable for primary endpoint. One p. was excluded because a histological review showing angioimmunoblastic T-Cell Lymphoma. The mean age was 70.32 (62-79), and M/F ratio 41/18. The Ann-Arbor stage was IIB in 12, III in 14 and IV in 33 patients, B-symptoms (y/n) 40/19. IPS was 0-2 in 19 and ≥ 3 in 40 p., P.S. (ECOG) was 0-1 in 53, 2 in 6 p., nonetheless most of them were frail, as ADL was ≥ 6 in 47 (79%) and IADL was ≥ 8 in 42 (71%) p. Most frequent co-morbidities were cardio-vascular disease (45) metabolism disorders (31) prostatic adenoma (11). 163 treatment-related adverse events (WHO 3-4) were recorded: neutropenia and lymphopenia, (134), infections (7), cutaneous reactions (5), liver toxicity (2). No case of grade > 2 peripheral neuropathy was recorded. Out of 59 p., 41 concluded and 18 interrupted the treatment for toxicity (8), progression (5), treatment failure (2), CMV reactivation (3). The latter was recorded in 17 p., 12/17 received valgancyclovir. 4 p. died with CMV viremia. After a mean follow-up of 20.6 (0.3-46.5) months, 37/59 (63%) were in CR, while 22 (37%) have progressed (5) or relapsed (17). The 2-y OS and PFS in ITT analysis were 83% (95% CI 71-96) and 54% (95% CI 41-72) and in PP 89% (95%CI 75-100) and 78% (95%CI 64-96), respectively. 22 p. had a PFS event: 5 progression (2 deaths), 17 relapse (8 deaths). 10 p. died for recurrent HL (5), sepsis (1), secondary malignancy (2), respiratory insufficiency (1) and unknown (1). Conclusions: The Be-BV combination, a novel anthracycline-free regiment for first line treatment of HL in elderly, proved effective in unselected, frail, poor-risk, HL p. aged more than 60 in daily hospital real life. The CMV reactivation is frequent and should be treated with preemptive antiviral therapy upon detection of CMV DNA in plasma. Clinical trial information: NCT02467946 .

Background REGOBONE, a non-comparative phase II, double-blind, PL-controlled trial was designed to evaluate the activity of REG, an oral multikinase inhibitor, in four parallel independent bone sarcomas cohorts: osteosarcoma, Ewing sarcoma, chondrosarcoma, and chordoma. REG demonstrated promising activity in the osteosarcoma cohort (Lancet Oncol 2019). We report here the CS cohort results. Methods Eligible CS pts were randomized (2:1) to receive either REG (160 mg/d, 21/28 d) or PL with optional cross-over at the time of centrally confirmed progressive disease (PD). Key-eligibility criteria were age ≥10 years, histologically confirmed diagnosis of CS, confirmed measurable PD not amenable to curative-intent, 1-2 previous chemotherapy (CT) regimen(s) for relapsed disease, ECOG 0-1. 24 pts were planned in the REG arm based on a A’Hern’s single-stage design for phase II trials (1-sided a = 0.05, and 80% power) to detect a 25% improvement in the progression-free rate (PFR) at 12 weeks (P0=50%) as evaluated by central review per RECIST1.1. Major secondary endpoints were PFS, OS and safety. Results From September 2014 to February 2019, 46 CS pts were included. Six pts were not eligible for efficacy analysis. Of 40 efficacy-evaluable pts (16 in PL arm and 24 in REG arm); 25 were men, median age was 61 (20-75) years. 13 pts (54.2%; one-sided CI95% = [35.8-[) were non-progressive at 12 weeks in the REG arm vs. 6 (37.5%; CI95% = [17.8-[) in the PL arm. Median PFS was 19.4 (CI95% = 11.4-35) vs. 8 (CI95%= 4.3-23.4) weeks for REG and PL arms, respectively. At the time of the analysis there is not enough event to describe OS. 14 pts crossed-over to REG after PD on PL. The most common Gr3-5 REG-related AEs during the double-blind period were hypertension (12%), cutaneous toxicity (8%), asthenia (8%), diarrhea (8%), thrombocytopenia (8%), and 1 fatal liver cytolysis. Conclusions Despite a PFR at 12 weeks lower than expected, this randomized non comparative study shows a promising signal of benefit of REG in relapsed CS, with a median of PFS of 19 weeks and, an acceptable toxicity. Clinical trial identification EudraCT: 2013-003910-42, NCT02389244. Legal entity responsible for the study UNICANCER. Funding Bayer HealthCare SAS. Disclosure F. Duffaud: Honoraria (self), Advisory / Consultancy: Bayer; Honoraria (self), Advisory / Consultancy: Roche; Advisory / Consultancy: Lilly; Travel / Accommodation / Expenses: Pharmamar; Travel / Accommodation / Expenses: Leo Pharma. J. Blay: Honoraria (self), Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Bayer; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Novartis; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): GSK. O. Mir: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options: Amgen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options: AstraZeneca; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options: Bayer; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options: Blueprint Medicines; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options: BMS; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options: Eli-Lilly; Honoraria (self), Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options: Incyte; Honoraria (self), Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options: Ipsen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options: Lundbeck; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options: MSD; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options: Novartis; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options: Pfizer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options: Roche; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options: Servier; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options: Vifor Pharma. P. Boudou Rouquette: Honoraria (self): BMS; Honoraria (self): Roche; Travel / Accommodation / Expenses: Pharmamar; Travel / Accommodation / Expenses: Pfizer; Travel / Accommodation / Expenses: Novartis. All other authors have declared no conflicts of interest.

The patients with refractory Hodgkin lymphoma have a poor prognosis. The nivolumab, an IgG4 monoclonal antibody inhibiting the program death 1 pathway has recently demonstrated its efficacy and its safety in patients with heavily pretreated refractory Hodgkin lymphoma. The side effects of this immunotherapy include autoimmune-like syndromes. A 75-year-old woman with no significant comorbidities was treated by nivolumab (3 mg/kg every 2 wk) as a third-line treatment for refractory Hodgkin lymphoma. A clinical response was observed with the first injection of nivolumab, with a reduction in superficial lymph nodes. After the second injection, the patient presented an authentic autoimmune hemolytic anemia with a profound anemia at 64 g/L and biologic characteristics of hemolysis (elevated unconjugated bilirubin, lactate dehydrogenase, and reticulocytes). The direct antiglobulin test was strongly positive for IgG antibodies, and the indirect antiglobulin test became positive with a very high level of autoantibodies. After 2 injections of nivolumab, the patient underwent a fluodeoxyglucose F 18 positron emission tomography-computed tomography, showing a partial response according to modified Cheson criteria. A treatment with prednisone (2 mg/kg), initiated after transfusion of 2 units of red blood cells, permitted the complete resolution of this autoimmune reaction after 3 months of corticotherapy. The fluodeoxyglucose F 18 positron emission tomography-computed tomography performed at the end of the corticotherapy showed a clear disease progression. Considering the very good response achieved after only 2 injections of nivolumab, the limited therapeutic resources for this old woman, and the complete resolution of the autoimmune hemolytic anemia, nivolumab was reintroduced at the same dose, with close clinical and biological monitoring. She received 6 more injections of nivolumab without recurrence of hemolysis.

Vascular adverse events have been reported with nilotinib, a tyrosine kinase inhibitor prescribed for chronic myeloid leukaemia. However, few data specify their incidence, or whether they occur in predisposed patients. Hence, we prospectively studied 30 consecutive patients to assess the frequency of such adverse reactions and determine whether the patients presenting with these adverse events bear predisposing factors. From 3 to 73 months after nilotinib initiation, 10 of the 30 patients experienced vascular events. Three patients of these 10 were devoid of any patent cardiovascular risk factor, except for age. This study points out an occurrence more frequent than expected of vascular adverse events associated with nilotinib (> 30% vs.

Background Sarcomas are rare but aggressive diseases. Specialized multidisciplinary management is not implemented for all patients in most countries. We investigated the impact of a multidisciplinary tumor board (MDTB) presentation before treatment in a nationwide study over 5 years. Patients and methods NETSARC (netsarc.org) is a network of 26 reference sarcoma centers with specialized MDTB, funded by the French National Cancer Institute to improve the outcome of sarcoma patients. Since 2010, presentation to an MDTB and second pathological review are mandatory for sarcoma patients in France. Patients' characteristics and follow-up are collected in a database regularly monitored and updated. The management and survival of patients presented to these MDTB before versus after initial treatment were analyzed. Results Out of the 12 528 patients aged ≥15 years, with a first diagnosis of soft tissue and visceral sarcoma obtained between 1 January 2010 and 31 December 2014, 5281 (42.2%) and 7247 (57.8%) were presented to the MDTB before and after the initiation of treatment, respectively. The former group had generally worse prognostic characteristics. Presentation to a MDTB before treatment was associated with a better compliance to clinical practice guidelines, for example, biopsy before surgery, imaging, quality of initial surgery, and less reoperations (all P

For early-stage Hodgkin lymphoma (HL), optimal chemotherapy regimen and the number of cycles to be delivered remain to settle down. The H9-U trial compared three modalities of chemotherapy followed by involved-field radiotherapy (IFRT) in patients with stage I-II HL and risk factors (NCT00005584).Patients aged 15-70 years with untreated supradiaphragmatic HL with at least one risk factor (age ≥ 50, involvement of 4-5 nodal areas, mediastinum/thoracic ratio ≥ 0.35, erythrocyte sedimentation rate (ESR) ≥ 50 without B-symptoms or ESR ≥ 30 and B-symptoms) were eligible for the randomised, open label, multicentre, non-inferiority H9-U trial. The limit of non-inferiority was set at 10% for the difference between 5-year event-free survival (EFS) estimates. From October 1998 to September 2002, 808 patients were randomised to receive either the control arm 6-ABVD-IFRT (n = 276), or one of the two experimental arms: 4-ABVD-IFRT (n = 277) or 4-BEACOPPResults in the 4-ABVD-IFRT (5-year EFS, 85.9%) and the 4-BEACOPPThe trial demonstrates that 4-ABVD followed by IFRT yields high disease control in patients with early-stage HL and risk factors responding to chemotherapy. Although non-inferior in terms of efficacy, four cycles of BEACOPP

International audience; Background: The aim of the study was to analyse efficacy, safety, and health-related quality of life (HRQoL) for sorafenib treatment in patients with metastatic uveal melanoma. Methods: A multicentre, single-arm phase II trial was conducted. The primary objective was to determine the non-progression rate (RECIST) at 24 weeks for patients receiving sorafenib at a dose of 800 mg per day. Secondary endpoints included progression-free survival (PFS), overall survival (OS), toxicity, and HRQoL. Results: Thirty-two patients were included. Ten patients showed non-progression at 24 weeks (31.2%) without objective tumour responses. The estimated 24-week PFS was 31.2% (95% CI: 14.8%-47.6%) and the estimated 24-week OS was 62.5% (95% CI: 45.4%-79.6%). Ten patients (34.3%) had at least one grade 3 or 4 adverse reaction and 12 patients (41.4%) required dose modifications due to toxicity. At 24 weeks, no patient had an improvement in global HRQoL and 87.5% experienced a permanent increase in physical fatigue. Conclusions: Sorafenib demonstrated non-progression at 24 weeks in 31.2% of patients. However, 41.4% of patients required dose modifications due to toxicity and no improvement in HRQoL was demonstrated.

Resume Introduction L’augmentation croissante de l’incidence des cancers chez des patients en dialyse a ete etudiee depuis les annees 1970. Parallelement, l’emergence des therapies ciblees oblige les oncologues, nephrologues et les pharmaciens a s’interroger sur le maniement en dialyse de ces nouvelles classes de medicaments pour lesquels on dispose peu de donnees. Methode Cette revue de la litterature fait le point sur la pharmacocinetique, la tolerance et l’efficacite des principales therapies ciblees en France, les anticorps monoclonaux et les inhibiteurs de tyrosine kinase. Cette revue a ete realisee en utilisant sur Pubmed les mots cles : rein, dialyse, hemodialyse, insuffisance renale terminale ainsi que le nom de chaque medicament. Resultats De la meme facon que pour les medicaments cytotoxiques, il n’existe dans la litterature que des rapports de cas isoles ou des series de cas isoles. Il est cependant possible d’emettre quelques recommandations : il n’est pas necessaire de modifier la posologie des anticorps monoclonaux de par leur nature meme. En revanche, la pharmacocinetique des inhibiteurs de tyrosine kinase differe d’un medicament a l’autre et il n’est pas possible de faire de recommandations globales. Conclusion Le recours aux therapies ciblees est possible chez les patients dialyses. Cependant, plusieurs medicaments necessitent une attention particuliere en situation de dialyse. De plus, dans la mesure oU ces medicaments sont recents, il est important que les oncologues, nephrologues et les pharmaciens soient particulierement vigilants dans l’evolution de leurs pratiques d’utilisation. La publication de toute information d’utilisation dans cette situation doit etre encouragee.

Resume Rationnel Les manifestations renales associees aux cancers sont frequentes et diverses mais assez peu decrites. Materiel et methodes Une analyse de la litterature en anglais ou francais issue de Medline a ete realisee avec les mots-cles suivants : « cancer », « rein », « syndrome paraneoplasique », « glomerulopathie » et « insuffisance renale ». Resultats Les atteintes renales liees aux neoplasies sont soit specifiques, liees a une atteinte renale directe par la pathologie cancereuse, soit liees a un syndrome paraneoplasique secondaire a la pathologie neoplasique associee. Elles comprennent des glomerulopathies paraneoplasiques (dont la glomerulonephrite extramembraneuse est la plus frequente), des troubles hydroelectrolytiques (une hypercalcemie, un syndrome de secretion inappropriee d’hormone antidiuretique [SIADH]…), un envahissement du parenchyme renal, une compression vasculaire ou des voies excretrices, une fibrose retroperitoneale, une microangiopathie thrombotique et un syndrome de lyse tumorale. Le traitement de la maladie causale ne garantit pas toujours une restitution ad integrum . Conclusion La gravite et la frequence des atteintes renales necessitent un bilan initial et un suivi orientes.

Resume Introduction L’augmentation croissante de l’incidence des cancers en dialyse a ete etudiee depuis les annees 1970. Ainsi, les oncologues, les nephrologues et les pharmaciens sont de plus en plus confrontes a la problematique de l’utilisation des cytotoxiques chez les patients hemodialyses qui representent un million de patients a travers le monde et environ 36 000 patients en France. Chez les patients hemodialyses, les questions sont de deux ordres. D’une part, les patients hemodialyses n’ont plus de fonction renale fonctionnelle, exposant ainsi ces patients a un risque de surdosage et a des effets indesirables en cas de non-adaptation posologique. D’autre part, la possible dialysance des medicaments doit etre prise en compte afin de planifier au mieux l’administration des medicaments par rapport aux seances de dialyse et d’eviter une epuration trop precoce des medicaments par la dialyse et donc une inefficacite. Methode Cette revue de la litterature fait le point sur la pharmacocinetique, la tolerance et l’efficacite des traitements anticancereux chez le patient hemodialyse en utilisant sur Pubmed les mots cles : rein, dialyse, hemodialyse, insuffisance renale terminale ainsi que le nom de chaque medicament. Resultats Il n’existe sur ce sujet que des cas isoles ou de courtes series de cas dans la litterature. Une adaptation posologique en hemodialyse est necessaire pour 57,1 % des medicaments et 64,3 % doivent etre administres apres les seances de dialyse. Conclusion Les traitements anticancereux sont faisables en dialyse. Un grand nombre de medicaments necessitent une adaptation posologique et/ou une chronologie d’administration ajustee par rapport aux seances de dialyse tenant compte de leur dialysance. Des scores de fragilite, tels que ceux proposes en geriatrie, sont probablement necessaires pour guider la decision therapeutique.

There is very limited data on isolated systemic relapses of primary central nervous system lymphomas (PCNSL). We retrospectively reviewed the clinical characteristics and outcome of 10 patients with isolated systemic disease among 209 patients with PCNSL mainly treated with methotrexate-based chemotherapy (CT) with or without radiation therapy (RT). Isolated systemic relapse remained rare (4.8%, 10/209 patients). Median time from initial diagnosis to relapse was 33 months (range, 3–94). Sites of relapse were mostly extranodal. Three patients presented with early extra-cerebral (EC) relapse 3, 5 and 8 months from the beginning of initial treatment, respectively, and 7 patients had later relapses (range, 17–94 months). Treatment at relapse included surgery alone, RT alone, CT with or without radiotherapy, or CT with autologous stem cell transplantation (ASCT). Median overall survival (OS) after relapse was 15.5 months (range, 5.8–24.5) compared to 4.6 months (range, 3.6–6.5) for patients with central nervous system (CNS) relapse (p = 0.35). In conclusion, isolated systemic relapses exist but are infrequent. Early EC relapse suggests the presence of systemic disease undetectable by conventional evaluation at initial diagnosis. Patient follow-up must be prolonged because systemic relapse can occur as late as 10 years after initial diagnosis. Whether EC relapses of PCNSL have a better prognosis than CNS relapses needs to be assessed in a larger cohort. Copyright © 2010 John Wiley & Sons, Ltd.

Peripheral T-Cell lymphomas (PTCL) are relatively rare diseases but appear to be highly aggressive and display worse remission and survival rates than B-cell lymphomas. Despite unsatisfactory results with the cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) regimen, it remains the reference front-line therapy in these diseases, but has not been challenged in phase III trials. The Groupe Ouest Est d'Etude des Leucemies et Autres Maladies du Sang (GOELAMS) devised an alternative therapeutic schedule including etoposide, ifosfamide, cisplatin alternating with doxorubicin, bleomycin, vinblastine, dacarbazine (VIP-reinforced-ABVD; VIP-rABVD) and compared it to CHOP/21 as front-line treatment in non-cutaneous PTCL. All newly diagnosed patients were eligible. The primary objective was to improve the 2-year event-free survival (EFS) rate. Secondary objectives were to compare the response rate, overall survival, and toxicities as well as identify prognostic factors. Eighty-eight patients were identified between 1996 and 2002. Both arms were well balanced for patients' characteristics in terms of histological and clinical presentation. No significant difference was observed between the two arms in terms of 2-year EFS. Anaplastic large cell lymphoma type and Ann Arbor stage I-II were identified as two independent favourable prognostic factors influencing survival. VIP-rABVD was not superior to CHOP/21 in terms of EFS as first-line treatment of PTCL, confirming that CHOP/21 remains the reference regimen in these lymphomas.

11523Background: the benefit of neo-adjuvant/adjuvant chemotherapy (CT) in rare bone sarcoma is poorly documented. Methods: retrospective study from the French sarcoma network for bone tumors ResOs...

11501Background: DT are a group of locally aggressive tumors of fibroblastic origin that can lead to significant morbidity. No randomized trial assessing systemic treatment activity in this rare di...

11504Background: Oral multikinase inhibitor REG has shown activity in GIST and non-adipocytic soft tissue sarcomas. We designed REGOBONE as a non-comparative phase II, double-blind, PL-controlled t...

Autologous stem cell transplantation (ASCT) as first-line therapy for follicular lymphoma (FL) remains controversial. The multicenter study randomized 172 patients with untreated FL for either immunochemotherapy or high-dose therapy (HDT) followed by purged ASCT. Conditioning was performed with total body irradiation (TBI) and cyclophosphamide. The 9-year overall survival (OS) was similar in the HDT and conventional chemotherapy groups (76% and 80%, respectively). The 9-year progression-free survival (PFS) was higher in the ASCT than the chemotherapy group (64% vs 39%; P = .004). A PFS plateau was observed in the HDT group after 7 years. On multivariate analysis, OS and PFS were independently affected by the per-formance status score, the number of nodal areas involved, and the treatment group. Secondary malignancies were more frequent in the HDT than in the chemotherapy group (6 secondary myelodysplastic syndrome/acute myeloid leukemia and 6 second solid tumor cancers vs 1 acute myeloid leukemia, P = .01). The occurrence of a PFS plateau suggests that a subgroup of patients might have their FL cured by ASCT. However, the increased rate of secondary malignancies may discourage the use of purged ASCT in combination with TBI as first-line treatment for FL. This trial has been registered with ClinicalTrials.gov under identifier NCT00696735.

Multidrug chemotherapy increases responses in advanced soft tissues sarcoma. Can a 20% increase of relative dose intensity of the MAID regimen, more improve responses? From 1994 to 1997, 162 patients were randomized in a phase III study to the conventional drug combination (6 cycles of MAID: 60, 7,500, 900 mg/m(2) for doxorubicin, ifosfamide and dacarbazine respectively), or at doses 20-33% higher per cycle (5 cycles of intensified MAID for similar cumulative doses) with systematic G-CSF. Primary endpoint was response rate; secondary were toxicity, event-free and overall survival. The objective response rate in assessable patients was 38% with intensified MAID and 35% with MAID (p = 0.72). Event-free and overall survivals were similar in both arms. Only grade 3-4 thrombocytopenia and anemia were significantly higher in intensified arm. Treatment with intensified MAID did not improve response rate neither survival and cannot be recommended for advanced or metastatic soft tissue sarcoma.

A 23-year-old man had stage IVB Hodgkin lymphoma (HL) with bone marrow involvement and supra- and sub-diaphragmatic nodes. Histological examination of an external iliac lymphadenopathy showed numer...

Multicenter, retrospective study of standard-dose RIT in eight heavily pre-treated patients with CD20-positive follicular lymphoma who had relapsed after previous autologous bone marrow transplantation (ABMT). Patients underwent nine courses of (90)Y-ibritumomab tiuxetan (0.3 or 0.4 mCi/kg body weight). Responses included five CR, two PR, one SD and one PD. Median DFS was 12 months with median follow-up of 17 months and 1-year OS was 83% (7/8 patients). Grade 4 thrombocytopenia occurred in 7/9 treatments, with no episodes of bleeding, and only two patients received a platelet transfusion. One patient, who had 20% bone marrow involvement at the time of relapse diagnosis, presented with Grade 4 thrombocytopenia and Grade 4 neutropenia and died of septic shock 6 months after RIT. One other case of Grade 4 neutropenia, without a serious infectious syndrome, was observed. Standard-dose RIT seems feasible and potentially effective after ABMT in correctly selected patients with follicular lymphoma.

This phase II study evaluated YM155, a novel small-molecule survivin suppressant, in combination with rituximab in patients with relapsed aggressive B-cell non-Hodgkin lymphoma (NHL) who failed or were not candidates for autologous stem cell transplant (ASCT). During 14-day cycles, 41 patients received YM155 (5mg/m(2)/d) by continuous intravenous (IV) infusion for 168 hours (day 1-7), and rituximab (375mg/m(2)) IV on days 1 and 8 during cycles 1-4 and repeated for 4 cycles every 10 cycles. Forty patients (97.6%) had prior rituximab and 15 patients (36.6%) prior ASCT. Most frequent grade 3-4 adverse events were neutropenia (19.5%) and thrombocytopenia (12.2%). In the per-protocol set (n = 34), objective response rate was 50% and median progression-free survival 17.9 months. Median overall survival was not reached at study termination (median follow-up, 23 months). YM155 in combination with rituximab was tolerable with encouraging antitumor activity and durable responses in relapsed aggressive B-cell NHL patients.

Summary Background Lenalidomide, an immunomodulatory drug with antineoplastic and antiproliferative effects, showed activity in many single-group studies in relapsed or refractory mantle cell lymphoma. The aim of this randomised study was to examine the efficacy and safety of lenalidomide versus best investigator's choice of single-agent therapy in relapsed or refractory mantle cell lymphoma. Methods The MCL-002 (SPRINT) study was a randomised, phase 2 study of patients with mantle cell lymphoma aged 18 years or older at 67 clinics and academic centres in 12 countries who relapsed one to three times, had Eastern Cooperative Oncology Group performance status of 0–2, at least one measurable lesion to be eligible, and who were ineligible for intensive chemotherpy or stem-cell transplantation. Using a centralised interactive voice response system, we randomly assigned (2:1) patients in a permuted block size of six to receive lenalidomide (25 mg orally on days 1–21 every 28 days) until progressive disease or intolerability, or single-agent investigator's choice of either rituximab, gemcitabine, fludarabine, chlorambucil, or cytarabine. Randomisation was stratified by time from diagnosis, time from last anti-lymphoma therapy, and previous stem-cell transplantation. Individual treatment assignment between lenalidomide and investigator's choice was open label, but investigators had to register their choice of comparator drug before randomly assigning a patient. Patients who progressed on investigator's choice could cross over to lenalidomide treatment. We present the prespecified primary analysis results in the intention-to-treat population for the primary endpoint of progression-free survival, defined as the time from randomisation to progressive disease or death, whichever occurred first. Patient enrolment is complete, although treatment and collection of additional time-to-event data are ongoing. This study is registered with ClinicalTrials.gov, number NCT00875667. Findings Between April 30, 2009, and March 7, 2013, we enrolled 254 patients in the intention-to-treat population (170 [67%] were randomly assigned to receive lenalidomide, 84 [33%] to receive investigator's choice monotherapy). Patients had a median age of 68·5 years and received a median of two previous regimens. With a median follow-up of 15·9 months (IQR 7·6–31·7), lenalidomide significantly improved progression-free survival compared with investigator's choice (median 8·7 months [95% CI 5·5–12·1] vs 5·2 months [95% CI 3·7–6·9]) with a hazard ratio of 0·61 (95% CI 0·44–0·84; p=0·004). In the 167 patients in the lenalidomide group and 83 patients in the investigator's choice group who received at least one dose of treatment the most common grade 3–4 adverse events included neutropenia (73 [44%] of 167 vs 28 [34%] of 83) without increased risk of infection, thrombocytopenia (30 [18%] vs 23 [28%]), leucopenia (13 [8%] vs nine [11%]), and anaemia (14 [8%] vs six [7%]). Interpretation Patients with relapsed or refractory mantle cell lymphoma ineligible for intensive chemotherapy or stem-cell transplantation have longer progression-free survival, with a manageable safety profile when treated with lenalidomide compared with monotherapy investigator's choice options. Funding Celgene Corporation.

Background Refractory or relapsed large B-cells lymphoma are usually treated with a high dose chemotherapy regimen followed by an autolougous stem cells transplantation. BEAM (carmustine, etoposide, cytarabine, melphalan) or more recently Z-BEAM (ibritumomab tiuxetan and BEAM) are commonly used regimens, but recently carmustine availability became difficult. The purpose of this study was to evaluate the feasibility and the safety of replacing carmustine by bendamustine in a new Z-BeEAM regimen (ibritumomab tiuxetan, bendamustine, etoposide, cytarabine, melphalan) prior to autologous stem cell transplantation. Findings This study was a retrospective analyze of six patients, with a median age of 60, treated by Z-BeEAM before autologous stem cell transplantation. We did not put in evidence any additional toxicities compared to conventional induction chemotherapy. The main toxicities were mucositis (3 grade III among 6 patients), gastrointestinal (2 grade III vomiting and 2 grade III diarrhea) and neutropenia (6 grade IV). Engraftment was successfully achieved for all patients. At the time of analysis of this study all patients were alive and in complete response based on the PET-CT evaluation. Conclusions BeEAM plus ibritumomab tiuxetan combined regimen before autologous stem cell transplantation is feasible and safe in aggressive relapsing large B-cell lymphoma.

Measurement of the alpha 1 (fast liver) fraction of alkaline phosphatases in the serum for 217 cancer patients, 92 patients with nonmalignant hepatic affections and 131 controls, revealed that the alpha 1 fraction offers better global value (94%), sensitivity (96%), and specificity (93%) than gamma GT or total alkaline phosphatase determinations for the detection of liver metastases during cancer. Initial data from study of the time of appearance of the alpha 1 fraction reveals that this fraction shows up earlier than rises in the gamma GT or total alkaline phosphatases. Results of a multiparametric study conducted on the alpha 1 fraction and various hepatic enzymatic tests (SGOT, SGPT, GLDH, ALP, gamma GT) indicate that the alpha 1 fraction used alone is better than any other test or combination of tests for biological detection of liver metastases. As concerns the influence of chemotherapy on the appearance of the alpha 1 fraction, the majority of the drugs used for anticancer chemotherapy do not seem to affect measurement of the alpha 1 ALP fraction. The alpha 1 fast liver fraction of alkaline phosphatases, detected by electrophoresis on cellulose acetate, can be considered one of the best known tests for the detection of liver metastases.

Dexamethasone alone increases life expectancy in patients with relapsed multiple myeloma (MM); however, no large randomized study has compared dexamethasone and dexamethasone-based regimens with standard melphalan-prednisone in newly diagnosed MM patients ineligible for high-dose therapy. In the Intergroupe Francophone du Myelome (IFM) 95-01 trial, 488 patients aged 65 to 75 years were randomized between 4 regimens of treatment: melphalan-prednisone, dexamethasone alone, melphalan-dexamethasone, and dexamethasone-interferon alpha. Response rates at 6 months (except for complete response) were significantly higher among patients receiving melphalan-dexamethasone, and progression-free survival was significantly better among patients receiving melphalan (P < .001, for both comparisons), but there was no difference in overall survival between the 4 treatment groups. Moreover, the morbidity associated with dexamethasone-based regimens was significantly higher than with melphalan-prednisone, especially for severe pyogenic infections in the melphalan-dexamethasone arm and hemorrhage, severe diabetes, and gastrointestinal and psychiatric complications in the dexamethasone arms. Overall, these results indicated that dexamethasone should not be routinely recommended as first-line treatment in elderly patients with MM. In the context of the IFM 95-01 trial, the standard melphalan-prednisone remained the best treatment choice when efficacy and patient comfort were both considered. These results might be useful in the context of future combinations with innovative drugs.

The first EORTC (European Organization of Research and Treatment of Cancer) acute myeloblastic leukemia (AML) pilot study (58872) was conducted between January 1988 and December 1991. Out of 108 patients, 78% achieved complete remission (CR), and event-free survival (EFS) and survival rates (s.e., %) at 7 years were 40 (5) and 51% (6%), respectively. It indicated that mitoxantrone could be substituted for conventional anthracyclines in the treatment of childhood AML without inducing cardiotoxicity. The aim of the next EORTC 58921 trial was to compare the efficacy and toxicity of idarubicin vs mitoxantrone in initial chemotherapy courses, further therapy consisting of allogeneic bone marrow transplantation (alloBMT) in patients with an HLA-compatible sibling donor or chemotherapy in patients without a donor. Out of 177 patients, recruited between October 1992 and December 2002, 81% reached CR. Overall 7-year EFS and survival rates were 49 (4) and 62% (4%), respectively. Out of 145 patients who received the first intensification, 39 had a sibling donor. In patients with or without a donor, the 7-year disease-free survival (DFS) rate was 63 (8) and 57% (5%) and the 7-year survival rate was 78 (7) and 65% (5%), respectively. Patients with favorable, intermediate and unfavorable cytogenetic features had a 5-year EFS rate of 57, 45 and 45% and a 5-year survival rate of 89, 67 and 53%, respectively.

Doxorubicin-based immunochemotherapy, with interferon, has been shown to improve survival in patients with advanced follicular lymphoma. High-dose chemotherapy with stem-cell support is effective in follicular lymphoma in relapse but remains controversial as a first-line therapy. In a randomized study using a purged autologous stem-cell support, we compared these 2 approaches in patients with advanced follicular lymphoma. Newly diagnosed advanced follicular lymphoma patients (172 patients) were randomly assigned either to an immunochemotherapy regimen (cyclophosphamide, doxorubicin, teniposide, prednisone, and interferon) or to a high-dose therapy followed by purged autologous stem-cell transplantation. Compared with the patients who received chemotherapy and interferon, patients treated with high-dose therapy had a higher response rate (69% vs 81%, P = .045) and a longer median event-free survival (not reached vs 45 months). This did not translate into a better survival rate due to an excess of secondary malignancies after transplantation. The Follicular Lymphoma Prognostic Index identified a subgroup of patients with a significantly higher event-free survival rate after high-dose therapy. Autologous stem-cell transplantation cannot be considered as the standard first-line treatment of follicular lymphoma for patients younger than 60 years old with a high tumor burden.

Summary Background Metastatic leiomyosarcomas of uterine or soft-tissue origin have poor prognosis and moderate chemosensitivity. Trabectedin has shown activity in pretreated leiomyosarcoma. We did a single-group, multicentre, phase 2 trial (LMS-02) to assess the effect of first-line doxorubicin and trabectedin combination on disease control and survival. Methods Adults (18 years to physiological age ≤70 years) with measurable metastatic or unresectable uterine leiomyosarcoma or soft-tissue leiomyosarcoma who had not received any previous chemotherapy were enrolled at 19 centres in France. Treatment consisted of 60 mg/m 2 intravenous doxorubicin followed by 1·1 mg/m 2 trabectedin in a 3 h intravenous infusion on day 1, both by the central venous route, and 6 mg subcutaneous pegfilgrastim on day 2, repeated every 3 weeks for up to six cycles. Surgery for residual disease was permitted. The primary endpoint was the proportion of patients achieving disease control, defined as complete or partial response or stable disease. Stratification was done by anatomical site and analyses were per protocol. This study is registered with ClinicalTrials.gov, number NCT02131480. Findings Between July 28, 2010, and May 10, 2013, 109 patients were enrolled and treated, of whom 108 were assessable for response: 47 in the uterine leiomyosarcoma group and 61 in the soft-tissue leiomyosarcoma group. 32 (68%) patients in the uterine leiomyosarcoma group and 45 (74%) in the soft-tissue leiomyosarcoma group received all six cycles of treatment. Of 47 patients with uterine leiomyosarcoma, 28 (59·6%, 95% CI 44·3–73·6) achieved a partial response and 13 (27·7%, 15·6–42·6) stable disease; 41 (87·2%, 74·3–95·2) patients achieved disease control. Of 61 patients with soft-tissue leiomyosarcoma, two (3·3%, 95% CI 0·4–11·7) achieved a complete response, 22 (36·1%, 25·0–50·8) had a partial response, and 32 (52·5%, 40·8–67·3) had stable disease; 56 (91·8%, 81·9–97·3) of patients achieved disease control. The most common grade 3–4 treatment-associated adverse events were neutropenia (84 [78%] of 108 patients), increased alanine aminotransferase concentration (42 [39%]), thrombocytopenia (40 [37%]), anaemia (29 [27%]), febrile neutropenia (26 [24%]), and fatigue (21 [19%]). Interpretation Despite expected but manageable toxic effects, these results support the activity of doxorubicin plus trabectedin as first-line treatment for uterine leiomyosarcoma and soft-tissue leiomyosarcoma. This combination should be developed further in a phase 3 trial against the present standard of care. Funding Pharmamar and Amgen.

Autologous stem cell transplant (ASCT) after high-dose chemotherapy (HDT) increases overall survival when used in relapsed non-Hodgkin lymphoma (NHL) in patients under 65 years old. Limited experience is available for older patients. We present a retrospective analysis of 73 consecutive patients aged over 65 years treated for aggressive or relapsed lymphoma by HDT with carmustine, etoposide, cytarabine and melphalan (BEAM) at full dosage followed by ASCT. Patient data were obtained from medical charts from two institutions. Median age was 67 years (65–74). Significant comorbidities were present in 24.7% of patients. The median number of days for grade 4 neutropenia was 9 (5–18). The early treatment-related mortality rate (< 100 days) was 2.7%. The estimated 2-year progression-free survival and overall survival rates were 67.2% and 78.5%, respectively. In conclusion, the full-dose HDT-ASCT regimen is feasible, safe and efficient in selected patients over 65 years old.

Posterior reversible encephalopathy syndrome (PRES) is a reversible clinical and radiological entity. The circumstances of occurrence are numerous and the pathophysiology is unclear. The main theory is related to the onset of hypertension leading to the deterioration of the cerebral autoregulation. This is an acute or subacute syndrome, often preceded by convulsive episodes. Symptoms are headaches, impaired consciousness, and vomiting or visual disturbances. The brain Magnetic Resonance Imaging (MRI) is the gold standard and highlights evidences of hyperintensities on T2 (bilateral, symmetrical, reversible, and predominantly posterior). Several cases have been reported as a complication during the treatment of childhood acute lymphoblastic leukemia (ALL), but few cases have been published in adult patients and especially in Philadelphia positive ALL. We report the first adult case of Philadelphia positive ALL with development of PRES after induction therapy.

Twenty-seven patients with recurrent soft-tissue sarcoma (STS) entered a multicenter study to determine the efficacy of the combination paclitaxel 200 mg/m 2 and epirubicin 75 mg/m 2 administered every 21 days. Patient characteristics included the following: 14 women and 13 men, median age of 52 years, 12 patients had local recurrence and 20 had metastasis. Eighteen patients had previously received chemotherapy for recurrent disease. The main grade III to IV hematologic toxicities were neutropenia (70%), anemia (3.7%), and thrombocytopenia (7.4%). Febrile neutropenia occurred in 5 patients (18.5%). Severe nonhematologic toxicities were rare. Two patients had a partial response (7.4%; 95% CI: 2.6-12.2%), with a median response duration of 3 and 5 months. Six patients had stable disease (22.2%), and 19 had progressive disease (70.5%). The median overall survival from study inclusion was 8 months. This study suggests the association paclitaxel-epirubicin does not increase the known activity of anthracycline in recurrent STS.

The EORTC Children Leukemia Group (CLG) is part of the offspring of the EORTC Hemopathies Working Party which in 1978 split into a paediatric and to an 'adult' branch. At that time, the Berlin-Frankfurt-Munster (BFM) designed by H. Riehm for acute lymphoblastic leukaemia (ALL) appeared much more efficacious than all others and the CLG decided to adapt that treatment strategy for its own clinical trials. The main results of these may be summarised as follows:for standard risk patients, the deletion of cyclophosphamide from consolidation and reconsolidation courses does not jeopardise the patient's outcomefor medium- and high-risk patients receiving high-dose methotrexate (MTX), cranial radiotherapy is superfluouswith the dose scheduling of the BFM regimen, E-Coli L-Asparaginase is more efficacious than Erwinia L-Asparaginasethe addition of monthly intravenous (i.v.) 6-mercaptopurine to conventional maintenance chemotherapy is detrimentalthe assessment by quantitative polymerase chain reaction (PCR) of minimal residual disease at completion of induction is feasible in a cooperative setting and can be used as a powerful and independent prognostic factor. The CLG also conducted clinical studies of acute myeloblastic leukaemia. Since 1989, lymphoblastic non-Hodgkin's lymphomas have been treated within the ALL trials. The CLG collaborates with other Groups within the I-BFM Study Group and participants in the meta-analytic studies conducted by the Oxford team by the Oxford Children ALL Collaborative Group.

Selection for targeted therapies in melanoma is currently based on the search for mutations in selected genes. We aimed at evaluating the interest of signalling and chemosensitivity studies in addition to genotyping for assessing the best suitable treatment in an individual patient. We extracted genomic DNA and melanoma cells from tumor tissue of a skin metastasis of a 17-year-old woman with stage IV melanoma progressing despite three successive lines of treatment. Despite the absence of mutation in BRAF, NRAS cKIT, the MAPK pathway was activated and a significant response to sorafenib, a mitogen-activated protein kinase (MAPK)/RAF inhibitor, was found in signalling and chemosensitivity assays. A treatment combining sorafenib and dacarbazine produced a partial response for 9 months, with marked necrosis in some lesions. Chemosensitivity assays and signalling pathway studies could be of great value in addition to genotyping for assessing the most appropriate treatment in melanoma.

A new sequential regimen for allogeneic stem-cell transplantation, comprising cytoreductive chemotherapy immediately followed by reduced-intensity conditioning (RIC), was evaluated in 17 intensively treated patients with refractory or early relapsed acute myeloid leukemia (AML). Cytoreductive chemotherapy comprised thiotepa (3 x 200 mg/m 2 ), etoposide (3 x 200 mg/m 2 ) and six mercapto-purine (75 mg/m 2 for 14 days) followed 2 days later, by RIC consisting of busilvex, Fludarabine and antithymocyte globulin. For six patients, the donor was a sibling and for 11, unrelated. The results showed that the procedure was safe. There were seven transplant-related deaths, mainly due to acute graft-versus-host disease and/or severe infection. Complete remission was observed in 13 patients at post-transplant Day 30. With a median follow-up of 14 months, overall survival and relapse-free survival were 29.4 and 17.7%, respectively. These results indicate a degree of antileukemia activity, which could probably be improved.