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Between December 1st 1984 and July 1st 1991, 20 patients, 11 males and 9 females, median age 36 years (range 14-54) with Hodgkin's disease were treated with high dose chemo-radiotherapy followed by autologous bone marrow rescue. At the time of autologous bone marrow transplantation, 8 patients were in complete remission, 9 in sensitive relapse and 3 were resistant to conventional treatments. There were 3 early procedure-related deaths: 1 cardiac failure due to cyclophosphamide treatment, 1 veno-occlusive disease, and 1 patient died from CMV interstitial pneumonitis, 4 months after ABMT. Of the 17 other patients, 15 are alive, 12 in complete remission, 2 in relapse and 1 patient is not evaluable due to short-follow-up follow-up. Disease free survival is 65% at 20 months with a follow-up of 60 months. There is a trend for a better disease-free survival in patients in complete remission at the time of autologous bone marrow transplantation vs patients in sensitive relapse, although it does not reach statistical significance (80% vs 37%).

Eleven patients with Hodgkin's disease were treated with high-dose chemotherapy followed by autologous bone marrow transplantation (ABMT). Four patients were resistant to initial therapy and 7 patients had relapsed but were progressing under second or third line therapy. The median time from initial diagnosis to transplantation was 44 months (range, 16 to 82). In 9 patients pre-ABMT consisted on high-dose CVB cyclophosphamide, etoposide and carmustine) chemotherapy, one patient was treated with BACT protocol (carmustine, cytosine arabinoside, cyclophosphamide and thioguanine) and other patient was treated with high-dose of busulfan and melphalan. In 8 patients complete remission (CR) was achieved, in one the remission was partial, one failed to respond and one case was not evaluable due to early death. Among CR patients, 2 died from late toxicity, and the other 6 remain in CR off therapy, one of them more than 33 months after ABMT. High-dose therapy produce severe myelosuppression in all patients. There were 3 treatment related death: one early death due to hemorrhagic myocarditis, one veno-occlusive disease of the liver and one due to cytomegalovirus sepsis. The high complete response rate in these heavily pretreated patients suggests that there may be an indication for high-dose therapy and ABMT in earlier resistant Hodgkin's disease. Moreover under such conditions, treatment related morbidity would be expected to be lower.

Introducción: El desarrollo de inhibidores frente al factor VIII en la hemofilia constituye una grave complicación. Se observa en el 20-30 % de los pacientes con hemofilia moderada y grave. El tratamiento más empleado es la inducción de inmunotolerancia con administración diaria de altas dosis de factor VIII. El 25-35% de los pacientes no responden, presentando hemartrosis frecuentes y riesgo de hemorragia vital. Otra alternativa terapéutica es la inmunosupresión. Recientemente se han empleado con éxito nuevos fármacos en el tratamiento de enfermedades autoinmunes refractarias al tratamiento convencional, como el rituximab que es un anticuerpo monoclonal anti-CD20 dirigido contra los linfocitos B. Caso clínico: Presentamos un niño de 7 años de edad, diagnosticado a la edad de 13 meses de hemofilia A grave (nivel de FVIII < 1 UI/dl). Desarrolló un inhibidor tras la primera dosis de factor VIII recombinante con un título de 11,8 U Bethesda (UB). Inició el tratamiento de inmunotolerancia con la administración diaria de 100 UI/kg de factor VIII recombinante a través de un porth-a-cath. El reservorio se colocó con el apoyo de administración de factor VII activado. El nivel del inibidor fluctuó durante los 2 años siguientes entre 0,1 y 29,3 UB, sin clínica hemorrágica significativa. Se cambió el tratamiento sustitutivo a factor VIII humano, con disminución transitoria del inhibidor, que se mantuvo durante 4 años entre 2 y 40 UB. A los 7 años de edad y tras un aumento del inhibidor a 49,8 UB comienzan a aparecer hematomas musculares frecuentes en pantorrillas y antebrazos, que precisan tratamiento con factor VII activado recombinante. Aparte del elevado coste del tratamiento, el paciente y su familia tenían muy limitada su calidad de vida, por la dependencia hospitalaria. Se informó a la familia de la posibilidad del tratamiento con rituximab y tras obtención del consentimiento informado para su uso compasivo, se inició la administración durante 4 semanas de una dosis semanal de rituximab a 375 mg/m2/dosis. Tras la primera dosis, presentó una reacción anafiláctica consistente en prurito, disnea, taquicardia e hipotensión que cedió tras la administración de difenhidramina e hidrocortisona y disminución del ritmo de infusión de rituximab. Los niveles de inhibidor tras las 4 semanas disminuyeron a 1,2 UB y se mantuvieron en valores inferiores a 3 UB durante las 18 semanas siguientes. La cifra total de linfocitos permaneció inalterada en tanto que los linfocitos B fueron indetectables durante este tiempo. Las concentraciones de inmunoglobulinas G, A y M disminuyeron ligeramente, pero permaneciendo en límites normales. No se observó aumento del número de infecciones. La profilaxis con factor VIII se redujo desde 200 UI/kg/ día hasta 50 UI/kg, tres veces por semana. Tras observar un aumento de los linfocitos B, se observó un incremento del inhibidor a 34,4 UB con reaparición de clínica hemorrágica. Se repitió la tanda semanal de rituximab durante 4 semanas, continuando con una administración mensual y espaciando posteriormente el intervalo de administración hasta llegar a cada 12 semanas, con monitorización del nivel de inhibidor. El paciente está libre de clínica hemorrágica y no se ha observado reaparición del inhibidor, siguiendo el tratamiento con administración de una dosis única de rituximab cada 12 semanas. Conclusión: Según nuestra experiencia, el tratamiento con rituximab puede ser eficaz en el tratamiento de inhibidores en la hemofilia grave y tras la dosis inicial, debe ser mantenido con la mínima dosis necesaria para la obtención de la respuesta clínico-biológica deseada.

Eater enolates are generated by reductive α-deacetoxylation of α-acetoxy-α-arylmalonic esters or a-acetoxy-α-arylalkanoic esters with lithium in liquid ammonia or sodium α-(dimethylamino)naphthalenide in hexa- methylphosphoramide-benzene. Since the requisite α-acetoxy esters are available from aryl nucleophiles. the reductions provide effective new synthetic routes to arylmalonic esters and α-arylalkanoic esters. For example, 2-(p-isobutylphenyl)propionic acid (ibuprofen. a commercially important nonsteroidal antiinflammatory agent) is obtained in 73% yield overall from isobutylbenzene. Arenes, aryllithiums, or aryhrtagnesium halides react with α-keto esters, e.g., diethyl oromalonate, ethyl pyruvate, methyl phenylglyouxalate, or alkyl glyoxylates, to afford α-hydroxy esters. These are acetylated with acetic anhydride-triethylamine and p-(dimethylamino)pyridine as a catalyst. Reductive α-deoxygenation then allows replacement of the acetoxy group by hydrogen or an alkyl group.

Diethyl allylmalonates or 2-arylalkanoic esters are prepared in good yield by reductive α-deoxygenation of the corresponding α-acetoxy or α-alkony esters. Since the intermediate ester enolates are generated under aprotic conditions, a one pot reductive-alkylation is also possible. One application of this procedure allows diethyl oxomalonate to serve as a conjunctive reagent for stitching together an alkene and an alkyl halide with a malonyl group as linchpin.

The results obtained in the treatment of 37 children with non Hodgkin lymphoma belonging to GICOP between january 1982 and december 1986 are analysed. The therapy depend on the anatomopathology following the working formulation; LSALL2 protocol is used in lymphoblastic lymphoma, Burkitt-82 in undifferentiated Burkitt lymphoma and COMP in the remaining complete remission was archived in 94.6%. Murphy's classification is used. Disease free survival is 81% at 30 months. The actuarial survival is 0.81 for LL and 0.84 for BK at 48 months. The results obtained in the treatment of Burkitt's lymphoma with Burkitt-82 protocol and specially the absence of CNS infiltration are remarkable.

On prepare une serie d'acides carboxyliques allyliques a partir des olefines correspondantes par un processus en deux etapes equivalent a: 1) une reaction ene avec l'oxomalonate de diethyle conduisant a l'ester α-hydroxymalonique; 2) une bisdecarboxylation oxydante de ce dernier

Pulmonary lymphangiomyomatosis occurs almost exclusively in women of reproductive age. We present the case of this entity in a 13 year-old male.

A case with chronic continuous bleeding on an eleven year old girl with lack of F. XIII with positive family antecedents and without declarate consanguinity is presented. Analytic data are widely clear as well as parent's research which shows the heterocygosity but with doubts exposed.

Brain tumors are the most common group of solid malignancies in childhood. The therapeutic arms available nowadays: surgery, radiotherapy and chemotherapy, have achieved considerable improvement in the survival of some types of CNS tumors, mainly due to the first two. We have carried out a retrospective study of 252 CNS tumors, diagnosed in the GICOP group during the last ten years. The primary location was: supratentorial, 42%; infratentorial, 51%; and both, 7%. Biopsies were performed in 190 cases (75%), resulting in the following histologic types: astrocytoma (38%), medulloblastoma (19%), ependymoma (14%), craniopharyngioma (7%), others (22%). The treatment was individualized according to the patient characteristics: age, location, histologic type and tumor spreading. Surgery was performed in 82% of patients (8% only derivative shunt), radiotherapy in 48% and chemotherapy in 23%. The life survival was 60% at 50 months.

We present the result obtained by GICOP in the treatment of 12 genitourinary rhabdomyosarcoma, located in vagina-uterus (5), bladder-prostate (4) and paratesticular (3). The age of the patients ranging from 1 to 15 years. Embryonal rhabdomyosarcoma was the most common histologic type (58 for 100) being the major number of cases in stadium II. The treatment was based in the combination of chemotherapy protocolised with vincristine, d-actinomycin, cyclophosphamide (VAC), vincristine, adriamycin (VAC-VAD) and/or iphosphamide, vincristine, d-actinomycin (IVA), use of radiotherapy, marrow auto-transplantation and radical surgery avoidance. Complete remission was achieved in 11 out of 12 cases (92 for 100), relapsing in 5 cases (38 for 100) of which 4 (80 for 100) achieved a second remission. An 82 for 100 disease free survival was achieved in a 5 year period.

Background MPM is a highly aggressive pleural tumor associated with asbestos exposure and with limited survival despite systemic therapy. The incidence of MPM in elderly is increasing and these patients (p) require special consideration due to multiple comorbidities and increased risk of toxicities. The objective of this study is to characterize elderly p diagnosed with MPM at our institution and evaluate overall survival in this population. Methods One hundred forty-seven MPM p diagnosed at Vall d´Hebron Institute of Oncology between November 2002 and December 2016 were reviewed. Associations between clinical variables and outcome were assessed with Cox regression models and survival data were calculated by the Kaplan-Meier method. Results Patient’s characteristics: median age 68 years (y) (51-86 years), males: 70%, performance status (PS)1: 67%, asbestos exposure: 72%, epithelioid subtype: 73%. First line chemotherapy was offered to 83% of p (73% cisplatin-pemetrexed and 21% carboplatin-pemetrexed). Median progression free survival (PFS) first line was 4.9 months (m;CI95% 3.6-5.6). Clinical trial was offered as second-line regimen in 34%. Median survival (OS) in overall population was 16.8 m (95%CI13.2-22.2) and in those treated with chemotherapy was 20.6 m (95%17.1-23.6). Epitheliod histology, PS 0, neutrophil-lymphocyte ratio >5 and treatment with cisplatin vs carboplatin were associated with significant improvements in OS. In total, 59 p were >70y, 42 p > 75y and 19 p > 80y. Elderly p (>70y) received first line in 66% of cases, with carboplatin-pemetrexed in 76%. Median PFS in first line was 4.8 m (95%CI 3.7-4.7m). No differences in treatment discontinuation by toxicity neither dose reductions were found (6% vs 4% and 6 vs 7% in elderly vs Conclusions In our real world experience, chemotherapy was feasible in most elderly p with MPM and does not associates with inferior outcomes or higher toxicity compared to younger population. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure S. Cedres: Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy: Bristol-Myers Squibb; Speaker Bureau / Expert testimony: Boehringer Ingelheim; Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Speaker Bureau / Expert testimony: Apmhera; Advisory / Consultancy: Lilly; Honoraria (institution): Merck. P. Iranzo: Advisory / Consultancy: Roche; Advisory / Consultancy: Grunenthal; Advisory / Consultancy, Travel / Accommodation / Expenses: Kyowa Kirin; Advisory / Consultancy: Rovi; Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy, Travel / Accommodation / Expenses: Pierre Fabre. A. Callejo: Advisory / Consultancy: Roche ; Advisory / Consultancy: Pfizer; Travel / Accommodation / Expenses: MSD; Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy: Bristol-Myers Squibb. N. Pardo: Advisory / Consultancy, Travel / Accommodation / Expenses: roche; Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy: Bristol Myers Squibb. A. Navarro: Advisory / Consultancy: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Travel / Accommodation / Expenses: Boehringer Ingelheim; Advisory / Consultancy: Bristol-Myers Squibb ; Speaker Bureau / Expert testimony: Orizon Genomics. A. Martinez-Marti: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche ; Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Boehringer Ingelheim ; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Advisory / Consultancy, Travel / Accommodation / Expenses: Merck Sharp. R. Dienstmann: Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Advisory / Consultancy: Novartis; Speaker Bureau / Expert testimony: Symphogen; Speaker Bureau / Expert testimony: Ipsen; Speaker Bureau / Expert testimony: Amgen; Speaker Bureau / Expert testimony: Sanofi; Speaker Bureau / Expert testimony: MSD; Speaker Bureau / Expert testimony: Servier; Research grant / Funding (institution): Merck. E. Felip: Advisory / Consultancy, Speaker Bureau / Expert testimony: Abbvie; Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy: Blue Print Medicines; Advisory / Consultancy, Speaker Bureau / Expert testimony: Boehringer Ingelheim; Advisory / Consultancy: Celgene; Advisory / Consultancy, Speaker Bureau / Expert testimony: Eli Lilly; Advisory / Consultancy: guardant health ; Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck KgaA; Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck, Sharp and Dohme; Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony: Takeda; Advisory / Consultancy: Janssen. All other authors have declared no conflicts of interest.