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We compared the efficacy of lenalidomide-dexamethasone (Rd) based treatments for relapsed/refractory multiple myeloma patients (pts), in a real-world setting. In addition, we evaluated adverse even...

Positron emission tomography-computed tomography (PET-CT) is part of the new diagnostic and therapeutic algorithms for Hodgkin lymphoma. PET-CT is a valuable tool for the assessment of treatment response and prognosis, both by means of interim PET-CT with 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) as well as end of treatment (EOT) PET-CT. Given the low specificity of [18F]FDG for the diffuse large B cell lymphoma (DLBCL), there is an emerging need for a more specific radiopharmaceutical agent. The recent approval of the radiotracer 3'-deoxy-[18F]-3'-flourothymidine ([18F]FLT), a phase-S mitosis cell proliferation marker, for clinical application in our country, shows as a promising radiopharmaceutical for diagnostic use with incremental value over [18F]FDG. In this study, non-human primates (Sapajus cay) were studied. PET-CT study was performed after the injection of [18F]FLT. Whole-body images were obtained to evaluate the biodistribution and to calculate the dosimetry of bone marrow, as this is a critic organ to this radiotracer. Time-activity curves were traced, normalized activity uptake of the organs of interest were calculated, and mean absorbed dose was also calculated using the established Medical Internal Radiation Dosimetry (MIRD) scheme. The mean dose obtained in the animal model per unit of activity administered was 8.7 uGy/MBq. This result was extrapolated to an adult human model resulting in 32 uGy/MBq, thereby suggesting that [18F]FLT is a secure diagnostic tool to be used on the tracing of patients with DLBCL.En el linfoma Hodgkin, la tomografía por emisión de positrones (PET-TC) forma parte de los nuevos algoritmos diagnósticos y de valoración de respuesta al tratamiento como método eficaz para evaluar supervivencia y pronóstico de la enfermedad, ya sea a través del PET-TC interino con 2-[18F]fluoro-2-desoxi-D-glucosa, ([18F]FDG), como también del PET-TC al final de la terapéutica. Sin embargo, la [18F]FDG presenta una baja especificidad en linfoma no Hodgkin de grandes células B. Ante la aprobación en nuestro país del radiotrazador 3'-desoxi-3'-[18F]fluorotimidina, [18F]FLT, indicador de proliferación celular de fase S, éste resultaría un prometedor radiofármaco de uso diagnóstico frente a [18F]FDG. Por lo tanto, el objetivo de este estudio fue valorar la utilización de [18F]FLT mediante un modelo animal en primates no humanos Sapajus cay. Se obtuvieron imágenes de cuerpo entero para evaluar la biodistribución y realizar un cálculo dosimétrico en la médula ósea, dado que este es un órgano crítico por la permanencia del radiofármaco. Para órganos de interés, se trazaron curvas de actividad en función del tiempo y se calculó la actividad acumulada normalizada. La dosis media absorbida en la médula ósea se determinó aplicando el esquema conocido como Medical Internal Radiation Dosimetry (MIRD). La dosis media obtenida en el modelo animal por unidad de actividad administrada fue de 8.7 uGy/MBq. Este resultado se extrapoló a un modelo humano adulto resultando en 32 uGy/MBq, de lo que se desprende que PET-TC con [18F]FLT es una herramienta segura para uso diagnóstico y de seguimiento en pacientes con enfermedad oncológica linfoproliferativa u otros tumores sólidos.

Direct oral anticoagulants have emerged as the drugs that have changed the management of the antithrombotic treatment in the last 15 years. Their advantages, like a more friendly way of anticoagulation and their lower risk of bleeding, especially in the brain, have positioned these new anticoagulants as the first drug of choice in the two most frequent indications of anticoagulation, atrial fibrillation, and the venous thromboembolic disease. However, not all the patients can receive these agents, not all the direct oral anticoagulants have the same characteristics, and most importantly, not all the diseases with an indication of an anticoagulant drug can be treated with them. Therefore, it is mandatory that all the faculties involved in the management of these drugs must know them in depth, to decide the best treatment for the patient. This position paper, from a group of experts in anticoagulation in Argentina, can help the general practitioner in the daily use of direct oral anticoagulants based on the new evidence and the experience of a wide group of professionals. The way we relate to the anticoagulant treatment has changed in the last years. The doctors who work with them must also do so.Los anticoagulantes orales directos han surgido como una de las herramientas que ha cambiado el manejo de la enfermedad trombótica en los últimos 15 años. Sus ventajas, desde el punto de vista de la facilidad de uso y menor riesgo de sangrado, especialmente de sangrado cerebral, han posicionado a estos nuevos anticoagulantes como la primera alternativa de tratamiento en las dos indicaciones más frecuentes en que necesitamos estas drogas, la fibrilación auricular y la enfermedad tromboembólica venosa. Sin embargo, no todos los pacientes pueden recibir estos agentes, no todos los anticoagulantes directos tienen las mismas propiedades y fundamentalmente, no todas las enfermedades con indicación de un anticoagulante pueden tratarse con ellos;con lo cual es necesario que todos los profesionales que están involucrados en el manejo de estos medicamentos estén obligados a conocerlos en profundidad, para poder decidir el mejor tratamiento en cada caso particular. Este documento de posición de expertos de diferentes especialidades de Argentina, presenta lineamientos para el uso correcto de los anticoagulantes directos en base a nueva evidencia y a la experiencia de uso de un amplio grupo de profesionales. La forma de relacionarnos con el tratamiento anticoagulante ha cambiado. Los médicos que trabajamos con ellos también debemos hacerlo.

Treating an anticoagulated patient with vitamin K antagonists (VKA) remains a challenge, especially in areas where dicoumarins are still the first drug of choice due to the cost of other oral anticoagulants. Anticoagulation clinics have proven to be the most efficient and safe way to avoid thrombotic and hemorrhagic complications and to keep patients in optimal treatment range. However, they require adequate infrastructure and trained personnel to work properly. In this Argentine consensus we propose a series of guidelines for the effective management of the anticoagulation clinics. The goal is to achieve the excellence in both the clinical healthcare and the hemostasis laboratory for the anticoagulated patient. The criteria developed in the document were agreed upon by a large group of expert specialists in hematology and biochemistry from all over the country. The criteria presented here must always be considered when indicating VKA although they had to be adapted to the unequal reality of each center. Taking these premises into consideration will allow us to optimize the management of the anticoagulated patient with VKA and thus minimize thrombotic and hemorrhagic intercurrences, in order to honor our promise not to harm the patient.El tratamiento de un paciente anticoagulado con antagonistas de la vitamina K (AVK) sigue siendo un desafío, especialmente en regiones donde, por el costo, los dicumarínicos son todavía la alternativa más buscada a la hora de elegir un anticoagulante oral. Las clínicas de anticoagulación han demostrado ser la forma más eficiente y segura de evitar complicaciones trombóticas y hemorrágicas y de mantener al paciente en rango óptimo de tratamiento. Sin embargo, requieren de una adecuada infraestructura y personal capacitado para que funcionen eficientemente. En este consenso argentino se propone una serie de parámetros para la gestión efectiva de una clínica de anticoagulación. El objetivo es lograr una elevada calidad desde el punto de vista clínico-asistencial a través de un laboratorio de hemostasia de excelencia. Los criterios desarrollados en el documento fueron consensuados por un amplio grupo de expertos especialistas en hematología y en bioquímica de todo el país. Estos criterios deben adaptarse a la irregular disponibilidad de recursos de cada centro, pero siempre se los debe tener en cuenta a la hora de indicar el tratamiento anticoagulante con estas drogas. Tener en consideración estas premisas nos permitirá optimizar la atención del enfermo anticoagulado con AVK y de esta forma minimizar las intercurrencias trombóticas y hemorrágicas a las que está expuesto, para así honrar nuestra promesa de no dañar al paciente.

We compared the efficacy of lenalidomide-dexamethasone (Rd) based treatments for relapsed/refractory multiple myeloma patients (pts), in a real-world setting. In addition, we evaluated adverse events (AE), progression-free survival (PFS) and overall survival (OS).In our retrospective, multicentric study, 156 pts with RRMM were included. 74/156 pts (47%) were refractory to bortezomib (V) and 43/156 (27%) pts to lenalidomide (R), with 24/156 (15%) of pts double refractory. Eighty-six pts (55%) received Rd with carfilzomib (KRd), 30 pts (19%) bortezomib (VRd), 30 pts (19%) daratumumab (DRd), and 10 pts (6%) ixazomib (IRd).The overall response (ORR) (≥ partial response) for the entire cohort was 71%, with a very good partial response rate or better (≥VGPR) of 35%. We found no significant differences in CR or ≥VGRP rates between treatments (p:0.229). Regardless of the combination received, those patients who achieved CR had significantly improved PFS (p: 0.007). The most frequent cause of treatment discontinuation was disease progression in 55/156 pts (35%). 8 pts (5%) discontinued treatment due to treatment-related adverse events (AE).This is the first report of Rd combinations for the treatment of RRMM in Latin America. All combinations proved to be effective with an acceptable toxicity.

The COVID-19 pandemic presented high mortality from its beginning, without effective treatment for seriously ill patients. Build on the experience in Argentine hemorrhagic fever with convalescent plasma, we incorporated 90 patients with COVID-19, of which 87 were evaluable, into a multicenter study. We collected 397 plasma donations from 278 convalescent donors. Patients received plasma with an IgG concentration of 0.7-0.8 (measured by Abbott chemiluminescence) for every 10 kg of body weight. Survival during the first 28 days was the primary objective; 77% were male, age 54 ± 15.6 y/o (range 27-85), body mass index 29.7 ± 4.4; hypertension 39% and diabetes 20.7%; 19.5% had an immunosuppressive condition, 23% were health workers. Plasma was administered to 55 (63%) on spontaneous breathing with oxygen supplementation (mainly oxygen mask with reservoir bag in 80%), and to 32 patients (37%) on mechanical ventilation. The 28-day survival rate was 80%; 91% in patients infused on spontaneous breathing and 63% in those on mechanical ventilation (p = 0.0002). There was a significant improvement in the WHO pneumonia clinical scale at 7 and 14 days, and in PaO2 / FiO2, ferritin and LDH, in the week post-infusion. We observed an episode of circulatory volume overload and a febrile reaction, both mild. Convalescent plasma infusions are feasible, safe, and potentially effective, especially before requiring mechanical ventilation. They are an attractive clinical option for treating severe forms of COVID-19 until other effective therapies become available.La pandemia de COVID-19, presentó desde su inicio elevada mortalidad, sin tratamiento efectivo para pacientes graves. Basados en experiencia previa con plasma de convaleciente en fiebre hemorrágica Argentina, incorporamos a un estudio multicéntrico 90 pacientes con COVID-19 de los que 87 fueron evaluables. Colectamos 397 donaciones de plasma de 278 convalecientes. El plasma fue suministrado con una concentración de IgG de 0.7-0.8 (medidos por quimioluminiscencia Abbott) por cada 10 kg/ peso. La supervivencia a 28 días fue la variable de resultado primario. El 77% fueron varones, edad 54 ± 15.6 años (rango: 27-85); índice de masa corporal de 29.7 ± 4.4; tenían hipertensión 39%, diabetes 20.7%; 19.5% tenían alguna condición de inmunosupresión, y el 23% era personal de salud. Se administró plasma a 55 (63%) en respiración espontánea con oxígeno (con máscara reservorio en 80%), y a 32 (37%) en ventilación mecánica. La supervivencia global a 28 días fue del 80%; 91% en quienes recibían oxígeno suplementario y 63% en los que permanecían en ventilación mecánica (p = 0.0002). Hubo mejora significativa en la escala clínica de neumonía de la OMS a los 7 y a los 14 días. La ferritina, LDH y PaO2/FiO2, mejoraron en la semana post-infusión. Observamos un episodio de sobrecarga de volumen circulatorio y una reacción febril, leves. Las infusiones de plasma de convaleciente son factibles, seguras y potencialmente efectivas, especialmente antes de requerir ventilación mecánica. Constituyen una opción clínica atractiva para tratar formas graves de COVID-19 hasta que estén disponibles otras terapias eficaces.

The coronavirus disease 2019 (COVID-19) pandemic requires rapid medical responses. The risk of venous and arterial thromboembolism increases in critically ill patients with SARS-CoV-2 infection. There is a hypercoagulable state that includes elevated levels of D-dimer, with an increased risk of organ failure and increased mortality. The abnormalities described in hemostasis should be considered for therapeutic decision making. We analyzed the available scientific evidence for the therapeutic approach of coagulopathy in the course of the disease with the objective of designing realistic therapeutic recommendations aimed at reducing morbidity and mortality in patients with COVID-19.La pandemia COVID-19 provocada por el betacoronavirus SARS-CoV-2 exige rápidas respuestas desde el campo de la medicina. El riesgo de tromboembolismo venoso y arterial está aumentado durante la infección, especialmente en pacientes críticos. En ese contexto se destaca una coagulopatía caracterizada por niveles elevados de dímero D, con tendencia a la falla multiorgánica, y aumento de la mortalidad. Esas anormalidades de la hemostasia responden a varios mecanismos que deben tenerse en cuenta para la toma de decisiones terapéuticas. Analizamos la evidencia científica disponible en la que se fundamenta el enfoque terapéutico de la coagulopatía descripta y sus complicaciones, con el objetivo de diseñar recomendaciones terapéuticas realistas tendientes a disminuir la morbilidad y la mortalidad en pacientes con COVID-19.

Background: Data on the safety and efficacy of copy drugs is usually unavailable. Imatinib mesylate is used to treat chronic myeloid leukemia (CML) patients in Argentina since 2002. During the last decade more than ten different imatinib copies are marketed by the different health-care systems in the country, usually for cost issues. In spite of the undoubted benefit of this tyrosine-kinase inhibitor indication in CML, there is no solid evidence that supports copy drug equivalent outcomes for this patient population. Aim: To compare the clinical presentation, treatment response and outcome of a chronic phase (CP) CML patient cohort treated with branded and copy imatinib in the real-life setting. Methods: Multicentric, retrospective trial based on data obtained from medical charts of adult CP CML patients treated with imatinib in 9 centers in Argentina from 2002 to 2020.We analyzed demographic characteristics and clinical characteristics described for branded and copy imatinib treated cohorts. Frequency of complete cytogenetic response (CCyR) at 12 months, Major molecular response or better(≥MMR) at 12, 18 and 24 months and overall MR4.0, MR4.5 and deep molecular response (MR4.0 +MR4.5 IS) were analyzed. Event was defined as failure, progression or CML related death. Kaplan Meier comparison of event free, progression free and overall survival. Statistics: IBM SPSS version 1. Results: A total of 568 CP CML adult patients (pt) treated with imatinib were included. Mean age at diagnosis: 45.7 years (range 18 - 85). Male 55.6% (316/568). Sokal Score was recorded in 471 pt: 57% (269/471) low, 26% (122/471) intermediate and 17% (80/471) high-risk. Median follow-up 107 months (RIQ: 36-149). Branded imatinib treatment 330 (58%) and imatinib copies 238 (42%). For branded and copy imatinib cohorts mean age 46,1 (18-85) and 45.3(18-80), male 53% (175/330) and 59% (141/238), median follow up 102 (RIQ 101-130) and 61 (RIQ 62-146) respectively. Sokal score low 58% (164/284) and 56% (105/187), intermediate 27% (77/284) and 24% (45/187) and high 15% (43/284) and19% (37/187). Frequency of CCyR at 12 months 71% (67/94) and 69% (41/59), ≥MMR at 12 months 57% (79/138) and 43% (39/89), ≥MMR 18m 66 % (61/92) and 71% (43/60), ≥MMR 24m 65% (96/147) and 79% (58/73). Overall MR4, MR 4.5 and Deep MR with branded imatinib 62.4% (186/298), 42% (118/276) and 63% (189/300), compared to 45(97/214), 24% (50/207) and 46% (99/215) with copies. Difference in evaluation throughout the treatment periods with loss of data did not allow response rate statistical comparison in predetermined timepoints. Kaplan Meier Event free survival median 229 months vs 75 months p 0.001, Progression free survival mean 318 months vs 208 pt 0.034 and Overall Survival mean 275 months vs 206 months for branded and copy imatinib respectively. Discussion: Several case reports have shown poor outcomes in patients treated with imatinib copy drugs, including loss of responses previously attained with branded imatinib. This study reports data from a large cohort of CP CML patients treated in daily practice during a long period of time. Treatment results at determined timepoints is comparable. Although management and treatment decisions were performed in different time periods, results show different outcomes in EFS and PFS between patients treated with branded vs copy imatinib. Overall survival in both cohorts is comparable. As studies assesing the safety and efficacy of the copy drugs compared with branded imatinib will hardly be performed this evidence calls for careful attention and strict follow up measures when managing CML patients with copy imatinib. Figure Disclosures Varela: Novartis: Consultancy, Speakers Bureau. Pavlovsky:Pint Pharma: Speakers Bureau; Pfizer: Speakers Bureau; BMS: Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Freitas:Pfizer: Consultancy, Other: Advisory Board. Pavlovsky:Varifarma: Speakers Bureau; Astra Zeneca: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Other: travel grants, Speakers Bureau; Abbvie: Membership on an entity's Board of Directors or advisory committees, Other: Travel grants, Speakers Bureau. Moiraghi:Novartis: Speakers Bureau; BMS: Speakers Bureau.

Resumen Uno de los objetivos de cualquier programa de salud debe ser alcanzar un alto grado de calidad asistencial, y para ello se debe tener en cuenta conceptos como nivel cientifico-tecnico, eficacia, efectividad, eficiencia, adecuacion, continuidad, accesibilidad, satisfaccion del usuario y otros como solidaridad, equidad y etica. Para cualquier plan de mejora de la calidad que se quiera implementar es importante la activa participacion de los profesionales. Por tal motivo se ha formado un nuevo modelo de gestion que se basa en pequenas unidades o grupos compuestos por los profesionales, y cuyas funciones son la planificacion, la ejecucion, el control y la evaluacion de las diversas actividades que se desprenden de un determinado proceso asistencial, tales como las relacionadas con la docencia, la investigacion, la gestion y la asistencia (grupos DIGA). En el presente estudio, uno de los grupos formados se encarga de las acciones de mejora del proceso asistencial prevencion de la enfermedad tromboembolica venosa (PETEV), para el que hay una gran variedad de criterios terapeuticos, por lo que resulta fundamental conocer que es lo que se hace, como se hace y cuales son los resultados alcanzados. Por tal motivo, el grupo de profesionales confecciona una guia con recomendaciones para la PETEV, participa en su difusion, y se encarga de implementar la medicion de los resultados y su posterior evaluacion y aplicacion. Dichos resultados muestran el grado de calidad alcanzado en el proceso asistencial en cuestion, y permiten detectar rapidamente situaciones de baja calidad, para tratar de revertirlas lo mas rapidamente posible y, de esa forma, garantizar la calidad.

The rationale of the present study is based on the property of technetium-SESTAMIBI to enter malignant and other highly metabolic cells, and then to be pumped out of them by the multidrug-resistant (MDR) system, strongly depending on the expression of the MDR-1 gene encoded P-glycoprotein (Pgp-170).Forty-one patients with malignant lymphoma were studied before chemotherapy. Images were taken 30 min (early) and 180 min (late) after intravenous injection of (99m)Tc-MIBI, and then visually interpreted. They were correlated with clinical response defined as chemosensitive (ChS) when a6 month remission was attained, and chemoresistant (ChR) to any other response. Of 41 patients, 27 had an early positive uptake, 18 (67%) were ChS, and 9 (33%) ChR. Of these 27 patients, 19 also had late positive scans; 15 (79%) were ChS, and only 4 were ChR (p = 0.037). Conversely, 10 of 14 remaining patients with negative early scans were ChR. Eight patients had an early positive study; however, the late retention of (99m)Tc-MIBI was negative and the relationship to chemotherapy response was not conclusive. A breakdown of data was made according to histology. Patients with low grade lymphoma had the strongest correlation between (99m)Tc-MIBI uptake and chemosensitivity. Patients with high grade lymphoma had only a trend, and patients with Hodgkin's disease had an indefinable correlation.This study takes advantage of the relationship between the ability to uptake and retain (99m)Tc-MIBI, a Pgp-170 substrate, by lymphomatous tumors. This attribute, combined with other clinical data, could help to select tailored treatments for patients that are likely to be chemoresistant before treatment.

Oligonucleotides (ODNs) of the PyNTTTTGT class directly stimulate B lymphocytes and plasmacytoid dendritic cells of the immune system of primates. Here we investigated the ability of the PyNTTTTGT ODN prototype IMT504 to regulate the expression of surface molecules and apoptosis in human B-chronic lymphocytic leukemia (CLL) cells. The surface molecules CD25, CD40, CD80 and CD86 were up-regulated upon incubation of the B-CLL cells with IMT504. Co-stimulation with IL-2 resulted in further up-regulation. IMT504-activated B-CLL cells were also good stimulators of T cells in allogeneic mixed lymphocyte reactions and co-stimulation with IL-2 improved this stimulation capacity. Apoptosis of the B-CLL cells in vitro was also stimulated by incubation with IMT504. In this case, co-stimulation with IL-2 was not significant. Furthermore, B-CLL cells of all the patients studied developed an immunogenic phenotype and entered stimulated apoptosis upon in vitro incubation with IMT504 independently of the mutational status of their IgV H genes, becoming a good marker for tumor progression.Los oligonucleótidos (ODNs) de tipo PyNTTTTGT estimulan directamente las células B y las células dendríticas plasmacitoides del sistema inmune de primates. En este trabajo, investigamos la habilidad del IMT504, prototipo de los ODN tipo PyNTTTTGT, para regular la expresión de moléculas de superficie y la apoptosis en células B de leucemia linfocítica crónica (LLC). La expresión de las moléculas de superficie CD25, CD40, CD80 y CD86 fue aumentada al incubar las células B-LLC con IMT504. La co-estimulación con IL-2 provocó un aumento mayor. Las células B-LLC activadas fueron buenas estimuladoras de las células T en cultivo mixto de linfocitos alogeneicos y la co-estimulación con IL-2 mejoró esta capacidad. La apoptosis de las células B-LLC también fue estimulada por incubación con IMT504. En este caso, la co-estimulación con IL-2 no fue significativa. Más aún, las células B-LLC de todos los pacientes estudiados, desarrollaron un fenotipo inmunogénico y entraron en apoptosis luego de la incubación in vitro con IMT504, independientemente del estado mutacional de sus genes IgV H , un indicador del pronóstico de la patología.

Different treatment guidelines suggest that advanced follicular lymphoma (AFL) subjects should be treated only when meeting criteria treatment, such as GELF, are present. Conversely, when absent the watch and wait (W&W) approach is recommended. However, in our country, we had the impression that in real life, a high percentage of patients without the above-mentioned criteria were treated. With the purpose of unravelling the medical approach of AFL patients at diagnosis and subsequent evolution, the Lymphoma Subcommittee of the Argentinian Society of Haematology undertook this retrospective survey. Results: From years 2006 to 2014 305 patients from 23 institutions were included. GELF criteria were encountered in 62% of patients at diagnosis and all of them were treated with immunochemotherapy (ICT). Among the 116 (38%) patients without meeting GELF criteria (GELF negative group), in only 30 (26%) W&W was the approach chosen, while the rest received ICT. The survey questionnaire revealed that own assessment of the treating physician was the main reason for treating the GELF negative group. In the W&W group, 60% required ICT at a mean of 17 months, being 15% of them transformed to DLBCL at time of treatment. The 89% of cases (271/305) received ICT at some time; 66% R-CHOP, 29% R-CVP, and 5% other regimes. Patient median age receiving R-CHOP and R-CVP was 57 and 62 years (p Conclusion: 1) When comparing with international reports, the percentage (62%) of patients with positive GELF criteria was higher at diagnosis. This fact may be due to delay in access to health care; 2) we found a remarkable discrepancy among guidelines recommendations and real life medical behaviour. Three out of four patients received treatment at diagnosis, when W&W ought to have been the guideline-recommended approach; 3) R-CHOP was the most used ICT scheme, while R-CVP was mostly reserved for the elderly. RM was indicated in the majority of patients, particularly after year 2011; 4) despite acknowledging the methodological limitations of this retrospective analysis, a high tumor mass (GELF positive) picture conferred a worse prognosis in term of PFS, while a W&W approach did not affect the OS for the GELF negative group. Disclosures Riveros: Roche: Speakers Bureau.

Similarly to nucleated cells, platelet life span is also controlled by an intrinsic apoptotic program that triggers collapse of the mitochondrial inner membrane potential, activation of caspases-3, -8 and -9, phosphatidylserine (PS) externalization and microparticle shedding. The aim of the present study was to investigate platelet apoptosis in adult patients with immune thrombocytopenia (ITP) under different treatment conditions and to search for its relationship with the type of auto-antibody and the platelet-activation status. Twenty-four patients with chronic ITP, age 42 (21-80) years (median and range) diagnosed according to current criteria (Rodeghiero et al, 2009) were included after written informed consent in accordance with the Declaration of Helsinki. The study was approved by the Ethics Committee from Instituto de Investigaciones Medicas Alfredo Lanari. Platelet count was 38x109/L (6-85). Platelet apoptosis was evaluated by phosphatidylserine (PS) exposure on the platelet surface using FITC-conjugated Anexin-V, mitochondrial electrochemical potential changes (ΔΨm) using the cell penetrating lipophilic cationic fluorochrome JC-1, and activated caspase-3 (a-casp3) measured by the cell-penetrating carboxyfluorescein-labelled fluoromethyl ketone tetrapeptide (FAM-DEVD-FMK). These parameters were studied in resting platelets and after stimulation with calcium ionophore (A23187). Platelet activation was evaluated by FITC-PAC-1 binding to activated GPIIb-IIIa and GPIb-IX internalization using PE-CD42b, in resting conditions and after stimulation either with ADP or TRAP. Apoptosis and activation parameters were evaluated by flow cytometry. In resting conditions, platelets from ITP patients showed increased PS expression and a- casp3 and abnormal ΔΨm (table 1). TablePSΔΨma-casp3Patients19.6 (1.9-82.0)31.2 (5.8-92.4)11.3 (1.8-40.9)Controls4.7 (1.9-10.8)10.3 (2.2-27.5)4.3 (1.9-8.2)p (Mann-Whitney)0.002 After stimulation with A23187, ITP platelets had similar levels of PS expression (p=0.305, n=20) and ΔmΨ (p=0.383, n=25) compared to normal controls. However, an increased sensitivity to the apoptotic stimulus was evidenced by elevated levels of a-casp3 at low and high A23187 concentrations (1-3 mM, p=0.097; 6-10 mM, p=0.002). Platelet apoptosis was not related to platelet activation, as PAC-1 binding was not increased in ITP platelets (basal p=0.847, ADP-induced p=0.059, TRAP-induced p=0.103, n=16). Besides, internalization of GPIb-IX after ADP and TRAP stimulation was also normal (p=NS, n=9 for both agonists). Platelets from ITP patients bearing two of the most frequently found auto-antibodies (5 with anti-GPIIb-IIIa and 1 with anti-GPIb-IX) had similar levels of PS expression and ΔmΨ at resting conditions than those who were negative for these auto-antibodies (n=14) (p=0.265 and 0.148, respectively). There were no differences in apoptosis markers either in resting platelets or after stimulation when comparing untreated patients (n=9) vs patients under any kind of treatment (n=15) (resting conditions, PS p=0.737; ΔmΨ p=0.270; stimulated, PS p=0.966; ΔmΨ p=0.987), although platelet count was similar in both groups. Normal platelets incubated during 1 hour with plasma from ITP had higher a-casp3 than those incubated with normal plasma (n=12 and 9, respectively, p=0.027), suggesting a plasmatic component could be responsible for the apoptotic stimulus. In conclusion, increased platelet apoptosis in ITP patients could be induced by a plasmatic factor, contributing to thrombocytopenia in this entity. Disclosures Riveros: Roche: Speakers Bureau.

Stroke is a well-documented complication of amphetamine abuse. Methylphenidate, chemically and pharmacologically similar to amphetamines, is widely used in the treatment of attention deficit disorder in children. The possibility of vasculitis connected to methylphenidate should not be surprising. A case is reported of stroke associated with ingestion of methylphenidate in an 8-year-old boy. Family history was negative and other causes of vasculitis were excluded. We draw your attention to the risk of using methylphenidate for a long period of time. ( J Child Neurol 2000; 15:265-267).

In this study, 54 patients with relapsed or refractory non-Hodgkin's lymphoma (NHL) were treated in a phase II, multicentric trial with ifosfamide-mesna 1500 mg/m2 IV days 1-3, idarubicin 12 mg/m2 IV day 1 and etoposide 100 mg/m2 IV day 1-3 (MIZE). Overall response was 72%; complete response (CR) and partial response (PR) were 46% and 26% respectively. In Stage I-II pts CR was 59% and in Stage III-IV pts CR was 40.5%. Patients who relapsed from an initial CR had a 64% CR rate when treated with MIZE, in contrast to refractory disease's patients who only had 19% CR (p = 0.004). The group of pts that had an objective response (CR + PR) to front line therapy had a 2 year survival rate of 55% compared with none for refractory disease (p = 0.029) after salvage therapy. Median survival for the entire group was 17.5 months. Better survival was seen in pts who were asymptomatic with low levels of LDH, previous CR, non high-grade histology, and limited disease stage at relapse. Toxicity was mainly hematologic: 91.5% had neutropenia, (56.5% grade III-IV), and 9.5% died from infectious complications. Other clinical toxicities including cardiac toxicity were negligible. MIZE chemotherapy was effective in patients with relapsed and refractory lymphoma and showed limited clinical and cardiac toxicity. Myelosupression was the most frequent single toxicity.

Introduction: Venous thromboembolism (VTE) is an important problem for medical patients. In spite of the existence of evidence-based guidelines for prevention of VTE, prophylaxis for venous thromboembolism is underutilized. Objective: To assess the global and individual adherences (adjust to risk groups) to venous thromboembolism prophylaxis guidelines (VTEPG) in medical ill patients. Desing: Prospective observational study. Setting: The 50-bed medical floors of a university hospital. Material and Methods: Patients: All consecutively medically ill patients (pt) admitted during a 6-month period (n: 452). VTEPG: the guide divided medical patients in risk groups (G); G1: No need of VTEP (35 pt); G2: myocardial infarction (9 pt); G3: Stroke (21 pt); G4: high risk with thrombophilia, previous VTE, cancer (113pt); G5: respiratory and congestive heart failure, pulmonary infection (137 pt); G6: trauma (5 pt); G7: not included in previous groups, required an individual evaluation to asses VTE risk (112pt). Prophylaxis methods included: low dose unfractionated heparin (UFH) or low molecular weight heparin (enoxaparin 40 mg/d) and mechanical methods. Main outcome measurements: 1- Global: correct application of the guide (defined by a coincidence between the prophylaxis received and the recommendation); 2-Adjust to risk group. Results: Global adherence: Correct application of the guide was noted in 252 pts (56%); Adjust to risk group: GR1:71%; GR2:44%; GR3:62%; GR4:76%; GR5:55%; GR6:60% and GR7:26%. Conclusion: In our experience in medical patients global adherence to guides was 56%, the best adherence was observed in high risk groups 76% and the lowest 26% in those patients that need an individual risk assessment. This study and follow up permitted us to detect inaccurate prophylaxis uses and take corrective measures.

Background: 90Y-ibritumomab tiuxetan (Zevamab®; ZEV; Bayer-Schering Pharma- Argentina) has been approved for the treatment of relapsed, refractory and transformed (high grade) follicular lymphomas. Methods: Between Sep. 2005 and Feb. 2008, 45 patients (pts) [22 F & 23 M; median age 62 yrs (45–83)] with refractory/relapsed lymphoma were enrolled. Diagnoses: 37 follicular lymphoma (FL), 5 were mantle cell lymphoma (ML) and 3 transformed lymphoma (TL); 18 pts had bulky disease, 8 had bone marrow involvement and 21 had stage III–IV disease. Median time from diagnosis was 5 yrs (0.5– 29). Twenty two pts had received 1–2 previous treatments, and 23 pts had received 3–5 previous treatments including 5 pts with autologous bone marrow transplantation. All had previously received anti-CD20 monoclonal antibody therapy. Six pts received previous radiotherapy. ZEV was administered at 0.3 or 0.4 mCi, based on initial platelet count. Seven days before, and the same day of the ZEV administration, pts received standard rituximab 250 mg/m2. In 3 pt, ZEV was part of the conditioning regimen of autologous bone marrow transplantation. Results: Forty pts were evaluable for response: 34 (86%) pts responded – 19 CR (48%), 15 PR (38%). Overall survival and PFS for the entire group at 18 months was 63% and 37% respectively, with a median follow-up of 12 months (1–29 months). Of the 45 patients, 5 pts (11%) had died before third month and response was not assessed, 6 pts (13%) did not respond, 3 (7%) died with response from other causes, 14 pts (31%) responded and subsequently relapsed. Finally 17 pts (38%) continue to be in response, 9 (20%) lasting more than twelve months (long lasting responders). Slight differences in duration of response and survival were observed between FL vs ML and TL favouring FL (RR 2.047). Forty six per cent of pts required filgrastim for neutropenia, 24% required platelet transfusions, 22% had neutropenia plus fever and were admitted for complicated pancytopenia, and 20% required red blood cells transfusion. Two patient died 30 & 40 days after treatment with hypoplastic bone marrow complicated with sepsis in the post autologous bone marrow transplantation period. Four pts with previous bone marrow transplantation required filgrastim, transfusions and 2/3 had febrile neutropenia. Conclusion: Our experience with ZEV in relapsed and refractory FL shows 48 % CR. Even heavily treated pts that had previous bone marrow transplantation were able to receive ZEV, although they required extra support. Our experience supports the use of ZEV in relapsed and refractory lymphomas even after autologous bone marrow transplantation.

The coexistence between Chronic Myeloproliferative Syndrome (CMS) and Chronic Lymphoproliferative syndrome (CLS) is a rare event with a few cases reported in literature. This association generates the hypothesis about whether both syndromes derive from the same malignant clonal cells or from independent ones with a common leukemogenic stimulus. In some cases both diseases occur simultaneously while others develop sequentially after exposure to alkylating agents or radiation therapy. We report four patients treated at our center who developed both myeloproliferative and lymphoproliferative syndromes. The CMS were two cases of Myelofibrosis (MF) and two cases of Chronic Myeloid Leukemia (CML). The CLS were two cases of Chronic Lymphocytic Leukemia (CLL), one case of Follicular Lymphoma and one case of Hairy Cell Leukemia. Patient A is a 66-year-old man who was diagnosed with CLL. Inmunophenotyping of peripheral blood (PB) and bone marrow (BM) showed CD45, CD19, CD20, CD5, CD23, CD11c, FMC7, CD38 positive cells with lambda light chain restriction. The BM biopsy showed infiltration of CLL with slight increase of reticulin. After six months, he developed severe tricytopenia. A new BM biopsy showed morphologically abnormal megakaryocytes and increased reticulin compatible with MF plus coexistence of CLL. Heterozygous JAK2 V617F mutation was detected in PB. Nuclear Magnetic Resonance was compatible with MF. He was treated with rituximab with disappearance of the leukemic clone. Treatment with thalidomide (50 mg/day) and dexamethasone (4 mg/day) was started because of rapidly progressing idiopathic MF. Nowadays we observe an improvement of the hematological counts. Patient B is an 88-year-old woman diagnosed with Philadelphia (Ph)-positive CML in chronic phase who was treated with hydroxyurea (500–1000 mg/day). Twenty months later, she developed CLL with inmunophenotyping of PB and BM lymphocytes positives for CD5, CD19, CD20, CD22 and CD23 with kappa light chain restriction. The 13q14 deletion was detected by FISH in the lymphoid cells. The BCR/ABL rearrangement by FISH was observed in all myeloid elements but none in the lymphoid cells. The patient started with chlorambucil (10 mg/m2/day for 15 days per month for 10 months). Patient C is a 73-year-old man who was simultaneously diagnosed with Ph+ CML and Follicular Lymphoma. He was treated with hydroxyurea for the CML and subsequently imatinib was started. At present, 7 years after the initial diagnosis, he developed a blast crisis. Patient D is a 50-year-old woman who was diagnosed with MF with myeloid metaplasia. Physical examination revealed splenomegaly. BM inmunophenotyping was normal. The patient received splenic irradiation, prednisone and thalidomide showing recovery of hematological counts. After 3 years she developed Hairy Cell Leukemia with inmunophenotyping of PB positive for CD45, CD19, CD20, CD11c, CD23, CD25, CD103, HLA-DR and CD79b with lambda light chain restriction. Some authors suggest that this association between CMS and CLS can be originated from a same pluripotent stem cell. Others suggest that coexistence between CMS and CLS is secondary to proliferation of two different progenitors, perhaps, under a single leukemogenic stimulus. Based on the incidence of these diseases, others propose that coexistence is a matter of chance. Of the 4 patients above mentioned, only patient B showed the independent origin of both disorders. As far as we know, this is one of the few reports in which cytogenetic, FISH and molecular studies shows CLL development during the course of CML, arising from a distinct Ph-positive stem cell. Although chemotherapy may increase the risk of secondary malignancies, this is not the case for patients A, B and C since they had not received any treatment before the diagnosis of the second pathology. We find that further investigation is needed to understand the mechanisms that originate the association of this disorders.

The radionucleid conjugate with monoclonal antibodies (antiCD20/90Y-ibritumomab tiuxetan) have been approved for the treatment of relapsed, refractory and transformed (high grade) follicular lymphomas. Between September 2005 and August 2007, 41 patients with refractory/relapsed lymphoma were enrolled. Median age was 62 yrs old (45–83). Twenty were women and 21 were men. Thirty three were follicular and 5 were mantle cell lymphoma and 3 transformed lymphoma. Eighteen patients had bulky disease, 8 had bone marrow involvement and 21 had stage III-IV disease. Median time from diagnosis was 5 years (0.5–29). Twenty one had received 1–2 previous treatments, and 20 pts had received 3–5 previous treatments including 5 pts with autologous bone marrow transplantation. All had previously received anti-CD20 monoclonal antibody therapy. Six pts received previous radiotherapy. 90Y-Ibritumomab (Zevamab™ Bayer-Schering Argentina) was administered at 0.3 or 0.4 mCi, based on initial platelet count. Seven days before, and on the same day of the immunoconjugate administration, pts received rituximab 250 mg/m2. Thirty eight were evaluable for response. Thirty four (89%) pts responded: 20 CR (53%) and 14 PR (36%). With a median follow-up of 10 months, 60% of pts were expected to continue in CR at 18 months. Overall survival at the same period for the entire group was 89%. Nineteen pts (46%) required filgrastim administration for neutropenia, Ten pts (24%) required platelet transfusions, 10 pts had neutropenia plus fever and they had to be admitted for complicated pancytopenia, 8 pts required red blood cells transfusion. Two patient died 30 and 40 days after treatment with hypoplastic bone marrow complicated with septicemia and in the post autologous bone marrow transplantation period, respectively. Four pts with previous bone marrow transplantation, required filgrastim, transfusions and 2/3 had febrile neutropenia. Our experience with 90Y-ibritumomab in relapsed and refractory folicullar lymphoma shows 53% CR. Even heavily treated pts, that had previous bone marrow transplantation were able to receive the radioimmunoconjugate, although they required extra support. Our experience favours the use of 90Y-Ibritumomab tiuxetan in relapsed and refractory lymphomas even if they had received previous autologous bone marrow transplantation.

Background. In our experience, in Argentina, the use of rituximab + chemotherapy in relapsed/refractory CD20+ follicular (FL) non-Hodgkin’s lymphoma results in Methods. Between September 2005 and November 2005, we recruited 10 patients (pts; 6 male/4 female; median age = 56 yr [range: 45–71 yr]) with platelets >100,000/mm3 and bone marrow involvement 5 cm). Three pts were Ann Arbor stage I or II and 7 pts were stage IV. Three pts had received 1–2 cycles of rituximab + chemotherapy and 7 pts had received 3–5 previous cycles. Three pts had undergone autologous transplant. Pts received rituximab 250 mg/m2 IV on days 0 and 7. After the second dose of rituximab, pts received 11 MBq (0.3 mCi) 90Y-Zevalin per kg or 15 MBq (0.4 mCi) 90Y-Zevalin per kg based on platelet counts, with a maximum dose of 32 mCi. Blood counts were monitored weekly until week 10 post-treatment and monthly thereafter. Patient tumor response was reevaluated 3 and 6 months after treatment according to standard criteria. Results. Five pts received a complete dose of 0.4 mCi 90Y-Zevalin per kg and 5 received a reduced dose of 0.3 mCi 90Y-Zevalin per kg. The overall response rate was 60% (CR = 5, PR = 1). Table 1 summarizes the responses. The 5 pts with a CR remained disease-free 8 months later. The pt with a PR progressed with adenopathies and visceromegaly 7 months after treatment. Seven of 10 pts experienced hematologic toxicity: 5 of these 7 pts required G-CSF because of grade 3/4 neutropenia and 3 of these pts developed neutropenic fever. Four of the 7 pts required platelet transfusions and 2 of them required red blood cell transfusions. All 3 pts with previous autologous transplant were in the group with hematologic toxicity. All of these pts required G-CSF and transfusion support, and 2 of these 3 pts were admitted to the clinic for this treatment; hematologic recovery occurred by week 9 post-treatment. Conclusion. The use of 90Y-Zevalin in the relapsed/refractory NHL setting resulted in better response rates and longer disease-free survival than with standard chemoimmunotherapy. Our finding with 50% CR in a heavily pretreated cohort, including 42.8% CR in stage IV pts and 33% CR after autologous transplantation, is encouraging. We are continuing to follow these patients. Table CR PR NR/PD Previous transplant (n=3) 1 1 1 Mantle cell (n=1) 0 0 1 Follicular (n=9) 5 1 3 Tumor volume > 5cm (n=4) 1 0 3 Tumor volume

Several studies (GELA 98.5, MInT) have demonstrated the benefit of combination rituximab (R) with chemotherapy to improve event free and overall survival in patients with DLBCL. We analyzed retrospectively the safety of combination R-CHOP for 6 cycles (rituximab 375 mg/m2 day 1; cyclophosphamide 750 mg/m2 day 1; doxorrubicin 50 mg./m2 day 1; vincristine 1.4 mg/m2 day 1 and prednisone 100 mg/m2 day 1 to 5) the tolerance and adverse effects. We evaluated the response (R), event free survival (EFS) and the overall survival (OS). Between March to December 2004, 28 patients with DLBCL were evaluated, 17 men and 11 women, with a median age 57 years old (range 28 – 84). They were IPI low 21,4 %, low - intermediate 25%, high - intermediate 35,7 % and high risk 17,9 %. Elevated LDH was present en 14 patients, bulky disease > 7 cm in 50% of cases. During the treatment they presented hematologic toxicity grade III 21,4 % and grade IV 25% of cases; 1 patient had anaphilactic reaction; 2 patients pneumonia; 1 patient sepsis; 4 patients neutropenia and fever; and gastric bleeding 1 patient. Response was achieve in 71,4 %: complete response (CR) in 57,1%, parcial (PR) in 14.3 %, and there was no response in 8 patients (28.6%). With follow up of 10 months (range 2 to 18.5) 15 patients were in CR 53,6%, 8 patients died, 7 of then primary no responders. Analyzed by IPI, 60% of CR in intermediate high and high was obtained. The R-CHOP combination is a feasible and safe treatment in our hospitals, and 71,4 % of response was obtained in all patients and 60% of CR in high risk group.

Objetives: To describe the clinical presentation, diagnosis and treatment of patients with carotid and vertebral artery dissection (CAD, VAD). Design: Retrospective, observational Patients and methods: Clinical recording were evaluated from 1996 to 2005; 6 patients (3 women, 3 men, mean age 37 years) with CAD (3) and VAD (3) were referred to our hematology unit. Clinical presentation: progressing stroke 4/6 and transient ischemic attack (TIA) 2/6; warning sings and symptoms preceding the onset of stroke in 80%. Vascular risk factors included smoking and hypertension; associated features were headache, visual symptoms and Horner’s syndrome; Predisposing factors as physical exercise and trauma were found in 4/6. One patient was at 20 weeks of pregnancy. Diagnosis: Diagnostic tests included: Doppler ultrasound, magnetic resonance imaging (MRI) and angiography (MRA). On admission angiographic studies showed occlusion or stenoses of dissected arteries. Treatment: Anticoagulation with heparin or low molecular weight heparin followed by oral anticoagulants. Outcome: No hemorrhagic complication, no recurrence, complete recovery in 5 patients and mild dysarthria in one. Conclusion: TIA and progressing stroke in young patients are presenting features of CAD and VAD. The diagnosis is based on clinical signs and confirming angiographic investigation. Our experience shows that anticoagulation is the treatment of choice, although controlled studies to show their effectiveness are lacking.

Hereditary hemorrhagic telangiectasia (HHT) is a relatively uncommon, autosomal dominant disorder characterized by telangiectases that develop in the skin, mucous membranes, and visceral organs. Mucous localization may seldom bleed profusely, especially epistaxis and upper gastrointestinal (GI) tract. Effective drug treatment is not well established, and multiple blood transfusions and endoscopic or surgical procedures may be the ultimate solution to the frequently bleeding HHT patient. Danazol (DZ) is a mild androgen that has been used in small series of HHT pts with ambiguous results. Its toxicity profile in long standing administration is now well known. Eighteen patients with HHT with transfusion requirements (TR) were treated with DZ at 400–600 mg/daily for the initial three months and 200–400 mg/daily thereafter as a maintenance treatment. At the time of initiation of DZ therapy, median age was 54 yr-old (32–73), nine were female and 9 male, and the median previous TR was 16 RBC units/yr. (2–46). All patients had epistaxis and oral cavity bleeding, with 2 additional upper gastrointestinal tract active bleeding that were detected in ten patients in which an upper GI endoscopy was performed. One patient had a cerebral angioma, surgically treated. None had pulmonary fistula. All patients had some kind of iron treatment. DZ was the first drug treatment intended to reduce the HHT bleeding in 10/18 pts. Median follow-up was 7 years (1.2–14) and two pts were lost to follow-up at 4 and 11 years respectively. At three months of DZ therapy, 12/18 pts (66.6%) showed a remarkable reduction of bleeding, and in 6 patients that showed no response, DZ treatment was stopped. In 7 pts (39%) TR dropped to none and in 5 pts median RT dropped from 22 RBC units/yr. to 10 units/yr. Two of responders had a relapse with upper GI tract bleeding and 1 pts with epistaxis within the first 2 years of DZ treatment. Attempts to reduce the maintenance dose below 200 mg/daily were related to new bleeding or worsening of the active sites. None of the long standing DZ therapy had any significant toxicity. DZ treatment have shown efficacy and safety in this cohort of HHT patients. Mecanism of action may involve the increase of synthesis or expression of ALK-1 dependent proteins and less likely of endoglin. We propose DZ as a first line treatment for the transfusion dependent HHT patients.

Immune cytopenias (IC) frequently require prolongued administration of immunosupressors, especially when associated with lymphoproliferative disorders (LPD). Rituximab causes in vivo selective destruction of B lymphocytes and supresses the production of antibodies. Three mechanisms are involved; complement dependent cytotoxicity, antibody dependent cellular citotoxicity and the induction of apoptosis. We present 10 patients with IC: 8 autoimmune hemolytic anemia (AIHA), and 2 AIHA plus immune thombocytopenia (Evans’ syndrome). Seven patients had IC associated with LPD, and 3 were idiopathic. LPD were: 3 follicular lymphoma (1 Grade 1, 1 Grade 2, 1 Grade 3), 1 small lymphocytic lymphoma, 3 chronic lymphocytic leukemia. Three patients with idiopathic cytopenias had a long history of recurrent AIHA (2) and Evans’ syndrome (1). Ages ranged between 43 and 81 (median 63 yrs); 6 were female gender and 4 male. All AIHA cases, except 1 pts with cryogrobulins, presented with warm IgG antibodies. Previous evolution included splenectomy in 2 pts and all pts received multiple courses of immunosupression with steroids and others, like azathioprine and cyclophosphamide. All patients with LPD received one or more chemotherapeutic regimens with alkylating agents, fludarabine or CHOP combination. Median time to IC in 7 pts with LPD was 75 months (2–228). Idiopathic cases had 12, 132 and 204 months of previous evolution. Rituximab was administered at 375 mg/m2 every 1 to 3 weeks for 3 to 8 doses (median 4). Six pts received rituximab as monotherapy and 4 pts in combination with chemotherapy. Toxicity was mainly related to the first cycle of rituximab and consisted in chills and fever grade I-II in three pts. Clinical resolution of cytopenia occured in 9/10 pts (90%). 4 of them (44%) resolved with negative direct antiglobuline test. Median time to response was 4 weeks (2–8). One AHIA died with hemolysis progression, six months after rituximab, and 1 pts with AHIA and follicular lymphoma died 8 months after rituximab treatment with progression of LPD without evidence of hemolysis. The rest of the patients remained without IC for 2–42 months (median 18). Rituximab, originally designed to treat B-cell neoplasms, is an active immunosupressive agent in either lymphoproliferative associated or idiopathic autoimmune cytopenias even in non splectomized pts. Its use may avoid the secondary effects of long term administration of steroids, alkylating agents or transfusions.

Transfusion associated graft versus host disease (TGVHD) is a complication of transfusion (T) among close relatives but this event is not usually registered. In a search in Medline, since 1966 to present, no references where found on the need to register consanguinity between donors and receptors. The object of this research was to determine the importance of recording consanguinity (C) transfusions in a random fashion to avoid TGVHD. Between January 2001 and June 2003 the presence of C between blood donors and patients (P) on the Donor’s Book and in the mother and satellite blood bags for platelets were registered. Donations (D) were directed (DD) or non-directed (ND). 10,827 D were registered, from which 18,406 units (U) of cellular hemocomponents (CH) apt for transfusion were obtained. Of these, 1,868 D (17.3%) were C with the P and 3,324 (18%) U of CH apt for transfusion were obtained. In order to investigate the chance of a random transfusion of CH to C we excluded from the probability analysis the following U: 1) ABO/Rh incompatible: 157 (4,7%). 2) Already transfused or discarded at the moment of the transfusion order: 304 (9,1%). 3) Not donated at the time of the transfusion order: 504 (15,2%). 4) Irradiated hemocomponents (for C, DD, inmunodeficiencies, etc.): 624 (18,8%). 5) Non-transfused because of absence of transfusion order for the C patient: 846 (25,5%). U from C donors ready for transfusion to a C patient was 889 from 3.324 (26,7%). According to the Accountant Book, at the moment of transfusion the pondered S from C donors was 1.067 U. In the same way, at the moment of transfusion for C receptors, the pondered S of all balance of CH not belonging to C donors was: 28,720 U. In this study the chance that a patient receives at least one U of CH from C donors in a random fashion was [1.067 /28.720 + 1.067] x 100 = 3,6 %. Although the incidence of TGVHD is unknown it is thought to be very low. The chance of 3.6% of receiving at least one U of CH from a C donor in a random way is high and justifies largely considering this event to be registered. This percentage could suffer significant variations for different modalities of Blood Banks with regards to donation, storage and supplying of CH.

Thrombotic and hemorrhagic complications are common in cancer patients and are an important cause of morbidity andmortality in these subjects.Hemostatic abnormalities, with or without these complications are found in nearly 95% of these patients .These abnormalities havebeen atributed to the presence of intravascular coagulation produced by an increased fibrin gene rat ion. We report apatient with adenocarcinoma of colon and multiple venous thrombosis, whose laboratory findings were consistent with anincreased proteolytic activity different from thrombin or plasmin.A 36 year old man with deep vein throrribosis and adenocarcinoma of colon was admitted^He started anti coagulationwith heparin and continued with acenocoimarine.In spite of a correct range of anticoagulation he developed a pulmonarthromboembolism and an axilar vein thrombosis.Coagulation studies on admissionwere as follows: Platelet count;250xl03/μl ,APTT;33 sec.,Prothrombin time;80%,FII; 150%,FV;110%,FVII-X;90%,FVIII;220%,FIX;210%,FDP;156pμ/ml.Thrombin time was shortened and clot solubility in urea 5 M was normal. Euglobulin lysis time and plasminogen(S-2251) were normal.The antithrombin 111 (AT III) concentration measured with specific antiserum (107%) and chromogenic substrates (95%) were normal.The ATIII crossed immunolectrophoresis(CIE) did not show the presence of thrombin-ATI 11 complexes .Studies on von Willebrand factor (vWF) revealed:elevation of vWF:Ag(511%) and normal ristocetin cofactor acti vity(vWF:RCof)(110%); the CIEshowed an increased mo-bi 1 ity( 1.46).Immunological levels of FXIII subunits A and S were decreased(30% and 41%) .Spontaneous proteolytic acti vity(SPA) measured with S-2288 was elevated.Though coagulation findings were consistent with consumption coagulopathy, classicaly related to thrombin gene rati on, thenormal levels of ATI 11 and the abscence of thrombin-ATIII complexes speaks against thrombin intervention.In addition, no evidence of primary fibrinolysis was observed.The increased SPA,the low levels of FXIII subunits A and S, and a faster mobility of vWF:Ag with an increased vWF:Ag/vWF:RCof ratio, suggest that hemostatic abnormalities in this patient could be due to proteolytic degradationof clotting factors by enzymes released from tumoral cells or granulocytes.