Machine learning identifies experimental brain metastasis subtypes based on their influence on neural circuits.

A high percentage of patients with brain metastases frequently develop neurocognitive symptoms; however, understanding how brain metastasis co-opts the function of neuronal circuits beyond a tumor mass effect remains unknown. We report a comprehensive multidimensional modeling of brain functional analyses in the context of brain metastasis. By testing different preclinical models of brain metastasis from various primary sources and oncogenic profiles, we dissociated the heterogeneous impact on local field potential oscillatory activity from cortical and hippocampal areas that we detected from the homogeneous inter-model tumor size or glial response. In contrast, we report a potential underlying molecular program responsible for impairing neuronal crosstalk by scoring the transcriptomic and mutational profiles in a model-specific manner. Additionally, measurement of various brain activity readouts matched with machine learning strategies confirmed model-specific alterations that could help predict the presence and subtype of metastasis.

TGF-ß/SMAD Pathway Is Modulated by miR-26b-5p: Another Piece in the Puzzle of Chronic Lymphocytic Leukemia Progression.

Clinical and molecular heterogeneity are hallmarks of chronic lymphocytic leukemia (CLL), a neoplasm characterized by accumulation of mature and clonal long-lived CD5 + B-lymphocytes. Mutational status of the IgHV gene of leukemic clones is a powerful prognostic tool in CLL, and it is well established that unmutated CLLs (U-CLLs) have worse evolution than mutated cases. Nevertheless, progression and treatment requirement of patients can evolve independently from the mutational status. Microenvironment signaling or epigenetic changes partially explain this different behavior. Thus, we think that detailed characterization of the miRNAs landscape from patients with different clinical evolution could facilitate the understanding of this heterogeneity. Since miRNAs are key players in leukemia pathogenesis and evolution, we aim to better characterize different CLL behaviors by comparing the miRNome of clinically progressive U-CLLs vs. stable U-CLLs. Our data show up-regulation of miR-26b-5p, miR-106b-5p, and miR-142-5p in progressive cases and indicate a key role for miR-26b-5p during CLL progression. Specifically, up-regulation of miR-26b-5p in CLL cells blocks TGF-ß/SMAD pathway by down-modulation of SMAD-4, resulting in lower expression of p21-Cip1 kinase inhibitor and higher expression of c-Myc oncogene. This work describes a new molecular mechanism linking CLL progression with TGF-ß modulation and proposes an alternative strategy to explore in CLL therapy.

Absolute monocyte count as a prognostic parameter in diffuse large B cell lymphoma / Recuento absoluto de monocitos como parámetro pronóstico en linfoma difuso de células B grandes

ABSTRACT Background Prognosis of patients with Diffuse Large B Cell Lymphoma (DLBCL) is highly variable, and despite the use of modern immunochemotherapy regimens, almost 50% of patients will eventually relapse. Standard risk models, like the International Prognostic Index or the Revised International Prognostic Index (R_IPI) incorporate patient and tumor characteristics but do not consider variables related to host adaptive immunity which have been shown to be of significant prognostic value in non-Hodgkin lymphomas. Aim To analyze the prognostic significance of the absolute monocyte count at diagnosis in diffuse large-B-cell lymphoma in a retrospective setting. Material and Methods We reviewed data of 171 patients with DLBCL treated with Rituximab-based immunochemotherapy at two reference public Hospitals in Montevideo-Uruguay. The outcome measures were overall and relapse free survival. Results The absolute monocyte count, analyzed as a dichotomized variable predicted progression-free and overall survival in low risk patients according to the R-IPI score. Worse outcomes were observed in those with high monocyte count al diagnosis. Conclusions Absolute monocyte count could help in the identification of high-risk patients otherwise expected to have a good prognosis according to traditional scores.

Antecedentes El pronóstico de pacientes con Linfoma Difuso de Células B Grandes (DLBCL) es muy variable y el 50% de los pacientes recae a pesar de uso de regímenes actualizados de inmuno-quimioterapia. Los modelos pronósticos clásicos como el International Prognostic Index o el Revised International Prognostic Index (R_IPI) incorporan características del paciente o del tumor pero no incorporan variables asociadas a la inmunidad adaptativa que tienen valor en linfomas no Hodgkin. Objetivo Analizar retrospectivamente el valor pronóstico del recuento absoluto de monocitos al momento del diagnóstico en pacientes con DLBCL. Material y Métodos Se revisó información de 171 pacientes con DLBCL tratados con inmuno-quimioterapia basada en rituximab en dos centros de referencia públicos de Montevideo, Uruguay. Las variables de resultado fueron la sobrevida global y libre de recaída. Resultados El recuento absoluto de monocitos, tratado como una variable dicotómica, predijo la sobrevida libre de recaída en pacientes de bajo riesgo, de acuerdo al puntaje R-IPI. El pronóstico fue peor en pacientes con altos recuentos al momento del diagnóstico. Conclusiones El recuento absoluto de monocitos puede identificar pacientes de alto riesgo, clasificados como de bajo riesgo por los puntajes tradicionales.

Absolute monocyte count as a prognostic parameter in diffuse large B cell lymphoma.

Background Prognosis of patients with Diffuse Large B Cell Lymphoma (DLBCL) is highly variable, and despite the use of modern immunochemotherapy regimens, almost 50% of patients will eventually relapse. Standard risk models, like the International Prognostic Index or the Revised International Prognostic Index (R_IPI) incorporate patient and tumor characteristics but do not consider variables related to host adaptive immunity which have been shown to be of significant prognostic value in non-Hodgkin lymphomas. Aim To analyze the prognostic significance of the absolute monocyte count at diagnosis in diffuse large-B-cell lymphoma in a retrospective setting. Material and Methods We reviewed data of 171 patients with DLBCL treated with Rituximab-based immunochemotherapy at two reference public Hospitals in Montevideo-Uruguay. The outcome measures were overall and relapse free survival. Results The absolute monocyte count, analyzed as a dichotomized variable predicted progression-free and overall survival in low risk patients according to the R-IPI score. Worse outcomes were observed in those with high monocyte count al diagnosis. Conclusions Absolute monocyte count could help in the identification of high-risk patients otherwise expected to have a good prognosis according to traditional scores.

LPL protein in Chronic Lymphocytic Leukaemia have different origins in Mutated and Unmutated patients. Advances for a new prognostic marker in CLL.

Lipoprotein lipase (LPL) mRNA expression in chronic lymphocytic leukaemia (CLL) is associated with an unmutated immunoglobulin profile and poor clinical outcome. We evaluated the subcellular localization of LPL protein in CLL cells that did or did not express LPL mRNA. Our results show that LPL protein is differently located in CLL cells depending on whether it is incorporated from the extracellular medium in mutated CLL or generated de novo by leukaemic cells of unmutated patients. The specific quantification of endogenous LPL protein correlates with mRNA expression levels and mutational IGHV status, suggesting LPL protein as a possible reliable prognostic marker in CLL.

S100-A9 protein in exosomes from chronic lymphocytic leukemia cells promotes NF-κB activity during disease progression.

Chronic lymphocytic leukemia (CLL) is an incurable disease characterized by accumulation of clonal B lymphocytes, resulting from a complex balance between cell proliferation and apoptotic death. Continuous crosstalk between cancer cells and local/distant host environment is required for effective tumor growth. Among the main actors of this dynamic interplay between tumoral cells and their microenvironment are the nano-sized vesicles called exosomes. Emerging evidence indicates that secretion, composition, and functional capacity of exosomes are altered as tumors progress to an aggressive phenotype. In CLL, no data exist exploring the specific changes in the proteomic profile of plasma-derived exosomes from patients during disease evolution. We hereby report for the first time different proteomic profiles of plasma exosomes, both between indolent and progressive CLLs as well as within the individual patients at the onset of disease and during its progression. Next, we focus on the changes of the exosome protein cargoes, which are found exclusively in patients with progressive CLL after disease progression. The alterations in the proteomic cargoes underline different networks specific for leukemia progression related to inflammation, oxidative stress, and NF-κB and phosphatidylinositol 3-kinase/AKT pathway activation. Finally, our results suggest a preponderant role for the protein S100-A9 as an activator of the NFκB pathway during CLL progression and suggest that the leukemic clone can generate an autoactivation loop through S100-A9 expression, NF-κB activation, and exosome secretion. Collectively, our data propose a new pathway for NF-κB activation in CLL and highlight the importance of exosomes as extracellular mediators promoting tumor progression in CLL.

Síndrome hemofagocítico: una rara complicación en el paciente con infección por el virus de inmunodeficiencia humana (VIH) / Hemophagocytic syndrome: a rare complication in patients with human immunodeficiency virus (HIV) infection

Resumen: El síndrome hemofagocítico es una enfermedad infrecuente y grave caracterizada por un estado de hiperinflamación sistémica con sobreproducción de citocinas. Puede responder a causas genéticas (primario) o desencadenarse por infecciones, fármacos, neoplasias o enfermedades autoinmunes. Existen criterios diagnósticos establecidos. El tratamiento consiste en el bloqueo de la respuesta inflamatoria sistémica, asociado al tratamiento de la causa desencadenante cuando se halla. La mortalidad es alta y usualmente está en relación a la causa que gatilla el fenómeno. Se presenta un caso de sindrome hemofagocítico en paciente infectada por el virus de la inmunodeficiencia humana.

Abstract: Hemophagocytic syndrome is a rare and serious disease characterized by a state of systemic hyperinflammation with overproduction of cytokines. Can respond to genetic causes (primary) or be triggered by infections, drugs, tumors or autoimmune diseases. There are established diagnostic criteria. Treatment consists in blocking the inflammatory response associated with the treatment of the underlying cause when it is. Mortality is high and usually is related to the cause that triggers the phenomenon. We report a case of hemophagocytic syndrome in HIV-infected patient.

Current imaging follow-up of non-Hodgkin lymphoma exposes patients to significant radiation but does not detect asymptomatic relapses.

The standard approach to the follow-up of lymphoma includes computed tomography (CT) every 6-12 months for the first 2 years and, then, as clinically indicated. Recent evidence suggests that most relapses are detected clinically, outside scheduled CT which, on the other hand, increases risk of second malignancies and cost. In early-stage lymphomas, involved site CT instead of full body CT may be a reasonable alternative to reduce radiation dose. We analyzed whether regular CT surveillance detects asymptomatic relapses in a single-center Uruguayan early stage non-Hodgkin lymphoma (NHL) population. We evaluated utility of full body CT halfway and at the end-of-treatment evaluation and calculated the radiation exposure. In our study, CT surveillance added nothing to clinical follow-up. Moreover, 44% of our patients received a cumulative effective dose that doubles the risk of malignancies. Involved-site CT scan would be enough to monitor response during treatment in early stage NHL.

Trasplante autólogo de progenitores hematopoyéticos en pacientes con Linfoma no Hodgkin agresivo: Experiencia de un centro / Autologous transplant of Haematopoietic Stem Cells in Patients with Aggressive Non Hodgkin Lymphoma: Experience of a center

Introducción: El Trasplante Autólogo de Progenitores Hematopoyéticos forma parte del tratamiento de pacientes con Linfoma No Hodgkin (LNH) agresivos en respuesta parcial y recaída. Objetivos: evaluar las respuestas y sobrevida en los pacientes con LNH agresivos trasplantados en Hospital Británico. Material y Métodos: estudio retrospectivo de pacientes con LNH agresivos que se trasplantaron entre el 1/01/1995 y el 1/07/2013. Total 65 pacientes. Resultados: el 95% logró una Remisión Completa post Auto-TPH y el 5% una Remisión Parcial. Con una mediana de seguimiento de 74 meses (5-219), la mediana de SG no se ha alcanzado. La media estimada es de 145 meses (122-169) con una SG a 5 años de 71% y a 10 años es de 60%. La mediana de SLE no se ha alcanzado, a 5 años es de 60% y a 10 años es de 58%. Conclusiones: el trasplante Autólogo de Progenitores Hematopoyéticos es una herramienta terapéutica útil. Los resultados de nuestro grupo son comparables a los reportados por grupos internacionales con una baja mortalidad relacionada al procedimiento.

Introduction: Autologous Hematopoietic Stem Cell Transplantation is part of the treatment of patients with aggressive lymphomas in partial response or relapsed. Objectives: To evaluate the responses and survival in aggressive NHL patients transplanted in Hospital Británico. Material and Methods: Retrospective study of patients with aggressive NHL that were transplanted into... between 01/01/1995 and 07/01/2013. Total 65 patients. Results: 95% achieved a complete remission after Auto-SCT and 5% partial remission. With a median follow up of 74 months (5-219), the median OS has not been reached. The estimated mean is 145 months (122-169) with a 5-year OS of 71% and 60% at 10 years. The median DFS has not been reached, at 5 years is 60 % and at 10 years is 58 %. Conclusions: Autologous Hematopoietic Stem Cell Transplantation is a useful therapeutic tool. The results of our group are comparable to those reported by international groups with low procedure-related mortality.

Uso de rituximab en trombocitopenia inmune: experiencia en el Hospital de Clínicas / Use of rituximab in immune thrombocytopenia at the University Hospital

Introducción: rituximab es un anticuerpo monoclonal que se une específicamente al antígeno CD20 expresado en los linfocitos B. El uso de rituximab en el tratamiento de la trombocitopenia inmune refractaria no se encuentra aprobado en su ficha técnica. Objetivo: describir las características clínicas, la respuesta terapéutica y los aspectos vinculados a la seguridad con el uso de rituximab en los pacientes con trombocitopenia inmune refractaria asistidos en la Cátedra de Hematología del Hospital de Clínicas y revisar la evidencia sobre el beneficio clínico esperado en este grupo de pacientes. Material y método: se realizó un estudio descriptivo de los pacientes con trombocitopenia inmune refractaria asistidos en la Cátedra de Hematología del Hospital de Clínicas a quienes se les prescribió rituximab. Se realizó una búsqueda bibliográfica en PubMed sobre el uso de rituximab en este tipo de patología. Resultados: se trataron cuatro pacientes con trombocitopenia inmune refractaria con rituximab. Se obtuvo respuesta en tres de cuatro pacientes. La media de tiempo de respuesta fue 9,25 semanas. La respuesta se ha mantenido en los tres pacientes. No se registraron efectos adversos durante la perfusión de rituximab. La evidencia publicada se limita a estudios observacionales, en adultos, con pocos pacientes, habiendo mostrado respuestas favorables. Conclusiones: existen limitaciones en la evidencia sobre el tratamiento de la trombocitopenia inmune refractaria, pero rituximab constituye una alternativa efectiva. Es indispensable la integración clínica para monitorizar la efectividad y seguridad del uso de anticuerpos monoclonales, especialmente en indicaciones no aprobadas...

[Comparison between CHOP-like and R-CHOP in diffuse large B cell and follicular lymphoma]. / Comparación entre CHOP-like y R-CHOP en pacientes con linfoma no Hodgkin difuso de grandes células B y folicular: 10 años de experiencia del Hospital de Clínicas de Montevideo, Uruguay.

BACKGROUND: The most common types of non-Hodgkin lymphoma (NHL) are diffuse large B cell (DLBCL) and follicular (FL). AIM: To analyze the benefit of Rituxi-mab in overall survival (OS) of patients with NHL. MATERIAL AND METHODS: Review of medical record of 230 adult patients with a first episode of NHL admitted between 2002 and 2011. We included 67 patients with DLBCL and 36 patients with FL. RESULTS: The overall response (OR) was 64% with 39% complete remissions (CR) in DLBCL treated with CHOP-like and 100% with 89% CR with R-CHOP. The median OS with CHOP-like was 21 months versus not attained R-CHOP (p = 0.016). There was a statistically significant difference in median event-free survival (EvFS) in favor of R-CHOP: not attained versus 8.3 months for CHOP-like (log rank (p = 0.002)). In FL, the OR in patients treated with R-CHOP or R-CHOP-like was 85%) with 54% CR. With CHOP-like the OR was 59%> with 18% CR. The OS at 24 and 36 months in patients treated with R-CHOP or R-CHOP-like was 83 and 65%. The figures for patients treated with CHOP-like were 80 and 66%> respectively. The progression free survival (PFS) was 21 months with CHOP-like versus not attained with R-QT (p = 0,043). CONCLUSIONS: When Rituximab was added to CHOP, there was a higher CR, EvFS and OS in DLBCL and higher CR and PFS in FL.

Comparación entre CHOP-like y R-CHOP en pacientes con linfoma no Hodgkin difuso de grandes células B y folicular: 10 años de experiencia del Hospital de Clínicas de Montevideo, Uruguay / Comparison between CHOP-like and R-CHOP in diffuse large B cell and follicular lymphoma

Background: The most common types of non-Hodgkin lymphoma (NHL) are diffuse large B cell (DLBCL) and follicular (FL). Aim: To analyze the benefit ofRituxi-mab in overall survival (OS) of patients with NHL. Material and Methods: Review of medical record of 230 adult patients with afirst episode of NHL admitted between 2002 and 2011. We included 67 patients with DLBCL and 36 patients with FL. Results: The overall response (OR) was 64% with 39% complete remissions (CR) in DLBCL treated with CHOP-like and 100% with 89% CR with R-CHOP. The median OS with CHOP-like was 21 months versus not attained R-CHOP (p = 0.016). There was a statistically significant difference in median event-free survival (EvFS) in favor of R-CHOP: not attained versus 8.3 months for CHOP-like (log rank (p = 0.002)). In FL, the OR in patients treated with R-CHOP or R-CHOP-like was 85%) with 54% CR. With CHOP-like the OR was 59%> with 18% CR. The OS at 24 and 36 months in patients treated with R-CHOP or R-CHOP-like was 83 and 65%. The figures for patients treated with CHOP-like were 80 and 66%> respectively. The progression free survival (PFS) was 21 months with CHOP-like versus not attained with R-QT (p = 0,043). Conclusions: When Rituximab was added to CHOP, there was a higher CR, EvFS and OS in DLBCL and higher CR and PFS in FL.

Manifestaciones articulares como debutde leucemia aguda linfoblástica: presentación de tres casos / Articular symptoms as an initial manifestation of acute lymphoblastic leukemia

La leucemia aguda linfoblástica tiene una incidencia global de 1,7/100.000 habitantes/año y es la enfermedad oncológica más frecuente en la infancia. La presentación con dolores óseos y articulares es frecuente en los adolescentes y niños, con una incidencia reportada de 1/3 de los casos.Se describen tres casos de leucemia aguda linfoblástica diagnosticados en la Cátedra de Hematología del Hospitalde Clínicas con debut bajo forma de artritis. Esta forma conlleva en general un retraso en el diagnóstico debido aun bajo índice de sospecha.

The worldwide annual incidence of acute lymphoblastic leukemia is 1.7 per 100,000 people and it constitutes the most common form of cancer in childhood. Bone and joint pain as an initial manifestation of cancer is frequent in adolescents and children, the incidence reported accounting for 1 out of three cases. The study describes three cases of acute lymphoblastic leukemia diagnosed in the Hematology Chair of the University Hospital, the initial presentation of which was arthritis, being diagnose delayed due to the low rates of suspicion.

A incidência global da leucemia aguda linfoblástica é de 1,7/100.000 habitantes/ano sendo a patologia oncológica mais frequente na infância. A apresentação com dores ósseas e articulares é frequente nos adolescentes e nas crianças, com uma incidência de 1/3 dos casos. Descrevemos três casos de leucemia aguda linfoblásticadiagnosticados na Cátedra de Hematologia do Hospital das Clínicas que se apresentaram ao principio como artrite. De maneira geral, esta forma de apresentação causa um atraso no diagnóstico, pois poucas vezes sesuspeita de leucemia.

Trasplante autólogo de progenitores hematopoyéticos en pacientes con mieloma múltiple: análisis de factores pronósticos y sobrevida: experiencia del Hospital Británico / Autologic transplant of hematopoietic progenitors in patients with multiple myeloma: a study of prognosis and survival at the British Hospital

Introducción: el trasplante autólogo de progenitores hematopoyéticos (TAPH) es considerado estándar en el tratamiento de primera línea en pacientes con mieloma múltiple (MM) menores de 65 años. Objetivo: analizar la sobrevida global (SG) y sobrevida libre de eventos (SLEv) de los pacientes con MM trasplantados en el Hospital Británico. Material y método: se realizó un estudio retrospectivo de los pacientes que recibieron un primer TAPH. Resultados: entre el 1° de julio de 1999 y el 30 de junio de 2010 se realizaron 56 TAPH a 48 pacientes con MM. Del análisis de los pacientes al primer TAPH, 46% eran mujeres y 54%hombres. La mediana de edad fue de 54 años (32-65 años). El 73% eran IgG, 17% IgA y 10% de cadenas livianas. El 60,4% logró una RC/nRC (RC, RC no confirmada y VGPR) posTAPH. Con una media de seguimiento de 58,6 meses (5,84-186,56), la mediana de SG fue de 121,8 meses (IC 95%: 70,1-173,54 meses). No se hallaron diferencias significativas en SG entre los pacientes que lograron RC/nRC posTAPH y quienes no lo lograron (log Rank p=0,162). La mediana de SLEv fue de 56 meses (IC 95%: 42,2-70,4 meses).Conclusiones: el TAPH es una herramienta fundamental en el tratamiento de los pacientes con MM y es un procedimiento seguro en la Unidad de Hematología del Hospital Británico.

Introduction: autologic transplant of hematopoietic progenitors is regarded as the standard in the first line treatmentof patients with multiple myeloma (MM) younger than 65 years old. Objective: to analyse global survival and incident freesurvival in patients with multiple myeloma transplanted at the British Hospital. Method: we conducted a retrospective study of patients who received the first autologic transplant of hematopoietic progenitors. Results: 56 autologic transplants of hematopoietic progenitors were performed from July 1, 1999 through June 30, 2010 in 48 patients with MM. Upon analysis of patients after the first transplant, 46% were women and 54% were men. Median age was 54 years old (32-65 years old). 73% were IgG, 17% were IgA and 10% were light chains.60.4% achieved CR/nCR (CR), non- confirmed CR and VGPR) after transplant. With an average follow-up of 58.6 months (5.84-186.56), the median global survival was121.8 months (IC 95%: 70.1-173.54 months). No significant differences were found in the global survival in patientswho achieved CR/nCR after autologic transplant of hematopoietic progenitors and those who failed to achieve it (log Rank p=0.162. The median incident-free survival was 56 months (IC 95%: 42.2-70.4 months). Conclusions: autologic transplant of hematopoietic progenitors is an essential tool to treat patients with MM and it is a safe procedure at the Hematology Unit of the British Hospital.

Introdução: o transplante autólogo de progenitores hematopoiéticos (TAPH) é considerado um padrão no tratamentode primeira linha de pacientes menores de 65 anos com mieloma múltiple (MM).Objetivo: analisar a sobrevida global (SG) e sobrevida livre de eventos (SLEv) dos pacientes com MMtransplantados no Hospital Britânico.Material e método: um estudo retrospectivo dos pacientes que receberam um primeiro TAPH foi realizado. Resultados: no período 1° de julho de 1999 a 30 de junho de 2010 foram realizados 56 TAPH a 48 pacientes com MM. A análise dos dados dos pacientes no primeiro TAPH mostrou que 46% eram mulheres e 54% homens. A mediana da idade foi 54 anos (32-65 anos). 73% eram IgG, 17% IgA e 10% de cadeias leves. 60,4% conseguiram uma RC/nRC (RC, RC não confirmada e VGPR) pósTAPH. Comuna media de seguimento de 58,6 meses (5,84-186,56), a mediana de SG foi de 121,8 meses (IC 95%: 70,1-173,54meses). Não foram encontradas diferenças significativas na SG entre os pacientes que conseguiram RC/nRCpósTAPH e os que não a conseguiram (log Rank p=0,162). A mediana de SLEv foi 56 meses (IC 95%: 42,2-70,4 meses). Conclusões: o TAPH é uma ferramenta fundamental para o tratamento de pacientes com MM e é umprocedimento seguro na Unidade de Hematologia do Hospital Britânico.

Enfermedad de Von Willebrand adquirida en un linfoma linfoplasmocitario/Macroglobulinemia de Waldenström: reporte de caso / Acquired Von Willebrand disease (aVWD) in a lymphoplasmocitary/Waldenstrõm Macroglobulinemia lymphoma: case report

La enfermedad de Von Willebrand adquirida es una situación infrecuente que se genera en el contexto de enfermedades autoinmunes, síndromes linfoproliferativos y mieloproliferativos. Se presenta el caso clínico de una paciente portadora de un linfoma linfoplasmocitario con enfermedad de Waldenström, presentándose con un síndrome hemorragíparo y alteraciones de la crasis sanguínea a nivel de la vía intrínseca. Las gammapatías monoclonales como la macroglobulinemia de Waldenström suelen presentarse con dosificaciones de IgM variables, siendo, en el caso que se describe, > 11 g/dl. La clínica puede ser muy proteiforme, afectando varios sistemas, presentando en este caso una complicación por adsorción tumoral: la enfermedad de Von Willebrand adquirida. Se indicó tratamiento quimioterápico en base a talidomida, ciclofosfamida y dexametasona para la enfermedad de base, evolucionando favorablemente, remitiendo el síndrome hemorragíparo con tendencia a la normalización de la crasis, de los valores globulares y plaquetarios en forma mantenida luego de seis series de tratamiento. Otras medidas terapéuticas dirigidas a revertir la coagulopatía, como la plasmaféresis, poseen acción transitoria, no estando exentas de riesgo, y se plantean antehiperviscosidad aguda manifiesta con riesgo vital. La valoración de la paciente en forma interdisciplinaria permitió el mejor acercamiento diagnóstico y terapéutico.

Acquired Von Willebrand disease is an unusual situation arising within the context of self-immune diseases, lymphoproliferative and mieloproliferative disorders. The study presents the clinical case of a patient carrier of a lymphoplasmocitary lymphoma with WaldenstrõmÆs disease which presented with a hemorrhagic syndrome and alterations of the blood crasis in the intrinsic way. Monoclonalgammopathies such as WaldenstrõmÆs macroglobulinemia usually appear with varied IgM dosifications, being it > 11 g/dl in the case described. Clinical symptoms may be very proteiform, affecting several systems, and inthis case it presented complications resulting from tumor adsorption: acquired Von Willebrand disease. Chemotherapy with thalidomide, cyclophosphamide and dexamethasone was indicated for the base disease and there was favourable evolution, the hemorrhagic syndrome remittedand there was a tendency to crasis normalization, the same as globular and platelets values ongoing normalizationafter six series of treatment. Other therapeutic measures aiming to reverse coagulopathy, such as plasmapheresis,are short-acting, and they are not exempt from risks, and they are considered as options upon obviousacute hyperviscosity with a risk of life. Multidisciplinary patient assessment enabled the best diagnosis and therapeutic approach.

A doença de Von Willebrand adquirida é pouco freqüente e surge no contexto de doenças auto-imunes, síndromes linfoproliferativos e mieloproliferativos. Descrevemos o caso de uma paciente portadora de linfoma linfoplasmocitario com doença de Waldenstrõm, que apresentava uma síndrome hemorragípara e alterações da crase sanguínea da via intrínseca. As gamapatias monoclonais como amacroglobulinemia de Waldenstrõm podem apresentar-se com dosificação variável da IgM que neste caso era > 11g/dl. O quadro clínico pode ser proteiforme afetando vários sistemas, apresentado nesta paciente uma complicação por adsorção tumoral: a doença de Von Willebrand adquirida. Para o tratamento da doença de base foi indicada quimioterapia com talidomida, ciclofosfamida e dexametasona que levou a uma evolução favorável com remissão da síndrome hemorragípara com tendência à normalização da crase e dos valores de glóbulos e plaquetas depois de seis séries de tratamento. Outras medidas terapêuticas orientadas à reversão da coagulopatia como a plasmaferese possuem ação transitória e não estão isentas de risco e são sugeridas quando há hiperviscosidade aguda com risco vital. A avaliação multidisciplinar da paciente favoreceu o diagnóstico e o tratamento.