Direct Oral Anticoagulants for the Treatment of Cancer-Associated Venous Thromboembolism: A Latin American Perspective.

Venous thromboembolism (VTE) is a leading cause of morbidity and mortality in patients with cancer. On the basis of results from randomized controlled trials, direct oral anticoagulants (DOACs) are now recommended for the treatment of cancer-associated VTE. The decision to use a DOAC requires consideration of bleeding risk, particularly in patients with gastrointestinal (GI) malignancies, the cost-benefit and convenience of oral therapy, and patient preference. While efficacy with apixaban, edoxaban, and rivaroxaban versus dalteparin has been consistent in the treatment of cancer-associated VTE, heterogeneity is evident with respect to major GI bleeding, with an increased risk with edoxaban and rivaroxaban but not apixaban. Although cost and accessibility vary in different countries of Latin America, DOACs should be considered for the long-term treatment of cancer-associated VTE in all patients who are likely to benefit. Apixaban may be the preferred DOAC in patients with GI malignancies and LMWH may be preferred for patients with upper or unresected lower GI tumors. Vitamin K antagonists should only be used for anticoagulation when DOACs and low molecular weight heparin are inaccessible or unsuitable.

Real-World Evidence of Epidemiology and Clinical Outcomes in Multiple Myeloma, Findings from the Registry of Hemato-Oncologic Malignancies in Colombia, Observational Study.

INTRODUCTION/BACKGROUND: Multiple Myeloma (MM) is a plasma cell derived clonal disorder that represents around 1% of all newly diagnosed neoplasms. Limited data regarding MM treatment in Latin America is available, and access to novel agents for a substantial portion of the population is limited by their high costs. MATERIALS (OR PATIENTS) AND METHODS: RENEHOC is a bidirectional (retrospective and prospective) multicenter observational registry of hematological malignancies in Colombia. MM patients included up to July 2020 were analyzed on this report. RESULTS: 890 are reported with a median follow-up of 18 months (IQR: 7-42 months). Patients were classified by age group (≤ or > 65 years). Median age at diagnosis was 67 years (IQR: 59-75 years) and 47.1% of patients were women. 709 patients (79.6%) received Bortezomib-based schemes as part of the first line. Two hundred and fifty-two patients (28.3%) were consolidated with Autologous Stem Cell Transplantation (ASCT) in first-line. ASCT consolidation and age were the main independent factors influencing outcomes; in the non-ASCT cohort, 5-year overall survival was 48.7% (CI 41.8-55.2) compared to 80.7% (CI 73-86.4) in ASCT patients. CONCLUSION: This data depicts the reality of MM in Colombia, which likely reflects other Latin American countries, where access barriers to diagnosis and treatment are echoed in advanced stage diagnosis and a low rate of transplants. These seem to negatively impact survival despite the availability of most novel drugs approved for this disease. Thus, emphasizing the paradox that prevails in most of the region: availability without equitable access.

Tromboprofilaxis, anticoagulación y coagulopatía en tiempos de pandemia: recomendación de la ACATA, ACMI, SCC CCV y ACMV / Thromboprophylaxis, anticoagulation and coagulopathy in times of pandemic: The ACATA, ACMI, SCC CCV and ACMV recommendation

Resumen Introducción La enfermedad por coronavirus 2019 (COVID-19) puede predisponer a tromboembolia venosa o trombosis arterial debido a una respuesta inflamatoria aumentada, hipoxia, inmovilización y coagulación intravascular diseminada; hasta en un 20 a 50% de pacientes hospitalizados con COVID-19 tienen alteraciones hematológicas relacionadas con coagulopatía (dímero D elevado, tiempo de protrombina prolongado, trombocitopenia y/o fibrinógeno bajo). Evaluaciones post mortem evidencian depósitos trombóticos microvasculares típicos, ricos en plaquetas en vasos pequeños de pulmones y otros órganos. Objetivo Brindar una aproximación práctica y actualizada en el manejo del paciente con riesgo elevado o que presentan eventos tromboembólicos en el marco de la actual pandemia por COVID-19. Material y métodos: Se realizó una revisión narrativa que incluyó estudios observacionales descriptivos. Se efectuó una búsqueda de la literatura de evidencia médica en diferentes buscadores como Science Direct y PubMed, usando las palabras claves “thromboprophylaxis”, “anticoagulation”, “thrombosis”, “anticoagulant”, “COVID-19”, “SARS-CoV-2”, “coronavirus”. Posteriormente se escribieron las recomendaciones generales referentes al tema. Conclusiones Existen diferentes formas en las que la pandemia por COVID-19 puede predisponer al desarrollo de enfermedades trombóticas o tromboembólicas, el efecto directo o indirecto de este virus relacionado con la tormenta de citocinas que precipita el inicio del síndrome de respuesta inflamatoria sistémica y predispone al desarrollo de eventos trombóticos; también las intervenciones disponibles pueden tener interacciones farmacológicas con antiagregantes y/o anticoagulantes.

Abstract Introduction Coronavirus 19 infection can predispose to VTE or arterial thrombosis due to a heightened inflammatory response, hypoxia, immobility and DIC. Up to 20-50% of hospitalized patients with COVID-19 have hematological disorders related to coagulopathies (elevated D-dimer, prolonged PT, thrombocytopenia and/or low fibrinogen). Post-mortem examinations show typical platelet-rich microvascular thrombotic deposits in the small vessels of the lungs and other organs. Objective To provide a practical, updated approach to the treatment of patients at high risk for or with ongoing thromboembolic events in the current COVID-19 pandemic setting. Material and methods A narrative review was performed including descriptive observational studies. A search of the medical evidence literature was carried out in different search engines such as ScienceDirect and PubMed, using the following key words: “thromboprophylaxis”, “anticoagulation”, “thrombosis”, “anticoagulant”, “COVID-19”, “SARS-CoV-2”, and “coronavirus”, and general recommendations on the topic were subsequently composed. Conclusions The are various ways in which the COVID-19 pandemic may predispose to the development of thrombotic or thromboembolic diseases. The virus may have a direct or indirect effect related to the cytokine storm which triggers the onset of systemic inflammatory response syndrome and predisposes to the development of thrombotic events. The available interventions may also have pharmacological interactions with antiplatelet drugs and/or anticoagulants.

Ixazomib-lenalidomide-dexamethasone in routine clinical practice: effectiveness in relapsed/refractory multiple myeloma.

Aim: To evaluate the effectiveness and safety of ixazomib-lenalidomide-dexamethasone (IRd) in relapsed/refractory multiple myeloma in routine clinical practice. Patients & methods: Patient-level data from the global, observational INSIGHT MM and the Czech Registry of Monoclonal Gammopathies were integrated and analyzed. Results: At data cut-off, 263 patients from 13 countries were included. Median time from diagnosis to start of IRd was 35.8 months; median duration of follow-up was 14.8 months. Overall response rate was 73%, median progression-free survival, 21.2 months and time-to-next therapy, 33.0 months. Ixazomib/lenalidomide dose reductions were required in 17%/36% of patients; 32%/30% of patients discontinued ixazomib/lenalidomide due to adverse events. Conclusion: The effectiveness and safety of IRd in routine clinical practice are comparable to those reported in TOURMALINE-MM1. Clinical trial registration: NCT02761187 (ClinicalTrials.gov).

Lay abstract Proteasome inhibitors are drugs used in multiple myeloma (MM), a blood cancer that develops from cells in the bone marrow. Ixazomib is the first oral proteasome inhibitor to be approved for use in MM, when given in combination with two other oral drugs, lenalidomide and dexamethasone, to adult patients who have received one prior therapy. Our study, which was conducted in routine clinical practice, found that the effectiveness and safety of ixazomib + lenalidomide + dexamethasone in previously treated MM patients were similar to those seen in the Phase III clinical trial on which approval was based. These findings are important because they suggest that MM patients in everyday practice can achieve the same benefits from this treatment as patients in clinical trials, despite often being in poorer health.

Epidemiology of Hematologic Malignancies in Real-World Settings: Findings From the Hemato-Oncology Latin America Observational Registry Study.

PURPOSE: Limited information is available on multiple myeloma (MM), chronic lymphocytic leukemia (CLL), and non-Hodgkin lymphoma (NHL) management in Latin America. The primary objective of the Hemato-Oncology Latin America (HOLA) study was to describe patient characteristics and treatment patterns of Latin American patients with MM, CLL, and NHL. METHODS: This study was a multicenter, retrospective, medical chart review of patients with MM, CLL, and NHL in Latin America identified between January 1, 2006, and December 31, 2015. Included were adults with at least 1 year of follow-up (except in cases of death within 1 year of diagnosis) treated at 30 oncology hospitals (Argentina, 5; Brazil, 9; Chile, 1; Colombia, 5; Mexico, 6; Panama/Guatemala, 4). RESULTS: Of 5,140 patients, 2,967 (57.7%) had NHL, 1,518 (29.5%) MM, and 655 (12.7%) CLL. Median follow-up was 2.2 years for MM, 3.0 years for CLL, and 2.2 years for NHL, and approximately 26% died during the study observation period. Most patients had at least one comorbidity at diagnosis. The most frequent induction regimen was thalidomide-based chemotherapy for MM and chlorambucil with or without prednisone for CLL. Most patients with NHL had diffuse large B-cell lymphoma (DLBCL; 49.1%) or follicular lymphoma (FL; 19.5%). The majority of patients with DLBCL or FL received rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. CONCLUSION: The HOLA study generated an unprecedented level of high-quality, real-world evidence on characteristics and treatment patterns of patients with hematologic malignancies. Regional disparities in patient characteristics may reflect differences in ethnoracial identity and level of access to care. These data provide needed real-world evidence to understand the disease landscape in Latin America and may be used to inform clinical and health policy decision making.

[Adequate diagnosis of acquired hemophilia A]. / Importancia de la orientación diagnóstica en hemofilia A adquirida.

Acquired hemophilia A (AHA) is a rare and life-threatening autoimmune hemorrhagic disorder where autoantibodies are developed against factor VIII. An early diagnosis is challenging and mandatory: an immediate hemostatic control is required to reduce morbidity and mortality. Laboratory features of AHA are: presence of autoantibodies against factor VIII, prolonged activated partial thromboplastin time (with normal prothrombin time and thrombin time) and decreased factor VIII levels. In some cases, the results of laboratory tests may be incorrect due to errors in analysis, blood extraction or manipulation of samples; also worth of consideration are limitations in the measurement range and low sensitivity of the tests. This review highlights the importance of adequate screening in patients with suspected AHA to make an adequate diagnosis and reduce overall fatal outcomes.

Importancia de la orientación diagnóstica en hemofilia A adquirida / Adequate diagnosis of acquired hemophilia A

Acquired hemophilia A (AHA) is a rare and life-threatening autoimmune hemorrhagic disorder where autoantibodies are developed against factor VIII. An early diagnosis is challenging and mandatory: an immediate hemostatic control is required to reduce morbidity and mortality. Laboratory features of AHA are: presence of autoantibodies against factor VIII, prolonged activated partial thromboplastin time (with normal prothrombin time and thrombin time) and decreased factor VIII levels. In some cases, the results of laboratory tests may be incorrect due to errors in analysis, blood extraction or manipulation of samples; also worth of consideration are limitations in the measurement range and low sensitivity of the tests. This review highlights the importance of adequate screening in patients with suspected AHA to make an adequate diagnosis and reduce overall fatal outcomes.

Cadenas ligeras libres en suero en el diagnóstico de Gammapatías Monoclonales / Free light chains in serum in the diagnosis of Monoclonal Gammopathies

Las gammapatías monoclonales son un conjunto de enfermedades causadas por la proliferación clonal de células plasmáticas que secretan un mismo tipo de inmunoglobulina, conocido como inmunoglobulina clonal. El pronóstico de estas enfermedades hematológicas depende del diagnóstico temprano, en el Mieloma Múltiple se asocia con una enfermedad menos grave. Las pruebas de laboratorio desempeñan un papel importante en las distintas etapas del manejo clínico del paciente con gammapatía monoclonal. Estas incluyen pruebas tradicionales como la electroforesis de proteínas en suero, la inmunofijación, y actualmente se adiciona la determinación de cadenas ligeras libres en suero, una prueba complementaria importante porque permite evidenciar la presencia de gammapatías monoclonales de forma temprana por su alta sensibilidad, así como cuantificar las cadenas ligeras libres kappa/lambda y determinar la monoclonalidad a través del respectivo cociente, parámetro que desde el 2014 está integrado en los criterios diagnósticos de mieloma según la International Myeloma Working Group.Como metodología se realizó la búsqueda de material bibliográfico: se definieron las palabras clave utilizando los descriptores DeCS y MeSH, se inició la búsqueda de información en las bases de datos bibliográficas PubMed, ScienceDirect y se ejecutó una búsqueda en internet con buscador "google académico" con los mismos términos. Se seleccionaron aquellos artículos y páginas de internet que contaran con información de interés, que cumplieran los requisitos para incluirse dentro del artículo de revisión, se almacenaron en una base de datos y finalmente se realizó la lectura crítica de la información.

Monoclonal gammopathies are a group of diseases caused by the clonal proliferation of plasma cells that secrete the same type of immunoglobulin, known as clonal immunoglobulin. The prognosis of these hematological diseases depends on the early diagnosis, in Multiple Myeloma is associated with a less serious disease. Laboratory tests play an important role in the different stages of clinical management of patients with Monoclonal gammopathies, including traditional tests such as serum protein electrophoresis, immunofixation, and the determination of free light chains in serum it is considered an important complementary test since it allows initially to show the presence of Monoclonal gammopathies in an early way due to its high sensitivity, likewise it allows to quantify the kappa / lambda free light chains and to determine the monoclonality through the respective quotient, this is a parameter that since 2014 is integrated into the myeloma diagnostic criteria according to the International Myeloma Working Group.As a methodology, the search of bibliographic material was carried out: the keywords were defined using the DeCS and MeSH descriptors, the search for information in the PubMed, ScienceDirect bibliographic databases was started and an internet search was carried out with the "google academic" search engine with the same terms. Those articles and internet pages that had information of interest, that met the requirements to be included in the review article, were stored in a database and finally the critical reading of the information was selected

[Three cases of de novo multiple myeloma after kidney transplantation].

Light chain-associated kidney compromise is frequent in patients with monoclonal gammopathies; it affects the glomeruli or the tubules, and its most common cause is multiple myeloma. It may develop after a kidney transplant due to recurrence of a preexisting multiple myeloma or it can be a de novo disease manifesting as graft dysfunction and proteinuria. A kidney biopsy is always necessary to confirm the diagnosis.We describe three cases of kidney graft dysfunction due to multiple myeloma in patients without presence of the disease before the transplant.

Tres casos de mieloma múltiple de novo después de trasplante renal / Three cases of de novo multiple myeloma after kidney transplantation

RESUMEN La enfermedad renal asociada a cadenas ligeras es frecuente en el contexto de las gammapatías monoclonales, afecta los glomérulos o los túbulos renales, y su causa más común es el mieloma múltiple. Puede desarrollarse después de un trasplante renal por recurrencia de un mieloma múltiple ya existente, o puede ser de diagnóstico nuevo y presentarse con deterioro de la función renal y proteinuria. Siempre se requiere una biopsia renal para confirmar el diagnóstico.

ABSTRACT Light chain-associated kidney compromise is frequent in patients with monoclonal gammopathies; it affects the glomeruli or the tubules, and its most common cause is multiple myeloma. It may develop after a kidney transplant due to recurrence of a preexisting multiple myeloma or it can be a de novo disease manifesting as graft dysfunction and proteinuria. A kidney biopsy is always necessary to confirm the diagnosis.

[Epidemiology of febrile neutropenia in adult patients with hematologic neoplasms in a period of 26 months in Hospital Pablo Tobón Uribe, Colombia]. / Epidemiología de la neutropenia febril en pacientes adultos con neoplasia hematológica, en un período de 26 meses en el Hospital Pablo Tobón Uribe, Colombia.

BACKGROUND: Febrile neutropenia (FN) is a significant adverse effect post-chemotherapy due to its high morbidity and mortality. There are few studies in our country with these kind of patients. OBJECTIVE: To describe the characteristics and mortality in patients with hematologic neoplasms who developed FN post-chemotherapy. METHODOLOGY: A descriptive case series in patients with hematologic neoplasms who developed FN post-chemotherapy in Hospital Pablo Tobón Uribe. RESULTS: 101 episodes of FN in 43 patients. The median age was 44 years. 63.5% of patients had no apparent clinical focus of infection at admission, 11.8% had soft tissue compromise and 8.9% urinary tract infection. Bacteremia was documented in 41.5% and catheter-associated bacteremia in 3.9%. The most common organisms were Escherichia coli 43.4%, Klebsiella pneumoniae 17.3% and Staphylococcus aureus 8.6%. Of those isolated in blood 84.7% were Gram negative rods and 15.2% were Gram positive bacteria. Piperacillin/tazobactam was the most common empirically prescribed antibiotic (81.1%). Mortality of FN episodes occurred in 8 (7.92%) patients, 5 (62.5%) attributable to infection and 3 (37.5%) due to progression of hematologic malignancy with a resolution of FN. CONCLUSIONS: In our case series of FN the microbiological characteristics differed significantly from developed countries, but a similar mortality rate per episode was observed.

Epidemiología de la neutropenia febril en pacientes adultos con neoplasia hematológica, en un período de 26 meses en el Hospital Pablo Tobón Uribe, Colombia / Epidemiology of febrile neutropenia in adult patients with hematologic neoplasms in a period of 26 months in Hospital Pablo Tobón Uribe, Colombia

Background: Febrile neutropenia (FN) is a significant adverse effect post-chemotherapy due to its high morbidity and mortality. There are few studies in our country with these kind of patients. Objective: To describe the characteristics and mortality in patients with hematologic neoplasms who developed FN post-chemotherapy. Methodology: A descriptive case series in patients with hematologic neoplasms who developed FN post-chemotherapy in Hospital Pablo Tobón Uribe. Results: 101 episodes of FN in 43 patients. The median age was 44 years. 63.5% of patients had no apparent clinical focus of infection at admission, 11.8% had soft tissue compromise and 8.9% urinary tract infection. Bacteremia was documented in 41.5% and catheter-associated bacteremia in 3.9%. The most common organisms were Escherichia coli 43.4%, Klebsiella pneumoniae 17.3% and Staphylococcus aureus 8.6%. Of those isolated in blood 84.7% were Gram negative rods and 15.2% were Gram positive bacteria. Piperacillin/tazobactam was the most common empirically prescribed antibiotic (81.1%). Mortality of FN episodes occurred in 8 (7.92%) patients, 5 (62.5%) attributable to infection and 3 (37.5%) due to progression of hematologic malignancy with a resolution of FN. Conclusions: In our case series of FN the microbiological characteristics differed significantly from developed countries, but a similar mortality rate per episode was observed.

Introducción: La neutropenia febril (NF) es un efecto adverso importante post-quimioterapia por su alta morbi-mortalidad. Hay pocos estudios en nuestro entorno con estos pacientes. Objetivo: Describir las características de los pacientes adultos con neoplasia hematológica que desarrollaron NF post-quimioterapia. Metodología: Estudio descriptivo de serie de casos, en pacientes con neoplasia hematológica y NF post-quimioterapia en el Hospital Pablo Tobón Uribe. Resultados: Ciento un episodios de NF en 43 pacientes con una mediana de edad de 44 años. El 63,5% no tenían foco infeccioso clínico aparente al ingreso, 11,8% tenía compromiso de tejidos blandos y 8,9% foco urinario. Se documentó bacteriemia primaria en 42 (41,5%) y bacteriemia asociada al catéter en 4 (3,96%). Los microorganismos más frecuentes fueron Escherichia coli 43,4%, Klebsiella pneumoniae 17,3% y Staphylococcus aureus 8,69%. De los aislados en sangre, 84,7% fueron bacilos gramnegativos y 15,2% cocáceas grampo-sitivas. Piperacilina/tazobactam fue la antibioticoterapia empírica inicial en 81,1% de los episodios. La mortalidad por episodios de NF fue de 7,92%, en 62,5% atribuible a la infección y en el resto a progresión de la neoplasia hematológica con resolución de la NF. Conclusión: Serie de casos de NF con características microbiológicas que difieren significativamente a los países desarrollados, pero con una mortalidad por episodios similar.

Púrpura trombocitopénica trombótica Descripción del diagnóstico y manejo de una entidad poco frecuente y de alta mortalidad / Thrombotic thrombocytopenic purpura Description of diagnosis and management of a rare entity with a high mortality

Presentamos dos casos con diagnóstico de púrpura trombocitopénica trombótica idiopática refractarios al tratamiento con recambio plasmático y en los cuales fue necesario emplear un tratamiento adicional. En uno de los casos hubo una adecuada respuesta con rituximab. También analizamos el papel de los niveles de ADAMTS 13 para el manejo y diagnóstico de esta enfermedad. (Acta Med Colomb 2012; 37: 201-206).

We report two patients diagnosed as having idiopathic thrombocytopenic purpura refractory to plasma exchange in which the use of additional treatment was necessary. In one case there was an adequate response to rituximab. We also analyze the role of ADAMTS 13 levels for the management and diagnosis of this disease. (Acta Med Colomb 2012; 37: 201-206).

Tromboelastografía: nuevos conceptos en la fisiología de la hemostasia y su correlación con la coagulopatía asociada al trauma / Thromboelastography: New concepts in haemostasis physiology and correlation with trauma associated coagulopathy

La interpretación inicial del proceso de coagulación mencionaba la presencia de 2 vías: la extrínseca, formada por el factor tisular (FT) y el factor VII, y la intrínseca, en la que participan los factores XII, XI, IX, VIII y V. Hoy en día este concepto ha cambiado y se acepta de forma categórica que el evento iniciador principal de la coagulación sanguínea es la exposición del FT. En este artículo revisamos los nuevos conceptos de la cascada de coagulación con los hallazgos de la tromboelastografía y los diferentes mecanismos que precipitan la coagulopatía asociada al trauma. Para tal fin se realizó una búsqueda sistemática en las principales bases de datos, como Medline, Embase y Lilacs, en el periodo comprendido entre 2000 y 2011. Se encontraron 114 artículos, de los cuales se tomaron 50 para realizar la revisión. Como hallazgo relevante se encontró que la tromboelastografía permite detectar con precisión el defecto subyacente en la cascada de coagulación, y de esta manera se ha convertido en una herramienta útil e indispensable para guiar el manejo de la coagulopatía asociada al trauma.

Initial interpretation of the process of coagulation refers to two pathways: (1) the extrinsic pathway, consisting of tissue factor (TF) and factor VII, and (2) the intrinsic pathway, in which factors XII, XI, IX, VIII and V are involved. Currently, this concept has changed and it is accepted that the main initiating event in blood coagulation is TF exposure. In this article, we review the new concepts of the coagulation cascade based on thromboelastography findings and the different mechanisms involved in trauma-associated coagulopathy. For this purpose, a systematic research was carried out using the main databases, including Medline, Embase and Lilacs between 2000 and 2011. One hundred and fourteen articles were found, and 50 were selected for the review. A relevant finding was that thromboelastography allows a precise detection of the underlying flaw in the coagulation cascade. Therefore, this procedure has become an essential tool and a guide for the management of trauma-associated coagulopathy.

Consenso sobre diagnóstico y tratamiento de Leucemia Mieloide Crónica En Colombia / Consensus on diagnosis and treatment of chronic Myeloid Leukemia in Colombia

Objetivo: Unificar criterios para organizar el diagnóstico de la Leucemia Mieloide Crónica (LMC) y racionalizar el uso de nuevos medicamentos para su tratamiento. Métodos: se realizó una búsqueda estructurada de la literatura médica en la base de datos Medline en el Registro de Estudios Clínicos (CCTR) de la Biblioteca Cochrane y EMBSE, usando la plataforma OVID. Todoso los artículos fueron revisados por un comité central y los resultados fueron validados por hematólogos, oncólogos y otros especialistas en una reunión de consenso. Resultados: Se generaron 11 recomedaciones sobre diagnóstico (criterios definitorios), tratamiento (fase crónica, fase acelerada, crisis molecular, evolución clonal, etc), y seguimiento según fase y tratamiento base (remisión hematológica, respuesta citogenética, respuesta molecular, evolución clonal, etc). Conclusiones. los esquemas de tratamiento disponibles permiten mejorar la supervivencia y calidad de vida de los pacientes. Todo paiente con LMC requiere confirmación histológica y citogenética de su enfermedad. El inicio temprano del tratamiento con inhibidores de la tirosina-quinasa y el seguimiento estricto de las respuestas hematológica, citogenética y molecular permitirán adecuar o modificar la terapia de manera oportuna en pacientes resistentes primarios o secundarios.

Leucemia mieloide crónica en crisis: blástica bases moleculares y diagnóstico / Chronic myelogenous leukemia in blastic crisis: molecular basis and diagnostic

La leucemia mieloide crónica es una enfermedad con comportamiento bifásico o trifásico, 90 por ciento de los pacientes debuta en fase crónica, 50 por ciento asintomáticos al diagnóstico. Un porcentaje con enfermedad crónica desarrollan en tiempo variable una enfermedad más agresiva definida por un período intermedio y crisis blástica. Se diagnostica al encontrar más del 20 por ciento de blastos en médula ósea, 30 por ciento en sangre periférica o enfermedad extramedular. El pronóstico es pobre, al lograr respuesta completa, con una mediana de sobrevida de 3-12 meses, independiente del fenotipo. El 50 por ciento de los pacientes tendrán una mieloide, 25 por ciento linfoide y 25 por ciento fenotipo indiferenciado. Un grupo de expertos clínicos de Bogotá, Colombia, revisaron la mejor evidencia sobre diagnóstico y tratamiento. La información se obtuvo de búsquedas estructuradas y varios registros de experimentos clínicos en curso. Presentamos conclusiones y recomendaciones para la toma de decisiones basadas en la mejor evidencia.

Terapia primaria en aplasia de médula ósea: trasplante alogénico de progenitores hematopoyéticos vs. terapia inmunosupresora / Primary therapy in bone marrow aplasia: allogeneic haematopoietic progenitor cell transplantation vs. immunosuppressive therapy

La aplasia de médula ósea (AMO) es una enfermedad poco frecuente caracterizada porun síndrome de falla medular con citopenias periféricas y médula ósea hipo o acelular, en ausenciade blastos y mielodisplasia. El trasplante alogénico de progenitores hematopoyéticos (TAPH) y la terapiainmunosupresora (TI) son tratamientos aceptados para pacientes con esta patología. Objetivo:determinar la supervivencia global a un año de los pacientes con AMO de acuerdo con el tratamientorecibido. Diseño: estudio de serie de casos. Lugar: servicio de hematología del Hospital de San Joséy unidad de trasplante de médula ósea de la Clínica de Marly. Pacientes: 36 con AMO. Intervención:trasplante alogénico de progenitores hematopoyéticos de un donante HLA-idéntico relacionado oterapia inmunosupresora. Medición: se realizó el análisis descriptivo a través de tablas de frecuencia.Las probabilidades de supervivencia fueron estimadas usando el método de Kaplan-Meier. Resultados:la supervivencia global a un año del grupo de TAPH fue de 64% y del grupo de TI 57%. Respecto alos factores pronósticos, se encontró que en los dos grupos de tratamiento los recuentos de neutrófilos>500 y de plaquetas >10.000 al momento del diagnóstico se relacionaron con una mayor supervivenciaen el primer año. Además un menor soporte transfusional tanto de PQ como de glóbulos rojos desdeel diagnóstico hasta el momento del tratamiento tiene una fuerte relación con la supervivencia al año.

Leucemia mieloide crónica en crisis blástica: perspectiva terapéutica según la evidencia (Parte II) / Chronic myelogenous leukemia in blastic phase: therapeutic perspective according to clinical evidence (Part II)

En la actualidad, el pronóstico de los pacientes con crisis blástica (CB) es pobre y depende, especialmente, de lograr una respuesta completa, con una mediana de supervivencia entre los tres y los doce meses, independientemente del fenotipo de la enfermedad. Hasta el momento, no existe un tratamiento estándar para la CB, que habitualmente manifiesta un curso similar al de las leucemias agudas quimiorresistentes; las aproximaciones más recientes han mostrado que el uso de regímenes similares a los empleados en el manejo de las leucemias agudas asociados al imatinib permiten mejorar las tasas de supervivencia global y libres de progresión de la enfermedad. No obstante, los pacientes con esta condición deberán ser considerados candidatos para estudios experimentales. A pesar de que la posibilidad de lograr respuesta completa es baja, la población que logra llegar a ella deberá consolidarse con trasplante alogénico de médula ósea. Un grupo de expertos conformado por hematólogos, oncólogos y epidemiólogos clínicos de Bogotá D. C., Colombia, se encargó de revisar y seleccionar la mejor evidencia sobre el diagnóstico y tratamiento de la CB. La información se obtuvo a partir de búsquedas estructuradas realizadas en MedLine, Embase, Cochrane, Biosis, Cinhal, Lilacs y de varios registros de experimentos clínicos en curso. Este documento presenta las principales conclusiones y algunas recomendaciones para mejorar los principales desenlaces de la CB, y permitir así la toma de decisio- nes basadas en la mejor evidencia, que promoverá el uso racional de los recursos en salud.

Chronic myelogenous leukemia traditionally has been characterized by a biphasic or triphasic course. Blastic phase overall prognosis is poor, with a median survival of 3 to 12 months. Approximately 50% of patients have a myeloid phenotype, 25% have a lymphoid phenotype, and 25% have an undifferentiated phenotype. There is currently no standard treatment for the blastic phase of chronic myeloid leukemia, which is a chemoresistant form of acute leukemia. Current approaches include using standard acute myeloid leukemia regimens associated with imatinib in an effort to induce remission, variations of these approaches with drugs that seem more active in this specific leukemia, and the direct entry of patients into studies of investigational agents. Although the likelihood of achieving remission is small, immediate bone marrow transplantation in remission should be considered because it provides the only opportunity for long-term survival at this time. An expert panel of hematologists, oncologists and clinical epidemiologists of Bogotá, D.C., Colombia reviewed selected literature related with BP of chronic myeloid leukemia obtained from advanced searches of medial literature in MedLine, Embase, Cochrane, Biosis, Cinhal, Lilacs and from several in course clinical trials databases. The following document present the principal conclusions and some recommendations to improve outcomes of BP, to assist practitioners to apply the best available research evidence to clinical decisions, and to promote responsible use of health care resources.