Consensus in acute myeloid leukemia in Mexico.

Acute myeloid leukemia (AML) comprises a heterogeneous group of hematopoietic cell neoplasms of myeloid lineage that arise from the clonal expansion of their precursors in the bone marrow, interfering with cell differentiation, leading to a syndrome of bone marrow failure. AML is a consequence of genetic and epigenetic changes (point mutations, gene rearrangements, deletions, amplifications, and arrangements in epigenetic changes that influence gene expression) in hematopoietic precursor cells, which create a clone of abnormal cells that are capable of proliferating but cannot differentiate into mature hematopoietic cells or undergo programmed cell death. The diagnosis requires more than 20% myeloid blasts in the bone marrow and certain cytogenic abnormalities. Treatment will depend on age, comorbidities, and cytogenetic risk among the most frequent.

La leucemia mieloide aguda (LMA) comprende un grupo heterogéneo de neoplasias de células hematopoyéticas de linaje mieloide que surgen de la expansión clonal de sus precursores en la médula ósea, interfiriendo con la diferenciación celular, lo que conlleva a un síndrome de falla medular. La LMA es una consecuencia de cambios genéticos y epigenéticos (mutaciones puntuales, rearreglos de genes, deleciones, amplificaciones y arreglos en cambios epigenéticos que influyen en la expression del gen) en las células hematopoyéticas precursoras, la cual crea una clona de células anormales que son capaces de proliferar, pero no se pueden diferenciar en células hematopoyéticas maduras ni sufrir una muerte celular programada. El diagnostic requiere más del 20% de blastos mieloides en médula ósea y ciertas anormalidades citogénicas. El tratamiento dependerá de la edad, comorbilidades, riesgo citogenético entre las más frecuentes.

Consensus on hemophilia in Mexico.

Hemophilia is a hemorrhagic disorder with a sex-linked inherited pattern, characterized by an inability to amplify coagulation due to a deficiency in coagulation factor VIII (hemophilia A or classic) or factor IX (hemophilia B). Sequencing of the genes involved in hemophilia has provided a description and record of the main mutations, as well as a correlation with the various degrees of severity. Hemorrhagic manifestations are related to levels of circulating factor, mainly affecting the musculoskeletal system and specifically the large joints (knees, ankles, and elbows). This document is a review and consensus of the main genetic aspects of hemophilia, from the inheritance pattern to the concept of women carriers, physiopathology and classification of the disorder, the basic and confirmation studies when hemophilia is suspected, the various treatment regimens based on infusion of the deficient coagulation factor as well as innovative factor-free therapies and recommendations for the management of complications associated with treatment (development of inhibitors and/or transfusion-transmitted infections), or secondary to articular hemorrhagic events (hemophilic arthropathy). Finally, relevant reviews of clinical and treatment aspects of hemorrhagic pathology characterized by acquired deficiency of FVIII secondary to neutralized antibodies named acquired hemophilia.

La hemofilia es un trastorno hemorrágico con patrón de herencia ligado al sexo, caracterizado por una incapacidad en la amplificación de la coagulación ocasionada por la deficiencia del factor VIII (hemofilia A o clásica) o del factor IX (hemofilia B). La secuenciación de los genes involucrados en la hemofilia ha permitido la descripción y registro de las principales mutaciones, así como la correlación con los diversos grados de severidad. Las manifestaciones hemorrágicas se relacionan con los niveles de factor deficiente circulante, afectando principalmente al sistema musculoesquelético y en particular a las grandes articulaciones (rodillas, tobillos y codos). El presente documento hace una revisión y consenso de los principales aspectos genéticos de la hemofilia, desde el patrón de herencia y el concepto de mujeres portadoras, la fisiopatología y clasificación de la enfermedad, los estudios básicos y de confirmación ante la sospecha de hemofilia, y de los diversos esquemas de tratamiento basados en la infusión del factor de coagulación deficiente hasta las terapias innovadoras libres de factor, así como de las recomendaciones para el manejo de las complicaciones asociadas al tratamiento (desarrollo de inhibidores y/o infecciones transmitidas por transfusión) o secundarias a los eventos hemorrágicos a nivel articular (artropatía hemofílica). La parte final del documento revisa los aspectos clínicos y de tratamiento relevantes de una patología hemorragica caracterizada por la deficiencia adquirida del FVIII mediada por anticuerpos neutralizantes denominada hemofilia adquirida.

Mexican Concensus of Multiple Myeloma.

To identify this increasingly common pathology, known as multiple myeloma (MM), it is necessary to refer to the specific factors that characterize it; to this end, the classic criteria known as CRAB (hyperkalemia, renal failure, anemia, and lytic lesions) are available, in which renal failure is one of the most frequent complications. Recently, three indisputable biomarkers have been described for the diagnostic support for MM, which are: more than 10% of clonal plasma cells in bone marrow or, a biopsy that corroborates the presence of a plasmacytoma, light chain ratio ≥ 100 mg/dL and more than one focal lesion on magnetic resonance imaging. A differential diagnosis for plasma cell leukemia, solitary bone plasmacytoma, and extramedullary plasmacytoma should always be considered. Being this an incurable disease, a lot of research has been done regarding its therapeutic management, whose main objective is the disappearance of plasma cells and the patient clinical improvement. Melphalan was the first drug that showed a benefit in 1958 and afterward, with the addition of a steroid as a second drug, it was possible to improve response rates. Subsequently, different molecules were studied, forming multiple combinations, and achieving better rates of overall survival and progression-free survival. Years later, with the arrival of proteasome inhibitors such as bortezomib, and immunomodulators such as thalidomide and lenalidomide, an important turnaround in the disease has been seen, as deeper responses, more prolonged remissions, and improvement in the quality of life of patients have been achieved. This consensus has the purpose of integrating a group of Mexican specialists and promoting the updating of this pathology.

Para identificar una patología cada vez más común, conocida como mieloma múltiple, es necesario hacer alusión de los factores específicos que la caracterizan. Para ello existen los clásicos criterios conocidos como CRAB (hipercalcemia, insuficiencia renal, anemia y lesiones líticas), siendo la insuficiencia renal una de sus complicaciones más frecuentes. Recientemente se han descrito tres biomarcadores indiscutibles para el apoyo diagnóstico del mieloma múltiple, que son: más del 10% de células plasmáticas clonales en medula ósea o biopsia que corrobora la presencia de un plasmocitoma, relación de cadenas ligeras ≥ 100 mg/dl y más de una lesión focal en resonancia magnética. Se debe tomar siempre en cuenta el diagnóstico diferencial con leucemia de células plasmáticas, plasmocitoma óseo solitario y plasmocitoma extramedular. Al ser una enfermedad incurable, se ha investigado mucho en cuanto al manejo terapéutico, el cual tiene como objetivo principal la desaparición de las células plasmáticas y la mejoría clínica del paciente. El primer fármaco que demostró algún beneficio fue el melfalán en el año 1958 y posteriormente al adicionar un esteroide como segundo fármaco se logró mejorar las tasas de respuesta. Después se fueron estudiando diferentes moléculas, con las que se han realizado múltiples combinaciones, alcanzando mejores tasas de supervivencia global y supervivencia libre de progresión. Años más tarde, con la llegada de los inhibidores de proteosoma como el bortezomib, así como de los agentes inmunomoduladores como la talidomida y la lenalidomida, se presenta un giro importante en la enfermedad, ya que se logran respuestas más profundas, periodo de remisiones más prolongadas y mejoría en la calidad de vida de los pacientes. Este consenso tiene la finalidad de integrar a un grupo de especialistas mexicanos y promover la actualización de esta patología.

Acute Myeloid Leukemia in Mexico: The Specific Challenges of a Developing Country. Results From a Multicenter National Registry.

BACKGROUND: In the past decades, long-term survival outcomes for younger patients with acute myeloid leukemia (AML) have improved. Nonetheless, developing nations might be lagging behind, highlighting the need to assess real-world outcomes in such regions. METHODS: We performed a multicenter retrospective study, which included patients with AML diagnosed between January 2013 and December 2017 from 13 centers in Mexico. RESULTS: A total of 525 patients with AML met the inclusion criteria and were included in the study. Median age for the entire cohort was 47 years. The patients were classified according to cytogenetic risk: favorable 16.0%, intermediate 55.6%, and unfavorable 28.4%. Most patients received intensive chemotherapy (80.2%), and among these 74.1% underwent a 7 + 3 induction regimen. A complete remission was achieved in 71.3% of patients. Induction-related mortality occurred in 17.8% and we identify the following as independent risk factors: >60 years (odds ratio [OR] 2.09 [1.09-4.02]), Eastern Cooperative Oncology Group >2 (OR 4.82 [2.46-9.43]), prior solid tumor (OR 3.8 [1.24-11.59]) and active infection (OR 1.82 [1.06-3.12]). Further, allogeneic hematopoietic stem-cell transplantation (AlloHSCT) was performed in 8.2% in CR1. The 3-year overall survival (OS) was 34.8%. In a multivariate analysis, several factors were independently associated with a worse OS, including secondary AML (hazard ratio [HR] 2.14 [1.15-4.01]) and unfavorable cytogenetic risk (HR 1.81 [1.16-2.82]), whereas maintenance therapy (HR 0.53 [0.32-0.86]) and AlloHSCT (HR 0.40 [0.17-0.94]) were associated with better OS. CONCLUSIONS: This is the first multicenter report analyzing AML survival in Mexico. Challenges in this setting include a high induction-related mortality and low AlloHSCT rate, which should be addressed to improve outcomes.

Consenso de leucemia mieloide aguda en México / Mexican consensus in acute myeloid leukemia in Mexico

resumen está disponible en el texto completo

Abstract Acute myeloid leukemia (AML) comprises a heterogeneous group of hematopoietic cell neoplasms of myeloid lineage that arise from the clonal expansion of their precursors in the bone marrow, interfering with cell differentiation, leading to a syndrome of bone marrow failure. AML is a consequence of genetic and epigenetic changes (point mutations, gene rearrangements, deletions, amplifications, and arrangements in epigenetic changes that influence gene expression) in hematopoietic precursor cells, which create a clone of abnormal cells that are capable of proliferating but cannot differentiate into mature hematopoietic cells or undergo programmed cell death. The diagnosis requires more than 20% myeloid blasts in the bone marrow and certain cytogenic abnormalities. Treatment will depend on age, comorbidities, and cytogenetic risk among the most frequent.

Atención integral y manejo del paciente con hemofilia en el contexto de la pandemia de COVID-19 / Comprehensive care and patient management with hemophilia, in the context of COVID-19 pandemic

Resumen El espectro clínico de la hemofilia severa ha evolucionado a lo largo de la historia desde una condición catastrófica y altamente fatal a principios del siglo xx, hasta un trastorno crónico y «manejable¼ en las últimas décadas, gracias a los notables avances en el tratamiento alcanzados en los últimos 40 años, avances impulsados y reforzados por algunas experiencias catastróficas pasadas, como lo fue el desastre biológico en la década de 1980 debido a infecciones virales fatales transmitidas por trasfusión, como hepatitis y virus de la inmunodeficiencia humana/sida, a partir de lo cual la aparición de nuevos agentes infecciosos son una preocupación constante para la comunidad de hemofilia, como lo es actualmente el caso al que nos enfrentamos con la pandemia de enfermedad por coronavirus 2019, que ha creado una situación extremadamente desafiante para los miembros de la comunidad mundial de trastornos hemorrágicos. Ante esta pandemia han surgido interrogantes sobre la posibilidad de si los pacientes con hemofilia tendrán mayor riesgo de infección y si la deficiencia de factor y su tratamiento podrían influir en las manifestaciones de la infección, su curso natural, tratamiento y complicaciones; aunado a la preocupación de que parece claro que la pandemia actual tendrá consecuencias definitivas sobre el manejo de la hemofilia en todo el mundo. Tales interrogantes han dado lugar a la revisión de la literatura, guías, consensos de expertos, incluyendo las recomendaciones de la Federación Mundial de Hemofilia, en un intento de responder a dichas interrogantes, generando así tanto pautas para la atención como ampliando algunas de ellas, impulsando el desarrollo de nuevos protocolos de investigación.

Abstract The clinical spectrum of severe hemophilia has evolved throughout history from a catastrophic and highly fatal condition in the early 20th century to a chronic and “manageable” disorder in recent decades, thanks to the remarkable advances in treatment achieved. in the last 40 years, advances driven and reinforced by some past catastrophic experiences, such as the biological disaster in the 1980s due to fatal viral infections transmitted by transfusion, such as hepatitis and HIV/AIDS, from which, the appearance of new infectious agents are an ongoing concern for the hemophilia community, as is currently the case facing us with the coronavirus disease 2019 pandemic, which has created an extremely challenging situation for members of the global bleeding disorders community. Faced with this pandemic, questions have arisen regarding the possibility of whether patients with hemophilia will have a higher risk of infection and whether factor deficiency and its treatment could influence the manifestations of the infection, its natural course, treatment and complications; coupled with the concern that it seems clear that the current pandemic will have definitive consequences on the management of hemophilia around the world. Such questions have led to a review of the literature, guidelines, and expert consensus, including the recommendations of the World Federation of Hemophilia, in an attempt to answer these questions, thus generating both guidelines for care, and expanding some of them, promoting the development of new research protocols.

Consenso de hemofilia en México / Mexican Consensus in Haemophilia

resumen está disponible en el texto completo

Abstract Hemophilia is a hemorrhagic disorder with a sex-linked inherited pattern, characterized by an inability to amplify coagulation due to a deficiency in coagulation factor VIII (hemophilia A or classic) or factor IX (hemophilia B). Sequencing of the genes involved in hemophilia has provided a description and record of the main mutations, as well as a correlation with the various degrees of severity. Hemorrhagic manifestations are related to levels of circulating factor, mainly affecting the musculoskeletal system and specifically the large joints (knees, ankles and elbows). This document is a review and consensus of the main genetic aspects of hemophilia, from the inheritance pattern to the concept of women carriers, physiopathology and classification of the disorder, the basic and confirmation studies when hemophilia is suspected, the various treatment regimens based on infusion of the deficient coagulation factor as well as innovative factor-free therapies and recommendations for the management of complications associated with treatment (development of inhibitors and/or transfusion transmitted infections) or secondary to articular hemorrhagic events (hemophilic arthropathy). Finally, relevant reviews of clinical and treatment aspects of hemorrhagic pathology charachterized by acquired deficiency of FVIII secondary to neutralized antibodies named acquired hemophilia.