Estimating the impact of improved management of haemophilia a on clinical outcomes and healthcare utilisation and costs.

OBJECTIVE: Haemophilia A (HA) is associated with high clinical and healthcare burden. We developed an Excel-based model comparing current practice to improved management in severe HA patients currently managed on demand (OD). Outcomes included short- and long-term bleed events. Expected annual bleeds were estimated based on locally-derived OD annualised bleed rate (ABR), adjusted by relative prophylaxis-related ABRs (published literature). The objective of our study was to explore the impact of improving HA prophylaxis in target countries with limited published data (Algeria, Argentina, Chile, India, Malaysia, Mexico, Taiwan and Thailand). Bleed-related healthcare resource use (HCRU) and costs were estimated as a function of bleed type, with inputs obtained from local expert estimates. Clotting factor concentrates (CFC) consumption related to treatment and prophylaxis was estimated based on locally relevant dosing. CFC costs were not included. RESULTS: When 20% of OD patients were switched to prophylaxis, projected reduction in bleeds was estimated between 3% (Taiwan) through 14% (Algeria and India); projected reductions in hospitalisations ranged from 3% (Taiwan) through 15% (India). Projected HCRU-related annual cost savings were estimated at USD 0.45 m (Algeria), 0.77 m (Argentina), 0.28 m (Chile), 0.13 m (India), 0.29 m (Malaysia), 2.79 m (Mexico), 0.15 m (Taiwan) and 0.78 m (Thailand). Net change in annual CFC consumption ranged from a 0.05% reduction (Thailand) to an overall 5.4% increase (Algeria). Our model provides a flexible framework to estimate the clinical and cost offsets of improved prophylaxis. Modest increase in CFC consumption may be an acceptable offset for improvements in health and healthcare capacity in resource constrained economies.

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.

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.

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.

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.

Building a hematopoietic cell transplantation outcomes registry in Mexico.

The aim of this study was to assess the feasibility of hematopoietic cell transplantation (HCT) data collection using an electronic platform at Mexican centers. Four public centers performing HCT in adults were included. A cloud-based electronic platform in Spanish was developed to allow real-time registration of demographic, clinical, and outcomes variables. Data were obtained from paper and electronic medical records and institutional databases. Data managers were hired to perform the collection. Data from January 2015 to December 2018 were retro and prospectively collected during a 10-month period. From 2015 to 2018, 473 HCT were performed. Most were autologous (55%). Patients undergoing autologous HCT had the highest median age (49 years) compared with patients undergoing allogeneic (34 years) or haploidentical HCT (29 years). The most common underlying disease for autologous HCT was multiple myeloma. Acute leukemias were the most common diagnoses among allogeneic and haploidentical HCT recipients. Two-year nonrelapse mortality was 2.5%, 18%, and 18% for autologous, allogeneic, and haploidentical HCT, respectively. We determined it was feasible to start a multicenter collaborative study in Mexico as it was very well received by the physicians and it can lead to the creation of a Mexican HCT Registry in the near future.

Hematopoietic stem cell transplantation in Puebla, México. Traveled roadand goals achieved

Introduction: In México there are only 4 cities that have significantly active hematopoietic stem cell transplantation programs; onlyin 3 of those cities, the most important national public health institution IMSS (Mexican Social Security Institute) count with them. The cities where these programs are found are Mexico City, Monterrey and Puebla. Since the beginning of this decade, and before, the productivity of these transplant programs in this public health institution is low, performing on average 148 transplants every year. Results: In the span comprised between April 1995 and October 2016, we have performed 474 hematopoietic transplants in our hospital; 229 of them were allogeneic and 245 autologous, in adult and children population. This accumulated experience has allowed the implementation of all the variety of hematopoietic stem cell transplantation available in our country, this has opened up the opportunity, for the first time in our institution, the possibility to provide a donor for every patient who requires an hematopoietic transplant, overcoming the phase in which patients could not be submitted to the procedure for lack of a compatible donor. Conclusions: The goals achieved in our hospital confirm the feasibility in developing uninterrupted long term transplant programs in hospitals not specially equipped with technology nor abundant funds of the public health system in the national province, and it shows that this programs can be created and developed in hospitals with similar conditions to ours in México, Latin America and middle-low income countries(AU)

Introducción: en méxico solo cuatro ciudades cuentan con programas de trasplante hematopoyético significativamente activos y en solo tres los tiene el IMSS, la principal institución de salud del país: Monterrey, Puebla y la ciudad de México .La productividad de estos centros del sector público es muy baja, realizando en conjunto 148 trasplantes en promedio por año desde el principio de la década actual. Resultados: en el lapso comprendido entre abril de 1995 y octubre de 2016, se efectuaron 474 trasplantes hematopoyéticos en nuestro hospital; 229 de ellos fueron alogénicos y 245 fueron autólogos, en población adulta e infantil. Esta experiencia acumulada ha permitido la implementación de todas las variedades disponibles en el país de estos procedimientos, lo que ha generado, por vez primera en la institución, poder contar con un donante para todo paciente que requiera un trasplante hematopoyético; superándose la etapa en la que los enfermos no se sometían al procedimiento por falta de un donador compatible. Conclusiones: la actividad acumulada en nuestra unidad hospitalaria confirma la factibilidad de desarrollar programas ininterrumpidos, a largo plazo, de estos procedimientos terapéuticos en hospitales no especialmente dotados de tecnología ni presupuesto del sector público de la provincia nacional y denota que estos mismos programas pueden ser creados y desarrollados en nosocomios con condiciones similares al nuestro en diversos territorios de México, de Latinoamérica y de países con ingreso medio-bajo(AU)

[Hematopoietic cells raising with plerixafor in non-Hodgkin lymphoma]. / Movilización de células hematopoyéticas con plerixafor en linfoma no Hodgkin folicular.

BACKGROUND: bone marrow autologous transplantation (BMAT) has proven benefits in patients treated for non-Hodgkin's lymphoma (NHL). Plerixafor is an inhibitor of CXCR4 receptor. The aim was to report the raise of hematopoietic cells with plerixafor in patients with NHL. CLINICAL CASES: patient 1 with follicular NHL, GI, intermediate FLIPI, CD20+, CD45+, BCL-2+, who reached complete response after three chemotherapy regimes. Mobilization failed after use of filgrastim (G-CSF) alone and G-CSF + cyclophosphamide. A new attempt was made with G-CSF + plerixafor (G-CSF, 10 µg/kg for 7 days + plerixafor, 240 µg/kg in days 4 to 7). Patient 2 with follicular NHL and CD20+ reached complete remission with MINE after therapeutic failure with other regimes, but develops severe marrow toxicity. Mobilization was supported with G-CSF 10 µg/kg/d + plerixafor in days 4 and 5. In case one, proper cell counts where obtained after three aphaeresis. In the second case, two harvests add of 2.7 × 106/kg were obtained. CONCLUSIONS: plerixafor raised the hematopoietic stem cells in peripheral blood and improves mobilization of proper cell population.