Impact of Hospital-based Multidisciplinary Anticoagulation Stewardship Programs.

Antithrombotic therapies, especially anticoagulants, are high-risk medications with increased potential for adverse events. The development and implementation of a well-functioning, designated, multidisciplinary anticoagulation stewardship program (MASP), tailored to each hospital-center's needs, has the primary objectives of improving patient-centered outcomes, minimizing undesirable anticoagulation-related adverse events and minimizing hospital length of stay (LOS) and other patient-related costs. Such stewardship programs are pivotal in supporting busy clinicians with consultation on challenging clinical case scenarios, ensuring appropriate use of valuable healthcare resources, achieving compliance with anticoagulant-associated accreditation standards, and positively impacting patient-specific morbidity/mortality outcomes. Herein, we review and discuss the critical need for antithrombosis stewardship and the benefit of formalized MASP in optimizing use of antithrombotic therapies.

Ruxolitinib as a treatment strategy for SARS-CoV-2 pneumonia: clinical experience in a real-world setting.

INTRODUCTION: Severe acute respiratory syndrome-related coronavirus (SARS-CoV-2) infection is characterised by a viral phase and a severe pro-inflammatory phase. The inhibition of the JAK/STAT pathway limits the pro-inflammatory state in moderate to severe COVID-19. METHODOLOGY: We analysed the data obtained by an observational cohort of patients with SARS-CoV-2 pneumonia treated with ruxolitinib in 22 hospitals of Mexico. The applied dose was determined based on physician's criteria. The benefit of ruxolitinib was evaluated using the 8-points ordinal scale developed by the NIH in the ACTT1 trial. Duration of hospital stay, changes in pro-inflammatory laboratory values, mortality, and toxicity were also measured. RESULTS: A total of 287 patients were reported at 22 sites in Mexico from March to June 2020; 80.8% received ruxolitinib 5 mg BID and 19.16% received ruxolitinib 10 mg BID plus standard of care. At beginning of treatment, 223 patients were on oxygen support and 59 on invasive ventilation. The percentage of patients on invasive ventilation was 53% in the 10 mg and 13% in the 5 mg cohort. A statistically significant improvement measured as a reduction by 2 points on the 8-point ordinal scale was described (baseline 5.39 ± 0.93, final 3.67± 2.98, p = 0.0001). There were 74 deaths. Serious adverse events were presented in 6.9% of the patients. CONCLUSIONS: Ruxolitinib appears to be safe in COVID-19 patients, with clinical benefits observed in terms of decrease in the 8-point ordinal scale and pro-inflammatory state. Further studies must be done to ensure efficacy against mortality.

Venetoclax-based combinations for acute myeloid leukemia: optimizing their use in Latin-America.

Objectives: Venetoclax combinations are a new standard for patients with acute myeloid leukemia (AML). We aimed to evaluate the safety and efficacy of these combinations in a period of accelerated approval in Latin-America.Methods: This observational study evaluated adults with acute myeloid leukemia who received venetoclax-based therapy in 11 public or private centers in Mexico and Peru for both newly diagnosed or relapsed and refractory AML.Results: Fifty patients were included; 28 with newly diagnosed (ND) AML and 22 with relapsed/refractory (RR) disease. ND patients were older (64 vs. 40 years; p < 0.001) with a lower functional capacity (ECOG ≥2 64.3% vs 9%; p < 0.001). Venetoclax was frequently combined with azacytidine (60%) and prophylactic azoles (82%) with a median maximum dose of 200 mg (range, 100-600 mg). Hematologic toxicities were common. Complete response rates including patients with incomplete hematopoietic recovery were 78.6% in ND and 45.5% in RR patients, with a median overall survival of 9.6 (95% CI 3.7-15.5) and 8 months (95% CI 4.8-11.2).Discussion: Our study showed a preferred use of venetoclax plus azacytidine over cyatrabine. Patients in the first-line setting were similar to those in the landmark studies, while most patients with relapsed disease had received prior intensive therapies. Responses were favorable, with a median survival in agreement to other reports, albeit shorter than that observed in the randomized phase-3 trials.Conclusion: Venetoclax-based therapy in AML was effective despite dose reductions and prophylactic antifungals in two middle-income countries outside of a clinical trial setting.

Gemtuzumab-ozogamicin and blinatumomab as treatment for refractory mixed-phenotype blast crisis in chronic myeloid leukaemia.

In the tyrosine kinase inhibitor era, the blast phase of chronic myeloid leukaemia (BP-CML) renders an uncommon presentation and has a poor prognosis with an estimated overall survival below 20%. Mixed-phenotype blast phase is even more infrequent, presenting in 3.3% of these patients. Blast phase manifests along haematological sarcomas, with extramedullary activity in lymph nodes, skin and bone. We report the case of a patient with an ovarian sarcoma as an extramedullary presentation of mixed-phenotype BP-CML refractory to conventional treatment which responded to immunotherapy against CD33 and CD19.

Nuevas opciones de tratamiento para el paciente con COVID-19. La experiencia hematológica / New therapeutic options for the COVID-19 patient. The experience from the hematologist

Resumen En la actual pandemia de enfermedad por coronavirus 2019 (COVID-19) se ha observado que las principales complicaciones se presentan como resultado de la liberación de múltiples citocinas como interleucina (IL) 1, IL-6, factor de necrosis tumoral alfa e interferones de tipo 1 que generan un estado proinflamatorio caracterizado por lesión tisular pulmonar y subsecuentemente falla orgánica múltiple. En el campo de la hematología se cuenta con experiencia en el uso de diversos fármacos diseñados para limitar estas citocinas los cuales se han utilizado ya en pacientes con COVID-19 entre los que se encuentran los inhibidores de la IL-6 como el tocilizumab, el sarilumab y el siltuximab, el inhibidor de IL-1 anakinra y los inhibidores de la janus cinasa ruxolitinib y baricitinib. Al conocer la base fisiopatológica de la COVID-19, la utilidad de este tipo de fármacos muestra resultados alentadores para los cuadros moderados a graves de la enfermedad y extender su uso en ensayos clínicos mayores.

Abstract In the current SARS-CoV-2 pandemic, it has been observed that the main complications arise as a result of the release of multiple cytokines such as IL-1, IL-6, TNF-α and type 1 interferons that generate a proinflammatory state characterized by lung tissue injury and subsequently multiple organ failure. In the hematology field, there is experience in the use of various drugs designed to limit these cytokines which have already been used in patients with COVID-19 including IL-6 inhibitors such as tocilizumab, sarilumab, and siltuximab; the IL-1 inhibitor anakinra; and the janus kinase inhibitors ruxolitinib and baricitinib. Knowing the pathophysiological basis of COVID-19, the usefulness of this type of drugs show encouraging results for moderate to severe symptoms of the disease and encourages its use in larger clinical trials.

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.