A modified CALGB 10403 in adolescents and young adults with acute lymphoblastic leukemia in Central America.

Mexico and Central America have a high incidence of acute lymphoblastic leukemia (ALL) in adolescents and young adults. Historically, this patient group has been treated using adult-based regimens, which entails a high rate of treatment-related mortality and a poor overall survival (OS). The use of the CALGB 10403, a pediatric-inspired regimen, has been proven effective in this patient subgroup. Nonetheless, low- and middle-income countries (LMICs) may present limited access to standard care treatments implemented elsewhere, warranting the need for further research to improve outcomes among vulnerable populations. In this study, we present the outcomes in terms of safety and effectiveness of using a modified CALGB 10403 regimen to reflect drug and resource availability in LMICs. Modifications included the use of Escherichia coli asparaginase,6-mercaptopurine instead of thioguanine and the use of rituximab among patients with CD20+. A total of 95 patients with a median age of 23 (range, 14-49) years treated with this modified scheme were prospectively assessed at 5 centers in Mexico and 1 in Guatemala. Among these, 87.8% achieved a complete response after induction. During follow-up, 28.3% of patients relapsed. Two-year OS rate was 72.1%. Factors associated with worse OS included hyperleukocytosis (hazard ratio [HR], 4.28; 95% confidence interval [CI], 1.81-10.10) and postinduction minimal residual disease (HR, 4.67; 95% CI, 1.75-12.44). Most patients presented hepatotoxicity (51.6% and 53.7% during induction and consolidation, respectively), and the treatment-related mortality was 9.5%. Overall, results highlight that implementing a modified CALGB 10403 regimen in Central America is feasible, and it is associated with improvements in clinical outcomes and a manageable safety profile.

Leucemia promielocítica aguda durante el embarazo: reporte de 17 casos de un país en desarrollo / Acute promyelocytic leukemia during pregnancy: report of 17 cases from a developing country

Resumen OBJETIVO: Recopilar casos atendidos en centros oncológicos de México y reportar los tratamientos exitosos, con respuestas completas y las complicaciones del embarazo. MATERIALES Y MÉTODOS: Estudio retrospectivo de serie de casos que incluyó a pacientes con leucemia promielocítica aguda asociada con el embarazo atendidas en diferentes hospitales de la zona metropolitana de la Ciudad de México entre 1999 y 2021. RESULTADOS: Se identificaron 17 pacientes con leucemia promielocítica aguda asociada con el embarazo, con mediana de edad de 23 años (14-40 años); 7 correspondieron a madres menores de 20 años. En relación con su entorno social 9 tenían baja escolaridad, 12 se dedicaban al hogar y 13 tenían una pareja al momento de la concepción. Por último, 11 eran originarias de una zona urbana. Las pacientes atendidas entre 1999-2010 se trataron con interferón plus citarabina (7 de 17) o mediante soporte transfusional y esteroide (2 de 17), en 8 de los 17 casos el tratamiento se inició con tretinoína en combinación con quimioterapia (daunorrubicina) como tratamiento de inducción. CONCLUSIONES: El tratamiento de pacientes embarazadas y con leucemia promielocítica aguda representa un reto debido al riesgo trombótico y hemorrágico. Si bien la adición de tretinoína ha modificado el pronóstico de las pacientes con esta leucemia, su indicación a las embarazadas sigue siendo motivo de controversia, sobre todo por el riesgo de teratogenicidad.

Abstract OBJECTIVE: To collect cases attended in oncology centers in Mexico and to report successful treatments, with complete responses and complications around gestation. MATERIALS AND METHODS: Retrospective case series study including patients with pregnancy-associated acute promyelocytic leukemia attended in different hospitals in the metropolitan area of Mexico City between 1999 and 2021. RESULTS: Seventeen patients with pregnancy-associated acute promyelocytic leukemia were identified, with a median age of 23 years (14-40 years); 7 corresponded to mothers younger than 20 years. In relation to their social environment, 9 had low schooling, 12 were homebased and 13 had a partner at the time of conception. Finally, 11 were originally from an urban area. Patients seen between 1999-2010 were treated with interferon plus cytarabine (7 of 17) or by transfusion support and steroid (2 of 17), in 8 of the 17 cases treatment was initiated with tretinoin in combination with chemotherapy (daunorubicin) as induction therapy. CONCLUSIONS: Treatment of pregnant patients and patients with acute promyelocytic leukemia represents a challenge due to thrombotic and hemorrhagic risk. Although the addition of tretinoin has modified the prognosis of patients with this leukemia, its indication in pregnant women remains controversial, especially because of the risk of teratogenicity.

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

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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.

Treating Acute Leukemia During the COVID-19 Pandemic in an Environment With Limited Resources: A Multicenter Experience in Four Latin American Countries.

PURPOSE: The COVID-19 pandemic is a colossal challenge for global health; nonetheless, specific subgroups face considerably higher risks for infection and mortality. Among patients with malignant diseases, those with hematologic neoplasms are at a higher risk for poor outcomes. The objective of this study was to register treatment modifications associated with the COVID-19 pandemic and their short-term consequences in Latin America. METHODS: Multicenter, prospective, observational, cohort study including patients older than 14 years from 14 centers in four countries (Mexico, Peru, Guatemala, and Panama) who had a confirmed diagnosis of acute leukemia, and who were undergoing active treatment since the first COVID-19 case in each country until the cutoff on July 15, 2020. RESULTS: We recruited 635 patients. Treatment modifications because of the COVID-19 pandemic were reported in 40.8% of cases. The main reason for such modifications was logistic issues (55.0%) and the most frequent modification was chemotherapy delay (42.0%). A total of 13.1% patients developed COVID-19 disease, with a mortality of 37.7%. Several factors were identified as independently associated with mortality, including a diagnosis of acute myeloid leukemia (odds ratio 2.38 [95% CI, 1.47 to 3.84]; P < .001), while the use of telemedicine was identified as a protective factor (odds ratio 0.36 [95% CI, 0.18 to 0.82]; P = .014). CONCLUSION: These results highlight the collateral damage of COVID-19 in oncology patients.

Embarazo y COVID-19. Consideraciones en la práctica de la hematología / Pregnancy and COVID-19. Considerations in the practice of Hematology

Resumen La enfermedad por coronavirus 2019 (COVID-19) en una población vulnerable, como es el caso de la mujer embarazada, feto y recién nacido, obliga a establecer estrategias efectivas y seguras centradas en la seguridad del binomio madre-hijo. El objetivo del presente reporte es presentar los resultados de la revisión de las fuentes de información secundaria (metaanálisis y revisión sistemática) del estado del arte en el avance del conocimiento de la COVID-19 durante el embarazo. En diferentes reportes se ha insistido en que la mortalidad materna por COVID-19 es baja. Sin embargo, la razón de mortalidad materna (RMM) aumentó de 30.9 a 45.5 defunciones por cada 100,000 nacimientos, es decir, mostró un incremento del 36.32% respecto a la misma semana del 2019. Pero el tema no se limita a la COVID-19, el aumento en la RMM es del 24.% para hemorragia materna, del 20% para la enfermedad hipertensiva y del 28.5% para sepsis puerperal. Sin embargo, por su naturaleza de condición inédita y el comportamiento particular de la COVID-19 durante el periodo perinatal, la generación de nuevos datos, su integración a información accesible y su análisis clínico epidemiológico inevitablemente proporcionarán nuevas evidencias que deberán integrarse a la gestión y práctica clínica. No existe un comportamiento hematológico característico o de las complicaciones trombóticas o hemorrágicas de la paciente con COVID-19, son características clínicas similares a las que se presenta en sus pares sin embarazo. El aumento global en todas las causas de mortalidad materna no son exclusivas de la COVID-19, lo que expone las deficiencias del sistema de salud en términos de atención primaria de la salud, vigilancia prenatal y planificación familiar, entre otros programas más; adicional al impacto de la COVID-19. Es una necesidad imperiosa el rediseño de las políticas públicas en términos de atención primaria para la salud a toda la población, en particular para las mujeres embarazadas.

Abstract Coronavirus disease 2019 (COVID-19) in a vulnerable population, such as the pregnant woman, fetus, and newborn, requires an establishment of effective and safe strategies focused on the safety of the mother-child binomial. The objective of this report is to present the results of the review of secondary information sources (meta-analysis and systematic review), of the state of the art in the advancement of knowledge of the disease due to COVID-19 during pregnancy. Different reports have insisted that maternal mortality from COVID-19 is low. However, the maternal mortality ratio (MMR) increased from 30.9 to 45.5 deaths per 100,000 births, that is, it showed an increase of 36.32% compared to the same week of 2019. Due to its unprecedented condition and the particular behavior of the COVID-19 disease during the perinatal period, the generation of new data, its integration into accessible information and its epidemiological clinical analysis will inevitably provide new evidence that must be integrated into clinical management and practice. But the issue is not limited to COVID-19, the increase in MMR is 24% for maternal obstetric hemorrhage, 20% for hypertensive disease, and 28.5% for puerperal sepsis. There is no characteristic hematological behavior and the appearance of thrombotic or hemorrhagic complications in the patient with COVID-19, without clinical characteristics similar to those seen in her non-pregnant peers. The global increase in all causes of maternal mortality are not exclusive to COVID-19, which exposes the deficiencies of the health system in terms of primary health care, prenatal surveillance, family planning, among other programs; additional to the impact of COVID-19. The redesign of public policies in terms of primary health care for the entire population is an urgent need, particularly for pregnant women.