Outcomes and survival predictors of Latin American older adults with acute myeloid leukemia: Data from a single center

ABSTRACT Introduction: Acute myeloid leukemia (AML) is most commonly presented in older adults; however, it appears 10 years earlier in Latin American countries. Clinical evolution in older adults from this populations has not been characterized. We analyzed outcomes and survival predictors. Methods: Patients ≥ 55 years old diagnosed with AML at a hematology referral center from 2005 to 2020 receiving intensive chemotherapy (IC), low-dose cytarabine (LDAC) and best supportive care (BSC) were included. Survival analysis included the Kaplan-Meier and Cox models and the cumulative incidence of relapse (CIR). Results: Seventy-five adults were included and the overall survival (OS) was 4.87, 1.67 and 1.16 months, using IC, LDAC and BSC, respectively. The IC led to a higher OS (p < 0.001) and was a protective factor for early death, at a cost of more days spent hospitalized and more non-fatal treatment complications; non-significant differences were found between the LDAC and BSC. Eight (10.7%) patients underwent hematopoietic cell transplantation, with a higher OS (p = 0.013). Twenty (26.7%) patients achieved complete remission; 12 (60%) relapsed with a 6-month CIR of 57.9% in those < 70 years old vs. 86.5% in those ≥ 70 years old, p = 0.034. Multivariate analysis showed the white blood cell count (WBC) and IC had a significant impact on the patient survival, whereas chronological age and the Charlson comorbidity index (CCI) did not. Conclusion: AML in low-middle income countries demands a different approach; the IC improves survival, even with a high incidence of relapse, and should be offered as first-line treatment. Eligibility criteria should include WBC and a multidimensional evaluation. The age per se and the CCI should not be exclusion criteria to consider IC.

Microorganismos aislados de hemocultivos en niños con leucemia y linforma: Seis años de seguimiento / Microorganisms isolated from blood cultures in children with leukemia and lymphoma: six years of follow-up

Las Leucemias y linfomas constituyen las enfermedades oncológicas más frecuentes en pediatría y las bacteriemias representan infecciones graves en estos pacientes. Objetivos: describir los microorganismos aislados de sangre en pacientes con leucemia aguda o linfoma pediátrico; comparar la incidencia de aislamientos según enfermedad de base; detallar las variaciones en la incidencia de dichos aislamientos y la evolución de su resistencia antimicrobiana. Estudio retrospectivo, observacional. Se incluyeron 823 episodios de bacteriemia en 467 pacientes pediátricos, entre julio-2016 y junio-2022, dividido en tres períodos (período-1: años 2016- 2018, período-2: años 2018-2020, período-3: años 2020-2022). Se aislaron 880 microorganismos: 55,3% gram negativos (GN), 40% gram positivos (GP) y 4,7% levaduras. En GN predominaron: enterobacterias (72%) y en GP: estreptococos del grupo viridans (SGV) (34,1%). Se encontró asociación entre LLA-enterobacterias (p=0,009) y LMA-SGV (p<0,001). Hubo aumento de GN entre los períodos 1 y 3 (p=0,02) y 2 y 3 (p=0,002) y disminución de GP entre 2 y 3 (p=0,01). Se registraron los siguientes mecanismos de resistencia: BLEE (16,4%), carbapenemasas: KPC (2,5%); MBL (2,7%) y OXA (0,2%); meticilinorresistencia en Staphylococcus aureus (20%) y estafilococos coagulasa negativos (95%), vancomicina resistencia en Enterococcus spp. (39%), SGV no sensibles a penicilina (44%) y a cefotaxima (13%). Hubo aumento de MBL entre los períodos 1 y 2 (p=0,02) y una tendencia en disminución de sensibilidad a penicilina en SGV entre el 1 y 3 (p=0,058). El conocimiento dinámico y análisis de estos datos es esencial para generar estadísticas a nivel local, fundamentales para el diseño de guías de tratamientos empíricos (AU)

Leukemias and lymphomas are the most common cancers in children and bacteremia is a severe infection in these patients. Objectives: to describe the microorganisms isolated from blood in pediatric patients with acute leukemia or lymphoma; to compare the incidence of isolates according to the underlying disease; and to detail the variations in the incidence of these isolates and the evolution of their antimicrobial resistance. Retrospective, observational study. We included 823 episodes of bacteremia in 467 pediatric patients seen between July-2016 and June-2022, divided into three periods (period-1: 2016- 2018, period-2: 2018-2020, period-3: 2020-2022). A total of 880 microorganisms were isolated: 55.3% were gram-negative (GN), 40% gram-positive (GP) and 4.7% yeasts. In GN there was a predominance of: enterobacteria (72%) and in GP viridans group streptococci (VGS) (34.1%). An association was found between ALL-enterobacteria (p=0.009) and AML-VGS (p<0.001). There was an increase in GN between periods 1 and 3 (p=0.02) and 2 and 3 (p=0.002) and a decrease in GP between 2 and 3 (p=0.01). The following resistance mechanisms were recorded: BLEE (16.4%), carbapenemases: KPC (2.5%), MBL (2.7%), and OXA (0.2%); methicillin resistance in Staphylococcus aureus (20%) and coagulase negative staphylococci (95%), vancomycin resistance in Enterococcus spp. (39%), VGS resistant to penicillin (44%) and to cefotaxime (13%). There was an increase in MBL between periods 1 and 2 (p=0.02) and a decreasing trend in penicillin sensitivity in VGS between periods 1 and 3 (p=0.058). Dynamic knowledge and analysis of these data is essential to generate statistics at the local level, which is fundamental for the design of empirical treatment guidelines (AU)

Enfermedad mínima residual en leucemia mieloide aguda no promielocítica: Resultados preliminares de un estudio colaborativo internacional / Minimal residual disease in non-myelocytic acute myeloid leukemia: preliminary results of an international collaborative study

A pesar de los avances en los protocolos de tratamiento y en las medidas de soporte en pacientes con Leucemia Mieloide Aguda (LMA), 27% presentan recaídas de la enfermedad. Esto se debe, entre otras causas, a la persistencia de pequeñas cantidades de células malignas (blastos) resistentes a la terapia. Estas pequeñas cantidades de blastos remanentes se denominan Enfermedad Mínima Residual (EMR). La determinación de EMR requiere de técnicas no solo muy sensibles, sino también específicas, y permite evaluar la respuesta individual a la terapia. La introducción de la EMR como parámetro de respuesta y estratificación está bien definida en Leucemia Linfoblástica Aguda (LLA). Por el contrario, aunque existen publicaciones sobre el impacto pronóstico de la EMR en LMA, aún no se encuentra incluida en forma sistemática en los protocolos nacionales actuales, entre otros motivos, por lo laborioso de la determinación y por la necesidad de validación de la misma. Debe tenerse en cuenta que el inmunofenotipo de los blastos mieloides suele ser más heterogéneo que el de los blastos en LLA, presentando, en muchos casos, subpoblaciones diferentes entre sí, lo cual dificulta su detección certera y no hay consenso definido en cuanto a la metodología más eficaz. En este trabajo describimos una nueva estrategia de marcación y análisis estandarizada en un estudio multicéntrico internacional para LMA y la utilidad de la EMR como parámetro de respuesta y de estratificación. Asimismo, detallamos los resultados preliminares de nuestra cohorte de pacientes (AU)

Despite the improvement in treatment and supportive care of patients with Acute Myeloid Leukemia (AML), 27% of them relapse. This is due to the persistence of small amounts of malignant cells (blasts) resistant to therapy, among other causes. These small amounts of blasts are called Minimal Residual Disease (MRD). The determination of MRD requires not only techniques with high sensitivity but also with high specificity, and allows to evaluate the individual response to treatment. The introduction of MRD as a response parameter is well established in Acute Lymphoblastic Leukemia (ALL), and it is used in current stratification protocols. On the other hand, even though there are some reports regarding the prognostic impact of MRD in AML, it is still not included in the current national protocols due to the lack of validation of the determination, among other causes. This is due to the fact that the immunophenotype of myeloid blasts is more heterogeneous than in ALL, presenting different subpopulations, which difficults their accurate detection. Thus, there is still no consensus regarding the most effective approach. In this article, we describe a new staining and analysis strategy standardized by an international multicentric study, and the utility of EMR as a response and stratification parameter. Additionally, we show the preliminary results of our patient cohort. (AU)

Prognostic value of serum progranulin in de novo adult acute myeloid leukemia patients

Abstract Background Elevated serum progranulin (PGRN) levels have been associated with a wide range of different human malignancies. However, data available on the role of PGRN in hematological malignancies are limited. Methods Measurement of the PGRN level in serum of adult de novo acute myeloid leukemia (AML) patients using enzyme-linked immunosorbent assay (ELISA) was performed. Results The mean serum PGRN level in AML patients was higher than that in controls (346.08 pg/ml ± 64.46 vs 155 pg/ml ± 63 respectively; p= 0.001). After a mean duration of follow-up equaling 140 days, patients with high serum PGRN (i.e., higher than 370.5 pg/ml) had inferior overall survival (OS) in comparison to patients with low serum PGRN (i.e., lower than 370.5 pg/ml) (OS = 25% vs 60.7%, mean survival = 107 days vs 256.5 days, p= 0.007). On the other hand, remitted patients on day 28 with high serum PGRN (i.e., higher than 307.5 pg/ml) did not differ from those with low serum PGRN (i.e., lower than 307.5 pg/ml) regarding disease-free survival (DFS) (DFS = 78.6% vs. 87.5%, mean survival = 301.3 days vs. 283.5 days, p= 0.789). Moreover, the serum PGRN level was associated with inferior OS (p= 0.024) on multivariate analysis. Conclusion Adult de novo AML patients have elevated serum PGRN levels and a high PGRN level is associated with an inferior OS.

Incidence and clinical significance of FLT3 and nucleophosmin mutation in childhood acute myeloid leukemia in Chile

Abstract Introduction Acute myeloid leukemia (AML) is a heterogeneous disease and approximately one-third of its carriers do not have evident genetic abnormalities. The mutation of specific molecular markers, such as fms-like tyrosine kinase 3 (FTL3) internal tandem duplication (ITD), FLT3 tyrosine kinase domain (TKD) and nucleophosmin (NPM1), are associated with an adverse and favorable prognosis, respectively. Objective The objective was to determine the prevalence of FLT3/ITD and NPM1 in Chilean patients and their association with clinical data and prognosis. Method and Results Two hundred and thirty-two children were studied between 2011 and 2017, the median being 8.6 years (ranging from 1 to 18 months). Acute promyelocytic leukemia (APL) was diagnosed in 29%. The FLT3/ITD-mutated in non-promyelocytic AML was at 10% (14/133) and the FLT3/TKD, at 3.7% (2/54). In APL, it was at 25.4% (16/63). In non-promyelocytic AML, the FLT3/ITD-mutated was associated with a high leucocyte count, the median being 28.5 x mm3 (n= 14) versus 19.4 x mm3 (n= 119), (p= 0.25), in non-mutated cases. In APL, the median was 33.6 x mm3 (n= 15) versus 2.8 x mm3 (n= 47), (p < 0.001). The five-year overall survival (OS) in non-promyelocytic AML with non-mutated and mutated FLT3/ITD were 62.7% and 21.4%, respectively, (p < 0.001); the 5-year event-free survival (EFS) were 79.5% and 50%, respectively, (p < 0.01). The five-year OS in APL with non-mutated and mutated FLT3/ITD was 84.7% and 62.5%, respectively, (p= 0.05); the 5-year EFS was 84.7% and 68.8%, respectively, (p= 0.122). The NPM1 mutation was observed in 3.2% (5/155), all non-promyelocytic AML with the normal karyotype. Conclusion The FLT3/ITD mutation was observed more frequently in APL and associated with a higher white cell count at diagnosis. However, the most important finding was that the FLT3/ITD mutation was associated with a shorter survival in non-promyelocytic AML.

Oral Mucositis in Children with Leukemia Undergoing Chemotherapy: A Case Series

ABSTRACT Objective: To report nine cases of pediatric patients with Acute Lymphoid Leukemia (ALL) or Acute Myeloid Leukemia who developed severe oral mucositis (SOM) at the first week of chemotherapy. Material and Methods: The cases were selected from a sample of 105 children followed for 10 consecutive weeks. Hematological and personal data were obtained from the patient's medical records. The oral cavity was examined weekly using the modified Oral Assessment Guide. Results: More of the patients were male (55.6%), had black/brown skin (55.6%), with ALL (66.7%), and the mean age was 5.55. Two patients had values below normal for leukocytes, platelets, and creatinine over the follow-up. However, all patients showed changes in the normality of hematological data in most weeks. The most used chemotherapeutic agents were aracytin, etoposide, and methotrexate, known for their high stomatotoxic potential. Patients had 2 to 6 (mean of 4) episodes of SOM and 4 to 7 (mean of 5.5) episodes of OM. One patient at week 7, one patient at week 5, and one patient at weeks 2 and 10 did not have OM. Saliva (84 times) and lips (44 times) were the most affected items. Conclusion: The patients showed oscillations in the severity of oral mucositis and hematological parameters over the follow-up. All patients were exposed to stomatotoxic drugs during the initial phase of cancer treatment.

Screening for myeloid mutations in patients with myelodysplastic syndromes and AML with myelodysplasia-related changes

ABSTRACT Introduction: One of the most critical complications in myelodysplastic syndromes (MDS) is the progression to acute myeloid leukemia (AML). The dynamics of clonal evolution in MDS and how acquired mutations can be used as biomarkers to track disease progression remains under investigation. Objective and method: Herein, we investigated the frequency of common myeloid clonal mutations (FLT3, NPM1, JAK2, IDH1 and IDH2) in 88 patients with MDS and 35 AML patients with myelodysplasia-related changes, followed at a single reference center in northeastern Brazil. Results: Overall, 9/88 (10%) ofthe MDSpatients and 9/35 (26%) of the secondary AML patients had at least one mutation. While the JAK2 V617F mutation was the most frequent in the MDS patients, the FLT3, NPM1, IDH1 and IDH2 mutations were more frequently found in the secondary AML group. Furthermore, there was a higher frequency of FLT3, NPM1, IDH1 and IDH2 mutations in MDS patients classified as high-risk subtypes than in those of lower risk. Conclusion: Despite the limited sample size, our data suggest that mutations in FLT3, NPM1, IDH1 and IDH2 genes could be potential biomarkers to detect early disease progression in MDS.

Improving awareness of several combination therapies for acute myeloid leukemia among oncology and hematology team members in Colorado, USA

ABSTRACT Introduction: Although several combination therapies for acute myeloid leukemia (AML) have emerged recently, there has been a lack of published surveys and educational projects focused on these important treatment options. We aimed to improve the oncology team members' knowledge and awareness of several FDA approved combination therapies for AML, including glasdegib (DAURISMO®), venetoclax (VENCLEXTA®), GO (MYOLOTARG®),CPX-351 (VYXEOS®), and midostaurin (RYDAPT®). Additionally, we aimed to examine these teams' perspectives, views, and attitudes towards these topics and finally identify barriers to the implementationof such therapies in clinical practice. Method: Initially, we developed booklets and then distributed them to each participating oncology and hematology office. Subsequently, all participating oncology and hematology team members were asked to complete an anonymous online survey to test their knowledge of and attitudes toward the subjects. Main results: There was a total of 52 survey respondents. The correct answer regarding various combination therapies for AML was identified by nearly 70% or more of survey takers. The level of awareness of project subjects significantly improved after reading our printing materials. Many survey respondents were motivated to learn more about combination therapies for AML as well as discuss these topics with others. Conclusions: Our booklets effectively improved understanding and awareness of combination therapies for AML. Future studies should explore awareness, knowledge, and perception of other new and emerging combination therapies for AML amongoncology and hematology team members in other areas.

Supervivencia de pacientes con leucemia aguda post trasplante de células hematopoyéticas: 8 años de experiencia de un centro único en México / Survival of patients with acute leukemia after hematopoietic cell transplantation: A 8-years single center study in Mexico

Introducción: El trasplante de células progenitoras hematopoyéticas (TCPH) es el trata-miento para la leucemia aguda en niños, el tipo de cáncer más común en edad pediátrica. El objetivo del presente estudio fue determinar la supervivencia global y libre de enferme-dad en un grupo de pacientes sometidos a TCPH y explorar los factores de riesgo pacientes pediátricos con leucemia aguda. Metodología: El presente estudio observacional incluye a pacientes pediátricos diagnosticados de leucemia mieloide aguda (LMA) o linfoide (LLA), sometidos a TCPH, de 2011 a 2018 presentados en el Hospital Infantil Federico Gómez. Se construyen curvas de Kaplan Meier para la supervivencia global, por subgrupos según tipo de leucemia y estado libre de enfermedad así como un estudio multivariable para medir factores de riesgo. Resultados: Se incluyeron 53 pacientes en el análisis. 5 pacientes (11%) tuvieron falla primaria del injerto. La supervivencia global fue del 28% a los 24 meses. Fallecieron 30 pacientes (67%). La mediana de supervivencia global fue de 11 meses. Para LMA fue de 8.9 meses y para LLA de 12.4 meses. Uno de los factores de riesgo constituyó la edad >10 años al momento del trasplante OR 5.2 (1.07-25.12), P=0.04 y el número de recaídas previas al trasplante OR 4.3 (1.2-15.07) P=0.025. Conclusión: Los pacientes que sobrevivieron un año libre de la enfermedad tenían un mejor pronóstico en general. En estudios relacionados a TCPH no se ha reportado que exista un rango de edad de los receptores de trasplante que esté relacionado a mayor mortalidad, por lo cual es un dato significativo como un factor de riesgo independiente.

Introduction: Hematopoietic stem cell transplantation (HSCT) is the treatment for acute leukemia in children, the most common type of cancer in children. The objective of the present study was to de-termine the overall and disease-free survival in a group of patients undergoing HSCT and to explore the risk factors for pediatric patients with acute leukemia. Methodology: This observational study includes all pediatric patients diagnosed with acute myeloid leukemia (AML) or lymphoid leukemia (ALL), undergoing HSCT from March 2011 to March 2018, presented at the Federico Gómez Children's Hospital. Kaplan Meier curves are constructed for overall survival by subgroups according to the type of leukemia and disease-free status, as well as a multivaria-ble study to measure risk factors. Results: 53 patients were included in the análisis. 5 patients (11%) had primary graft failure. Overall survival was 28% at 24 months. Thirty patients (67%) died. The median overall survival was 11 months. For AML, it was 8.9 months, and for ALL, it was 12.4 months. One of the risk factors was age >10 years at the time of transplant OR 5.2 (1.07-25.12) P=0.04 and the number of relapses prior to transplant OR 4.3 (1.2-15.07) P=0.025. Conclusión: Patients who survived one year free of the disease had a better prognosis. In studies relat-ed to HSCT, it has not been reported that there is an age range of transplant recipients that is related to higher mortality, which is why it is a significant and independent risk factor.

Aspectos citogenéticos y moleculares en los síndromes mielodisplásicos / Cytogenetic and molecular aspects in myelodysplastic syndromes

Introducción: Los síndromes mielodisplásicos constituyen un grupo heterogéneo de alteraciones de la célula progenitora hematopoyética. Estos se caracterizan por presentar una médula ósea hipercelular, una hematopoyesis inefectiva, displasia y citopenia periférica y la posibilidad de evolución a leucemia mieloide aguda. Objetivo: Describir las alteraciones citogenéticas y moleculares más frecuentes de los síndromes mielodisplásicos. Métodos: Se realizó una revisión de la literatura en los idiomas inglés y español, a través del sitio web PubMed y el motor de búsqueda Google académico, de artículos publicados en los últimos cinco años. Se realizó análisis y resumen de la bibliografía. Análisis y síntesis de la información: En los síndromes mielodisplásicos están presentes alteraciones citogenéticas frecuentes como la deleción de los cromosomas 5q, 7q y 20q, la monosomía del cromosoma 7, la trisomía del cromosoma 8 y la presencia de cariotipos complejos, que, unido a mutaciones somáticas en diferentes genes, intervienen en la patogénesis de la enfermedad y su conocimiento permite la estratificación pronóstica de los pacientes. Conclusiones: El diagnóstico a través de los estudios citogenéticos convencionales, la hibridación in situ por fluorescencia y la secuenciación génica permite una mayor comprensión de la biología de la enfermedad, la estratificación del riesgo y la toma de decisiones terapéuticas(AU)

Introduction: Myelodysplastic syndromes constitute a heterogeneous group of alterations of the hematopoietic progenitor cell, characterized by hypercellular bone marrow, ineffective hematopoietic, dysplasia and peripheral cytopenia; and the possibility of progressing to acute myeloid leukemia. Objective: To describe the most frequent cytogenetic and molecular alterations of myelodysplastic syndromes. Methods: A review of the literature in English and in Spanish was carried out, in the PubMed website and using the search engine Google, for articles published in the last five years. We performed analysis and summary of the reviewed bibliography. Analysis and synthesis of information: In myelodysplastic syndromes, frequent cytogenetic alterations are present such as deletion of chromosomes 5q, 7q and 20q, as well as the monosomy of chromosome 7, trisomy of chromosome 8 and the presence of complex karyotypes, which together with somatic mutations in different genes intervene in the pathogenesis of the disease and allow prognostic stratification of patients. Conclusions: Diagnosis through conventional cytogenetic studies, fluorescence in situ hybridization and gene sequencing allow a better understanding of the biology of the disease, risk stratification and therapeutic decision making(AU)

Importancia de la monitorización de concentraciones plasmáticas de voriconazol y dificultad en ajuste de dosis en un paciente pediátrico / Voriconazole monitorization in pediatric patients, difficulties in dose adjustment

Resumen Presentamos el caso de un escolar de 10 años, con el diagnóstico de una recaída de una leucemia mieloide aguda que cursó con un episodio de una neutropenia febril de alto riesgo, posterior a un ciclo intensivo de quimioterapia, evolucionando con una infección fúngica invasora demostrada por histopatología. Se inició tratamiento con voriconazol intravenoso, evolucionando con concentraciones plasmáticas erráticas que requirieron sucesivos ajustes de dosis, lo que también ocurrió con la administración oral del medicamento. Finalmente, tuvo una respuesta favorable al tratamiento, a pesar de la dificultad de la dosificación para alcanzar niveles terapéuticos. La búsqueda activa y la terapia antifúngica anticipada, así como la monitorización seriada de concentraciones terapéuticas de voriconazol, permitieron un tratamiento antifúngico óptimo y oportuno, mejorando el pronóstico del paciente.

Abstract We present a 10-year-old male patient with a diagnosis of relapsed acute myeloid leukemia (AML), presenting with high-risk febrile neutropenia (HRFN), after a cycle of intensive chemotherapy, evolving with an invasive fungal infection demonstrated by histopathology. Treatment with intravenous voriconazole was started, with erratic plasmatic levels, which require successive dose adjustments which also occurred with oral administration. Finally, he had a favorable response to treatment, despite of the dosing difficulties to reach therapeutic levels. Active search as well as preemptive antifungal therapy, together with plasmatic level monitorization of voriconazole allowed a prompt recovery and improved the patient prognosis.

Trastornos mieloproliferativos y leucemia en síndrome de Down. Presentación de dos casos clínicos en el período neonatal / Myeloproliferative disorders and leukemia related to Down syndrome. Report of two clinical cases in neonatal period

ElsíndromedeDownpredisponeatrastornosmieloproliferativos. Se estima que del 5 % al 30 % de los neonatos con esta condición desarrollarán mielopoyesis anormal transitoria. El tratamiento no está estandarizado; la exanguinotransfusión y la citarabina podrían ser efectivos. Se describen dos casos de pacientes con síndrome de Down, quienes durante el período neonatal presentaron leucemia mieloide aguda y mielopoyesis anormal transitoria, los tratamientos utilizados y sus desenlaces. Se considera que la sospecha y el diagnóstico temprano de esta entidad son factores determinantes en el pronóstico.

Down syndrome predisposes to haematological disorders. It is estimated that 5-30% of neonates with this condition will develop transient abnormal myelopoiesis. Treatment is not standardized; exchange transfusion and the use of cytarabine could be effective. We present two clinical cases of patients with Down syndrome, who during the neonatal period showed acute myeloid leukemia and transient abnormal myelopoiesis, the treatments used and their outcomes. Suspicion and early diagnosis of this entity are considered determining factors in prognosis.

Biomarcador FLT3-ITD: perspectivas y retos / FLT3-ITD biomarker: perspectives and challenges

Introducción: Las mutaciones del gen que codifica para el factor de la tirosina quinasa 3 (FLT3) son de especial importancia en la leucemia mieloide aguda debido a que sirven de guía para la confirmación del diagnóstico, la estimación del pronóstico y la toma de decisiones terapéuticas. Entre las alteraciones más importantes está la duplicación interna en tándem (FLT3-ITD). Objetivo: Exponer los aspectos más relevantes respecto al biomarcador FLT3-ITD en el contexto de la leucemia mieloide aguda. Métodos: Se realizó una búsqueda de artículos científicos actualizados en los idiomas inglés y español, en PubMed, EMBASE, Google Scholar y SciELO. Se seleccionaron artículos publicados en los últimos cinco años. Se revisaron los aspectos más relevantes sobre el biomarcador en el contexto de la leucemia mieloide aguda, su base biológica, el impacto del tamaño de los fragmentos y la carga alélica en la estimación del pronóstico de los pacientes, las nuevas estrategias terapéuticas y los retos en cuanto a los métodos de laboratorio para su diagnóstico. Análisis y síntesis de la información: Más allá de la positividad o no de dicho biomarcador, el tamaño de la duplicación interna en tándem, así como la carga alélica -determinada por la razón alelo mutado/alelo salvaje-, podrían tener un gran impacto en el pronóstico. Sin embargo, persisten diferencias en los criterios para establecer los algoritmos de predicción del riesgo, el punto de corte a utilizar como referencia y el protocolo de laboratorio específico para un estudio más detallado del biomarcador. Conclusiones: La comunidad científica necesita seguir trabajando en el esclarecimiento de la utilidad práctica de estos parámetros, validándolos en series amplias y diversas epidemiológicamente. Se debe determinar el punto de corte exacto para comparar la razón y estandarizar los métodos de laboratorio más adecuados y factibles para su estudio(AU)

ABSTRACT Introduction: Mutations in the tyrosine kinase 3 gene (FLT3) are of special importance in acute myeloid leukemia because they serve as a guide to confirm the diagnosis, estimate the prognosis, and make therapeutic decisions in the patient. Internal tandem duplication (FLT3-ITD) is the most important alteration of this gene. Objective: To present the most relevant aspects regarding the FLT3-ITD biomarker in the context of acute myeloid leukemia. Methods: a search was carried out for updated scientific articles, in English and Spanish, in PubMed, EMBASE, Google Scholar and SciELO. Articles published in the last five years were selected. The most relevant aspects of the biomarker in the context of acute myeloid leukemia, its biological basis, the impact of the size of the fragments and the allelic load in the estimation of the prognosis of the patients, the new therapeutic strategies and the challenges in regarding the laboratory methods for its diagnosis. Information analysis and synthesis: Beyond the biomarker positivity or not, the size of the ITD, as well as the allelic ratio determined by the mutated allele / wild-type allele, could have a great impact on the prognosis of patients. However, differences persist in the criteria for establishing risk prediction algorithms, the cut-off point to be used as a reference, and the specific laboratory protocol for a more detailed study of the biomarker. Conclusions: The scientific community needs to continue working to clarify the practical utility of these parameters, validating them in broad and epidemiologically diverse series. The exact cut-off point should be determined as a reference to compare the relationship and standardize the most suitable and feasible laboratory methods for its study(AU)

Sarcoma Granulocítico Cutâneo de Apresentação Concomitante ao Diagnóstico de Leucemia Promielocítica Aguda / Cutaneous Granulocytic Sarcoma Concomitant to the Diagnosis of Acute Promyelocytic Leukemia / Sarcoma Granulocitico Cutaneo de Presentacion Concomitente al Diagnostico de Leucemia Promielocitica Aguda

Introdução: O sarcoma granulocítico (SG) é um tumor extramedular raro, composto por células mieloides imaturas. Ocorre em 2% a 14% dos pacientes com leucemia mieloide aguda (LMA). A associação com leucemia promielocítica (LPA) é ainda mais rara, especialmente como manifestação no momento do diagnóstico. O presente estudo expõe o caso de um paciente com SG cutâneo de apresentação concomitante ao diagnóstico de LPA. Relato do caso: Paciente do sexo masculino, 30 anos, encaminhado ao Departamento de Hematologia por febre, odinofagia, intensa adinamia, hiporexia, perda de 5 kg, sudorese noturna, além de dispneia progressiva ao longo de um mês. Realizou exames laboratoriais com evidência de anemia grave, prosseguindo investigação etiológica com mielograma, que evidenciou 84% de blastos, e imunofenotipagem compatível com LPA, PML-RARA positivo (90%). Apresentava ainda lesões ulceradas em região genital e coxa direita, cuja biópsia evidenciou proliferação de células redondas suspeita para infiltração por LMA/SG. A imuno-histoquímica confirmou SG. O paciente foi submetido à quimioterapia, com boa resposta ao tratamento e melhora das contagens sanguíneas. As lesões cutâneas evoluíram com cicatrização. Após terceira consolidação, o PML-RARA negativou. Conclusão: Este relato de caso descreve uma apresentação rara de uma doença hematológica maligna, o SG, também conhecido como cloroma, na pele. Uma estratégia de diagnóstico incluindo imagens, histopatologia, imuno-histoquímica e exames laboratoriais foi necessária para confirmá-lo. O diagnóstico oportuno é essencial para que o tratamento adequado seja instituído logo, beneficiando o paciente em sobrevida e qualidade de vida

Introduction: Granulocytic sarcoma (GS) is a rare extramedullary tumor, made up by immature myeloid cells. It occurs in 2% to 14% of patients with acute myeloid leukemia (AML). The association with promyelocytic leukemia (APL) is even more rare, especially as manifestation at the time of diagnosis. The present study exposes the case of a patient with cutaneous GS concomitant with a diagnosis of APL. Case report: Male patient, 30 years old, referred to the Hematology Department due to fever, odynophagia, intense adynamia, hyporexia, loss of 5 kg, night sweating, in addition to progressive dyspnea over one month. Laboratory exams were run with evidence of severe anemia, proceeding to etiological investigation with myelogram, which showed 84% of blasts, and immunophenotyping compatible with promyelocytic leukemia (APL), PML-RARA positive (90%). Also, presented ulcerated lesions in the genital region and right leg, whose biopsy showed proliferation of suspected round cells for infiltration by AML/GS. Immunohistochemistry confirmed GS. The patient underwent chemotherapy, with good response to the treatment and improvement of blood counts. Skin lesions evolved with healing. After the 3rd consolidation, PML-RARA was negative. Conclusion: This case report describes a rare presentation of a malignant hematological disease, GS, also known as skin chloroma. A diagnostic strategy including images, histopathology, immunohistochemistry and laboratory tests were needed for confirmation. Timely diagnosis is essential, so that appropriate treatment is instituted soon, benefiting the patient regarding survival and quality of life

Introducción: El sarcoma granulocítico (SG) es un tumor extramedular poco frecuente, compuesto por células mieloides inmaduras. Ocurre en 2% a 14% de los pacientes con leucemia mieloide aguda (AML). La asociación con leucemia promielocítica (LPA) es aún más rara, especialmente como manifestación en el momento del diagnóstico. El presente estudio expone el caso de un paciente con SG cutáneo que presenta un diagnóstico de LPA. Relato del caso: Paciente masculino de 30 años, remitido al Servicio de Hematología por fiebre, odinofagia, adinamia intensa, hiporexia, pérdida de 5 kg, sudoración nocturna, además de disnea progresiva a lo largo de un mes. Realizó exámenes de laboratorio con evidencia de anemia severa, continuando investigación etiológica con mielograma, que mostró 84% de blastos, e inmunofenotipificación compatible con LPA, PML-RARA positivo (90%). También presentaba lesiones ulceradas en región genital y muslo derecho, en las que la biopsia mostró proliferación de células redondas sospechadas para infiltración por LMA/SG. La inmunohistoquímica confirmó SG. El paciente fue sometido a quimioterapia, con buena respuesta al tratamiento y mejoría de los hemogramas. Las lesiones cutáneas evolucionaron con la curación. Después de la tercera consolidación, el PML-RARA fue negativo. Conclusión: Este reporte de caso describe una presentación poco común de una enfermedad hematológica maligna, el SG, también conocido como cloroma, en la piel. Se necesitaba una estrategia de diagnóstico que incluyera imágenes, histopatología, inmunohistoquímica y pruebas de laboratorio para confirmarlo. El diagnóstico oportuno es fundamental para que pronto se instaure el tratamiento adecuado