Analyzing the incidence, survival, and demographic trends of B-cell prolymphocytic leukemia

Background: B-cell prolymphocytic leukemia (B-PLL) is a rare disease, consisting <1% of mature B-cell malignancies. B-PLL is often refractory to chemotherapy, with a median survival of 3 years. Due to its rarity, no large cohort studies exist elucidating outcomes. Methods: All B-PLL patients >15 years were identified in the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database between 2000-2020. Statistical analysis explored demographic variables like age; categorized as adolescent or young adult (AYA) and adults. In adults, differences in survival due to factors such as sex, race/ethnicity, household income, rurality, and age categorized in 10-15 year buckets was analyzed. Results: B-PLL patients were predominantly white (78%), over 40 years (96%) and mostly residing in metropolitan areas (90%). Interestingly, the AYA cohort were mostly female (70%). 35% of the AYA patients were Hispanic, while being only 9% in adults. Among adults, the rate of Asian/Pacific-Islander patients that were alive at the time of the data query was 53% compared to 34% in Hispanic, 31% in black, and 24% in white patients (p=0.025). Younger age was also associated with greater chances of survival (p<0.001). Conclusions: In line with known poor prognosis of the disease, 23% patients were alive at the time of data query. Female and Hispanic patients were overrepresented in the AYA age group. In the adult group Asian/Pacific-Islander patients had better survival outcomes, as did younger patients. Further research is necessary to explore why B-PLL incidence in AYA patients is higher among Hispanic and females.

Comparative analysis of leukemia and risk estimation in working age population between provinces of Ecuador / Análisis comparativo de leucemia y estimación del riesgo en la población en edad laboral entre provincias del Ecuador

Leukemia is associated with exposure to radiation, benzene derivatives, and pesticides. Previous research has documented an increase in work-related leukemia in the Latin American Andean region. To date, there are only few studies in Ecuador on the impact of oil exploitation on adjacent indigenous communities. Our study aims to show the impact of leukemia on the working-age population. For the calculation of morbidity and mortality rates, we used hospital discharge and death records from the National Institute of Statistics of Ecuador. These data were collected and adjusted to the corresponding province's population for further analysis. Large differences were observed between provinces in adjusted rates of leukemia mortality and morbidity in the working-age population. The variations in altitude among different areas in Ecuador give the provinces a distinct geographic identity. Likewise, the provinces with the highest morbidity and mortality rankings, such as Azuay, Loja, Imbabura, and Tungurahua, have an average altitude above 2000 meters. As a result, there are variations in the average temperature, exposure to solar and cosmic radiation, and mining and farming methods. The observed differences warrant the future collection of geolocation data for affected individuals. This could help to better understand how leukemia cases have demogrpahic hotspots in the country, identify possible risk factors associated with the disease in each region, and design more effective prevention and control strategies.

La leucemia es una enfermedad a consecuencia, además de factores genéticos, de la exposición a radiaciones, derivados del benceno y pesticidas. Investigaciones anteriores han documentado un aumento de la leucemia ocupacional en la región andina de América Latina. Hasta la fecha, existen sólo unos pocos estudios en Ecuador sobre el impacto de la explotación petrolera en las comunidades indígenas. Nuestro objetivo es mostrar el impacto de la leucemia en la población en edad de trabajar. Para el cálculo de las tasas de morbimortalidad se utilizaron los registros de altas hospitalarias y defunciones del Instituto Nacional de Estadística del Ecuador. Estos datos fueron recopilados y estimadas las tasas ajustadas. Se observaron grandes diferencias entre provincias en las tasas ajustadas de mortalidad y morbilidad por leucemia en la población en edad de trabajar. Asimismo, las provincias con mayor ranking de morbilidad y mortalidad, como Azuay, Loja, Imbabura y Tungurahua, coinciden en tener una altitud promedio superior a los 2000 metros. Hay provincias de baja altitud en la costa y provincias por encima de los 2000 metros en la sierra, lo que le da a las provincias del Ecuador una identidad geográfica distintiva. Como resultado, existen variaciones en la temperatura promedio, la exposición a la radiación solar y cósmica, y actividades de minería y agricultura. Las diferencias observadas, recomiendan la recopilación futura de datos de geolocalización de las personas afectadas. Esto podría ayudarnos a comprender mejor cómo se distribuyen los casos de leucemia, identificar posibles factores de riesgo asociados a la enfermedad en cada región y diseñar estrategias de prevención y control más efectivas.

Disseminated juvenile xanthogranuloma secondary to chemotherapeutic treatment of acute lymphoblastic leukemia

Juvenile xanthogranuloma is a benign, reactive, self-limiting disorder within the non-Langerhans cell histiocytosis group. It primarily affects infants and preschoolers, and occasionally in adults. Some cases report concurrent non-LCH and leukemia, with bone marrow being the second common pathology. We present a case of JXG with acute lymphoblastic leukemia in a 17-year-old male. Emphasizing the importance of considering the possibility of apparently disparate disorders in a patient, especially with unusual clinical findings.

Sangrado uterino anormal como presentación inicial de malignidades hematológicas / Abnormal uterine bleeding as the initial presentation of hematologic malignancies

El sangrado uterino anormal tiene una etiología variable, que va desde causas estructurales hasta causas funcionales, que se describen clásicamente en el acrónimo PALM-COEIN. No obstante, hay una pobre sensibilización de este síntoma como un marcador de enfermedades graves. En esta revisión se describe la relación de la hemorragia uterina anormal como síntoma clave o de presentación de malignidad hematológica, así como la posible relación con la hemofilia adquirida secundaria a neoplasia hematológica como causal del evento hemostático. Se realizó búsqueda en la literatura, con la mayoría de los artículos obtenidos de Medline, 24 de los cuales cumplieron con los objetivos para resolver la pregunta de investigación. Se encontraron diferentes malignidades hematológicas asociadas a sangrado uterino anormal, de las cuales la hemofilia adquirida y la trombocitopenia como potenciales causales de esta; la mayor correlación fue con leucemia, seguido de linfomas, y en menor cuantía la asociación con mieloma múltiple.

Abnormal uterine bleeding has a variable etiology, ranging from structural to functional causes, classically described by the acronym PALM-COEIN. However, there is poor awareness of this symptom as a marker of serious disease; in this review, we describe the relationship of abnormal uterine bleeding as a key symptom or debut of hematologic malignancy, as well as its possible relationship to acquired hemophilia secondary to hematologic neoplasia as causative of the hemostatic event. A literature search was performed, with most of the articles obtained from Medline, 24 of which met the objectives to solve the research question. Different hematological malignancies associated with abnormal uterine bleeding were found, of which acquired hemophilia and thrombocytopenia were found as potential causes; the highest correlation was with leukemia, followed by lymphomas, and to a lesser extent the association with multiple myeloma.

Resultados de dos protocolos de tratamiento para la leucemia linfoide aguda infantil en un hospital peruano / Results of two treatment protocols for children's acute lymphoid leukemia in a Peruvian hospital

Resumen Introducción. La leucemia linfoide aguda (LLA) es la neoplasia infantil más frecuente. Existen diversos protocolos de tratamiento, por lo que resulta importarte conocer su impacto en la supervivencia. Materiales y métodos. Estudio comparativo, cohorte retrospectiva. Se incluyeron pacientes menores de 16 años con diagnóstico de LLA tratados con protocolo ALL IC-BFM 2009 o esquema LLA 2008 durante enero 2020 a noviembre 2023. Se revisaron historias clínicas de los pacientes. Como instrumento se tuvo una ficha de recolección de datos. Se empleó el análisis de supervivencia de Kaplan Meier para determinar la sobrevida global (SG) y supervivencia libre de enfermedad (SLE). Resultados. Se incluyeron 107 pacientes. El grupo etario de 2-9 años fue el más prevalente en ambos grupos (57.1% y 63.3%). La SG a 32.2 meses fue 73.6% con el protocolo ALL IC BFM 09 y 43.5% con el esquema LLA 2008 (p=0.03). La SLE a 30.8 meses fue 82.3% y 51.8% respectivamente (p=0.04). Discusión. En nuestro estudio, la SG y SLE fue mayor al 70% para el protocolo ALL IC BFM 09, siendo estos hallazgos similares a lo reportado por literatura internacional. La supervivencia con el protocolo ALL IC BFM 2009 fue superior al esquema LLA 2008.

Abstract Introduction. Acute lymphoid leukemia is the most common childhood neoplasm. There are various treatment protocols, so it is important to know their impact on survival. Material and methods. Comparative study, retrospective cohort. Patients under 16 years of age with a diagnosis of ALL treated with the ALL IC-BFM 2009 protocol or the LLA 2008 scheme were included during January 2020 to November 2023. The patients' medical records were reviewed, and a data collection sheet was used as an instrument. Kaplan Meier survival analysis was used to determine overall survival (OS) and disease-free survival (DFS). Results. 107 patients were included. The age group of 2-9 years was the most prevalent in both groups (57.1% and 63.3%). OS at 32.2 months was 73.6% with the ALL IC BFM 2009 protocol and 43.5% with the LLA 2008 scheme (p=0.03). The DFS at 30.8 months was 82.3% and 51.8% respectively (p=0.04). Discussion. In our study, OS and DFS were greater than 70% for the ALL IC BFM 2009 protocol, these findings being similar to those reported in international literature. Survival with the ALL IC BFM 2009 protocol was superior to the previous institutional protocol.

Periodontal status in adult patients with leukemia: a literature review / Condição periodontal em pacientes adultos com leucemia: revisão de literatura

Periodontal disease is a highly prevalent chronic inflammatory disease that affects the tissues that support the teeth, while leukemia is a type of malignous cancer that affects the production of blood cells. Recent studies suggest that immune response and microbial disbiosis related to periodontal disease may be associated with an increased risk of developing leukemia and may affect its prognosis, as well as leukemia type and treatment may also have effects on the periodontium, demanding a interdiscipinary approach of these patients. The aim of this study was to conduct a literature review to assess the association between periodontal disease and leukemia in adult patients. An electronic database serch using the descriptors was performed. Clinical studies with periodontal examination in adult individuals with leukemia were selected. After literature search, 9 studies were reviewed. Gingival bleeding and periodontal pockets were frequent findings. Periodontitis prevalence varied among studies, ranging from 29% to 82,4% in patients diagnosed with leukemia. The relationship between periodontal disease and leukemia is complex and multifaceted and there are few studies available in adults, with heterogeneous exam protocols. Still, the high prevalence of gingivitis and periodontitis found in the studies suggest that periodontal diagnosis and treatment could be a helpful tool to prevent further complications in leukemia treatment.

A doença periodontal é uma doença inflamatória crônica altamente prevalente e que afeta os tecidos que sustentam os dentes, enquanto a leucemia é um tipo de câncer maligno que afeta a produção de células sanguíneas. Estudos recentes sugerem que a resposta imune e a disbiose microbiana relacionada a doença periodontal podem estar associadas a um risco aumentado de desenvolver leucemia e pode afetar o prognóstico da doença, assim como o tipo de leucemia e o tratamento também podem ter efeitos no periodonto, exigindo uma abordagem interdisciplinar desses pacientes. O objetivo deste estudo foi realizar uma revisão de literatura para avaliar a associação entre doença periodontal e leucemia em pacientes adultos. Foi realizada uma busca eletrônica em bancos de dados utilizando os descritores. Foram selecionados estudos clínicos com exame periodontal em indivíduos adultos com leucemia. Após busca na literatura, 9 estudos foram revisados. Sangramento gengival e bolsas periodontais foram achados frequentes. A prevalência da periodontite variou entre os estudos, sendo de 29% a 82,4% em pacientes diagnosticados com leucemia. A relação entre doença periodontal e leucemia é complexa e multifacetada e existem poucos estudos disponíveis em adultos, com protocolos de exames heterogêneos. Ainda assim, a alta prevalência de gengivite e periodontite encontrada nos estudos sugere que o diagnóstico e o tratamento periodontal podem ser uma ferramenta útil para prevenir maiores complicações no tratamento da leucemia.

Mycobacterium tuberculosis y virus linfotrópico humano, una co-infección fatal / Mycobacterium tuberculosis and human lymphotropic virus, a fatal co-infection

La tuberculosis es una infección de alta incidencia en Latinoamérica. Su presentación como infección activa está determinada por factores de riesgo del hospedero. Comunicamos el caso clínico de una mujer joven que presentó una forma grave de tuberculosis pulmonar. Al explorar sus factores de riesgo se confirmó un estado de inmunosupresión profundo, causado por un linfoma de células T, asociada a una co-infección por virus linfotrópico T humano tipo 1. Se destacan los aspectos microbiológicos y de pronóstico de la co-infección de Mycobacterium tuberculosis y HTLV-1

Tuberculosis is a high-incidence infection in Latin America. Its presentation as an active infection is determined by risk factors in the host. We report the case of a young woman who presented a severe form of pulmonary tuberculosis. When exploring her risk factors, a profound state of immunosuppression was found, caused by T-cell lymphoma, associated with co-infection with human lymphotropic virus. Microbiological and prognostic aspects of Mycobacterium tuberculosis and HTLV-1 co-infection are highlighted.

Priapismo y leucemia mieloide crónica en adolescente. Debut poco frecuente. Reporte de caso / Priapism and chronic myeloid leukemia in an adolescent. Rare debut presentation. A case report

El priapismo es una erección dolorosa y persistente acompañada o no de estímulo sexual. Una causa poco frecuente de esta anormalidad es la leucemia mieloide crónica. Se han reportado pocos casos de priapismo como manifestación inicial de una leucemia de este tipo en pacientes adolescentes. A continuación, se informa el caso de un paciente de 16 años de edad que presentó priapismo como manifestación inicial de una leucemia mieloide crónica. Durante su evolución, no se realizó aspiración de los cuerpos cavernosos. Se inició tratamiento hematológico específico y, ante la persistencia del priapismo, fue necesario realizar un shunt de cuerpos cavernosos en dos ocasiones, tratamiento a pesar del cual existen altas probabilidades de secuelas.

Priapism is a painful and persistent erection, with or without sexual stimulation. A rare cause of such abnormality is chronic myeloid leukemia. Few cases of priapism as an initial manifestation of this type of leukemia have been reported in adolescent patients. Here we describe the case of a 16-year-old patient who presented with priapism as the initial manifestation of chronic myeloid leukemia. No cavernosal aspiration was performed. A specific hematological treatment was started and, given the persistence of priapism, the patient required 2 corpora cavernosa shunt procedures; despite this treatment, there is a high probability of sequelae.

Therapeutic Choices in Patients with Ph-Positive Chronic Myelogenous Leukemia In Mexico in the Era of Tyrosine Kinase Inhibitors: Stem Cell Transplantation or Tyrosine Kinase Inhibitors? Fifteen Years Later

ABSTRACT Background: Chronic myelogenous leukemia is a neoplastic proliferation of the granulocytic series. In Mexico, chronic myelogenous leukemia accounts for approximately 10% of all leukemias. Tyrosine-kinase inhibitors are considered front-line therapy in high-income countries, whereas allogeneic hematopoietic stem cell transplantation is a recognized therapeutic approach, mainly in low- and middle-income countries. Objective: To analyze the overall survival of persons with chronic myelogenous leukemia who have received tyrosine-kinase inhibitors or allogeneic hematopoietic stem cell transplantation in a medical center, since 1994, and briefly discuss the current indications of these treatments in the tyrosine-kinase inhibitors era. Methods: We retrospectively analyzed all patients with a diagnosis of chronic myelogenous leukemia treated in a medical center between 1994 and 2023; subsets of individuals who received an allogeneic hematopoietic stem cell transplantation or tyrosine-kinase inhibitors therapy as first-line treatment were analyzed. Results: 60 persons with chronic myelogenous leukemia were treated with allogeneic hematopoietic stem cell transplantation or tyrosine-kinase inhibitors: 35 received an allogeneic hematopoietic stem cell transplantation, whereas 25 were given tyrosine-kinase inhibitors. All patients who underwent an allogeneic hematopoietic stem cell transplantation engrafted successfully, and the procedure was completed on an outpatient basis in most cases (29/35). The median survival in allogeneic hematopoietic stem cell transplantation was 78.3 months (CI 95%: 0-205.6) and in persons given tyrosine-kinase inhibitors the median was not reached. Conclusion: Tyrosine-kinase inhibitors were significantly superior to allogeneic hematopoietic stem cell transplantation in prolonging the overall survival of persons with chronic myelogenous leukemia in our single institution experience. (Rev Invest Clin. 2024;76(2):91-6)

Study of automated hematology analyzer抯 scatterplot patterns in white blood cell disorders

Background: Automated hematology analyzers produce scattergrams that can be used as screening tool for various hematological conditions and efficiently shorten turnaround times. Aim was to study scattergram patterns of various while blood cell disorders and assess their efficacy compared to a peripheral blood smear for diagnosis of various disorders. Methods: Scattergram findings generated by UniCel� DxH 800 automated hematology analyzer, a 5-part differential analyzer. The graphic displays have been compiled over a period of 3 months from blood samples received for CBC. Samples that the counter flagged as abnormal for white blood cell were chosen. Based on the scatterplots, a preliminary diagnosis was formed. It was compared with the peripheral blood smear (PBS) findings which were taken as the gold standard. Results: The scatterplots showed unique patterns for various disorders on the basis of location, shape, size, density of the cells and their clustering. The scattergram analyser showed 90% sensitivity and 88% specificity for diagnosing hematological disorders. A 97-100% accuracy rate was reported showing excellent correlation between PBS result and WBC parameter result in cell counter analyzers. Conclusions: Not all cases of haematological malignancy exhibit cytopenias or cytosis at initial presentation. Therefore, these scatter plots offer helpful information that prompts a hematopathologist to suspiciously screen the peripheral smear in cases with normal counts. Scattergram analysis suspects a diagnosis earlier than peripheral smear examination. Given their strong correlation with a variety of WBC disorders and confirmed by PBS, WBC scatterplots can be used as a screening tool.

Megakaryoblastic Acute Myeloid Leukemia Associated with a Testicular Tumour in a Young Adult: a Case Report / Leucemia Mieloide Aguda Megacarioblástica Associada a Tumor de Testículo em Adulto Jovem: um Relato de Caso

Acute megakaryoblastic leukemia (M7 AML) is a rare subtype of acute myeloid leukemia in adults, the incidence of which is higher in children aged 1 to 3 years, especially in patients with Down Syndrome; and in the age group between 60 and 70 years old, with an adverse prognosis. We report the case of a 28-year-old male patient, with a history of non-seminoma germ cell tumour of the testis, diagnosed with M7 AML. Nine months after performing an orchiectomy to remove the testicular tumour, the patient developed dyspnea, dry cough and asthenia, associated with the presence of erythematous-purple lesions on the skin, ascites and pleural effusion. The myelogram demonstrated medullary hypocellularity, with the presence of 53% of blastic, pleomorphic and bulky cells, with positivity for the markers CD34, CD31 and CD117 in immature cells in immunohistochemistry. Despite undergoing cycles of chemotherapy with cisplatin and a BEP regimen (Bleomycin, Etoposide and Cisplatin), the patient presented with chest tomography with the presence of pulmonary nodules and magnetic resonance imaging of the skull and neuraxial with infiltration of the bone marrow in the spine and cranial vault, resulting in with neurological impairment and died. In view of the case presented, we observed agreement with previous reports of the adverse prognosis of M7 AML in young adults and we questioned its relationship with germ cell tumour. (AU)

A leucemia megacarioblástica aguda (LMA M7) é um subtipo raro em adultos de leucemia mielóide aguda, cuja incidência é maior em crianças de 1 a 3 anos, especialmente em pacientes portadores de Síndrome de Down; e na faixa etária entre 60 e 70 anos, com um prognóstico adverso. Relatamos o caso de um paciente, do sexo masculino, 28 anos, com histórico de tumor germinativo não seminoma de testículo, diagnosticado com LMA M7. Nove meses após a realização de uma orquiectomia para a retirada do tumor testicular, o paciente apresentou quadro de dispneia, tosse seca e astenia, associado a presença de lesões eritemato-arroxeadas na pele, ascite e derrame pleural. O mielograma demonstrou hipocelularidade medular, com presença de 53% de células blásticas, pleomórficas e volumosas, com a positividade para os marcadores CD34, CD31 e CD117 em células imaturas na imunohistoquímica. Apesar da realização de ciclos de quimioterapia com cisplatina e esquema BEP (Bleomicina, Etoposídeo e Cisplatina), o paciente apresentou Tomografia de tórax com presença de nódulos pulmonares e ressonância magnética de crânio e neuroeixo com infiltração da medula óssea em coluna vertebral e calota craniana, intercorrendo com comprometimento neurológico e foi a óbito. Diante do caso apresentado observamos a concordância com relatos prévios do prognóstico adverso da LMA M7 em jovens adultos e indagamos a sua relação com o tumor de células germinativas. (AU)

Linfoma extranodal de epiglotis en un paciente con recaída de leucemia linfoide aguda de células T. Presentación de un caso / Extranodal lymphoma of the epiglottis in a patient with relapsed T-cell acute lymphoid leukemia. Case report

Los linfomas localizados en la laringe representan un porcentaje muy bajo dentro de los comprendidos en los tumores de cabeza y cuello en la edad pediátrica. El linfoma no Hodgkin es el subtipo más comúnmente reportado en la literatura, el cual dependiendo de su etiología y extensión determinará el pronóstico del paciente. La certeza del diagnóstico, que suele ser muy difícil de alcanzar, se confirma generalmente mediante una biopsia de tejido. En la actualidad, no hay reportes de la literatura acerca de linfomas leucemoides diseminados a laringe. Se presenta el caso de un paciente masculino adolescente de 17 años con diagnóstico de una leucemia linfoide aguda con recaída extra-nodal en la laringe por falla en el esquema quimioterapéutico instaurado.

Lymphomas located at the level of the larynx represent a very low percentage of head and neck tumors in the pediatric age group. Non-Hodgkin's lymphoma is the most reported subtype in the literature, which depending on its etiology and extension will determine the patient's prognosis. Diagnostic certainty, which is often very difficult to achieve, is usually confirmed by tissue biopsy. At present, there are no reports in the literature about leukemoid lymphomas disseminated to the larynx. We present the case of a 17-year-old adolescent male patient diagnosed with acute lymphoid leukemia with extranodal relapse in the larynx due to failure of the chemotherapeutic regimen.

Clinical outcome and prognosis of patients with acute myeloid leukemia submitted to chemotherapy with 5 years of follow-up

Abstract Objective The purpose of this study was to evaluate the clinical-epidemiological profile, associated risk factors and clinical outcomes of patients with acute myeloid leukemia (AML), identifying the main causes of morbidity and mortality and overall survival rate of patients at five years of follow-up. Method This was a retrospective cohort study evaluating the prognosis and clinical outcomes of 222 patients diagnosed with AML at three large hematology centers in Ceará (northeastern Brazil) over a period of five years. Results The mean age at diagnosis was 44.1 ± 16 years, with a female prevalence of 1.3:1. No additional relevant risk factors associated with the development of AML were found, except for the well-established cytogenetic assessment. The overall 5-year survival rate was 39.4% (95%CI: 35.47 - 42.17). The main causes of death were disease progression (37.72%; n = 84) and sepsis (31.58%; n = 70). Conclusion The clinical outcomes in our sample of AML patients were similar to those of other reported groups. Disease progression and infection were the main causes of death. Access to diagnostic flow cytometry and karyotyping was greater in our sample than in the national average. As expected, overall survival differed significantly according to the risk, as determined by cytogenetic testing.

Tratamiento de la recaída de pacientes pediátricos con leucemia linfoblástica aguda en la Argentina: resultados de un ensayo clínico y una cohorte prospectiva / Treatment of Relapse in Pediatric Patients with Acute Lymphoblastic Leukemia in Argentina: Results from a Clinical Trial and a Prospective Cohort

Introducción: desde 2002, el Grupo Argentino para el Tratamiento de la Leucemia Aguda (GATLA) implementa protocolos del grupo Berlín-Frankfurt-Münster (BFM) como tratamiento estándar de las recaídas de la leucemia linfoblástica aguda (LLA). En 2010, el BFM generó el protocolo IntReALL 10, que en la Argentina se implementó con las limitaciones propias de la región. Población y métodos: 180 pacientes menores de 18 años fueron tratados entre 2010 y 2015 por una LLA recaída de alto riesgo en la Argentina siguiendo un protocolo de recaída del BFM que comparó en forma abierta el tratamiento estándar con una terapéutica innovadora (experimental); esta incluyó el fármaco clofarabina. Se evaluaron 171 pacientes, de los cuales 78 pacientes fueron aleatorizados en forma centralizada (ensayo clínico) y 93 fueron asignados a una de las ramas según el criterio del grupo tratante (cohorte prospectiva). La cohorte donde la asignación del tratamiento no fue aleatorizada fue analizada realizando un ajuste por sexo, edad y por la presencia o no de síndrome de Down, cromosoma Philadelphia e inmunofenotipo T. Resultados: los pacientes que recibieron el tratamiento experimental tuvieron peores resultados (el doble de mortalidad a cinco años) que los que recibieron tratamiento estándar. Esta diferencia alcanzó significancia estadística tanto en el ensayo clínico (p=0,001) como en la cohorte prospectiva (p=0,0009). Conclusiones: nuestros resultados avalan continuar con la rama estándar de los protocolos tipo BFM para el tratamiento de las recaídas de la LLA y fueron concordantes con las conclusiones del grupo ALLIC-REC. (AU)

Introduction: since 2002, the Grupo Argentino para el Tratamiento de la Leucemia Aguda (GATLA) has been implementing protocols from the Berlin-Frankfurt-Münster (BFM) group as the standard treatment for relapses of acute lymphoblastic leukemia (ALL). In 2010, BFM developed the IntReALL 10 protocol, implemented in Argentina with the inherent limitations of the region. Population and Methods: we treated a total of 180 patients under 18 years of age between 2010 and 2015 for high-risk relapsed acute lymphoblastic leukemia (ALL) in Argentina following a BFM relapse protocol. This protocol openly compared standard treatment with an innovative (experimental) therapeutic approach that included Clofarabine. Out of these, 171 patients were assessable, with 78 patients being centrally randomized in a clinical trial, and 93 were assigned to one of the arms based on the treating group's criteria (prospective cohort). The cohort where the treatment assignment had not been randomized, was analyzed with adjustments for gender, age, and the presence or absence of Down Syndrome, Philadelphia Chromosome, and T-cell immunophenotype. Results: patients who received the experimental treatment had worse outcomes (double the five-year mortality) compared to those who received the standard treatment. This difference reached statistical significance in the clinical trial (p=0.001) and the prospective cohort (p=0.0009). Conclusions: our results support the continuation of the standard arm in BFM-type protocols for relapsed ALL treatment and were consistent with the conclusions of the ALLIC-REC group. (AU)

Hematological, histopathological and oxidative stress responses to n-hexane extract of Terminalia catappa nuts in leukemia-induced Wistar rats

Background: Terminalia catappa nut possesses antioxidant and anticancer properties, but its effects on leukemia are unclear. This study investigates the effects of n-hexane extract of Terminalia catappa nut (TCN) on some hematological parameters, oxidative stress markers, and bone/spleen histopathology in a Wistar rat model of benzene-induced leukemia. Methods: Leukemia was induced in Wistar rats with 0.2 ml/kg Benzene solution and treated with 200, 400 or 800 mg/kg/day of Terminalia catappa nut extract (TCN) for 42 days and with 5-fluorouracil (20 mg/kg) via intraperitoneal injection twice a week for 6 weeks. Hematological parameters, antioxidant markers, and bone and spleen histology were analysed. Results: All TCN doses significantly lowered elevated WBCs by 32-53% and normalized RBC parameters compared to leukemic controls, mitigating cancer-induced anemia. TCN also exhibited potent antioxidant effects by enhancing SOD, GSH, and catalase while reducing MDA versus untreated rats. Bone marrow analysis revealed TCN conferred dose-dependent benefits on cellularity and architecture, reducing myeloid blasts and leukocyte infiltration. A near-normal bone microarchitecture was attained with the highest TCN dose. Similarly, TCN elicited marked improvements in splenic cytoarchitecture and attenuation of hypercellularity, lymphocytic infiltration and megakaryocytes compared to leukemic controls in a dose-dependent manner. Conclusions: Terminalia catappa nut extract demonstrated anti-leukemic, haematopoietic, antioxidant, and organ protective effects in leukemic Wistar rats induced with benzene solution, supporting its potential as an adjuvant therapeutic agent.

Research progress on factors influencing the therapeutic effect of gemtuzumab ozo-gamicin for acute myeloid leukemia / 中国肿瘤临床

Acute myeloid leukemia(AML)is a heterogeneous myeloid malignancy.Currently,chemotherapy combined with hematopoietic stem cell transplantation is the primary treatment option;however,over-all prognosis remains poor.Gemtuzumab ozogamicin(GO)is a hu-manized CD33 monoclonal antibody conjugated with calicheamicins.It is primarily used to treat CD33-positive AML.Although studies have found that GO can improve the prognosis of patients with CD33-positive AML,some patients with AML do not benefit from it.Recent stud-ies have found that the effect of GO on AML is primarily associated with the expression of CD33 and its single nucleotide polymorphism(SNP),ATP-binding cassette subfamily B member 1(ABCB1)gene and SNP,as well as specific molecular biology and cytogenetics.This paper reviews the research progress on the factors influencing efficacy of GO for treating AML.

Efficacy of venetoclax combined with azacitidine in the treatment of patients with newly diagnosed unfit acute myeloid leukemia / 中国现代医生

Objective To observe the efficacy and safety of VA regimen(venetoclax + azacitidine)in the treatment of patients with newly diagnosed unfit acute myeloid leukemia(AML).Methods From April 2021 to February 2023,55 unfit AML patients who were treated with VA regimen in the First Affiliated Hospital of Anhui Medical University were retrospectively analysed.The therapeutic efficacy and safety of VA regimen were evaluated.Results The median treatment courses of AML patients was 3(1-10),and complete response(CR)/CR with incomplete blood count recovery(CRi)rate was 78.2%and minimal residual(MRD)negative conversion rate was 61.8%after the first treatment course.CR/CRi rate and MRD negative conversion rate increased gradually with the increase of treatment course.Patients with IDH1/IDH2,NPM1,ASXL1 mutations and without TP53 mutations responded well to the VA regimen.The median follow-up time was 9.1(1.2-24.0)months.39 patients survived and 16 patients died.The median overall survival(OS)was 17.4 months.Patients with CR/CRi had significantly longer OS duration than patients with partial response or non-response(P<0.001).Almost all patients had different degrees of anemia,thrombocytopenia,leukopenia.In terms of non-hematological adverse events,infection was the most common.Conclusion The VA regimen achieved a higher treatment response rate in newly diagnosed unfit AML patients,and partial response patients could quickly obtain negative MRD.IDH1/IDH2,ASXL1,NPM1,TP53 mutations may be the predictors of patient outcomes.

Study on apoptosis mechanism of Jurkat cells induced by CAHB in adult acute lymphoblastic leukemia / 中国现代医生

@#Objective To explore the mechanism of apoptosis induced by diacetyl hexamethylene diamine(CAHB)in adult acute lymphoblastic leukemia Jurkat cells,and to provide theoretical basis for the clinical application of CAHB.Methods Annexin V+/PI-cell rate of Jurkat cells after CAHB induction was analyzed by flow cytometry.The Annexin V+/PI-cell rate was observed after treatment with caspase-9 inhibitor Z-LEHD-FMK.The expressions of apoptosis-related proteins caspase-8,caspase-9 and caspase-3 were observed by Western blotting.Results After CAHB induction,Jurkat cells were reduced in size,cell membrane crinkling,chromatin thickening,nuclear pyknosis or fragmentation,etc.Typical apoptotic bodies could be seen.CAHB induced Jurkat cell apoptosis by activating caspase-9 and caspase-3 in a dose-effect and time-dependent manner.Caspase-9 inhibitors could inhibit apoptosis induction of CAHB to a certain extent.Conclusion CAHB induced Jurkat cell apoptosis was related to caspase-9 and caspase-3 activation.

The clinical significance of CD7 expression in children acute myeloid leukemia / 中国现代医生

@#Objective To investigate the clinical significance of CD7 expression in childhood acute myeloid leukemia(AML).Methods A retrospective analysis was performed on 60 children with AML admitted to Jiangxi Province Children's Hospital from October 2016 to December 2020.According to the results of immunophenotyping,the children were divided into CD7 positive(CD7+)group and CD7 negative(CD7-)group.The clinical characteristics,immunophenotype and treatment effect of the two groups were compared.Results Among 60 children with AML,18 cases were CD7+,and the positive rate was 30.00%,mainly M2 and M5,the expression rate of M2 was 55.56%,which was higher than that of other subtypes.The CD7+ group had significantly higher white blood cell count and bone marrow blast granulocyte count than the CD7-group(P<0.05).There were no significant differences in platelet count,hemoglobin,lactate dehydrogenase,creatinine and other laboratory indicators between the two groups(P>0.05).After 1 course of standard induction chemotherapy,the CD7+ group had a significantly lower complete remission rate than the CD7-group(P<0.05).There was no statistically significant difference(P>0.05)in the overall survival rate and disease free survival rate between the two groups of patients at 1 year and 2 years.Conclusion Compared with CD7-children,the peripheral white blood cell count and bone marrow blast cell count of CD7+ children were significantly higher,and the complete remission rate of induction chemotherapy was significantly lower.The expression of CD7 antigen has a significant predictive value for the poor prognosis of children with AML,which may provide new ideas for the treatment strategy of children with AML,and lay the foundation for further exploring the mechanism of CD7 in the development of AML.

Application of Histone Deacetylase Inhibitor in Acute Myeloid Leukemia / 生物化学与生物物理进展

Acute myeloid leukemia (AML) is a malignant clonal disease of hematopoietic stem cells, characterized by the proliferation of abnormal primordial cells of myeloid origin in bone marrow, blood and other tissues. At present, the standard induction therapy for AML mainly includes “3+7” standard treatment(anthracycline combined with cytarabine), allogeneic hematopoietic stem cell transplantation (Allo-HSCT) and targeted drug therapy. However, AML cells usually express high levels of P-glycoprotein, which mediates the efflux of chemotherapeutic drugs, which makes AML cells resistant to chemotherapy, resulting in many patients who are not sensitive to chemotherapy or relapse after complete remission. And some patients can not tolerate intensive therapy or lack of donors and can not use Allo-HSCT therapy. Therefore, it is of great clinical significance to find new drugs to improve the efficacy of AML patients. Epigenetic disorders play a key role in the pathogenesis of many diseases, especially cancer. Studies have shown that most AML patients have epigenetic regulatory gene mutations, such as DNMT3A, IDH and TET2, and these mutations are potentially reversible, which has become one of the therapeutic targets of AML. Histone deacetylase inhibitors (HDACi) can regulate the balance between histone acetylation and deacetylation, change the expression of proto-oncogenes or tumor suppressor genes that control cancer progression from epigenetics, and play an important role in many kinds of tumor therapy. At present, HDACi has shown the ability to induce differentiation, cell cycle arrest and apoptosis of AML cells. The mechanism may be mainly related to HDACi inducing chromatin conformation opening of tumor suppressor gene by inhibiting HDAC activity, promoting oncogene damage and preventing oncogene fusion protein from recruiting HDAC. Although the preclinical outcome of HDACi is promising, it is not as effective as the conventional therapy of AML. However, the combination strategy with various anticancer drugs is in clinical trials, showing significant anti-AML activity, improving efficacy through key targeting pathways in a typical synergistic or additive way, increasing AML sensitivity to chemotherapy, reducing tumor growth and metastasis potential, inhibiting cell mitotic activity, inducing cell apoptosis, regulating bone marrow microenvironment, which provides a good choice for the treatment of AML. Especially for those AML patients who are not suitable for intensive therapy and drug resistance to chemotherapy. This review introduces the relationship between HDAC and cancer; the classification of HDAC and its function in AML; the correlation between HDAC and AML; the clinical application of five types of HDACi; preclinical research results and clinical application progress of six kinds of HDACi in AML, such as Vrinota, Belinostat, Panobinostat, Valproic acid, Entinostat, and Chidamide, the mechanism of HDACi combined with other anticancer drugs in AML indicates that the current HDACi is mainly aimed at various subtypes of pan-HDAC inhibitors, with obvious side effects, such as fatigue, thrombocytopenia, nausea, vomiting, diarrhea. In recent years, the next generation of HDACi is mainly focused on the selectivity of analogues or isomers. Finding the best combination of HDACi and other drugs and the best timing of administration to balance the efficacy and adverse reactions is a major challenge in the treatment of AML, and the continued development of selective HDACi with less side effects and more accurate location is the key point for the development of this drug in the future. It is expected to provide reference for clinical treatment of AML.