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

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.

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.

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.

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.

Linfoma extranodal de epiglotis en un paciente con recaída de leucemia linfoide aguda de células T. Presentación de un caso

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.

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)

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.

All about blinatumomab: the bispecific T cell engager immunotherapy for B cell acute lymphoblastic leukemia

ABSTRACT Introduction: B cell acute lymphoblastic leukemia-lymphoma (B-ALL) accounts for approximately 75% of ALL cases and is observed in children and adults. Recent advances in disease diagnosis, stratification and prognostication have led to a better characterization of different subgroups of ALL. Notwithstanding the significant improvement in the complete remission rate of B-ALL, patients with minimal residual disease (MRD) and relapsed/refractory (R/R) settings suffer from poor outcomes. Hypothesis: However, novel therapies, such as agents targeting tyrosine kinases or the CD20 molecule, combination therapies and improved supportive care, have changed the treatment landscape of B-ALL. Method and results: Meanwhile, blinatumomab has been FDA-approved for MRD-positive or R/R B-ALL patients. Blinatumomab is a bispecific T cell engager containing the CD3 and CD19 that recognize domains redirecting cytotoxic T cells to lyse B cells. Promising outcomes, including long-term overall survival and improved MRD-negative response rates, have been reported in patients who received this drug. Adding blinatumomab to new ALL regimens seems promising for achieving better outcomes in poor prognosis B-ALL patients. Nevertheless, the neurotoxicity and cytokine release syndrome are the two major adverse events following the blinatumomab therapy. Conclusion: This review summarizes the function and effectiveness of blinatumomab in R/R and MRD positive B-ALL patients. Furthermore, blinatumomab's positive and negative aspects as a novel therapy for B-ALL patients have been briefly discussed.

Rhinocerebral mucormycosis and Trichosporon asahii fungemia in a pediatric patient with acute lymphoblastic leukemia: a rare coinfection

ABSTRACT Mucormycosis is a rare life-threatening opportunistic infection, with rhinocerebral mucormycosis (ROCM) being the most common presentation. Trichosporon asahii is an emerging pathogen that often causes fatal infections in patients with underlying hematologic malignancies due to its high drug resistance. We report a rare case of concomitant rhinocerebral mucormycosis and T. asahii fungemia secondary to Pseudomonas aeruginosa sepsis in a patient with neutropenia and acute lymphoblastic leukemia. A boy aged one year and two months was diagnosed with B-cell acute lymphoblastic leukemia on January 10 and underwent three courses of regular chemotherapy. He experienced neutropenia for 154 days and was hospitalized for vomiting, diarrhea and fever for 3 days. The day after hospitalization, Pseudomonas aeruginosa was isolated by blood culture and ceftazidime/avibactam was administered. Extracorporeal Membrane Oxygenation (ECMO) was used to provide continuous extracorporeal respiration and circulation for the patient. On day 8, the patient developed T. asahii fungemia. On day 10, he presented with necrotizing skin caused by Rhizopus delemar. He was treated with liposomal amphotericin B for Rhizopus delemar and voriconazole for T. asahii infection. Unfortunately, his health deteriorated and he died on day 11 due to the rapid progression of the infection and multiple organ failure. The management and treatment of such a complex infection requires a multidisciplinary approach and close monitoring of the patient's condition. Therefore, it is imperative to continue to research and report rare cases such as this to further understand the complexities of mucormycosis and trichosporidiosis coinfection and improve patient outcomes.

Epidemiologia de la leucemia neonatal en bolivia

Introducción. La leucemia neonatal se presenta durante las cuatro primeras semanas de vida extrauterina, corresponde al 1% de todas las leucemias pediátricas. Se caracteriza por leucemogénesis en útero y está relacionada con la genotoxicidad y el medio ambiente contaminado. La leucemia mieloide aguda representa la gran mayoría de los casos (60%), las alteraciones cromosómicas afectan a la región 11q23. La infiltración cutánea leucémica, la hepatoesplenomegalia y la leucocitosis mayor a 100.000/ul son signos comunes en esta enfermedad. Objetivo. Determinar las características epidemiológicas de la leucemia neonatal en Bolivia. Material y métodos. Estudio descriptivo retrospectivo de leucemias neonatales diagnosticadas entre 2007 y 2023. Se recolectó datos epidemiológicos concernientes a características clínicas, características morfológicas e immunofenotípicas, resultados de laboratorio correspondientes al momento del diagnóstico y seguimiento, así como, la radicatoria de la madre durante la gestación. Resultados. Se evidenció 13 casos, la edad media neonatal fue 20 días y mayor incidencia en neonatos varones (n=9, 69%). La LMA (9 casos, 69 %) fue el tipo de leucemia más frecuente (subtipo preponderante LMA M7), seguida de la LLA-B (n=4). 7 casos fueron procedentes de Santa Cruz (54 %), 3 de Cochabamba (23 %), sucesivamente La Paz, Beni y Chuquisaca con un caso cada uno (23 %). Leucocitosis media 106.000/ul, hemoglobina media 13,2 g/dl y plaquetas 209.000/ul fueron características laboratoriales. Conclusiones. La incidencia de leucemia neonatal en Santa Cruz y Cochabamba constituye un interés de salud pública, lo que demanda escudriñar sobre factores de riesgo relacionados con su etiología y el impacto de la contaminación del medio ambiente en esas regiones.

Introduction. Neonatal leukemia occurs during the first four weeks after birth, corresponding to 1% of all pediatric leukemias. It is characterized byleukemogenesis in the uterus, which is related to genotoxicity and polluted environment. Acute myeloid leukemia representas the vast majority of cases (60%), chromosomal alterations concerning 11q23 region. Common signs involve leukemia cutis, hepatosplenomegaly and leukocytosis higher than 100,000/ul. Objective. To determine the epidemiological characteristics of neonatal leukemia in Bolivia. Material and methods. Retrospective descriptive study of neonatal leukemias diagnosed between 2007 and 2023. Epidemiological data regarding clinical characteristics, morphological and immunophenotypic features, laboratory results at diagnosis and follow-up, as well as, residency of the mother during pregnancy were collected. Results. A total of 13 cases were evidenced, mean neonatal age was 20 days, with a higher incidence in male neonates (n=9, 69%). AML (9 cases, 69%) was the most common type of leukemia (mainly AML M7 subtype), followed by B-ALL (n=4). 7 cases were from Santa Cruz (54%), 3 from Cochabamba (23%), consecutively La Paz, Beni and Chuquisaca with 1 case each (23%). Laboratory characteristics displayed mean leukocytosis of106,000/ul, mean Hb 13,2 g/dl and platelets 209.000/ ul. Conclusions. The incidence of neonatal leukemia in Santa Cruz and Cochabamba stands a public health interest, which requires scrutinizing risk factors related to its etiology and the impact of environmental pollution in those region.

Avaliação da saúde bucal de crianças e adolescentes com leucemia atendidas no Hemorio / Evaluation of the oral health of children and adolescents with leukemia treated at Hemorio

Esta pesquisa transversal, descritiva e observacional objetivou avaliar a saúde bucal dos participantes infantojuvenis diagnosticados com leucemia, assistidos pela odontologia. Foram incluídas todas as crianças e adolescentes de 3 a 18 anos matriculadas no centro de referência hematológico e diagnosticados com leucemia, atendidos pela instituição, entre junho/2022 e janeiro/2023. Foram coletados os dados sociodemográfcos, médicos, odontológicos e laboratoriais, seguidos de uma avaliação clínica odontológica e registro fotográfco. Para avaliação da prevalência de cárie utilizou-se o índice de dentes cariados, perdidos, obturados, por dente e o índice de dentes decíduos cariados, indicado a extração e obturado. A avaliação das manifestações orais fo irealizada conforme protocolo da Organização Mundial de Saúde. Compuseram a pesquisa 25 participantes, 14 masculinos e 11 femininos, a média deidade foi de 10,12 anos (d.p. = 4,8).A leucemia linfoide aguda foi a mais prevalente (80%), a maioria dos participantes apresentou índice de cárie zero (60%), as manifestações orais foram diagnosticadas em 60% deles, sendo as mais frequentes: alteração de paladar (24%), mucosite (16%) e xerostomia (12%). Os participantes também apresentaram alta incidência de manifestações orais, condição de higiene bucal insatisfatória, porém baixo índice de cárie. Outrossim, observa-se a importância de os cirurgiões dentistas conhecerem as manifestações orais mais encontradas em crianças com leucemia, a necessidade da higiene bucal de qualidade, bem como a condição de saúde bucal total, buscando garantir que a boca não seja uma fonte de infecção que prejudique a condição de saúde geral e o tratamento oncológico.

This study aimed to evaluate the oral health of child and adolescent participants diagnosed with leukemia, assisted by dentistry. The research was configured a cross-sectional, descriptive and observational. All. All children and adolescents enrolled in the hematological reference center, aged 3 to 18 years, diagnosed with leukemia, treated by the institution, between June 2022 and January 2023 were included. Sociodemographic, medical, dental and laboratory data were collected; followed by a clinical dental evaluation and photographic recording. To assess the prevalence of caries, the index of decayed, missing,filled teeth per tooth and the index of decayed primary teeth, indicated for extraction and filling, were used. The evaluation of oral manifestations was carried out according to the World Health Organization protocol.The research included 25 participants, 14 male and 11 female and the average age was 10.12 years (SD = 4.8). Acute lymphoblastic leukemia was the most prevalent (80%). Regarding the caries index, the majority of participants had zero (60%) and oral side effects were diagnosed in 60% of them, the most frequent being:change in taste (24%), mucositis (16%) and xerostomia (12%). Participants also had a high incidence of oral manifestations, unsatisfactory oral hygiene, but a low rate of caries. Furthermore, it is important for dental surgeons to know the ora manifestations most commonly found in children with leukemia, the need for quality oral hygiene, as well as the oral health condition as a whole, seeking to ensure that the mouth is not a source of infection, which harms the general health condition and cancer treatment.

Subpoblaciones de linfocitos T en adultos mayores cubanos con leucemia linfoide crónica / Subpopulations of T lymphocytes in Cuban older adults with chronic lymphoid leukemia

Introducción: la inmunosenescencia está asociada con un mayor riesgo de desarrollo de cáncer. Dentro de las hemopatías malignas que afectan a este grupo de edad, está la leucemia linfoide crónica (LLC), caracterizada por trastornos en la inmunidad adaptativa que incluye las subpoblaciones de linfocitos T. Objetivo: Determinar la frecuencia de las subpoblaciones de linfocitos T en los pacientes adultos mayores con leucemia linfoide crónica evaluados en el Instituto de Hematología e Inmunología de Cuba. Métodos: Se realizó un estudio transversal en 30 adultos mayores con leucemia linfoide crónica. Se cuantificaron los linfocitos TCD3+CD4+ y TCD3+CD8+ en sangre periférica por citometría de flujo. Para la lectura y el análisis de los datos se empleó un citómetro de flujo Beckman Coulter Gallios. Se utilizaron los valores porcentuales, la media y la desviación estándar. Se consideró estadísticamente significativo si p≤0.05. Resultados: Hubo un predominio de hombres que representaron el 56,7 por ciento y del grupo de 70-79 años de edad. No se reportó ningún adulto mayor con LLC con valores altos ni normales de linfocitos TCD3+CD4+. Predominaron los hombres con valores bajos porcentuales de linfocitos TCD3+CD4+, TCD3+CD8+ e inversión del índice CD4/CD8 en relación con las mujeres. Conclusiones: Los adultos mayores con LLC presentan alteraciones en el número de las subpoblaciones de linfocitos T. La acción de estas células en relación al crecimiento de células B malignas aún es desconocido y resulta importante determinar si esto puede reflejar un intento de evasión de las células tumorales al control inmunológico(AU)

Introduction: Immunosenescence is associated with an increased risk of cancer development. Among the malignant hemopathies that affect this age group, it is chronic lymphoid leukemia (CLL), characterized by disorders in adaptive immunity, which include subpopulations of T lymphocytes. Objective: To determine frequency of T lymphocyte subpopulations in older adult patients with chronic lymphoid leukemia evaluated at the Institute of Hematology and Immunology of Cuba. Methods: A cross-sectional study was conducted in 30 older adults with chronic lymphoid leukemia. TCD3+CD4+ and TCD3+CD8+ lymphocytes were quantified in peripheral blood by flow cytometry. A Beckman Coulter Gallios flow cytometer was used to read and analyze the data. The percentage values, the mean and the standard deviation were used. It was considered statistically significant if p≤0.05. Results: There was a predominance of men who represented 56.7 percent and the age group of 70-79 years. No older adults with CLL with high or normal values of TCD3+CD4+ lymphocytes were reported. Men predominated with low percentage values of TCD3+CD4+, TCD3+CD8+ lymphocytes and inversion of the CD4/CD8 ratio in relation to women. Conclusions: Older adult with CLL present alterations in the number of T lymphocyte subpopulations. The role of these cells in relation to the growth of malignant B cells it is unknown and it turns out important to determine if this may reflect an attempt to evade tumor cells from immune control(AU)

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.

Clinical observation of venetoclax combined with homoharringtonine and cytarabine in the treatment of acute myeloid leukemia / 中国药房

OBJECTIVE To observe the short-term efficacy and safety of venetoclax combined with homoharringtonine and cytarabine in the treatment of acute myeloid leukemia （AML）. METHODS The data of 40 newly diagnosed AML patients admitted to our hospital from October 2022 to November 2023 were retrospectively collected and divided into observation group and control group according to treatment plan， with 20 cases in each group. The patients in the control group were given Daunorubicin hydrochloride for injection+Cytarabine for injection， and the patients in the observation group were given Venetoclax tablets+ Homoharringtonine injection+Cytarabine for injection. The patients in both groups were given relevant medicine， with 28 days as one cycle. The short-term efficacy， negative rate of minimal residual disease （MRD）， duration of granulocyte deficiency， duration of platelet （PLT） ＜20×109 L－1， transfusion volume of suspended red blood cells and platelet， and the occurrence of adverse drug reactions were evaluated in both groups after 1 cycle of induction chemotherapy. RESULTS The complete remission or complete remission with incomplete hematologic recovery （CR/CRi） rate in the observation group was significantly higher than control group （P＜0.05）， and the negative rate of MRD in the observation group was also significantly higher than control group （P＜0.05）. However， in low-， medium- and high-risk patients， there was no statistical significance in CR/CRi rates between the two groups （P＞0.05）. There were no significant differences in the duration of agranulocytosis， the duration of PLT ＜20×109 L－1， the amount of suspended red blood cell transfusion， the amount of platelet transfusion， the incidence of hematologic toxicity and the incidence of non-hematologic toxicity between 2 groups （P＞0.05）. CONCLUSIONS Venetoclax combined with homoharringtonine and cytarabine show good short-term efficacy and safety in the treatment of AML.

Blood group changes in acute myeloid leukemia and their relationship with therapeutic effect / 中国输血杂志

【Objective】 To explore the blood group changes of two acute myeloid leukemia patients with suspected O type, and their relationship with the therapeutic effect. 【Methods】 Serological analysis of ABO blood group of patients was carried out by microcolumn gel method, tube method and absorption-elution test, ABO blood group genotyping was performed by microfluidic chip method. Exons E2 to E7 of ABO gene were amplified by PCR and sequenced by Sanger method. 【Results】 The forward typing of two cases were both O type, but the reverse typing were both A type. The absorption-elution test results all showed detection of antigen A. ABO gene phenotype of the two cases were both A, with genotyping results as A102/A102 and A102/O01, respectively. Sequencing results showed that SNP sites of ABO blood group were 467T/T, 261G/delG and 467C/T, respectively.In one case, the intensity of anti-A agglutination reaction changed significantly from weak to strong with the progress of treatment. 【Conclusion】 For clinical samples of acute myeloid leukemia patients with ABO forward and reverse typing discrepancy and suspected O type, the result of reverse typing should be valued, and absorption-elution test should be performed to further confirm the ABO blood type combining the genetic test results, so as to develop appropriate blood transfusion strategies for patients.

Strategy of Targeted T Cell Immunotherapy for Acute Myeloid Leukemia / 肿瘤防治研究

T cell dysfunction is a common feature in patients with acute myeloid leukemia (AML). The up-regulation of immune checkpoint (IC) proteins resulting in T cell exhaustion is a key reason for T cell dysfunction. Immunotherapy with IC inhibitors exerts a remarkable effect on AML. However, due to the heterogeneity of T cell exhaustion and other factors that impair T cell function in patients with AML, the optimization of targeted T cell immunotherapy strategy for AML might be based on the multidimensional investigation of immune deficiency with different T cell subtypes.

Clinical analysis of lung transplantation for lung chronic graft-versus-host disease after hematopoietic stem cell transplantation / 器官移植

<b>Objective</b> To evaluate clinical efficacy of lung transplantation for lung chronic graft-versus-host disease (cGVHD) after hematopoietic stem cell transplantation (HSCT). <b>Methods</b> Clinical data of 12 patients undergoing lung transplantation for lung cGVHD were retrospectively analyzed. Preoperative clinical manifestations and involved organs of patients were analyzed. The lung function before and after lung transplantation was compared, and the survival of patients after lung transplantation was analyzed. <b>Results</b> Eleven patients underwent HSCT due to primary hematological malignancies, including 9 cases of leukemia, 1 case of myelodysplastic syndrome, 1 case of lymphoma. And 1 case underwent HSCT for systemic lupus erythematosus. Among 12 cGVHD patients, skin involvement was found in 8 cases, oral cavity involvement in 5 cases, gastrointestinal tract involvement in 4 cases and liver involvement in 3 cases. All 12 patients developed severe respiratory failure caused by cGVHD before lung transplantation, including 9 cases of typeⅡ respiratory failure and 3 cases of type Ⅰ respiratory failure. Two patients underwent right lung transplantation, 2 cases of left lung transplantation and 8 cases of bilateral lung transplantation. The interval from HSCT to lung transplantation was 75 (19-187) months. Upon the date of submission, postoperative follow-up time was 18 (7-74) months. Ten patients survived, 1 died from severe hepatitis at postoperative 22 months, and 1 died from gastrointestinal bleeding at postoperative 6 months. No recurrence of primary diseases was reported in surviving patients. <b>Conclusions</b> Lung transplantation is an efficacious treatment for lung cGVHD after HSCT, which may prolong the survival time and improve the quality of life of the recipients.

Progress of gene-mediated precision immunotherapy in the treatment of acute myeloid leukemia / 中国药科大学学报

@#Acute myeloid leukemia (AML) is a disease caused by abnormal cloning of hematopoietic stem cells in the bone marrow, which leads to accumulation of a large number of abnormally differentiated myeloid cells. It is difficult to cure by traditional treatment. The successful application of chimeric antigen receptor T cell (CAR-T) immunotherapy indicates that the treatment of hematological tumors has entered a new stage of precision immunotherapy. However, CAR-T immunotherapy has been found to have many problems in clinical applications, including long treatment cycle, expensive prices, off-target effects, cytokine release syndrome, etc. Therefore, it is necessary to expand the application of CAR or adopt improved measures to enhance the therapeutic effect. This article reviews the new strategies for genetic engineering modification of CAR immune cells and the research progress and application of in situ programming to generate CAR-T, and besides, briefly introduces the new methods about the delivery of gene drugs in vivo, aiming to provide new ideas and theoretical basis for expanding and improving the application of precision immunotherapy in AML.