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1.
Hematol., Transfus. Cell Ther. (Impr.) ; 44(3): 358-364, July-Sept. 2022. tab, graf
Article in English | LILACS | ID: biblio-1405011

ABSTRACT

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.


Subject(s)
Humans , Adult , Middle Aged , Aged , Aged, 80 and over , Young Adult , Leukemia, Myeloid, Acute , Surveys and Questionnaires , Drug Therapy, Combination
3.
Rev. ecuat. pediatr ; 23(2): 146-153, 15 de agosto 2022.
Article in Spanish | LILACS | ID: biblio-1397276

ABSTRACT

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.


Subject(s)
Humans , Child, Preschool , Child , Child , Bone Marrow Transplantation , Bone Marrow , Leukemia, Myeloid, Acute , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Survivorship
4.
Rev. cuba. hematol. inmunol. hemoter ; 38(2): e1516, abr.-jun. 2022.
Article in Spanish | LILACS, CUMED | ID: biblio-1408444

ABSTRACT

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)


Subject(s)
Humans , Bone Marrow , Chromosomes, Human, Pair 7 , Chromosomes, Human, Pair 8 , Hematopoietic Stem Cells , Leukemia, Myeloid, Acute , In Situ Hybridization , Cytogenetics , Decision Making
7.
Rev. chil. infectol ; 39(2): 203-207, abr. 2022. ilus
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1388341

ABSTRACT

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.


Subject(s)
Humans , Male , Child , Leukemia, Myeloid, Acute/microbiology , Leukemia, Myeloid, Acute/drug therapy , Invasive Fungal Infections/diagnosis , Invasive Fungal Infections/drug therapy , Retrospective Studies , Voriconazole/therapeutic use , Antifungal Agents/therapeutic use
8.
Arch. argent. pediatr ; 120(2): e89-e92, abril 2022.
Article in Spanish | LILACS, BINACIS | ID: biblio-1363982

ABSTRACT

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.


Subject(s)
Humans , Male , Female , Infant, Newborn , Leukemia, Myeloid, Acute/complications , Leukemia, Myeloid, Acute/diagnosis , Down Syndrome/complications , Down Syndrome/diagnosis , Leukemoid Reaction/diagnosis , Leukemoid Reaction/etiology , Leukemoid Reaction/therapy , Myeloproliferative Disorders/complications , Myeloproliferative Disorders/diagnosis
9.
Article in Spanish | LILACS-Express | LILACS, CUMED | ID: biblio-1408440

ABSTRACT

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)


Subject(s)
Humans , Reference Standards , Biomarkers , Leukemia, Myeloid, Acute , Residence Characteristics
12.
Frontiers of Medicine ; (4): 459-466, 2022.
Article in English | WPRIM | ID: wpr-939879

ABSTRACT

Whether Fanconi anemia (FA) heterozygotes are predisposed to bone marrow failure and hematologic neoplasm is a crucial but unsettled issue in cancer prevention and family consulting. We retrospectively analyzed rare possibly significant variations (PSVs) in the five most obligated FA genes, BRCA2, FANCA, FANCC, FANCD2, and FANCG, in 788 patients with aplastic anemia (AA) and hematologic malignancy. Sixty-eight variants were identified in 66 patients (8.38%). FANCA was the most frequently mutated gene (n = 29), followed by BRCA2 (n = 20). Compared with that of the ExAC East Asian dataset, the overall frequency of rare PSVs was higher in our cohort (P = 0.016). BRCA2 PSVs showed higher frequency in acute lymphocytic leukemia (P = 0.038), and FANCA PSVs were significantly enriched in AA and AML subgroups (P = 0.020; P = 0.008). FA-PSV-positive MDS/AML patients had a higher tumor mutation burden, higher rate of cytogenetic abnormalities, less epigenetic regulation, and fewer spliceosome gene mutations than those of FA-PSV-negative MDS/AML patients (P = 0.024, P = 0.029, P = 0.024, and P = 0.013). The overall PSV enrichment in our cohort suggests that heterozygous mutations of FA genes contribute to hematopoietic failure and leukemogenesis.


Subject(s)
Anemia, Aplastic/genetics , Epigenesis, Genetic , Fanconi Anemia/genetics , Germ Cells , Hematologic Neoplasms/genetics , Humans , Leukemia, Myeloid, Acute/genetics , Retrospective Studies
13.
Frontiers of Medicine ; (4): 403-415, 2022.
Article in English | WPRIM | ID: wpr-939874

ABSTRACT

The morbidity and mortality of myeloproliferative neoplasms (MPNs) are primarily caused by arterial and venous complications, progression to myelofibrosis, and transformation to acute leukemia. However, identifying molecular-based biomarkers for risk stratification of patients with MPNs remains a challenge. We have previously shown that interferon regulatory factor-8 (IRF8) and IRF4 serve as tumor suppressors in myeloid cells. In this study, we evaluated the expression of IRF4 and IRF8 and the JAK2V617F mutant allele burden in patients with MPNs. Patients with decreased IRF4 expression were correlated with a more developed MPN phenotype in myelofibrosis (MF) and secondary AML (sAML) transformed from MPNs versus essential thrombocythemia (ET). Negative correlations between the JAK2V617F allele burden and the expression of IRF8 (P < 0.05) and IRF4 (P < 0.001) and between white blood cell (WBC) count and IRF4 expression (P < 0.05) were found in ET patients. IRF8 expression was negatively correlated with the JAK2V617F allele burden (P < 0.05) in polycythemia vera patients. Complete response (CR), partial response (PR), and no response (NR) were observed in 67.5%,10%, and 22.5% of ET patients treated with hydroxyurea (HU), respectively, in 12 months. At 3 months, patients in the CR group showed high IRF4 and IRF8 expression compared with patients in the PR and NR groups. In the 12-month therapy period, low IRF4 and IRF8 expression were independently associated with the unfavorable response to HU and high WBC count. Our data indicate that the expression of IRF4 and IRF8 was associated with the MPN phenotype, which may serve as biomarkers for the response to HU in ET.


Subject(s)
Biomarkers , Humans , Hydroxyurea/therapeutic use , Interferon Regulatory Factors/genetics , Janus Kinase 2/genetics , Leukemia, Myeloid, Acute/genetics , Mutation , Phenotype , Primary Myelofibrosis/genetics , Thrombocythemia, Essential/genetics
14.
Article in Chinese | WPRIM | ID: wpr-939711

ABSTRACT

OBJECTIVE@#To investigate the clinical characteristics and prognosis of hematological malignancies superimposed patients with solid tumors.@*METHODS@#The clinical data of 30 patients with more than two kinds of malignancy (the second is hematological malignancy) from October 2011 to October 2020 in Department of Hematology, Jiangning Hospital Affiliated to Nanjing Medical University were collected and analyzed retrospectively. The overall survival time was used as the prognostic evaluation standard, and the survival of patients were analyzed by KaplanMeier method. Logrank test and Cox regression model were used to carry out univariate and multivariate retrospective analysis on clinical and laboratory parameters of 30 patients.@*RESULTS@#Among 30 cases, 20 were male, 10 were female, the median age of onset of the second tumor was 70 years old. The common types of the secondary hematological malignancies to solid tumors are myelodysplastic syndrome, acute myeloid leukemia, multiple myeloma. Univariate analysis showed that patients' gender, age, type of solid tumors, the onset of interval between two kinds of tumor, chromosome karyotype were not related to do with the patients' overall survival time. Type of hematologic disease, ECOG score were associated with patients' overall survival time, and the multivariate analysis showed that the type of hematologic disease and ECOG score were independent risk factors for patients with poor prognosis.@*CONCLUSION@#Patients superimposed with solid tumors complicated with myelodysplastic syndrome or acute leukemia and ECOG score ≥3 have poor prognosis and shorter overall survival time, which are independent risk factors influencing the prognosis. Bone marrow injury, immune dysfunction and genetic susceptibility after chemoradiotherapy may be the main causes of these diseases.


Subject(s)
Aged , Female , Hematologic Neoplasms/complications , Humans , Leukemia, Myeloid, Acute/complications , Male , Myelodysplastic Syndromes/complications , Prognosis , Retrospective Studies
15.
Article in Chinese | WPRIM | ID: wpr-939684

ABSTRACT

OBJECTIVE@#To investigate the characteristics of gene mutation in elderly patients with acute myeloid leukemia (AML) and its effect on prognosis.@*METHODS@#The clinical and laboratorial characteristics of 54 AML patients (≥60 years old) in Department of Hematology, Tangdu Hospital were analyzed retrospectively during April 2016 to October 2019. Thirty-four AML/myelodysplastic syndrome/myeloproliferative neoplasm related mutant genes were detected by second-generation sequencing technology, and their clinical characteristics, treatment effect, and influence on prognosis were analyzed.@*RESULTS@#All the patients received DAC+CAG induction treatment, after 1-2 couses of treatment, 36 cases (66.7%) achieved complete response, with a total effective rate of 75.9%, and the median survival time was 17 months. The most frequent mutant genes were TET2 (33.3%), CEBPA (31.5%), DNMT3A (18.5%), ASXL1 (16.7%), NRAS (14.8%), RUNX1 (14.8%), FLT3-ITD (12.9%), TP53 (12.9%), NPM1 (12.9%), and IDH2 (12.9%). Among 7 patients with TP53 mutation, 6 cases obtained complete response after 1-2 courses of induction treatment, but there was no statistically significant difference in the effect on prognosis. Patients with FLT3-ITD and NRAS mutations had shorter overall survival time compared with who had no mutation (P=0.47, P=0.48). Multivariate analysis showed that FLT3-ITD and NRAS mutations were poor prognostic factors.@*CONCLUSION@#The incidence of TET2 gene mutation is high in elderly AML patients. AML patients with TET2 and TP53 mutations may benefit from Decitabine-based chemotherapy. However, patients with FLT3-ITD and NRAS mutations have a short survival time, and may have a poor prognosis.


Subject(s)
Aged , Humans , Leukemia, Myeloid, Acute/genetics , Middle Aged , Mutation , Nucleophosmin , Prognosis , Retrospective Studies , fms-Like Tyrosine Kinase 3
16.
Article in Chinese | WPRIM | ID: wpr-939682

ABSTRACT

OBJECTIVE@#To explore the expression of cellular apoptosis susceptibility protein (CAS) in acute myeloid leukemia (AML) and its correlation with clinical characteristics.@*METHODS@#The expression of CAS in bone marrow tissue of 54 patients with AML and 24 patients with non-hematological malignant diseases was detected by Western blot and immune-histochemical method, and compared between AML group and control group. Also the relationship of CAS expression in AML and sex, age, WBC count, Hb, platelet count, bone marrow blast cell ratio, ki-67 index, cytogenetic and molecular biological prognostic risk stratification, extramedullary infiltration and other clinical characteristics was analyzed.@*RESULTS@#Western blot showed that the expression of CAS protein in bone marrow biopsies of AML patients was significantly higher than that in control group (P<0.05). Immune-histochemical method revealed that CAS was mainly located in the cytoplasm in both AML group and control group. Among 54 AML patients, 14 patients (25.9%) showed high expression of CAS, while all the 24 patients in the control group showed low expression of CAS. The high expression rate of CAS in AML patients was significantly higher than that in the control group (P<0.05). There were statistically significant differences in prognostic risk stratification and the remission rate of the first chemotherapy between CAS high expression group and CAS low expression group in AML (P<0.05). The proportion of high risk patients and unremission patients after the first chemotherapy in CAS high expression group were significantly higher than those in CAS low expression group (57.1% vs 27.5%, 30.8% vs 7.9%), while the proportion of low risk patients and complete remission patients after the first chemotherapy were significantly lower than those in CAS low expression group (14.3% vs 37.5%, 53.8% vs 84.2%). In AML patients, the ki-67 index of bone marrow tissue in CAS high expression group was higher than that in CAS low expression group (60% vs 50%) (P<0.05).@*CONCLUSION@#CAS is localized in cytoplasm in both AML and non-hematological malignant diseases, and its expression increases in AML. CAS is related to the risk stratification of cytogenetics and molecular biology, the remission rate after the first chemotherapy and ki-67 index in AML, which suggests that CAS may be involved in the occurrence and development of AML.


Subject(s)
Bone Marrow/metabolism , Cellular Apoptosis Susceptibility Protein/metabolism , Humans , Ki-67 Antigen/metabolism , Leukemia, Myeloid, Acute/drug therapy , Prognosis , Remission Induction
17.
Article in Chinese | WPRIM | ID: wpr-939681

ABSTRACT

OBJECTIVE@#To investigate the prognostic significance of dynamic detection of minimal residual disease (MRD) in patients with acute myeloid leukemia (AML) by 8-color flow cytometry.@*METHODS@#MRD of 282 AML patients who achieved remission after initial therapy was detected by 8-color flow cytometry. MRD threshold for predicting recurrence was determined by receiver operating characteristic (ROC) curve, and time from MRD-positive to clinical recurrence was analyzed. The differences in overall survival (OS) time and relapse-free survival (RFS) time of patients with different MRD-changes were compared, and the related factors of recurrence in patients with MRD-negative were analyzed by univariate and logistic regression analysis.@*RESULTS@#ROC curve determined that the MFC-MRD threshold for predicting the recurrence of AML was 0.105%, and the recurrence rate of MRD-positive patients was significantly higher than that of MRD-negative patients [52.45% (75/143 cases) vs 35.97% (50/139 cases), P=0.005]. The patients in MRD persistent positive group and negative to positive group recurred earlier than those in positive to negative group and negative-positive fluctuation group (P<0.005). Survival analysis showed that OS and RFS time of patients with MRD persistent positive were significantly shorter than those of patients with MRD persistent negative, positive to negative, and negative-positive fluctuation (P<0.005). There was no significant difference in OS and RFS between MRD negative to positive group and MRD persistent positive group (P>0.005), either between MRD persistent negative group and MRD positive to negative group (P>0.005). Among 139 MRD-negative patients, 50 recurred. Univariate and logistic regression analysis showed that the risk of recurrence increased with the increase of white blood cells level (95%CI: 1.000-1.013, P=0.045). The risk of recurrence in patients without hematopoietic stem cell transplantation (HSCT) was 9.694 times higher than that in patients who received HSCT (95%CI: 1.720-54.651, P=0.010), and in the high-risk group was 5.848 times higher than that in the low-risk group (95%CI: 1.418-24.121, P=0.015).@*CONCLUSION@#The prognosis of AML patients with different MRD changes is significantly different. No matter MRD-positive or MRD-negative at the initial remission, dynamic detection of MRD after treatment is more helpful to accurately guide treatment.


Subject(s)
Flow Cytometry , Hematopoietic Stem Cell Transplantation , Humans , Leukemia, Myeloid, Acute/drug therapy , Neoplasm, Residual/diagnosis , Prognosis , Recurrence , Transplantation, Homologous
18.
Article in Chinese | WPRIM | ID: wpr-939679

ABSTRACT

OBJECTIVE@#To analyze and compare the efficacy of recombinant human thrombopoietin (rhTPO) and recombinant human interleukin-11 (rhIL-11) in the treatment of thrombocytopenia after chemotherapy in acute leukemia patients.@*METHODS@#180 patients with acute leukemia complicated with thrombocytopenia after chemotherapy in the First Affiliated Hospital of Anhui Medical University were analyzed retrospectively. Among them, 50 patients who treated with rhTPO and did not receive platelet transfusion were set as group A, 50 patients treated with rhTPO and receive platelet transfusion were set as group B, Forty patients treated with rhIL-11 without platelet transfusion were set as group C, Forty patients who treated with rhIL-11 and received platelet transfusion were set as group D. The duration of PLT below 20×109/L, the days it takes for PLT to recover to more than 100×109/L, and the incidence of different bleeding degrees were compared among several groups.@*RESULTS@#The duration of PLT<20×109/L in group A(3.72±1.14 d) was significantly shorter than that in group C(4.93±1.33 d) (P<0.001), and there was no significant difference from group B (P>0.05). The duration of PLT<20×109/L in group B(3.06±0.91 d) was significantly shorter than that in group D(4.65±0.98 d) (P<0.001), while the difference in duration of days between group C and D was not statistically significant (P>0.05). The times for PLT to recover to 100×109/L in group A(13.46±1.67 d) were significantly shorter than that in group C(16.85±2.13 d) (P<0.05), but there was no significant difference from group B (P>0.05). The time required for PLT to recover to 100×109/L in group B(13.36±1.49 d) were significantly shorter than that in group D(16.18±1.78 d) (P<0.05), while the difference in the days required for group C and group D was not statistically significant (P>0.05). The incidence of high bleeding risk in group B was significantly lower than that in group A (22% vs 44%, P<0.05), the incidence of high bleeding risk in group D was significantly lower than that in group C (32% vs 65%, P<0.05), and the incidence of high bleeding risk in group A was significantly lower than that in group C (44% vs 65%, P<0.05). The incidence of high bleeding risk in group B(22%) was lower than that in group D(32.5%), and the difference was not statistically significant (P>0.05).@*CONCLUSION@#In the treatment of acute leukemia patients with thrombocytopenia after chemotherapy, compared with rhIL-11, rhTPO can significantly shorten the duration for patients in a status with extremely low levels of PLT and the recovery time of PLT to normal range. In addition, PLT transfusion cannot speed up the time for patients to raise platelets to a safe range, nor can it shorten the duration of low PLT levels, but it can reduce the incidence of high bleeding risk events.


Subject(s)
Humans , Interleukin-11 , Leukemia, Myeloid, Acute/drug therapy , Platelet Count , Recombinant Proteins/therapeutic use , Retrospective Studies , Thrombocytopenia , Thrombopoietin/therapeutic use
19.
Article in Chinese | WPRIM | ID: wpr-939678

ABSTRACT

OBJECTIVE@#To construct cytarabine-resistant acute myeloid leukemia (AML) cell lines, and explore the correlation between Sirt1, PGC-1α expression levels and drug resistance.@*METHODS@#Human acute promyelocytic leukemia Kasumi-1 cells were induced by the method of gradually increasing the concentration of Ara-C drug. The IC50 value of Kasumi-1 cells before and after drug addition was detected by CCK-8 method, so as to construct Ara-C resistant cell lines. The expression levels of Sirt1 and PGC-1α mRNA in Kasumi-1 drug-resistant cell lines and their parental cell lines were detected by real-time fluorescence quantitative PCR, and the expression levels of Sirt1 and PGC-1α protein in kasumi-1 drug-resistant cell lines and their parental cell lines were detected by Western blot.@*RESULTS@#The constructed Kasumi-1 cell line had common morphological characteristics of drug-resistant cell lines under microscope, and the drug resistance index was greater than 5, indicating that Kasumi-1 drug-resistant cells had good drug resistance after the construction. The RT-qPCR and Western blot assays showed that the expression levels of Sirt1 and PGC-1α mRNA and protein in the drug-resistant cell lines were higher than those of the parental cell lines (P<0.001).@*CONCLUSION@#AML cell lines resistant to Ara-C can be successfully induced by the method of gradually increasing the concentration, and the co-high expression of Sirt1 and PGC-1α may mediate the drug resistance of AML cells.


Subject(s)
Cell Line , Cytarabine/pharmacology , Drug Resistance , Humans , Leukemia, Myeloid, Acute/genetics , RNA, Messenger/genetics , Sirtuin 1
20.
Article in Chinese | WPRIM | ID: wpr-939674

ABSTRACT

OBJECTIVE@#To investigate the effects of paclitaxel, quizartinib and their combination on proliferation, apoptosis and FLT3/STAT5 pathway of human leukemia cell line MV4-11 (FLT3-ITD+).@*METHODS@#MV4-11 cells were treated with paclitaxel and quizartinib at different concentrations for 24 h, 48 h and 72 h, respectively, and then the two drugs were combined at 48 h to compare the inhibition of proliferation, the apoptosis rate was detected by flow cytometry, the expression of FLT3 and STAT5 mRNA was determined by fluorescence quantitative PCR, and the protein expression of FLT3, p-FLT3, STAT5 and p-STAT5 was determined by Western blot.@*RESULTS@#Different combination groups of paclitaxel and quizartinib had synergistic inhibitory effect. The cell survival rate in the combination group was significantly lower than that in the single drug group (P<0.05). The cell apoptosis rate in the combination group was significantly higher than that in the single drug group (P<0.001). The expression of FLT3 mRNA in combination group was significantly higher than that in two single drugs (P<0.01). The expression of STAT5 mRNA in combination group was significantly higher than that in quizartinib group (P<0.001); increased compared with paclitaxel group, but there was no statistical significance. The expression level of p-FLT3、p-STAT5 protein in the combination group was significantly lower than that in the single drug group (P<0.05, P<0.05).@*CONCLUSION@#Paclitaxel combined with quizartinib can synergistically inhibit the proliferation of MV4-11 cell line and promote the apoptosis of MV4-11 cell line by inhibiting the activity of FLT3/STAT5 pathway.


Subject(s)
Apoptosis , Benzothiazoles , Cell Line, Tumor , Humans , Leukemia, Myeloid, Acute/genetics , Paclitaxel/therapeutic use , Phenylurea Compounds , RNA, Messenger , STAT5 Transcription Factor/pharmacology , Signal Transduction , fms-Like Tyrosine Kinase 3
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