Identification of novel Carnobacterium maltaromaticum strains in bone marrow samples of patients with acute myeloid leukemia using a metagenomic binning approach / Identificación de nuevas cepas de Carnobacterium maltaromaticum en muestras de médula ósea de pacientes con leucemia mieloide aguda mediante un enfoque de combinación metagenómica

The aim of this study aimed to examine the existence of a bacterial metagenome in the bone marrow of patients with acute myeloid leukemia (AML). We re-examined whole-genome sequencing data from the bone marrow samples of seven patients with AML, four of whom were remitted after treatment, for metagenomic analysis. After the removal of human reads, unmapped reads were used to profile the species-level composition. We used the metagenomic binning approach to confirm whether the identified taxon was a complete genome of known or novel strains. We observed a unique and novel microbial signature in which Carnobacterium maltaromaticum was the most abundant species in five patients with AML or remission. The complete genome of C. maltaromaticum “BMAML_KR01,” which was observed in all samples, was 100% complete with 8.5% contamination and closely clustered with C. maltaromaticum strains DSM20730 and SF668 based on single nucleotide polymorphism variations. We identified five unique proteins that could contribute to cancer progression and 104 virulent factor proteins in the BMAML_KR01 genome. To our knowledge, this is the first report of a new strain of C. maltaromaticum in patients with AML. The presence of C. maltaromaticum and its new strain in patients indicates an urgent need to validate the existence of this bacterium and evaluate its pathophysiological role.(AU)

Aging-related genes related to the prognosis and the immune microenvironment of acute myeloid leukemia

Background Acute myeloid leukemia (AML), one of the common malignancies of the hematologic system, has progressively increased in incidence. Aging is present in both normal tissues and the tumor microenvironment. However, the relationship between senescence and AML prognosis is still not elucidated. Methods In this study, RNA sequencing data of AML were obtained from TCGA, and prognostic prediction models were established by LASSO-Cox analysis. Differences in immune infiltration between the different risk groups were calculated using the CIBERSORT and ESTIMATE scoring methods. The KEGG and GO gene enrichment and GSEA enrichment were also used to enrich for differential pathways between the two groups. Subsequently, this study collected bone marrow samples from patients and healthy individuals to verify the differential expression of uncoupling protein 2 (UCP2) in different populations. Genipin, a UCP2 protein inhibitor, was also used to examine its effects on proliferation, cell cycle, and apoptosis in AML cell lines in vitro. Results It showed that aging-related genes (ARGs) expression was correlated with prognosis. And there was a significant difference in the abundance of immune microenvironment cells between the two groups of patients at high risk and low risk. Subsequently, UCP2 expression was found to be elevated in AML patients. Genipin inhibits UCP2 protein and suppresses the proliferation of AML cell lines in vitro. Conclusion ARGs can be used as a predictor of prognosis in AML patients. Moreover, suppressing UCP2 can reduce the proliferation of AML cell lines, alter their cell cycle, and promote apoptosis in vitro (AU)

Systemic Mastocytosis with Associated Hematological Neoplasms. Diagnostic features and unique response pattern to tyrosine kinase inhibitors and allo-bone marrow transplantation therapy / Mastocitosis sistémica con neoplasias hematológicas asociadas. Características diagnósticas y patrón de respuesta único a los inhibidores de la tirosina cinasa y al tratamiento de trasplante de médula ósea

Systemic Mastocytosis is a clonal proliferation of mast cells; in a significant fraction of cases it is associated with another concurrent hematological neoplasm. Molecular analysis of KIT mutations and other associated genetic alterations suggest a common origin in the stem cell compartment. Mast cell infiltration patterns in bone marrow biopsy may be subtle in cases associated with t (8;21) AML. Here we report three cases of clonally related SM-AHN, two cases with SM-CMML and one case with SM- t (8;21) AML. We describe in detail the bone marrow infiltration pattern at diagnosis and during the course of treatment with allogeneic stem cell transplant and novel TK inhibitors, showing the unique dynamics of mast cell clearance after therapy.(AU)

La mastocitosis sistémica es una proliferación clonal de mastocitos que puede asociarse con otra neoplasia hematológica concurrente en una fracción significativa de los casos. El análisis molecular de mutaciones de KIT y otras alteraciones genéticas asociadas indican un origen común en el compartimento de células madre. Los patrones de infiltración de mastocitos en la biopsia de médula ósea pueden ser sutiles en los casos asociados con AML t (8; 21). Aquí se describen 3 casos de MS-NHA, 2 casos con MS-LMMC y un caso con MS-t (8; 21) LMA. Describimos en detalle el patrón de infiltración de la médula ósea en el momento del diagnóstico y durante el curso del tratamiento con alotrasplante de células madre y nuevos inhibidores de TK, mostrando la dinámica de la depuración de mastocitos después de la terapia.(AU)

Characterization of cuproptosis identified immune microenvironment and prognosis in acute myeloid leukemia

Background Recent studies have reported that cuproptosis, a novel cell death pathway, strongly correlates with mitochondrial metabolism. In addition, the studies reported that cuproptosis plays a role in the development of several cancers and is regulated by protein lipoylation. During cuproptosis, copper binds to the lipoylated proteins and mediates cancer progression. However, the role of cuproptosis in acute myeloid leukemia (AML) patients is yet to be explored. Methods This study curated seven cuproptosis-related-genes (CRGs): FDX1, DLAT, PDHB, PDHA1, DLD, LIAS, and LIPT1 to determine cuproptosis modification patterns and the CRGs signature in AML. The CIBERSORT and ssGSEA algorithms were utilized to evaluate the infiltration levels of different immune cell subtypes. A cuproptosis score system based on differentially expressed genes (DEGs) was constructed using the least absolute shrinkage and selection operator (LASSO) regression analysis. The developed cuproptosis score system was validated using two immunotherapy datasets, IMvigor210 and GSE78220. Results Three distinct cuproptosis regulation patterns were identified using the Beat AML cohort. The results demonstrated that the three cuproptosis regulation patterns were correlated with various biological pathways and clinical outcomes. Tumor microenvironment (TME) characterization revealed that the identified cuproptosis regulation patterns were consistent with three immune profiles: immune-desert, immune-inflamed, and immune-excluded. The AML patients were grouped into low- and high-score groups based on the cuproptosis score system abstracted from 486 cuproptosis-related DEGs. Patients with lower cuproptosis scores were characterized by longer survival time and attenuated immune infiltration. It was found that lower cuproptosis scores were strongly correlated with lower somatic mutation frequency (AU)

Exploring underlying mechanism of artesunate in treatment of acute myeloid leukemia using network pharmacology and molecular docking

Background Acute myeloid leukemia (AML) is a highly heterogeneous hematological cancer. The current diagnosis and therapy model of AML has gradually shifted to personalization and accuracy. Artesunate, a member of the artemisinin family, has anti-tumor impacts on AML. This research uses network pharmacology and molecular docking to anticipate artesunate potential mechanisms of action in the therapy of AML. Methods Screening the action targets of artesunate through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), PubChem, and Swiss Target Prediction databases; The databases of Online Mendelian Inheritance in Man (OMIM), Disgenet, GeneCards, and Drugbank were utilized to identify target genes of AML, and an effective target of artesunate for AML treatment was obtained through cross-analysis. Protein–protein interaction (PPI) networks are built on the Cytoscape platform. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted on the relevant targets using R software. Finally, using molecular docking technology and Pymol, we performed verification of the effects of active components and essential targets. Results Artesunate 30 effective targets for treating AML include CASP3, EGFR, MAPK1, and STAT3, four targeted genes that may have a crucial function in disease management. The virus infection-related pathway (HeptatisB (HBV), Human papillomavirus (HPV), Epstein-Barr virus (EBV) infection and etc.), FoxO, viral carcinogenesis, and proteoglycans in cancer signaling pathways have all been hypothesized to be involved in the action mechanism of GO, which is enriched in 2044 biological processes, 125 molecular functions, 209 cellular components, and 106 KEGG pathways (AU)

Identification of tumor antigens and immune subtypes of acute myeloid leukemia for mRNA vaccine development

Background Acute myeloid leukemia (AML) is a highly aggressive hematological malignancy, and there has not been any significant improvement in therapy of AML over the past several decades. The mRNA vaccines have become a promising strategy against multiple cancers, however, its application on AML remains undefined. In this study, we aimed to identify novel antigens for developing mRNA vaccines against AML and explore the immune landscape of AML to select appropriate patients for vaccination. Methods Genomic data and gene mutation data were retrieved from TCGA, GEO and cBioPortal, respectively. GEPIA2 was used to analyze differentially expressed genes. The single cell RNA-seq database Tumor Immune Single-cell Hub (TISCH) was used to explore the association between the potential tumor antigens and the infiltrating immune cells in the bone marrow. Consensus clustering analysis was applied to identify distinct immune subtypes. The correlation between the abundance of antigen presenting cells and the expression level of antigens was evaluated using Spearman correlation analysis. The characteristics of the tumor immune microenvironment in each subtype were investigated based on single-sample gene set enrichment analysis. Results Five potential tumor antigens were identified for mRNA vaccine from the pool of overexpressed and mutated genes, including CDH23, LRP1, MEFV, MYOF and SLC9A9, which were associated with infiltration of antigen-presenting immune cells (APCs). AML patients were stratified into two immune subtypes Cluster1 (C1) and Cluster2 (C2), which were characterized by distinct molecular and clinical features. C1 subtype demonstrated an immune-hot and immunosuppressive phenotype, while the C1 subtype had an immune-cold phenotype. Furthermore, the two immune subtype showed remarkably different expression of immune checkpoints, immunogenic cell death modulators and human leukocyte antigens (AU)

The stimulator of interferon genes (STING) agonists for treating acute myeloid leukemia (AML): current knowledge and future outlook

Acute myeloid leukemia (AML) is an aggressive hematologic cancer in adults. Some patients exhibit restricted T cell infiltration and do not respond to routine treatments. This may be prevented by enhancing adaptive immunity by stimulating innate immune cells inside the tumor microenvironment (TME). To activate the adaptive immunological reaction against tumors, type I interferons (IFNs) can promote the presentation of tumor-specific cytotoxic T lymphocyte (CTL) cell recruitment. During the activation of innate immunity, cyclic di-nucleotides (CDNs) bind to and stimulate the stimulator of interferon genes (STING), a protein localized inside the endoplasmic reticulum (ER) membrane, resulting in the expression of type I IFNs. The efficacy of STING agonists as effective stimulators of the anti-tumor response in AML is being investigated in numerous clinical studies. Therefore, the purpose of this investigation was to thoroughly review existing knowledge in this field and provide perspective into the clinical potential of STING agonists in AML (AU)

A novel prognostic model of methylation-associated genes in acute myeloid leukemia

Background There is growing evidence that methylation-associated genes (MAGs) play an important role in the prognosis of acute myeloid leukemia (AML) patients. Thus, the aim of this research was to investigate the impact of MAGs in predicting the outcomes of AML patients. Methods The expression profile and clinical information of patients were downloaded from public databases. A novel prognostic model based on 7 MAGs was established in the TCGA training cohort and validated in the GSE71014 dataset. To validate the clinical implications, the correlation between MAGs signature and drug sensitivity was further investigated. Results 76 genes were screened out by the univariate Cox regression and significantly enriched in multiple methylation-related pathways. After filtering variables using LASSO regression analysis, 7 MAGs were introduced to construct the predictive model. The survival analysis showed overall survival of patients with the high-risk score was considerably poorer than that with the low-risk score in both the training and validating cohorts (p < 0.01). Furthermore, the risk score system as a prognostic factor also worked in the intermediate-risk patients based on ELN-2017 classification. Importantly, the risk score was demonstrated to be an independent prognostic factor for AML in the univariate and multivariate Cox regression analysis. Interestingly, GSEA analysis revealed that multiple metabolism-related pathways were significantly enriched in the high-risk group. Drug sensitivity analysis showed there was a significant difference in sensitivity of some drugs between the two groups. Conclusion We developed a robust and accurate prognostic model with 7 MAGs. Our findings might provide a reference for the clinical prognosis and management of AML (AU)

Measurable residual disease study through three different methods can anticipate relapse and guide pre-emptive therapy in childhood acute myeloid leukemia

Purpose Although outcomes of children with acute myeloid leukemia (AML) have improved over the last decades, around one-third of patients relapse. Measurable (or minimal) residual disease (MRD) monitoring may guide therapy adjustments or pre-emptive treatments before overt hematological relapse. Methods In this study, we review 297 bone marrow samples from 20 real-life pediatric AML patients using three MRD monitoring methods: multiparametric flow cytometry (MFC), fluorescent in situ hybridization (FISH) and polymerase chain reaction (PCR). Results Patients showed a 3-year overall survival of 73% and a 3-year event-free survival of 68%. Global relapse rate was of 25%. All relapses were preceded by the reappearance of MRD detection by: (1) MFC (p = 0.001), (2) PCR and/or FISH in patients with an identifiable chromosomal translocation (p = 0.03) and/or (3) one log increase of Wilms tumor gene 1 (WT1) expression in two consecutive samples (p = 0.02). The median times from MRD detection to relapse were 26, 111, and 140 days for MFC, specific PCR and FISH, and a one log increment of WT1, respectively. Conclusions MFC, FISH and PCR are complementary methods that can anticipate relapse of childhood AML by weeks to several months. However, in our series, pre-emptive therapies were not able to prevent disease progression. Therefore, more sensitive MRD monitoring methods that further anticipate relapse and more effective pre-emptive therapies are needed (AU)

Therapeutic applications of toll-like receptors (TLRs) agonists in AML

Acute myeloid leukemia (AML) is an aggressive type of blood cancer affecting bone marrow (BM). In AML, hematopoietic precursors are arrested in the early stages of development and are defined as the presence of ≥ 20% blasts (leukemia cells) in the BM. Toll-like receptors (TLR) are major groups of pattern recognition receptors expressed by almost all innate immune cells that enable them to detect a wide range of pathogen-associated molecular patterns and damage-associated molecular patterns to prime immune responses toward adaptive immunity. Because TLRs are commonly expressed on transformed immune system cells (ranging from blasts to memory cells), they can be a potential option for developing efficient clinical alternatives in hematologic tumors. This is because several in vitro and in vivo investigations have demonstrated that TLR signaling increased the immunogenicity of AML cells, making them more vulnerable to T cell-mediated invasion. This study aimed to review the current knowledge in this field and provide some insight into the therapeutic potentials of TLRs in AML (AU)

Autophagy in acute myeloid leukemia: a paradoxical role in chemoresistance

Autophagy is a lysosomal degradation pathway that is constitutively active in almost every cell of our body at basal level. This self-eating process primarily serves to remove superfluous constituents of the cells and recycle the degraded products. Autophagy plays an essential role in cell homeostasis and can be enhanced in response to stressful conditions. Impairment in the regulation of the autophagic pathway is implicated in pathological conditions such as neurodegeneration, cardiac disorders, and cancer. However, the role of autophagy in cancer initiation and development is controversial and context-dependent. Evidence from various studies has shown that autophagy serves dual purpose and may assist in cancer progression or suppression. In the early stages of cancer initiation, autophagy acts as a quality control mechanism and prevents cancer development. When cancer is established and progresses to a later stage, autophagy helps in the survival of these cells through adaptation to stresses, including exposure to anti-cancer drugs. In this review, we highlight various studies on autophagic pathways and describe the role of autophagy in cancer, specifically acute myeloid leukemia (AML). We also discuss the prognostic significance of autophagy genes involved in AML leukemogenesis and implications in conferring resistance to chemotherapy. (AU)

Midostaurin en combinación de quimioterápia como tratamiento de leucémia mieloblástica aguda con mutación FTL3, a propósito de un caso / Midostaurin in combination with chemotherapy as a treatment for acute myeloblastic leukemia with FTL3 mutation, a case report

La leucemia mieloblástica aguda (LMA) es una enfermedad heterogénea caracterizada por el crecimiento descontrolado de precursores mieloides indiferenciados que provoca un fallo medular. Según datos del programa de Vigilancia, Epidemiología y Resultados Finales (SEER) se estima una incidencia anual de 4,2 por cada 100.000 habitantes. El porcentaje de incidencia en menores de 20 años es 5,1% y en personas entre 65-84 años, es 46,5%. La tasa de supervivencia a 5 años varía en función de la edad de los pacientes, siendo en menores de 20 del 67% y en mayores a dicha edad disminuye al 25%. La leucemia mieloide aguda representa el 40% del total de leucemias y la mediana de edad de los pacientes es 65 años. Las alteraciones citogenéticas más frecuentes son: traslocación (8;21), inversión cromosoma 16, traslocación (16;16), trisomía del cromosoma 8, deleciones en los cromosomas 5 y 7, y mutación en el gen FLT3 (13q12), la cual está presente en el 30% de los nuevos diagnósticos. El tratamiento estándar de quimioterapia sigue basándose en el esquema intensivo 3+7 que consiste en citarabina con antraciclinas. El objetivo de las nuevas terapias en LMA es el tratamiento dirigido debido a los avances en el diagnóstico y la tipificación. (AU)

Acute myeloblastic leukemia (AML) is a heterogeneous disease characterized by uncontrolled growth of undifferentiated myeloid precursors leading to bone marrow failure. According to data from the Surveillance, Epidemiology and End Results (SEER) program, the annual incidence is estimated at 4.2 per 100,000 population. The incidence rate in children under 20 years of age is 5.1% and in people between 65-84 years of age, it is 46.5%. The 5-year survival rate varies according to the age of the patients, being 67% in those under 20 years of age and 25% in those older than 20 years of age. Acute myeloid leukemia represents 40% of all leukemias and the median age of the patients is 65 years. The most frequent cytogenetic alterations are: translocation (8;21), inversion of chromosome 16, translocation (16;16), trisomy of chromosome 8 and deletions in chromosomes 5 and 7, mutation in the FLT3 gene (13q12), which is present in 30% of new diagnoses. Standard chemotherapy treatment is still based on the intensive 3+7 scheme consisting of cytarabine with anthracyclines. The focus of new therapies in AML is targeted therapy due to advances in diagnosis and typing. (AU)

The contributing factors of resistance or sensitivity to epigenetic drugs in the treatment of AML

Drug resistance is the drug-effectiveness reduction in treatment and is a serious problem in oncology and infections. In oncology, drug resistance is a complicated process resulting from enhancing the function of a pump that transports drugs out of tumor cells, or acquiring mutations in drug target. Surprisingly, most drugs are very effective in the early stages, but the response to the drug wears off over time and resistance eventually develops. Drug resistance is caused by genetic and epigenetic changes that affect cancer cells and the tumor environment. The study of inherited changes in the phenotype without changes in the DNA sequence is called epigenetics. Because of reversible changes in epigenetics, they are an attractive target for therapy. Some of these epigenetic drugs are effective in treating cancers like acute myeloid leukemia (AML), which is characterized by the accumulation and proliferation of immature hematopoietic cells in the blood and bone marrow. In this article, we outlined the various contributing factors involved in resistance or sensitivity to epigenetic drugs in the treatment of AML.

Distinct power of bone marrow microRNA signatures and tumor suppressor genes for early detection of acute leukemia

BackgroundAcute leukemia involving lymphocytic and myeloid cells is cancer with a high mortality rate. Swift and timely diagnosis might be a potential approach to improving patient prognosis and survival. The microRNA (miRNA) signatures are emerging nowadays for their promising diagnostic potential. MiRNA levels from bone marrow can be used as prognostic biomarkers.MethodsThe current study was designed to evaluate if the microRNAs and tumor suppressor genes (TSGs) profiling of hematopoietic bone marrow could help in acute leukemia early detection. Also, we assessed the DNA methyltransferase 3A (DNMT3A) expression and its possible epigenetic effects on miRNAs plus TSGs expression levels. The expression levels of ten miRNAs and four TSGs involved in acute lymphocytic leukemia (ALL) as well as acute myeloid leukemia (AML) were quantified in 43 and 40 bone marrow samples of ALL and AML patients in comparison with cancer-free subjects via real-time quantitative PCR (RT-qPCR). The receiver-operating-characteristic (ROC) analysis of miRNAs was performed in the study groups. Further, the correlation between the DNMT3A and TSGs was calculated.ResultsSignificant differences were detected in the bone marrow expression of miRNAs and TSGs (P < 0.05) between acute leukemia patients and healthy group. ROC analysis confirmed the ability of miR-30a, miR-101, miR-132, miR-129, miR-124, and miR-143 to discriminate both ALL and AML patients with an area under the ROC curve of ≥ 0.80 (P < 0.001) and high accuracy. The correlation between DNMT3A and P15/P16 TSGs revealed that DNMT3A plays a vital role in epigenetic control of TSGs expression. Our findings indicated that the downregulation of bone marrow miRNAs and TSGs was accompanied by acute leukemia development.ConclusionsThe authors conclude that this study could contribute to introducing useful biomarkers for acute leukemia diagnosis.

Impact of risk scores in outcome of patients with myeloid neoplasms after allogeneic stem cell transplant / Impacto de las puntaciones del riesgo en los resultados de los pacientes con neoplasias mieloides tras el trasplante alogénico de células madre

Background:The main causes of failure of allogeneic hematopoietic stem cell transplantation (allo-transplant) in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) are relapse and transplant-related mortality. Different scores have been designed to predict the prognosis of these patients. The objective of this study was to assess which score or combination has better outcome predictive capacity.Methods:Retrospective analysis of patients with AML and MDS who received a first peripheral blood allo-transplant in a single center, between December 2001 and October 2019. Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI), European Group for Blood and Marrow Transplantation (EBMT) and Disease Risk Index (DRI) scores were calculated. For each score and for the HCT-CI/DRI and HCT-CI/EBMT combinations, overall survival (OS), cumulative incidence of relapse (CIR), non-relapse-related mortality (NRM), and graft versus host disease-free relapse-free survival (GRFS) were analyzed.Results:175 patients were evaluated. With a median (range) follow-up of 3.96 (0.32–17.22) years, the 5-year probabilities (95% CI) of OS, CIR, NRM, and GRFS were 36% (28%–44%), 28% (21%–35%), 38% (30%–46%) and 24% (17%–31%), respectively. For OS, only the DRI score selected two groups with statistically significant differences (DRI 0–1: 41% vs. DRI ≥2: 24%; p=0.011). The combination of DRI 0–1 and HCT-CI 0–2 showed OS probabilities of 45% vs. 26% for those with DRI 0–1 and HCT-CI ≥3; p=0.041.Conclusions:In patients with AML and MDS submitted to allo-transplant, the combination of HCT-CI and DRI scores provided the best stratification for OS. (AU)

Antecedentes:Las principales causas de fallo del trasplante alogénico de células madre hematopoyéticas (alotrasplante) en pacientes con leucemia mieloide aguda (LMA) y síndromes mielodisplásicos (SMD) son las recaídas y la mortalidad debida al trasplante. Se han diseñado diferentes puntuaciones para predecir el pronóstico de dichos pacientes. El objetivo de este estudio fue evaluar qué puntuación o combinación tiene la mejor capacidad predictiva del resultado.Métodos:Análisis retrospectivo de pacientes con LMA y SMD que recibieron un primer alotrasplante de sangre periférica en un único centro, entre diciembre de 2001 y octubre de 2019. Se calcularon las puntuaciones del Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI), del European Group for Blood and Marrow Transplantation (EBMT) y del Disease Risk Index (DRI). Para cada puntuación y para las combinaciones HCT-CI/DRI y HCT-CI/EBMT se analizaron la supervivencia global (SG), la incidencia acumulada de recaídas (CIR), la mortalidad no relativa a las recaídas (NRM) y la supervivencia libre de recaídas y libre de enfermedad de injerto versus huésped (GRFS).Resultados:Se evaluaron 175 pacientes. Con un seguimiento medio (rango) de 3,96 (0,32-17,22) años, las probabilidades a 5años (IC95%) de SG, CIR, NRM y GRFS fueron del 36% (28-44), del 28% (21-35), del 38% (30-46) y del 24% (17-31), respectivamente. Para la SG, solo la puntuación DRI seleccionó dos grupos con diferencias estadísticamente significativas (DRI 0-1: 41% vs. DRI≥2: 24%; p=0,011). La combinación de DRI 0-1 y HCT-CI 0-2 reflejó probabilidades de SG del 45% vs. 26% para los pacientes con DRI 0-1 y HCT-CI≥3 (p=0,041).Conclusiones:En los pacientes con LMA y SMD sometidos a alotrasplante la combinación de las puntuaciones HCT-CI y DRI proporcionó la mejor estratificación para la SG. (AU)

Debut y manejo de leucemia mieloblástica aguda durante la gestación: a propósito de un caso / Debut and management of acute myeloblastic leukaemia during pregnancy: a case report

La leucemia mieloide aguda (LMA) es una de las neoplasias hematológicas más mortales. Durante el embarazo es una complicación rara, que puede dar resultados adversos, como la muerte, sin tratamiento adecuado. El manejo de la LMA durante el embarazo sigue siendo un desafío. Presentamos el caso de una mujer primigesta de 34 años con 18 semanas de gestación que acudió a Urgencias por cuadro de dolor e hipertrofia de mucosa oral, acompañado de astenia intensa. Se diagnóstico leucemia mieloblástica aguda (LAM-M4). Se ofertó posibilidad de interrumpir la gestación, dada la poca evidencia referente a la evolución materno-fetal, que la paciente rechazó, por lo que se inició tratamiento quimioterápico. En los controles ecográficos no se evidenciaron alteraciones teratogénicas; el crecimiento fetal tuvo parámetros normales, sin alteraciones en los valores del flujo Doppler. Se decidió finalizar gestación a las 32 semanas y tres días. Nació un varón pretérmino mediante parto eutócico con test de Apgar y pH de cordón umbilical normales, sin precisar reanimación. El puerperio fue favorable y a los 15 días del alta ingresó para un trasplante de médula ósea de su hermana, HLA idéntica. La paciente finalmente falleció por rechazo del trasplante y las complicaciones derivadas de este suceso.

Acute myeloid leukaemia (AML) is one of the deadliest haematological malignancies. During pregnancy it is a rare comorbidity and can lead to adverse outcomes, such as death, without adequate treatment. The management of AML during pregnancy remains a challenge. We report the case of a primigravida 34-year-old, with 18 weeks of amenorrhoea, who attended the emergency department presenting with pain and hypertrophy of the oral mucosa, accompanied by intense asthenia. Acute myeloblastic leukaemia was diagnosed. The possibility of terminating the pregnancy was offered given the lack of evidence regarding the maternal-foetal outcome, but the patient rejected it, so chemotherapy treatment was started. In the ultrasound controls there was no evidence of teratogenic alterations nor foetal growth restriction, and there were no alterations in Doppler flow values. It was decided to end the pregnancy at 32+3 GW. A preterm male was born through eutocic delivery with a normal Apgar test and umbilical cord pH, and did not require resuscitation. The puerperium was favourable and 15 days following discharge she was admitted for a bone marrow transplant from her HLA identical sister. The patient died due to rejection of the transplant and the complications derived from this event.

Linezolid-induced thrombocytopenia in patients with acute myeloid leukemia: a matched case–control study

PurposeAfter the wide use of linezolid (LZD), numerous reports of uncontrolled studies have suggested that LZD is associated with high rates of thrombocytopenia. We conducted this matched case–control study to identify the risk factors for LZD-induced thrombocytopenia in patients with acute myeloid leukemia (AML) during the period of myelosuppression.MethodsWe retrospectively retrieved laboratory and clinical data from the medical records of 180 Chinese with AML. Among them, 60 received ≥ 72 h of therapy with LZD during myelosuppression. The remaining patients who did not receive LZD therapy were matched individually in a ratio of 1:2 according to the basic characteristics of the LZD group.ResultsWe found that in the LZD group, age, history of liver or kidney disease, the baseline level of bilirubin, and creatinine clearance rate (CCR) did not affect the recovery time of platelets. Patients who received LZD for more than 7 days during the period of myelosuppression had a significantly longer time of platelet recovery and platelet count increase.ConclusionThe use of LZD > 7 days during the course of myelosuppression and the low level of albumin can prolong the time required for platelet count increase and recovery. Further study is needed to assess the potential adverse effects of LZD in larger AML patient populations.

Immunotherapy in AML: a brief review on emerging strategies

Acute myeloid leukemia (AML), the most common form of leukemia amongst adults, is one of the most important hematological malignancies. Epidemiological data show both high incidence rates and low survival rates, especially in secondary cases among adults. Although classic and novel chemotherapeutic approaches have extensively improved disease prognosis and survival, the need for more personalized and target-specific methods with less side effects have been inevitable. Therefore, immunotherapeutic methods are of importance. In the following review, primarily a brief understanding of the molecular basis of the disease has been represented. Second, prior to the introduction of immunotherapeutic approaches, the entangled relationship of AML and patient’s immune system has been discussed. At last, mechanistic and clinical evidence of each of the immunotherapy approaches have been covered (AU)