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BACKGROUND AND OBJECTIVES: Providing red blood cell (RBC) transfusion to paediatric patients with a haemoglobin (Hb) level of <7 g/dL is the current best practice, but it is often difficult to ensure appropriateness of RBC transfusion on a health system level. Electronic health record (EHR) clinical decision support systems have been shown to be effective in encouraging providers to transfuse at appropriate Hb thresholds. We present our experience with an interruptive best practice alert (BPA) at a paediatric healthcare system. MATERIALS AND METHODS: An interruptive BPA requiring physician response was implemented in our EHR (Epic Systems Corp., Verona, WI, USA) in 2018 based on Hb thresholds for inpatients. The threshold was initially <8 g/dL and later changed to <7 g/dL in 2019. We assessed total activations, number of RBC transfusions and hospital metrics through 2022 compared to the 2 years prior to implementation. RESULTS: The BPA activated 6956 times over 4 years, slightly less than 5/day, and the success rate, with no RBC transfusions within 24 h of order attempt, was 14.5% (1012/6956). There was a downward trend in the number of total RBC transfusions and RBC transfusions per admission after implementation, non-significant (p = 0.41 and p = >0.99). The annual case mix index was similar over the years evaluated. The estimated cost savings based on acquisition costs for RBC units were 213,822 USD or about $51,891 per year. CONCLUSION: BPA implementation led to sustained change in RBC transfusion towards best practice, and there were long-term savings in RBC expenditure.
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Transfusión de Eritrocitos , Hemoglobinas , Humanos , Niño , Hemoglobinas/análisis , Hospitales , Costos y Análisis de Costo , Registros Electrónicos de SaludRESUMEN
Digital pathology has a crucial role in diagnostic pathology and is increasingly a technological requirement in the field. Integration of digital slides into the pathology workflow, advanced algorithms, and computer-aided diagnostic techniques extend the frontiers of the pathologist's view beyond the microscopic slide and enable true integration of knowledge and expertise. There is clear potential for artificial intelligence (AI) breakthroughs in pathology and hematopathology. In this review article, we discuss the approach of using machine learning in the diagnosis, classification, and treatment guidelines of hematolymphoid disease, as well as recent progress of artificial intelligence in flow cytometric analysis of hematolymphoid diseases. We review these topics specifically through the potential clinical applications of CellaVision, an automated digital image analyzer of peripheral blood, and Morphogo, a novel artificial intelligence-based bone marrow analyzing system. Adoption of these new technologies will allow pathologists to streamline workflow and achieve faster turnaround time in diagnosing hematological disease.
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Algoritmos , Inteligencia Artificial , HumanosRESUMEN
Hemoglobinopathies are the most common single-gene disorders in humans. There are 1,424 variants of human hemoglobin described with 951 involving the ß-globin gene. Ancestry and geography play a significant role in the incidence and nature of hemoglobinopathies, with African, Asian, and Mediterranean populations and their descendants being amongst the most affected. Investigation of variants in individuals of Hispanic descent is needed to reflect the changing demographics of the United States. Hemoglobin ß-globin evaluation through gel electrophoresis, high-performance liquid chromatography, and HBB gene sequencing was performed on patients from Texas hospitals between 2010 and 2015 and demographic parameters (age, sex, ethnicity) was subsequently analyzed. A total of 846 patients underwent hemoglobinopathy evaluation. A ß chain variant was detected in 628 of the 846 total patients. Hispanic patients represented 37% (314/846 patients), which were equally distributed between females (50%; 156/314) and males (50%; 156/314). A ß-globin chain variant was found in 67% of Hispanic patients with a distribution across 10 variants seen in greater than 1% of patients. For hemoglobin variants, an understanding of the regional and ethnic prevalence will improve patient care through more effective screening and identification of the variant, early diagnosis, and appropriate treatment if necessary, and better genetic counseling.
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Hemoglobinopatías , Hemoglobinas Anormales , Masculino , Femenino , Humanos , Globinas beta/genética , Hemoglobinas Anormales/genética , Texas/epidemiología , Hemoglobinopatías/diagnóstico , Hemoglobinopatías/epidemiología , Hemoglobinopatías/genética , Hispánicos o Latinos/genéticaRESUMEN
Chromosomal microarray analysis (CMA) frequently yields inconclusive results. We reexamined inconclusive CMA results from 33 previously tested patients and reached a definitive diagnosis in 3 (9.1%) and identified the need for additional testing in 4 (12.1%). Reinterpretation may resolve inconclusive CMA results.
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Cromosomas , Diagnóstico Prenatal , Niño , Aberraciones Cromosómicas , Femenino , Humanos , Análisis por Micromatrices/métodos , Embarazo , Diagnóstico Prenatal/métodosRESUMEN
Tau aggregation underlies neurodegeneration in Alzheimer's disease and related tauopathies. We and others have proposed that transcellular propagation of pathology is mediated by Tau prions, which are ordered protein assemblies that faithfully replicate in vivo and cause specific biological effects. The prion model predicts the release of aggregates from a first-order cell and subsequent uptake into a second-order cell. The assemblies then serve as templates for their own replication, a process termed "seeding." We have previously observed that heparan sulfate proteoglycans on the cell surface mediate the cellular uptake of Tau aggregates. This interaction is blocked by heparin, a sulfated glycosaminoglycan. Indeed, heparin-like molecules, or heparinoids, have previously been proposed as a treatment for PrP prion disorders. However, heparin is not ideal for managing chronic neurodegeneration, because it is difficult to synthesize in defined sizes, may have poor brain penetration because of its negative charge, and is a powerful anticoagulant. Therefore, we sought to generate an oligosaccharide that would bind Tau and block its cellular uptake and seeding, without exhibiting anticoagulation activity. We created a compound, SN7-13, from pentasaccharide units and tested it in a range of assays that measured direct binding of Tau to glycosaminoglycans and inhibition of Tau uptake and seeding in cells. SN7-13 does not inhibit coagulation, binds Tau with low nanomolar affinity, and inhibits cellular Tau aggregate propagation similarly to standard porcine heparin. This synthetic heparinoid could facilitate the development of agents to treat tauopathy.
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Heparina de Bajo-Peso-Molecular/metabolismo , Proteínas tau/metabolismo , Animales , Células HEK293 , Heparina de Bajo-Peso-Molecular/química , Heparina de Bajo-Peso-Molecular/farmacología , Hipocampo/metabolismo , Humanos , Ratones , Neuronas/metabolismo , Tiempo de Tromboplastina Parcial , Enfermedades por Prión/metabolismo , Enfermedades por Prión/patología , Agregado de Proteínas/efectos de los fármacos , Unión Proteica , Tiempo de Protrombina , Proteínas Recombinantes/biosíntesis , Proteínas Recombinantes/química , Proteínas Recombinantes/aislamiento & purificación , Proteínas tau/química , Proteínas tau/genéticaRESUMEN
OBJECTIVE: To investigate the utility of a detailed medical history in the interpretation of chromosomal microarray results for pediatric patients with a constitutional disease. STUDY DESIGN: A retrospective review and reinterpretation of test results from chromosomal microarrays performed from 2011 to 2013. Previously reported genetic variants were reanalyzed after review of the patient's complete electronic medical record (cEMR). A 3-tier system was used for reclassification of variants: pathogenic or likely pathogenic (P/LP); variant of uncertain significance (VUS); or benign or likely benign (B/LB). RESULTS: Over an 18-month period, 998 patients with chromosomal microarray results were identified. The most common reasons for chromosomal microarray testing were developmental delay (n = 336), autism spectrum disorder (n = 241), and seizures (n = 143). Chromosomal microarray testing identified 1 or more variants in 48% (482 of 998) of patients; 516 patients had a negative report. For the 482 patients with variants, the original interpretations were composed of 19.3% P/LP (93 of 482), 44.8% VUS (216 of 482), and 35.9% B/LB (173 of 482) variants. After review of the cEMR, 34% of patient results (164 of 482) were changed in interpretation. One case changed from B/LB to VUS, 7 VUS were upgraded to P/LP, and 156 VUS were downgraded to B/LB. No P/LP variants had a change in interpretation. CONCLUSIONS: Overall, 16.4% (164 of 998) of patients with chromosomal microarray testing had a change in interpretation. Access to the patient's cEMR improves the interpretation of chromosomal microarrays by decreasing the number of uncertain (VUS) interpretations.
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Trastorno del Espectro Autista/diagnóstico , Cromosomas/genética , Predisposición Genética a la Enfermedad , Pruebas Genéticas/métodos , Anamnesis/métodos , Trastorno del Espectro Autista/genética , Niño , Femenino , Humanos , Masculino , Estudios RetrospectivosRESUMEN
BACKGROUND: The microparticle content (MP%) of apheresis platelets-a marker of platelet activation-is influenced by donor factors and by external stressors during collection and storage. This study assessed the impact of apheresis technology and other factors on the activation status (MP%) of single-donor apheresis platelets. STUDY DESIGN AND METHODS: Data from six US hospitals that screened platelets by measuring MP% through dynamic light scattering (ThromboLUX) were retrospectively analyzed. Relative risks (RRs) were derived from univariate and multivariable regression models, with activation rate (MP% ≥15% for plasma-stored platelets; ≥10% for platelet additive solution [PAS]-stored platelets) and MP% as outcomes. Apheresis platform (Trima Accel vs Amicus), storage medium (plasma vs PAS), pathogen reduction, storage time, and testing location were used as predictors. RESULTS: Data were obtained from 7511 platelet units collected using Trima (from 16 suppliers, all stored in plasma, 20.0% were pathogen-reduced) and 2456 collected using Amicus (from four different collection facilities of one supplier, 65.0% plasma-stored, 35.0% PAS-stored, none pathogen-reduced). Overall, 30.0% of Trima platelets were activated compared to 45.6% of Amicus platelets (P < .0001). Multivariable analysis identified apheresis platform as significantly associated with platelet activation, with a lower activation rate for Trima than Amicus (RR: 0.641, 95% confidence interval [CI]: 0.578; 0.711, P < .0001) and a 6.901% (95% CI: 5.926; 7.876, P < .0001) absolute reduction in MP%, when adjusting for the other variables. CONCLUSION: Trima-collected platelets were significantly less likely to be activated than Amicus-collected platelets, irrespective of the storage medium, the use of pathogen reduction, storage time, and testing site.
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Donantes de Sangre , Plaquetas/metabolismo , Conservación de la Sangre , Activación Plaquetaria , Plaquetoferesis , Plaquetas/citología , Femenino , Humanos , Masculino , Estudios RetrospectivosRESUMEN
We describe Hb Alcorn County, a heterozygous hemoglobin (Hb) variant, in a 6-month-old Hispanic male and his mother. DNA sequencing demonstrated a mutation on the HBB gene [ß40(C6)ArgâThr; HBB: c.122G>C (p.Arg41Thr)], predictive of a substitution of arginine to threonine at position 40 of the ß-globin protein. This amino acid substitution involves the α1ß2 contact and occurs at the same position as Hb Austin [ß40(C6)ArgâSer; HBB: c.[123G>C or 123G>T] (p.Arg41Ser)] and Hb Athens-GA [ß40(C6)ArgâLys; HBB: c.122G>A (p.Arg41Lys)], both of which show increased oxygen affinity.
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Alelos , Sustitución de Aminoácidos , Mutación , Oxígeno/metabolismo , Globinas beta/genética , Globinas beta/metabolismo , Cromatografía Líquida de Alta Presión , Análisis Mutacional de ADN , Predisposición Genética a la Enfermedad , Genotipo , Hemoglobinopatías/diagnóstico , Hemoglobinopatías/genética , Hemoglobinopatías/metabolismo , Humanos , Lactante , Masculino , Fenotipo , Unión Proteica , Globinas beta/análisisRESUMEN
BACKGROUND: Genetic information is unique among all laboratory data because it not only informs the current health of the specific person tested but may also be predictive of the future health of the individual and, to varying degrees, all biological relatives. CONTENT: As DNA sequencing has become ubiquitous with decreasing cost, large repositories of genomic data have emerged from the domains of research, healthcare, law enforcement, international security, and recreational consumer interest (i.e., genealogy). Broadly shared genomic data are believed to be a key element for future discoveries in human disease. For example, the National Cancer Institute's Genomic Data Commons is designed to promote cancer research discoveries by providing free access to the genome data sets of 12000 cancer patients. However, in parallel with the promise of curing diseases, genomic data also have the potential for harm. Genomic data that are deidentified by standard healthcare practices (e.g., removal of name, date of birth) can be reidentified by methods that combine genomic software with publicly available demographic databases (e.g., phone book). Recent law enforcement cases (i.e., Bear Brook Murders, Golden State Killer) in the US have demonstrated the power of combining DNA profiles with genealogy databases. SUMMARY: We examine the current environment of genomic privacy and confidentiality in the US and describe current and future risks to genomic privacy. Reidentification and inference of genetic information of biological relatives will become more important as larger databases of clinical, criminal, and recreational genomic information are developed over the next decade.
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Privacidad Genética , Pruebas Genéticas , Seguridad Computacional/ética , Seguridad Computacional/legislación & jurisprudencia , Bases de Datos Factuales , Genética Forense/ética , Genética Forense/legislación & jurisprudencia , Privacidad Genética/ética , Privacidad Genética/legislación & jurisprudencia , Pruebas Genéticas/ética , Pruebas Genéticas/legislación & jurisprudencia , Pruebas Genéticas/métodos , Genoma Humano , Regulación Gubernamental , Humanos , Difusión de la InformaciónRESUMEN
ß-Thalassemia (ß-thal) results from homozygous or compound heterozygous inheritance of ß-globin alleles that yield decreased or absent synthesis of the ß chain. Disease is frequently severe, requiring lifelong transfusion therapy. Heterozygosity for a ß-thal allele results in an asymptomatic carrier state with mild but characteristic hematological findings. More than 200 ß-globin alleles have been demonstrated to produce ß-thal. For populations with a high prevalence of ß-thal, screening for carrier status, genetic counseling and prenatal diagnosis are important components of efforts to both reduce disease incidence and provide early diagnosis and treatment. It is therefore important to define and characterize potential ß-thal alleles. We sought to further characterize the previously reported ß-thal allele, HBB: c.*233G > C. This variant is provisionally included in the HbVar database based on a study of Palestinians in the Gaza Strip with ß-thal disease or carrier status (known or suspected) where 4.2% of subjects were found to have HBB: c.*233G > C. In our patient population, we detected the HBB: c.*233G > C variant in 17.3% of individuals (17 heterozygotes, one homozygote) undergoing ß hemoglobin (Hb) gene sequencing at our laboratory over a 25-month period. Hematological parameters were analyzed to determine if these individuals demonstrated findings consistent with inheritance of a ß-thal allele. Individuals with the HBB: c.*233G > C variant did not demonstrate any abnormalities in hematological parameters characteristic of ß-thal carrier state (17 heterozygotes) or clinical evidence of disease (homozygote). Our data demonstrate no evidence for pathogenicity of the HBB: c.*233G > C variant but rather demonstrate that this variant is a common benign polymorphism.
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Polimorfismo de Nucleótido Simple , Globinas beta/genética , Talasemia beta/genética , Adolescente , Niño , Preescolar , Femenino , Frecuencia de los Genes , Heterocigoto , Humanos , Lactante , Masculino , Fenotipo , Estudios Retrospectivos , Talasemia beta/sangreRESUMEN
Conventional microscopy is the gold standard for malaria diagnosis. The CellaVision DM96 is a digital hematology analyzer that utilizes neural networks to locate, digitize, and preclassify leukocytes and characterize red blood cell morphology. This study compared the detection rates of Plasmodium and Babesia species on peripheral blood smears utilizing the CellaVision DM96 with the rates for a routine red blood cell morphology scan. A total of 281 slides were analyzed, consisting of 130 slides positive for Plasmodium or Babesia species and 151 negative controls. Slides were blinded, randomized, and analyzed by CellaVision and microscopy for red cell morphology scans. The technologists were blinded to prior identification results. The parasite detection rate was 73% (95/130) for CellaVision and 81% (105/130) for microscopy for positive samples. The interobserver agreement between CellaVision and microscopy was fair, as Cohen's kappa coefficient equaled 0.36. Pathologist review of CellaVision images identified an additional 15 slides with parasites, bringing the total number of detectable positive slides to 110 of 130 (85%). Plasmodium ovale had the lowest rate of detection at 56% (5 of 9); Plasmodium malariae and Babesia spp. had the highest rate of detection at 100% (3/3 and 6/6, respectively). The detection rate by CellaVision was 100% (23/23) when the parasitemia was ≥2.5%. The detection rate for <0.1% parasitemia was 63% (15/24). Technologists appropriately classified all negative specimens. The percentage of positive specimens detectable by CellaVision (73%) approaches results for microscopy on routine scan of peripheral blood smears for red blood cell morphology.
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Células Sanguíneas/parasitología , Pruebas Hematológicas/instrumentación , Pruebas Hematológicas/métodos , Enfermedades Parasitarias/diagnóstico , Enfermedades Parasitarias/parasitología , Animales , Eritrocitos/parasitología , Pruebas Hematológicas/normas , Humanos , Malaria Falciparum/diagnóstico , Malaria Falciparum/parasitología , Microscopía , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
Acute myeloid leukemia is classified based upon recurrent cytogenetic abnormalities. The t(15;17)(q24.1;q21.1) abnormality is found in 5% to 8% of de novo acute myeloid leukemia and is diagnostic of acute promyelocytic leukemia (APL). The translocation results in fusion of the retinoic acid receptor-α (RARA) gene at 17q21.1 and the promyelocytic leukemia (PML) gene at 15q24.1. Standard APL therapy is a combination of all-trans retinoic acid and anthracycline-based chemotherapy. Anthracycline treatment is associated with secondary clonal chromosomal aberrations that can lead to therapy-related secondary myeloid neoplasms. We present a pediatric case of relapsed APL coexistent with treatment-associated secondary myeloid neoplasm with t(11;19)(q23;p13.1).
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Antraciclinas/efectos adversos , Aberraciones Cromosómicas , Leucemia Mieloide Aguda/inducido químicamente , Leucemia Promielocítica Aguda/tratamiento farmacológico , Neoplasias Primarias Secundarias/genética , Tretinoina/administración & dosificación , Antineoplásicos/administración & dosificación , Niño , Cromosomas Humanos Par 15 , Cromosomas Humanos Par 19 , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Promielocítica Aguda/genética , Masculino , Proteínas Nucleares/genética , Proteína de la Leucemia Promielocítica , Receptores de Ácido Retinoico/genética , Recurrencia , Receptor alfa de Ácido Retinoico , Factores de Transcripción/genética , Proteínas Supresoras de Tumor/genéticaRESUMEN
Artificial intelligence (AI) and machine learning (ML) are anticipated to transform the practice of medicine. As one of the largest sources of digital data in healthcare, laboratory results can strongly influence AI and ML algorithms that require large sets of healthcare data for training. Embedded bias introduced into AI and ML models not only has disastrous consequences for quality of care but also may perpetuate and exacerbate health disparities. The lack of test harmonization, which is defined as the ability to produce comparable results and the same interpretation irrespective of the method or instrument platform used to produce the result, may introduce aggregation bias into algorithms with potential adverse outcomes for patients. Limited interoperability of laboratory results at the technical, syntactic, semantic, and organizational levels is a source of embedded bias that limits the accuracy and generalizability of algorithmic models. Population-specific issues, such as inadequate representation in clinical trials and inaccurate race attribution, not only affect the interpretation of laboratory results but also may perpetuate erroneous conclusions based on AI and ML models in the healthcare literature.
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Objective: The objective was to identify information loss that could affect clinical care in laboratory data transmission between 2 health care institutions via a Health Information Exchange platform. Materials and Methods: Data transmission results of 9 laboratory tests, including LOINC codes, were compared in the following: between sending and receiving electronic health record (EHR) systems, the individual Health Level Seven International (HL7) Version 2 messages across the instrument, laboratory information system, and sending EHR. Results: Loss of information for similar tests indicated the following potential patient safety issues: (1) consistently missing specimen source; (2) lack of reporting of analytical technique or instrument platform; (3) inconsistent units and reference ranges; (4) discordant LOINC code use; and (5) increased complexity with multiple HL7 versions. Discussion and Conclusions: Using an HIE with standard messaging, SHIELD (Systemic Harmonization and Interoperability Enhancement for Laboratory Data) recommendations, and enhanced EHR functionality to support necessary data elements would yield consistent test identification and result value transmission.
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Infecciones Oportunistas Relacionadas con el SIDA/diagnóstico , Síndrome de Inmunodeficiencia Adquirida/diagnóstico , Médula Ósea/microbiología , Fungemia/microbiología , VIH/aislamiento & purificación , Histoplasma/aislamiento & purificación , Histoplasmosis/diagnóstico , Infecciones Oportunistas Relacionadas con el SIDA/tratamiento farmacológico , Infecciones Oportunistas Relacionadas con el SIDA/orina , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Síndrome de Inmunodeficiencia Adquirida/orina , Anciano , Anfotericina B/administración & dosificación , Anfotericina B/farmacología , Antirretrovirales/administración & dosificación , Antirretrovirales/farmacología , Histoplasma/efectos de los fármacos , Histoplasmosis/tratamiento farmacológico , Histoplasmosis/orina , Humanos , Itraconazol/administración & dosificación , Itraconazol/farmacología , Masculino , Carga ViralRESUMEN
Chronic myelogenous leukemia (CML) is very rare in the pediatric population. We report the case of a 2-year-old female with CML and concurrent myelodysplastic syndrome (MDS) associated cytogenetic abnormalities. The co-existence of t(9;22) and chromosomal deletions that are associated with MDS poses a unique diagnostic challenge. Given the reported association of t(9;22) and genomic instability, we hypothesize that the chromosomal deletions represent clonal evolution of the CML.
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Aberraciones Cromosómicas , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Síndromes Mielodisplásicos/genética , Preescolar , Femenino , Citometría de Flujo , Humanos , Hibridación Fluorescente in Situ , Leucemia Mielógena Crónica BCR-ABL Positiva/fisiopatologíaRESUMEN
INTRODUCTION: Myeloperoxidase (MPO) is considered a specific marker of myeloid/non-monocytic lineage in the diagnosis of mixed phenotype acute leukemia (MPAL). However, the clinical significance of isolated dim MPO expression in otherwise typical B lymphoblastic leukemia (B-ALL; referred to as B/myeloid MPALisoMPO ) in adult patients is unknown. METHODS: We compared flow cytometric immunophenotype and clinicopathological findings among cases of B/myeloid MPALisoMPO (n = 13), other MPAL subtypes (n = 10, B/myeloid and T/myeloid MPAL), B-ALL (n = 64), and acute myeloid leukemia (AML, n = 58), using the 2016 WHO classification. For MPAL cases, MPO was reported as the percent of MPO positive blasts and its intensity (dim or moderate/strong). The pattern of heterogenous antigen expression (inversely coordinated expression between myeloid and lymphoid markers and cell size) was assessed. RESULTS: Cases of B/myeloid MPALisoMPO showed a fairly homogenous single B-lineage blast population with dim MPO expression whereas cases of other MPAL subtypes displayed heterogeneous antigen expression and moderate/strong MPO expression. The percent of MPO positive blasts in these two groups was similar. Expressions of CD15, CD117, and monocytic markers were more common in other MPAL than in B/myeloid MPALisoMPO . B/myeloid MPALisoMPO patients had similar overall and leukemia free survivals as B-ALL patients and better than other MPAL patients. CONCLUSION: This is the first study to investigate the clinical significance of adult B/myeloid MPALisoMPO using the 2016 WHO classification. Our results suggest that B/myeloid MPALisoMPO clinically behaves more similarly to B-ALL than to other MPAL subtypes, supporting the 2016 WHO classification to segregate this entity from other MPAL subtypes.