New and Emerging Targeted Therapies for Pediatric Acute Myeloid Leukemia (AML)

Chen, Jing; Glasser, Chana L.

doi:10.3390/children7020012

Cited by 22 publications

(17 citation statements)

References 84 publications

(112 reference statements)

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“…Anetumab ravtensine, or BAY 94-9343, is an ADC consisting of anti-MSLN linked to tubulin polymerase inhibitor DM4. In view of a favorable safety profile for this agent in an adult trial of patients with advanced solid tumors, a COG phase I study is in development for second or greater relapse pediatric patients with mesothelin-positive AML [69,70].…”

Section: Targeting Mesothelinmentioning

confidence: 99%

Antibody–Drug Conjugates for the Treatment of Acute Pediatric Leukemia

Stokke

Bhojwani

2021

JCM

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The clinical development of antibody–drug conjugates (ADCs) has gained momentum in recent years and these agents are gradually moving into frontline regimens for pediatric acute leukemias. ADCs consist of a monoclonal antibody attached to a cytotoxic payload by a cleavable linker. This structure allows for highly cytotoxic agents to be directly delivered to leukemia cells leading to cell death and avoids excessive off-tumor toxicity. Near universal expression on B-cell acute lymphoblastic leukemia (ALL) blasts and the ability of rapid internalization has rendered CD22 an ideal target for ADC in B-ALL. Inotuzumab ozogamicin, the anti-CD22 antibody linked to calicheamicin led to complete remission rates of 60–80% in patients with relapsed/refractory B-ALL. In acute myeloid leukemia (AML), the CD33 targeting gemtuzumab ozogamicin has demonstrated modest improvements in survival and is the only ADC currently licensed in the United States for pediatric patients with de novo AML. Several other ADCs have been developed and tested clinically for leukemia but have achieved limited success to date. The search for additional leukemia-specific targets and optimization of ADC structure and specificity are ongoing efforts to improve their therapeutic window. This review provides a comprehensive overview of ADCs in acute leukemias, with a focus on pediatric ALL and AML.

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Section: Targeting Mesothelinmentioning

confidence: 99%

Antibody–Drug Conjugates for the Treatment of Acute Pediatric Leukemia

Stokke

Bhojwani

2021

JCM

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“…CPX-351 is now being evaluated by several pediatric AML study groups (for an overview of new agents for AML see [117][118][119] ). Venetoclax, a small-molecule inhibitor of BCL-2, recently showed significant efficacy against relapsed pediatric AML.…”

Section: New Agents For Pediatric Amlmentioning

confidence: 99%

“…Significant success in AML therapy has been achieved by liposomal reformulation such as CPX‐351, which contains cytarabine and daunorubicin in a fixed, 5:1 molar ratio 116 and may be less cardiotoxic. CPX‐351 is now being evaluated by several pediatric AML study groups (for an overview of new agents for AML see 117–119 ). Venetoclax, a small‐molecule inhibitor of BCL‐2, recently showed significant efficacy against relapsed pediatric AML 120 .…”

Section: What Are Innovations Of Treatment For Pediatric Aml?mentioning

confidence: 99%

Treatment of acute myeloid leukemia in children: A practical perspective

Egan

Chopra

Mourad

et al. 2021

Pediatric Blood & Cancer

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Pediatric acute myeloid leukemia (AML) is a heterogeneous disease that requires a multifaceted treatment approach. Although outcomes for low-risk AML have improved significantly over recent decades, high-risk AML continues to be associated with an adverse prognosis. Recent advances in molecular diagnostics, risk stratification, and supportive care have contributed to improvements in outcomes in pediatric AML. Targeted approaches, for example, the use of tyrosine kinase inhibitors to treat FLT3-ITD AML, offer promise and are currently undergoing clinical investigation in pediatric patients. New approaches to hematopoietic stem cell transplantation, including the use of haploidentical donors, are significantly expanding donor options for patients with high-risk AML. This review provides an overview of recent advances in the treatment of pediatric AML that are likely to have clinical impact and reshape the standard of care. K E Y W O R D Sacute myeloid leukemia, childhood AML, HSCT, pediatric AML Historically, risk stratification rested on blast morphology and cytogenetics. Improvement of cytogenetic techniques, flow cytometry, and introduction of molecular techniques, such as targeted sequencing and the detection of fusion transcripts, have identified a larger number of prognostic markers. 5 A summary is shown in Table 1. Mutations of uncertain prognostic significance in pediatric AML include point mutations targeting the c-KIT receptor tyrosine kinase and the FLT3

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“…El reto de la determinación de blancos terapéuticos en la leucemia mieloide aguda ha sido su heterogénea composición genética y molecular, que frecuentemente evoluciona en variantes génicas que impulsan el inicio y la progresión de la enfermedad (15). Aunque ha habido mejoras en su tratamiento, solo alrededor del 60 % de los pacientes logra una supervivencia a largo plazo y hasta el 10 % de los niños con la enfermedad muere por complicaciones directas del tratamiento (6).…”

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Grupos de riesgo citogenético de leucemia mieloide aguda pediátrica a partir del análisis de supervivencia en un hospital de referencia para cáncer en Perú

Llimpe

2021

biomedica

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Introducción. La leucemia mieloide aguda es una neoplasia heterogénea caracterizada por la proliferación de células mieloides inmaduras. El análisis citogenético ha revelado la presencia de aberraciones cromosómicas de importancia en el pronóstico del paciente.Objetivo. Determinar los grupos de riesgo citogenético de pacientes pediátricos con leucemia mieloide aguda a partir de la supervivencia global.Materiales y métodos. Se hizo un estudio observacional de corte transversal. Se incluyeron los registros clínicos de los pacientes pediátricos con diagnóstico de leucemia mieloide aguda de novo admitidos en el Instituto Nacional de Enfermedades Neoplásicas entre el 2001 y el 2011 y sometidos a análisis citogenético de médula ósea. Los grupos de riesgo citogenético se establecieron según los criterios del Medical Research Council. Las curvas de supervivencia global se elaboraron con el método de Kaplan-Meier y se compararon mediante la prueba de Mantel-Cox y una regresión de Cox, utilizando el programa R, versión 3.3.2.Resultados. Se incluyeron 130 pacientes, 68 varones (52,3 %) y 62 mujeres (47,7 %), mayoritariamente del subtipo M2 (33 %). La edad promedio fue de 7,7 (rango de 0 a 15 años). Se observaron aberraciones cromosómicas en el 60,8 % y la más frecuente fue la traslocación t(8;21). Según el análisis de supervivencia global, se observaron dos grupos de riesgo citogenético: favorable y desfavorable.Conclusión. Se determinaron dos grupos de riesgo citogenético: alto (o desfavorable) y estándar (o favorable).

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New and Emerging Targeted Therapies for Pediatric Acute Myeloid Leukemia (AML)

Cited by 22 publications

References 84 publications

Antibody–Drug Conjugates for the Treatment of Acute Pediatric Leukemia

Antibody–Drug Conjugates for the Treatment of Acute Pediatric Leukemia

Treatment of acute myeloid leukemia in children: A practical perspective

Grupos de riesgo citogenético de leucemia mieloide aguda pediátrica a partir del análisis de supervivencia en un hospital de referencia para cáncer en Perú

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