Personalized AML treatment with DNA and chemotherapy drug symbols.

Precision Medicine: Can a New Test Predict AML Treatment Success?

"Researchers develop a novel ex vivo test to predict the effectiveness of chemotherapy in acute myeloid leukemia (AML) patients, paving the way for personalized treatment strategies."


Acute Myeloid Leukemia (AML) is a complex disease, and predicting how a patient will respond to treatment has always been a challenge. While factors like cytogenetic and molecular alterations offer some clues, the ultimate indicator is how sensitive the leukemia cells are to the chemotherapy itself. Achieving complete remission (CR) after the initial treatment is crucial for better long-term outcomes.

The standard initial treatment for many younger AML patients involves a combination of idarubicin (IDA) and cytarabine (CYT), known as the 3 + 7 schedule. While this approach is often effective, not all patients respond, and identifying those who will benefit most remains a key goal. Those who don't achieve CR after induction therapy, termed as primary refractory or resistant, face a grim prognosis.

Now, researchers are exploring a promising avenue: a precision medicine test that assesses a patient's leukemic cells ex vivo—outside the body—to predict their response to the 3 + 7 regimen. This approach, known as the PharmaFlow platform, aims to identify the most suitable candidates for this standard treatment.

Decoding the PharmaFlow Platform: How Does It Work?

Personalized AML treatment with DNA and chemotherapy drug symbols.

The PharmaFlow platform is designed to mimic the real-world conditions within the bone marrow as closely as possible. Instead of isolating leukemic cells, the test uses whole bone marrow samples, preserving the complex interactions between different cell types. This method evaluates a vast array of drug combinations commonly used in AML treatment protocols.

Here's a breakdown of the key steps:

  • Sample Incubation: Bone marrow samples are incubated for 48 hours in specialized plates containing IDA, CYT, or a combination of both.
  • Automated Flow Cytometry: This technique uses lasers and fluorescent markers to count and analyze live leukemic cells in the samples.
  • Data Analysis: Sophisticated software and population pharmacodynamic (PD) models estimate the response to each drug, generating a unique pharmacological profile for each patient.
  • Response Prediction: Based on these profiles, patients are classified as either responders (likely to achieve CR/CRi with 3 + 7) or resistant (less likely to respond).
Researchers from 43 Spanish institutions collaborated on a study, enrolling adult patients newly diagnosed with AML. The goal was to assess whether the PharmaFlow PM test could accurately predict response to the standard CYT and IDA (3 + 7) induction therapy.

The Future of AML Treatment: Personalized Approaches

This study offers a promising glimpse into the future of AML treatment. The PharmaFlow PM test demonstrates the potential to move beyond a one-size-fits-all approach and tailor treatment strategies to the individual patient. While these results are encouraging, further validation in independent studies is crucial before this test can be implemented in routine clinical practice. If validated, this could lead to more effective treatment decisions, improved outcomes, and a higher quality of life for individuals battling AML.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1016/j.leukres.2018.11.006, Alternate LINK

Title: A Precision Medicine Test Predicts Clinical Response After Idarubicin And Cytarabine Induction Therapy In Aml Patients

Subject: Cancer Research

Journal: Leukemia Research

Publisher: Elsevier BV

Authors: David Martínez-Cuadrón, Cristina Gil, Josefina Serrano, Gabriela Rodríguez, Jaime Pérez-Oteyza, Raimundo García-Boyero, Santiago Jiménez-Bravo, Susana Vives, María Belén Vidriales, Esperanza Lavilla, José A. Pérez-Simón, Mar Tormo, Mercedes Colorado, Juan Bergua, Juan A. López, Pilar Herrera, Pilar Hernández-Campo, Julián Gorrochategui, Daniel Primo, Jose Luis Rojas, Jesús Villoria, Federico Moscardó, Iñaki Troconiz, María Linares Gómez, Joaquín Martínez-López, Joan Ballesteros, Miguel Sanz, Pau Montesinos

Published: 2019-01-01

Everything You Need To Know

1

What is the 3 + 7 regimen used to treat AML, and why is it important?

The 3 + 7 regimen is the standard initial treatment for many younger Acute Myeloid Leukemia (AML) patients. It involves a combination of two chemotherapy drugs: idarubicin (IDA) and cytarabine (CYT). This approach aims to induce complete remission (CR) in patients. Achieving CR after the initial treatment is crucial for better long-term outcomes. The importance lies in its effectiveness in many cases, but the challenge is that not all patients respond, making it necessary to identify those who will benefit most.

2

How does the PharmaFlow platform work to predict treatment success in AML?

The PharmaFlow platform is an *ex vivo* test that assesses a patient's leukemic cells outside the body to predict their response to the 3 + 7 regimen, which includes idarubicin (IDA) and cytarabine (CYT). The process involves incubating whole bone marrow samples with these drugs, mimicking the conditions within the bone marrow. The platform utilizes automated flow cytometry to analyze live leukemic cells and sophisticated software with population pharmacodynamic (PD) models to estimate the response, generating a pharmacological profile. Based on these profiles, patients are classified as responders or resistant.

3

What are the potential benefits of using the PharmaFlow test in AML treatment?

The PharmaFlow test offers several potential benefits. It allows for a personalized approach to AML treatment by identifying the most effective therapies upfront. This is in contrast to a one-size-fits-all approach. If validated, the test could lead to more effective treatment decisions and improved outcomes. This includes a higher rate of complete remission (CR) or complete remission with incomplete blood count recovery (CRi) and, ultimately, a higher quality of life for individuals battling AML, by avoiding ineffective treatments.

4

What are the key steps involved in the PharmaFlow platform's process?

The key steps in the PharmaFlow platform's process include: First, Sample Incubation: Bone marrow samples are incubated for 48 hours with idarubicin (IDA), cytarabine (CYT), or a combination of both. Second, Automated Flow Cytometry: Lasers and fluorescent markers count and analyze live leukemic cells in the samples. Third, Data Analysis: Sophisticated software and population pharmacodynamic (PD) models estimate the response to each drug, creating a pharmacological profile. Fourth, Response Prediction: Based on these profiles, patients are classified as responders or resistant.

5

How does the PharmaFlow test improve upon existing methods of predicting AML treatment response?

Existing methods often rely on factors like cytogenetic and molecular alterations, which offer some clues but are not definitive predictors of treatment response. The PharmaFlow test improves on these methods by directly assessing the sensitivity of leukemic cells to chemotherapy drugs *ex vivo*. Unlike approaches that isolate leukemic cells, the PharmaFlow platform uses whole bone marrow samples, preserving the complex interactions between different cell types. This allows a more accurate prediction of response to the 3 + 7 regimen, which is crucial for patients undergoing idarubicin (IDA) and cytarabine (CYT) treatment.

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