St. Anna CCRI chosen for transatlantic consortium on spectral flow cytometry

A transatlantic consortium of 20 leading centers is investigating how spectral flow cytometry can improve and standardize the detection of minimal residual disease in acute myeloid leukemia. St. Anna Children’s Cancer Research Institute is one of only five participating centers in Europe – and the only European center in the initiative with a dedicated focus on childhood cancer.

The project brings together clinicians and scientists from Europe, North America and South America to evaluate spectral flow cytometry, one of the most advanced flow cytometry technologies currently available. The aim is to determine how the technology can be used reproducibly across laboratories and integrated into standardized workflows for assessing minimal residual disease in acute myeloid leukemia (AML).

Michael Dworzak and Margarita Maurer-Granofszky will contribute St. Anna CCRI’s expertise in pediatric AML and flow cytometry to the initiative.

Why is assessing minimal residual disease important?

Even when leukemia cells can no longer be detected using conventional diagnostic methods, a small number of malignant cells may remain in the body. This is known as minimal residual disease (MRD).

MRD assessment can detect leukemia cells at very low levels and provides important information about treatment response. It can help estimate the risk of relapse and inform subsequent treatment decisions. The more accurately leukemia cells can be distinguished from normal cells, the more precisely MRD can potentially be assessed. This is where flow cytometry plays an important role.

From one marker to up to 30

Flow cytometry analyzes individual cells by labeling them with fluorescent antibodies. These antibodies bind to specific molecules – or markers – on or within the cells. The resulting pattern helps distinguish cell populations and identify abnormal leukemia cells.

The technology has advanced substantially over the past decades: In the 1980s, only individual markers could be analyzed on a cell, increasing to around three markers by the 1990s, and to about four in the early 2000s. Current approaches can routinely analyze around 13 markers simultaneously.

Spectral flow cytometry allows for a quantum leap forward: In this initiative, panels containing up to 30 markers per cell will be investigated. This higher level of detail could help researchers distinguish leukemia cells from healthy or regenerating blood cells more precisely. For MRD assessment in AML, where leukemia cells may represent only a very small fraction of all cells in a sample, this additional information could be particularly valuable.

More information – but also greater complexity

With more complex technology come important methodological questions. Addressing them is at the core of the consortium’s work to develop evidence-based best practices for spectral flow cytometry.

Rather than evaluating the technology in isolation, the project will examine the entire methodological chain required for reliable multicenter application. This includes:

• harmonization of antibody panels and preanalytical workflows,
• standardized instrument setup and data acquisition,
• manual and computational approaches to data analysis,
• inter-laboratory alignment and quality assurance, and
• identification of technical requirements and unmet needs in routine laboratory environments.

A transatlantic effort involving 20 centers

The initiative, coordinated by Wolfgang Kern at MLL Münchner Leukämielabor, brings together around 20 centers across Europe and the Americas, including:

• St. Anna Children’s Cancer Research Institute,
• Hospital Israelita Albert Einstein,
• Hospices Civils de Lyon,
• Memorial Sloan Kettering Cancer Center,
• Quest Diagnostics,
• The Royal Marsden NHS Foundation Trust,
• Stanford University,
• St. Jude Children’s Research Hospital,
• University of Miami Health System,
• Jackson Health System,
• the University of Birmingham
• and the University of Washington.

Initial panel development and instrument setup will be led by MLL Münchner Leukämielabor and The Royal Marsden NHS Foundation Trust. Beckman Coulter Life Sciences is supporting the project scientifically, technically and organizationally.

For St. Anna CCRI, participating in this effort provides an opportunity to help shape how one of the most advanced technologies in the field may be used in the future – while ensuring that the perspective of childhood cancer research is part of that development from the beginning.