CRYSTAL-Immune pump-priming project update, December 2025

Update by Prof Christina Halsey

The CRYSTAL Immune Pump Priming project was designed to address the technical feasibility of studying immune dynamics within the central nervous system (CNS) niche of children with acute lymphoblastic leukemia (ALL), and to establish the foundations for large-scale collaborative funding applications.

Progress to date

As anticipated for a multi-institutional project, the initial phase has focused on governance, ethics, and infrastructure. The collaboration agreement between participating institutions is now fully executed, and required amendments to existing ethical approvals have been granted. An additional recruiting site is currently being added, with approvals expected to be in place by January 2026.

In parallel, we have initiated prospective CSF sample collection from key clinical cohorts central to the CRYSTAL Immune objectives, including:

  • patients with CNS3 disease, and
  • patients receiving first-cycle blinatumomab, where immune engagement within the CNS compartment is of particular interest.

These samples are being collected and stored using novel protocols optimized for low-input immune profiling.

Ongoing and planned analyses

Collected CSF samples will undergo:

  • a spectral flow cytometry pilot to characterize immune composition and activation states of T cells within the CSF during immunotherapy, and
  • a single-cell RNA sequencing (scRNA-seq) pilot, designed to assess the feasibility and data quality of transcriptomic profiling from CSF immune cells.

We anticipate completing sufficient sample accrual to initiate our first scRNA-seq run in January 2026, with pilot analyses continuing through 2026. These studies will directly inform technical optimization, power calculations, and study design for subsequent large-scale work.

Future directions and impact

Importantly, the CRYSTAL Immune consortium has now secured €1.5 million in future funding from Fight Kids Cancer to support a pan-European study that will expand this work. This funding will enable deeper mechanistic exploration of CNS immune biology in ALL.

The EHA SWG award is playing a critical role in de-risking the project’s most challenging technical elements. Support from EHA has been instrumental in positioning CRYSTAL Immune for the next phase of large-scale, collaborative investigation into CNS-specific immune responses in pediatric leukemia

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