The aim of the DIRECT Study is to establish a robust pipeline to identify those patients with high-grade B cell lymphoma most suitable for novel agent clinical trials based upon genomic subtype and an integrated response evaluation determined early in first-line therapy.

This will be done by integrating data and samples collected from patients undergoing standard of care treatment for high-grade B cell lymphoma

Data will be integrated from

1. Clinical risk factors from the International Prognostic Index (IPI)
2. Up-front genomic subtype based on molecular profiling of diagnostic biopsy
3. Serial ctDNA monitoring during treatment.
4. Radiological response imaging

• Have given written informed consent to participate.
• Age ≥ 18 years at the time of consent.
• Histologically confirmed diagnosis of previously untreated high-grade B cell lymphoma.
• Planned to receive immunochemotherapy as first-line therapy, e.g. R-CHOP therapy.
• Planned or completed standard of care imaging (CT or PET-CT)
• Able to give blood.

Exclusion Criteria:

• Unable to receive immunochemotherapy as first-line therapy due to co-morbidity or personal choice.
• Patients who have already started high dose steroids as a treatment for their lymphoma.
• Known diagnosis of infectious blood-borne virus e.g. Hep B, Hep C or HIV.

Patients with diffuse Large B Cell Lymphoma (DLBCL) or closely related high-grade B cell lymphomas including, but not limited to:

• DLBCL NOS
• Transformed follicular lymphoma
• High grade B cell lymphoma with rearrangement of BCL2/BCL6 and MYC
• Plasmablastic lymphoma
• Primary Mediastinal Large Cell lymphoma
• Burkitt lymphoma
• Primary Central Nervous System lymphoma
• High grade B cell lymphoma NOS

Undergoing Standard of Care treatment for their lymphoma.