Synopsis
Recognise rapidly progressive lymphoma, secure adequate tissue and defining genetics before treatment, stabilise lysis and compression and deliver subtype-specific curative immunochemotherapy with response and relapse planning.
- Aggressive NHL is an umbrella: diffuse large B-cell lymphoma is common, but Burkitt, high-grade B-cell, primary mediastinal and peripheral T-cell lymphomas need different protocols.
- First-line diagnostic procedure is excision biopsy; if unsafe, obtain multiple large cores and preserve tissue for morphology, flow, immunohistochemistry, FISH and molecular tests.
- In newly presenting high-grade B-cell lymphoma, test MYC rearrangement; if present, add BCL2 and BCL6 FISH and identify the MYC partner as recommended by NICE.
- Baseline FDG PET-CT is the preferred staging study for FDG-avid aggressive lymphoma; record largest mass, extranodal sites, IPI and potential CNS risk.
- Start tumour-lysis prophylaxis before systemic therapy when burden or LDH is high; rasburicase is contraindicated in G6PD deficiency.
- R-CHOP-21 remains a curative standard for many DLBCL groups; NICE recommends polatuzumab vedotin with R-CHP for untreated adult DLBCL with IPI 2–5.
- Burkitt lymphoma requires an immediate dose-intensive, CNS-active specialist regimen and cannot be treated as ordinary DLBCL.
- Do not give routine CNS prophylaxis from one risk factor: assess CNS-IPI, kidney or adrenal, testis, breast and other high-risk sites and discuss evidence and toxicity in MDT.
- Use end-of-treatment PET with Deauville scoring; biopsy residual avidity when feasible because inflammation and necrosis can mimic refractory lymphoma.
- Primary refractory or relapse within 12 months increasingly follows a CAR-T pathway; later chemosensitive relapse may proceed through salvage and autologous transplant.
Key red flags
A mass doubling over days, LDH rise, spontaneous lysis, cytopenias or extranodal organ failure suggests highly aggressive biology and needs same-day haemato-oncology review.
Orthopnoea, stridor, facial swelling, neurological deficit, bowel obstruction or renal obstruction requires emergency anatomical management before an ordinary outpatient biopsy pathway.
Fever, hypotension, hypoxia or confusion during or after immunochemotherapy is neutropenic sepsis until treated, even if the last neutrophil count was normal.
New confusion, cranial neuropathy, testicular disease, renal or adrenal involvement or high CNS-IPI raises CNS lymphoma risk and needs specialist staging rather than automatic prophylaxis.
Rising urate, phosphate, potassium, LDH and creatinine with falling calcium can precede treatment in a bulky highly proliferative lymphoma.
Stridor, facial swelling, cord symptoms, obstruction or perforation requires simultaneous stabilisation and expedited tissue diagnosis.
Investigation priorities
Establish architecture, lineage and exact aggressive lymphoma entity.
Map nodal and extranodal burden and establish response baseline.
Management branches
A rapidly progressive nodal or extranodal mass, lysis or organ compromise is present.
- Assess airway, vascular, cord, bowel, renal and CNS threat and begin lysis and sepsis management.
- Obtain excision or multiple large cores before steroids when possible, allocating tissue for flow, histology, genetics and microbiology.
- Stage with PET-CT, obtain organ and viral baseline and classify subtype, IPI and CNS risk in the lymphoma MDT.
Integrated pathology confirms DLBCL without a subtype-specific alternative pathway.
- Review stage, IPI, cardiac reserve, neuropathy, lysis, hepatitis B and fertility before the first cycle.
- Use R-CHOP or NICE-supported polatuzumab-R-CHP for IPI 2–5 with exact cycle, G-CSF and antimicrobial protocol.
- Complete on-time systemic treatment, add selected radiotherapy and assess end PET rather than escalating from an unvalidated interim scan.