A 58-year-old man presents with B-symptoms, progressive abdominal pain, and early satiety. CT abdomen shows a bulky mesenteric mass (marked **A** in the diagram) measuring 10 cm, encasing mesenteric vessels with aneurysmal dilatation of an adjacent small bowel loop. Excisional biopsy reveals sheets of large atypical lymphoid cells with CD20+, CD79a+, BCL6+, MUM1+ immunophenotype and Ki-67 index of 80%. FISH testing is negative for MYC, BCL2, and BCL6 rearrangements. The mass marked **A** is consistent with diffuse large B-cell lymphoma (DLBCL). Given the patient's age, markedly elevated LDH, stage IV disease with extranodal involvement, and germinal center B-cell-like phenotype, which of the following represents the most appropriate first-line treatment regimen?
A. 6 cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) every 21 days
B. DA-EPOCH-R (dose-adjusted etoposide, prednisone, doxorubicin, cyclophosphamide, vincristine, rituximab)
C. 3 cycles of R-CHOP followed by involved-site radiotherapy
D. 4 cycles of R-CHOP followed by autologous stem-cell transplantation
Explanation
Why 6 cycles of R-CHOP every 21 days is right
The bulky mesenteric mass marked A represents DLBCL with advanced-stage (stage IV) extranodal involvement and constitutional symptoms. According to NCCN guidelines and WHO 5e, the standard first-line treatment for advanced-stage DLBCL (stages III–IV) is 6 cycles of R-CHOP administered every 21 days. This regimen combines rituximab (anti-CD20 monoclonal antibody) with the CHOP chemotherapy backbone and achieves cure rates of 60–70% in DLBCL overall. The patient's negative FISH for double/triple-hit status and germinal center B-cell-like phenotype do not warrant intensification at initial presentation; DA-EPOCH-R is reserved for confirmed double/triple-hit disease. Autologous stem-cell transplantation is reserved for relapsed/refractory disease after salvage chemotherapy, not as frontline therapy.
Why each distractor is wrong
3 cycles of R-CHOP followed by involved-site radiotherapy: This abbreviated regimen with radiotherapy is appropriate for stage I–II non-bulky DLBCL, not advanced-stage disease with bulky extranodal involvement. Advanced stage requires full 6-cycle chemotherapy.
DA-EPOCH-R (dose-adjusted etoposide, prednisone, doxorubicin, cyclophosphamide, vincristine, rituximab): This intensive regimen is reserved for double/triple-hit DLBCL (MYC, BCL2, and/or BCL6 rearrangements). This patient's FISH is negative for all three rearrangements, making standard R-CHOP the appropriate choice.
4 cycles of R-CHOP followed by autologous stem-cell transplantation: Autologous stem-cell transplantation is not part of first-line therapy for newly diagnosed DLBCL. It is reserved for relapsed or refractory disease after salvage chemotherapy in chemo-sensitive patients, or as a bridge to CAR-T cell therapy in chemo-refractory cases.
High-YieldNEET PG
Advanced-stage DLBCL (stage III–IV) is treated with 6 cycles of R-CHOP every 21 days; DA-EPOCH-R is reserved for double/triple-hit disease; autologous SCT and CAR-T are salvage options for relapsed/refractory disease.
WHO 5e Hematolymphoid; NCCN B-cell Lymphomas v3.2026
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