G-CSF Supported CHOP-14 with Rituximab in Patients <60 Years with High-Risk Diffuse Large B Cell Lymphoma (DLBCL).

Introduction: During recent years studies have shown that elderly patients with aggressive lymphoma may benefit from dose-intensified chemotherapy (CHOP-14). In addition, the addition of rituximab (R) to CHOP-21, seems to improve response rates and survival in elderly patients and younger patients with low and low/intermediate risk factors. Given these promising results we early decided to use G-CSF supported R-CHOP-14 in patients < 60 years with previously untreated DLBCL and risk factors.

Patients and methods: Between March 2000 and June 2003, 25 consecutive and previously untreated patients with CD20+, stage II–IV DLBCL and ≥ 1 risk factor (IPI) were included. HIV+ patients and patients with CNS involvement were not eligible. The median age was 56 years (range 27–60). The CHOP regimen (6–8 cycles) was delivered every 14 days with R (375mg/m²) iv on day 1. G-CSF (300ug/day) was given sc from day 5 to day 13 or until an absolute granulocyte count >4.0x10⁹/l. Re-staging studies were routinely performed every two cycles. Non-responding patients were planned to receive MIME chemotherapy followed by high-dose therapy and autologous stem cell support (ASCS). Four patients were given local radiotherapy to previous bulky disease.

Results: Seven (28%) patients had an IPI score of 1 and 72% IPI 2 or 3. 23/25 (91%) had elevated S-LDH, 12/25 (48%) had bulky disease and 14/25 (56%) had an extranodal lymphoma manifestation. 17/25 (68%) of tumors were positive for bcl-2 (immunohistochemistry). 22/25 (88%) patients achieved a CR. One SD patient (IPI 3) died from progressive disease and two patients with PR and SD after 4 courses received dose-escalated MIME chemotherapy and BEAM high-dose therapy with ACSC and remain in CR. After a median observation time of 32 months (range 21–37 months) 4 (3 with IPI 3) of 22 CR patients have relapsed following R-CHOP. Two (both IPI 3) of relapsing patients died from lymphoma. R-CHOP was delivered on day 15 in 83% of cycles. Grade 3–4 neutropenia and thrombocytopenia were observed in 80% and 16% of patients, respectively. Five patients developed neutropenic fever and pneumonia was diagnosed in additional 3 patients. Non-hematological toxicity was in general mild. Grade 3 or 4 adverse events related to the infusion of R were not observed.

Conclusion: G-CSF supported R-CHOP-14 immunochemotherapy is feasible, safe and effective in young patients with advanced aggressive DLBCL and risk features. Innovative treatment approaches are needed for non-responding and relapsing patients.