Anthracyline-reduced sequential combination chemotherapy for younger patients with good-prognosis aggressive B-cell non-Hodgkin's lymphoma

Abstract

Introduction: Anthracyline-based chemotherapy is the treatment of choice for patients with aggressive B-cell non-Hodgkin's lymphoma (NHL). However, anthracyclines have been associated with long-term cardiac toxicity.

Methods: We conducted a study using a sequential combination chemotherapy with a reduced cumulative dose of anthracyclines in younger patients with good-prognosis aggressive NHL. Chemotherapy consisted of one cycle of vincristine, ifosfamide, etoposide, and dexamethasone, followed by three cycles of epirubicin, cyclophosphamide, vincristine, and dexamethasone, and a fifth cycle containing carboplatin, etoposide, and dexamethasone. 86 patients were treated, 65 without and 21 with additional rituximab. Consolidating involved-field irradiation was applied in patients with stage I/II, bulky disease, or localized residual lymphoma.

Results: Complete and partial remissions were achieved in 67 and 27% of patients, respectively, and the 3-year event-free and overall survival estimates were 75 and 87%. The survival estimates were substantially better in patients who received rituximab. Main toxicity was grade 3/4 leukocytopenia in 89% patients with neutropenic fever in 30%. Two patients died of septic shock.

Conclusion: The treatment appears to be effective in this group of patients. The hematological toxicities, particularly after the first and fifth cycle, require the use of G-CSF and/or a dose reduction in selected patients.

Fig. 1

The treatment protocol is depicted. IF ifosfamide, VP16 etoposide, VCR vincristine, DM dexamethasone, Cy cylcophosphamide, EPR epirubicin, CP carboplatin, d day. The anthracycline-based cycle was given thrice. The indication for radiotherapy is given in the text

Fig. 2

The Kaplan–Meier estimates of event-free survival (a) and overall survival are depicted (b)

Fig. 3

Event-free survival (a) and overall survival curves (b) stratified according to the number of risk factors based on the age-adjusted International prognostic index (aa-IPI)

Fig. 4

Event-free survival (a) and overall survival curves (b) stratified according to whether patients were treated with (+rituximab) and without rituximab (−rituximab)

Fig. 5

Kaplan–Meier estimates of event-free survival (a) and overall survival curves (b) with respect to pretreatment serum levels of soluble interleukin-2 receptor (sIL-2R)