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Long-Term Follow-Up of a Prospective Study of Combined Modality Therapy for Stage I–II Indolent Non-Hodgkin’s Lymphoma

From the Department of Haematology, The Peter MacCallum Cancer Institute, East Melbourne, Victoria, Australia; Departments of Lymphoma/Myeloma, Radiation Oncology, Hematopathology, and Biostatistics, The University of Texas, M.D. Anderson Cancer Center, Houston, TX.

Address reprint requests to Peter McLaughlin, MD, Department of Lymphoma/Myeloma, Box 429, University of Texas, M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030; email: pmclaugh{at}mail.mdanderson.org.

Purpose: Standard therapy for patients with stage I–II indolent lymphoma has been involved-field radiation therapy (IF-XRT), which achieves 10-year disease-free survival in 40% to 50% of patients, with many of these patients cured. We investigated the potential for combined-modality therapy to increase the disease-free survival for such patients.

Patients and Methods: A total of 102 eligible patients with stage I–II low grade lymphoma (International Working Formulation criteria) were enrolled from 1984 to 1992. Treatment comprised 10 cycles of risk-adapted chemotherapy (cyclophosphamide, vincristine, prednisone, bleomycin [COP-Bleo], and with doxorubicin added for some [CHOP-Bleo]) and 30 to 40 Gy IF-XRT.

Results: The patients’ median age was 56 years (range, 28 to 77), with follicular histology in 83%, bulky disease ( 5 cm) in 24%, and stage II in 52%. There were no treatment-related deaths and 99% of patients attained complete remission. With a median follow-up of 10 years, the 10-year time to treatment failure and overall survival were 76% and 82%, respectively. For patients with follicular lymphoma, these figures were 72% and 80%, respectively. The only factor associated with treatment failure, for follicular lymphoma patients, was stage-modified International Prognostic Factors Index score (P = .02). None of 17 patients with diffuse small lymphocytic or mucosa-associated lymphoid tissue histology have relapsed. Elevated serum beta₂-microglobulin was associated with shorter survival (P < .0001). The 10-year survival after relapse was 46%. There have been two cases of myelodysplasia and 12 other new malignancies, including four arising within radiation fields.

Conclusion: With prolonged follow-up, combined-modality therapy with risk-adapted COP-/CHOP-Bleo and IF radiation has attained higher rates of disease control and survival than previously reported with IF-XRT alone. This apparent improvement is being further explored in an ongoing randomized trial.

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