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High Molecular Response Rate and Clinical Correlation in Patients with Follicular Lymphoma Treated with Cyclophosphamide-Vincristine-Prednisone plus Interferon 2b¹

Unidad de Biología Molecular [E. F-R., M. C., M. O., M. S-R.], Servicio de Hematología [C. B., P. L., J. M. F-R., R. A.], and Servicio de Anatomía Patológica [S. N., A. A.], Hospital Universitario de la Princesa, Universidad Autónoma de Madrid, Madrid 28006, Servicio de Hematología, Hospital Severo Ochoa, Leganés [G. P.], and Servicio de Hematología, Hospital Central de Asturias, Oviedo, Spain [C. N.]

Purpose: The role of molecular monitoring of minimal residual disease (MRD) in low-grade non-Hodgkin’s lymphoma is controversial. We have performed a prospective study of the molecular behavior of 35 patients with follicular non-Hodgkin’s lymphoma who received cyclophosphamide-vincristine-prednisone chemotherapy in conjunction with IFN- 2b.

Experimental Design: Bcl-2 and clonal immunoglobulin heavy chain (IgH) gene rearrangements were assayed at diagnosis by PCR in lymph node and bone marrow (BM) and sequentially after treatment.

Results: Molecular markers were detected in BM of 29 (83%) patients at diagnosis: Bcl-2 rearrangement in 20 patients (90% major breakpoint and 10% minor cluster) and clonal IgH rearrangement in 9 of 15 patients negative for Bcl-2. Molecular and clinical response was noted in 25 (86%) patients after induction treatment. Progression-free survival at 5 years was 78.1 ± 8%. A correlation between clinical and molecular response was found in 24 patients with molecular markers in BM at diagnosis and >2 years of follow-up: 94% of patients with undetectable MRD showed continuous clinical remission, whereas 50% of patients who reverted back to positive molecular markers relapsed (P < 0.05).

Conclusions: The rate of molecular response is high in patients treated with cyclophosphamide-vincristine-prednisone and IFN and MRD sequential analysis is useful for disease surveillance.