Background: Follicular Lymphoma (FL) is characterized by t(14:18)(q32;q21) in 80% patients. Persistence of expression bcl2/JH gene translocation is related to frequent relapses in FL.

Purpose: To determine the efficacy of Fludarabine-Mitoxantrone (FLD/MTX) + monoclonal anti CD20 antibody (Rituximab) to induce clinical and molecular response in relapsed FL in base to the presence of bcl-2.

Methods: Prospective trial in 31 patients with relapsed FL. An outpatient regimen i.v./28d: FLD 30 mg/m2 1–3 + MTX 10 mg/m2 1 followed by Rituximab (375 mg/m2/weekly x4). Eligibility criteria: adults patients with both (relapsed FL by biopsy + bcl-2 immunohistochemistry expression in nodal biopsy), ECOG<3, normal renal function and liver tests. Exclusion criteria: previous anti-CD20 therapy, chemotherapy within 4 weeks previously, other malignancies, AIDS or other infectious disease. Patients were eligible for registration previous inform consent. Evaluation at baseline included: complete blood counts, serum and urine biochemistry, b2 microglobuline and LDH, body scan, bone marrow (BM) biopsy and PCR-ELISA for t(14;18) in BM. Patients were classified according ECOG, clinical stage and FLIPI. Follow-up monitoring: after FLD/MTX and 2 months after Rituximab, including clinical examination, laboratory, scan, BM examination and t(14;18). Response criteria: Complete remision (CR):resolution tumour mass and BM involvement; partial remission (PR):>75% reduction in tumour mass and BM infiltration <10%. Progression: increase in measurable mass lesion >25% during therapy. Molecular remision (MR): negative PCR-ELISA assay in BM. Statistical analysis: descriptive and frequency distribution, overall survival (OS), relapsed free survival (RFS). Survival curves were estimated using Kaplan-Meier survival analysis.

Results: Mar-99 to July03, 31 patients with relapsed FL were enrolled. Mean age: 56.00± 12.44 (range 32–77); M/F: 13/18. ECOG: 0(22), 1(5), 2(2), 3(2). Clinical stage II(4), III(8), IV(19). Previous therapies 1(19), 2(4), and 3 or more(8), FLIPI 0 (3), 1(6), 2(15), 3(7). PCR t(14:18) was positive in BM in 12 cases (40 %). Response: after FLD-MTX, clinical response was obtained in 27 patients, CR 13 (43.3%) and PR 14(46.67%), 2 failed. One not valuable. Rituximab started in 27/28 patients with clinical response (1 refused). After Rituximab: CR 23 (81.4%), PR 4(13.3%) and 2 failures (6.4%) After Rituximab (26 responsive patients): 22 (84.6%) achieved MR, 4 (15.3%) persist PCR-ELISA positive in BM. PBSCT was underwent in 14 CR patients (63.6%). OS: 117 months (range 36–200), median RFS 44,22 months (range 0–73). Relapse was observed in 13(43,3%) and 8 died, only one patient had persistence of t(14;18), mean time to relapse 24.1 m (0–57), 3 patients relapsed after PBSCT. Four patients in CR have died by other causes. Nowadays17 patients remain alive and 12 are in CR.

Conclusions: The response to FLD-MTX is obtained in 90 % of patients with relapsed FL, with CR rates 43.3%. The addition of Rituximab does not influence on overall response but improves CR rates (81.4%). The median RFS of group is 117 months only 13 patients developed relapse apparently it is not related to persistence of t(14;18).

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