Front-Line High Dose Therapy with Following Autologous Stem Cell Transplantation (ASCT) for Follicular Lymphoma Patients

BACKGROUND: Follicular lymphoma (FL) is one of the most frequent types of B-cell lymphomas and accounts for about 22% of all non-Hodgkin lymphomas in Russia. The disease is usually a long-term condition with frequent relapse. At the same time 15-20% of pts have fast-tumor progression. Patients (pts) of this group die within the first 1.5-2 years from the time of diagnosis. High-dose chemotherapy (HDT) followed by ASCT in the presence of nonfavorable characteristics of FL (fast growth of tumor volume, B-symptoms, third citological grade of tumor, large tumor size, absence of anti-tumor response to R-CHOP courses in the first remission) increases the overall survival and progression-free survival of pts.

AIM: To estimate HDT with ASCT efficiency among pts with FL in front-line therapy who received treatment in the National Research Center for Hematology during 2000-2013.

PATIENTS AND METHODS: The results of ASCT among 12 pts with FL have been analyzed: 8 male and 4 female aged from 31 to 50 with median age 43. Patients in the main group (11/12) were on the IVth stage of tumor growth. In 6/12 cases the tumor size was more than 6 sm. Among 7/12 pts, besides lesions of lymphatic nodes, extra nodal lesions were found: infiltration in psoas (1/12), kidney (1/12), stomach (1/12), lungs (1/12), thyroid (1/12), pancreas (1/12). In 2/12 cases leukaemization was observed. Based on FLIPI criteria all the pts were divided into three groups: in the first risk group - 5/12 pts, in the second - 3/12, in the third - 4/12. B-symptoms were in the majority of cases (9/12). 9/12 pts were diagnosed with I-II cytological grade of FL, among 3/12 - III A/B. Based on the character of tumor growth the dispersion was the following: nodular tumor growth - 5/12, nodular-diffuse tumor growth-6/12, diffuse tumor growth - 1/12. Immuno-chemical investigation of protein serum and urine was performed in 9/12 cases, and among them rising serum β2-microglobulin above the norm was observed in 4/9 pts. A rise in lactate dehydrogenase concentration above the norm was observed among 4/12 pts. Lesion of bone marrow at the beginning of the disease was identified among half of the pts (6/12). Induction courses were performed on the R-CHOP programs, with intensive therapy - on protocol mNHL-BFM-90.

RESULTS: Anthracycline courses were prescribed for nearly all of the pts as an inductive therapy: R-CHOP (11/12). mNHL-BFM-90 protocol was chosen as an inductive regime because of the fast growth of tumor size, IIIB grade of FL in 1/12 case. This tumor growth behaved like diffuse large B-cell lymphoma. In three cases medical-diagnostic splenectomy was undertaken before chemotherapy. After the inductive regimes the pts were given HDT based on the following scheme: two courses R-DHAP, course with rituximab and high-doses cyclophosphamide, a course with rituximab and high doses of etoposide, R-BEAM. All 12 pts, who were given ASCT are in full remission on the main disease. The period of observation is from 13 to 164 months.

CONCLUSION: This first experience of intensive therapy in FL in Russia demonstrates that ASCT as a front-line therapy leads to complete remission of FL among pts who have nonfavorable prognosis factors.