Autologous Stem Cell Transplantation In Mantle Cell Lymphoma: Total Body Irradiation (TBI) Plus Cyclophosphamide (or Melphalan) Is Not Superior to BEAM, A Single Institution Experience

Abstract 3563

Mantle cell lymphoma (MCL) is a B-cell non-Hodgkin's lymphoma (NHL) characterized by overexpression of cyclin D1 as a result of the t(11;14)(q13;q32). MCL is considered among the most aggressive NHLs entity with a median overall survival (OS) of approximately 6 years. It has been showed that intensive chemotherapy followed by autologous stem cell transplantation (ASCT) upfront provides a high complete remission rate. Furthermore, Dreyling et al. demonstrated that ASCT upfront is superior to conventional chemotherapy alone (Dreyling et al; Blood 2005). However, the question of the best conditioning regimen prior autologous stem cell reinjection is still pending. One major issue is the use of a total body irradiation (TBI). To answer this question, the outcome of all MCL patients (pts) (n=73) who underwent ASCT in our institution (Hematology Department of Nantes Medical University, Nantes; France) between 1990 to December 2008 were retrospectively analyzed in regard of the use or not of TBI as part of the conditioning regimen. In all cases, local pathologic experts confirmed the initial diagnosis. There were 50 males and median age at diagnosis was 54 years (34-69). All pts at diagnosis presented with stage III-IV. The most frequent extra-nodal involved sites were bone marrow (71%), digestive track (26%) and spleen (13%). MCL international prognostic index (MIPI) was lower or equal to intermediate risk in 51 cases and higher or equal to intermediate risk in 22 cases (data missing in 9 cases). Nineteen percent of the pts presented with a blastoid feature. Sixty-seven pts received ASCT upfront while 4 underwent ASCT at first relapse and 2 at second relapse. Prior ASCT, pts received (R)-CHOP/(R)-CHOP-like (n=36), (R)-DHAP (n=22) alone or (R)-DHAP plus (R)-CHOP (n=12) (data missing in 3 cases). Disease status at the time of transplantation were a partial response (PR) in 52 cases and a complete remission (CR) in 20 cases (data missing in 1 case). A TBI-based conditioning regimen was given to 44 pts (TBI group): TBI/melphalan in 5 cases or TBI/cyclophosphamide in 39 cases. In contrast, 28 pts received BEAM but one patient who received melphalan alone (non-TBI group). According to sex, age, Ann Arbor stage, extra-nodal involvement, MIPI and blastoid feature and the number of lines of chemotherapy prior ASCT, there was no statistical difference between the two groups (TBI vs non-TBI group). After ASCT, 63 pts reached CR (37 in the TBI group compared to 26 in the non-TBI group) and 5 PR (3 in the TBI group compared to 2 in the non-TBI group). For all pts, the median follow up (FU) calculated from time of diagnosis is 3,2 years (range: 0.75–13.3) and 2.5 years from time of ASCT (range: 0.22–12.9). After ASCT, the 1- and 3-year OS rates are 90 and 70% and the event free survival (EFS) rates are 84 and 58%, respectively. In bivariate analysis, the 1- and 3-year OS rates are similar in the non-TBI vs the TBI group: 89% vs 90% and 71% vs 70% (p= 0.82), respectively. The comparison between the 2 groups shows also no difference in term of 1- and 3-year EFS rates (85% vs 83% and 55% vs 58%; p= 0.89). In multivariate analysis only the MIPI and blastoid feature have an impact for both EFS and OS. CONCLUSION: The present analysis shows no advantage for the use of TBI/cyclophosphamide (or melphalan) as compared to BEAM for the conditioning regimen. The present analysis also confirms the interest of the MIPI to predict transplanted MCL patient outcomes.