Allogeneic Hematopoietic Stem Cells Transplantation for Non-Hodgkin’s Lymphoma. The Swiss Experience 1985-2014

Background: Efficacy of autologous hematopoietic stem cell transplantation (HST) and historically high NRM reported make allogeneic HSCT in Non-Hodgkin’s lymphoma (NHL) still a third line treatment. However, despite of a quick development of highly efficient targeted therapeutic antibodies alloHSCT still represents the only potentially curable treatment for several type of NHL. Introduction of reduced intensity conditioning regimens, amelioration of supportive care and graft-versus –host (GvHD) treatment lead to a global decreased of NRM rates, making use of alloHSCT much more attractive in a setting of relapse/refractory NHL. We report here the 20 years of Swiss experience in allo-HSCT for NHL.

Materials and Methods: The study included 225 NHL pts who received 241 transplantation in tree University Hospitals of Switzerland (Zurich, Basel and Geneva) between September 1985 and April 2014, including CLL=72, DLBCL=50, MCL=33, 27=Follicular, 5=MZL, 6=Burkitt, 5= Lymphoplasmacytic, 16=T-cell, ALCL=4 and AITL= 12. All pts relapsed after the best conventional therapy available. Impact on OS, DFS, RI and NRM was assessed in univariate analysis for:

i) year of transplantation: before and after 2000, ii) prior autoHSCT or allo-HSCT, iii) disease status at alloHSCT, including CR, PR, SD, PD iv) number of remission: 1^st vs >1^stv) Karnofsky index< 80% vi) donor type: identical siblings, MUD, MMUD, vii) HLA mismatch, if present viii) donor’s age: >60 ix) stem cell source: BM vs PBSC x) conditioning type: RIC vs MAC xi) TBI usage xii) acute GvHD xiii) chronic GvHD xiv) T vs B-cell origin, xv) indolent vs aggressive NHL, xvi) NHL type.

Results: Median follow up was 4 years (0.1-22.6 years). Pts median age was 44.5 (range, 19-66). Four years OS, DFS, RI and NRM were 59 ±7%, 55±7%, 35±8% and 25±6% respectively. Karnovsky < 80%, more than 1^stremission status at HSCT and prior SCT transplantation (auto or allo) were associated with both shorter OS p=0.002, 0.004 and 0.046 and worse DFS p=0.005, 0.002, and 0.038 respectively.The presence of aGvHD and TBI use as a part of conditioning were associated with longer DFS: p<0.001 and p=0,004. TBI use, patient being in CR1, Karnovsky>80%, presence of aGvHD were also associated with decreased RI: p=0.003, p=0.09, p=0.005 and p<0.001 respectively. NRM was influenced by donor’s type, with the worse survival curves for the MUD vs Id-sib (p=0.01) and presence of aGvH (p=0.034).

Conclusions: Our analysis of mixed-type NHL cohort confirms efficacy of alloHSCT in heavily pretreated/refractory patients showing promising 4 years OS and acceptable NRM rate. Interestingly, OS was found to be independent of NHL type and disease condition (CR vs PR, PD or primary refractory disease). Patient’s status according to Karnofsky index >80% and absence of heavy pretreatment were associated with better OS and DFS. Importantly, aGvHD was both associated with longer DFS but also higher NRM rates. However those results should be interpreted carefully due to the nature of the analysis (retrospective), the long period analysed, the heterogeneity of disease and conditioning regimen.