Long Term Outcomes of Allogeneic Stem Cell Transplant in Diffuse Large B Cell Lymphoma

Abstract

Introduction The outcomes of diffuse large B cell lymphoma (DLBCL) patients failing autologous transplant (autoSCT) are poor. Moreover, patients with high risk DLBCL and refractory disease have lower chances of remission to autoSCT. Allogeneic stem cell transplant (alloSCT) could be a viable option in these circumstances. Here we report outcomes of DLBCL patients who received alloSCT in upfront settings or following failed autoSCT. Methods The objectives were to determine GVHD, overall survival (OS), relapse rate, progression-free survival (PFS) and non-relapse mortality (NRM) of adult DLBCL patients following alloSCT. Results Between January 2005 and December 2017, 81 patients underwent alloSCT. Of these, 73 patients had de novo, 7 had transformed and one had testicular DLBCL. The median age at transplant was 52 years (range, 21-68). The median number of treatments prior to alloSCT was 3 (range, 1-6). Twenty-four patients (30%) had prior failed autoSCT, and 57 (70%) underwent upfront alloSCT. Disease status at transplant were: complete remission in 22 patients (27%), partial remission in 6 (7%), relapse in 31 (38%) and refractory in 22 (27%). Thirty-three patients (41%) underwent matched related and 48 (59%) had matched unrelated alloSCT. CNS and bone marrow involvement at the time of transplant was noted in 10% and 47% of patients, respectively. Patients received following conditioning regimens: R-BEAM (58%), BU-FLU-TBI (27%), BU-FLU (2%), CY-TBI (2%), BU-CY (2%), CY-FLU-TBI (2%), and others (5%). With a median follow-up of 5 years (95% CI, 4.01-9.89), the 1-year cumulative incidences of grade III-IV acute GVHD and chronic GVHD were 27.2% (95% CI, 18-37.2%) and 37% (95% CI, 26.5-47.6%), respectively. At 1-year, OS was 48% (95% CI, 38.4-60.3%), PFS was 43.2% (95% CI, 33.6-55.4%) and GRFS was 13.5% (95% CI, 7.8-23.5%). One-year relapse rate was 24.7% (95% CI, 15.9-34.5%), and NRM was 32.1% (95% CI, 22.2-42.4%). Sixteen patients (20%) patients were alive without chronic GVHD and relapse. Relapse disease at the time of transplant was associated with higher post-transplant relapse rate, and poor performance status was adversely associated with OS and PFS. No effect of prior autoSCT, conditioning regimen or type of donor was found in multivariable analysis on OS, PFS, relapse and NRM. Twenty-seven out of 81 patients (33%) were alive at the time of data analysis. Causes of death included relapse (37%), infection (31%), acute GVHD (13%) and multiorgan failure (11%). Conclusion Our study indicates that alloSCT provides long-term survival in these high-risk patients indicating graft-verus-lymphoma effect with low relapse rate; although non-relapse mortality was high in this group where about a third had failed prior autoSCT.