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

Introduction: About 40-45% of relapsed chemo-sensitive diffuse large B cell lymphoma (DLBCL) patients achieve long term survival with autologous transplant (autoSCT). However, the outcomes of patients who fail autoSCT are extremely poor. In addition, patients with high risk DLBCL and refractory disease have lower chances of response to autoSCT. Allogeneic stem cell transplant (alloSCT) could be a viable option in these circumstances, in part due to cytoreductive effect of conditioning regimen and graft-versus-lymphoma effect. Here we report outcomes of DLBCL patients who received alloSCT in upfront settings or following failed autoSCT.

Methods: We retrospectively evaluated clinical outcomes of adult DLBCL patients at Karmanos Cancer institute. The objectives were to determine rate of GVHD, overall survival (OS), relapse rate, progression-free survival (PFS) and non-relapse mortality (NRM) following alloSCT.

Results: Between January 2005 and December 2017, 81 patients underwent alloSCT. Of these, 73 patients had de novo, 7 had transformed DLBCL and one had testicular involvement. 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%) had 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 were 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 cumulative incidences of grade III-IV acute GVHD at 6-month and chronic GVHD at 1-year 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 with low relapse rate; although non-relapse mortality was high in this group where about a third had failed prior autoSCT.

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