Comparison of autologous and allogeneic hematopoietic cell transplantation strategies in patients with primary plasma cell leukemia, with dynamic prediction modelling

Primary Plasma Cell Leukaemia (pPCL) is a rare and challenging malignancy. There is limited data regarding optimum transplant approaches. Therefore we undertook a retrospective analysis from 1998-2014 of 751 patients with Primary Plasma Cell Leukaemia (pPCL) undergoing one of four transplant strategies; single autologous transplant (single-auto), single allogeneic transplant (allo-first) or a combined tandem transplant either auto-allo or auto-auto. To avoid time bias multiple analytic approaches were employed including Cox models with time dependent covariates and dynamic prediction by landmarking. Initial comparisons were made between patients undergoing allo-first (n=70) versus auto first (n=681), regardless of subsequent administration of second transplant. The allo-first group had lower relapse rate (45.9%, 95%CI 33.2-58.6 vs. 68.4%, 64.4-72.4) but higher NRM (27%, 95%CI 15.9-38.1 vs 7.3%, 5.2-9.4) at 36 months. Allo-first had remarkably higher risk in the first 100 days for both OS and PFS. Autoallo (n=122) had no increased risk in the short term and significant benefit in PFS post-100 days compared to single auto (HR 0.69, 95%CI: 0.52-0.92, p=0.012). Auto-auto (n=117) was an effective option for patients achieving CR prior to first transplant, whereas in patients without CR prior to transplant our modelling predicted that auto-allo was superior. This is the largest retrospective study reporting on transplant in pPCL to date. We confirm significant mortality risk within the first 100 days for allo-first and suggest that tandem transplant strategies are superior. Disease status at time of transplant influences outcome, this knowledge may help guide clinical decisions on transplant strategy.