Outcomes of Hematopoietic Stem Cell Transplantation for Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL).

Abstract Considerable advancements have been made in our understanding of the biology and treatment of CLL/SLL. Despite these advances, CLL/SLL essentially remains an incurable illness. Hematopoietic stem cell transplantation (HSCT) has been used in an attempt to improve remission duration and survival. However little high level data exists on outcomes for patients (pts) undergoing HSCT for CLL/SLL. We evaluated the long-term survival of 65 CLL/SLL pts who underwent allogeneic or autologous HSCT from 1995 until 2006 at the University of Nebraska Medical Center. The median duration of follow-up for surviving pts is 8.8 years. The median age was 49 years and there was no significant difference in age between the autologous and allogeneic groups. Thirty nine pts underwent allogeneic HSCT (n=25 matched related donor, n=14 matched unrelated donor) and 26 pts underwent autologous HSCT. For the group undergoing allogeneic HSCT, the stem cell source was mobilized peripheral blood progenitor cells in 74% and bone marrow in 26%. In the autologous HSCT group, 81% of pts received peripheral blood and 19% received bone marrow as their stem cell source. In the autologous group there were 19 deaths (10 from progression) over the period of follow-up. In the allogeneic group there were 29 deaths (including 8 from acute regimen related toxicity, 9 from infection, 3 from complications of GVHD, 1 from late pulmonary toxicity, one from PTLD, one from MDS/AML) and 10 pts are alive at end of follow-up. One hundred day mortality was significantly higher in the allogeneic group (20% vs. 6%; p=0.05). For the allogeneic group the cumulative incidence of grade II-IV acute graft versus host disease (GHVD) was 64% (95% confidence interval [CI]=47–76) and the cumulative incidence of chronic extensive GHVD was 50% (95% CI=29–68). One-year progression free survival (PFS) was significantly better among autologous SCT when compared to allogeneic HSCT (77% versus 45%; P=0.006), but at 5 years these differences were no longer apparent. Similarly, one-year overall survival (OS) was significantly better for autologous SCT (81% versus 48%; P=0.003) but at 5 years these differences were no longer significant (49% versus 31%; p=0.15). Among all patients undergoing allogeneic HSCT, 5-year PFS was significantly higher for patients with SLL vs. CLL (36% vs. 25%; P=0.04). In addition, 5 year OS was better for pts with SLL compared to CLL (51% vs. 33%, P=0.06). There was no difference in PFS or OS following autologous SCT between patients with a diagnosis of CLL versus SLL. The group of pts undergoing autologous HSCT demonstrates no plateau on the PFS curve, whereas for pts undergoing allogeneic HSCT there is a suggestion of a plateau in PFS at approximately 25%. In conclusion, CLL/SLL patients undergoing allogeneic SCT had a higher incidence of early treatment related mortality, mainly from regimen related toxicity and infection. In a subgroup analysis pts with CLL appear to have an inferior PFS compared with pts with SLL. This difference may be due to a more prominent underlying immune deficiency in CLL patients that leads to a higher probability of treatment related mortality. Pts with CLL/SLL undergoing autologous HSCT had a lower incidence of treatment related mortality, but there is no evidence of a plateau in progression-free survival.