Reduced-intensity conditioning hematopoietic stem cell transplantation for chronic lymphocytic leukemia and Richter’s transformation

Abstract

Allogeneic hematopoietic stem cell transplantation (HSCT) may potentially cure patients with chronic lymphocytic leukemia (CLL) and Richter’s transformation (CLL-RT) or CLL without RT, but the impact of novel agents on HSCT is unclear. CLL-RT patients have a grave prognosis, and their outcomes after HSCT are uncertain. We conducted a retrospective analysis of all 58 CLL patients, including 23 CLL-RT patients, who underwent reduced intensity conditioning (RIC) HSCT at Memorial Sloan Kettering Cancer Center (New York, NY) between September 2006 and April 2017. With a median follow-up of 68 months (range, 24-147 months), 5-year progression-free survival (PFS) was 40% (95% confidence interval [CI], 28%-56%), and overall survival (OS) was 58% (95% CI, 48%-74%). The 1-year graft-versus-host disease/relapse-free survival (GRFS) was 38% (95% CI, 25%-50%). Patients with CLL-RT and CLL patients without RT had comparable outcomes. In both cohorts, treatment-sensitive response and ≤3 previous lines of therapy produced superior PFS and OS. Outcomes were agnostic to adverse cytogenetic and molecular features. Novel agents did not have a negative impact on HSCT outcomes. Total body irradiation (TBI)-containing RIC yielded inferior PFS, OS, and GRFS. CLL-RT patients older than age 55 years who had an HSCT Comorbidity Index score of ≥2 demonstrated inferior OS. This study, which is the largest series of RIC-HSCT for patients with CLL-RT, provides evidence supporting RIC-HSCT in early remission courses for patients with CLL-RT and poor-risk CLL patients. TBI-containing RIC should be considered with caution.

Biology and Treatment of Richter Transformation

“…Young age (<60 years), deeper response at SCT and having received <3 previous lines of therapy positively correlated with outcomes, while cytogenetic/molecular features and exposure to novel agents did not show an impact on PFS/OS ( 77 , 78 ). Total body irradiation (TBI) resulted in poorer outcomes ( 77 ).…”

“…A single-center retrospective analysis of 23 RT patients undergoing reduced intensity conditioning (RIC-SCT) reports a 5-year PFS of 40% and OS of 58% ( 77 ). Young age (<60 years), deeper response at SCT and having received <3 previous lines of therapy positively correlated with outcomes, while cytogenetic/molecular features and exposure to novel agents did not show an impact on PFS/OS ( 77 , 78 ). Total body irradiation (TBI) resulted in poorer outcomes ( 77 ).…”

Richter Transformation in Chronic Lymphocytic Leukemia: Update in the Era of Novel Agents

“…The 3 year OS was estimated at 36% for allogeneic SCT and 59% for autologous SCT, with an age younger than 60 years, chemo-sensitive disease, and RIC being associated with a better prognosis after allogeneic SCT in RT [77]. The benefits of RIC preceding allogeneic SCT in RT were also underlined in a recent retrospective study including 58 CLL patients, 23 of them with RT with a median follow-up of 68 months that revealed a 5 year OS of 58% and a 5 year PFS of 40% [78]. Another single center study showed encouraging results in 10 patients with RT referred to allogeneic SCT after objective response to therapy, with a 4 year OS of 50%, a non-relapse mortality at both 1 and 4 years post-transplantation of 40%, and a 4 year incidence of relapse/progression of 10% [79].…”

Cellular Therapy in High-Risk Relapsed/Refractory Chronic Lymphocytic Leukemia and Richter Syndrome

“…The key clinical features associated with an improved PFS/OS following RIC alloSCT were treatment-sensitive response and ≤3 lines of prior therapy at alloSCT. Use of total body irradiation (TBI) containing RIC regimens was associated with an inferior PFS, OS, and relapse-free survival ( 58 ).…”

“…The 1-year NRM remains significant at 12%–23%. In both groups, one-third of the patients relapsed within 3–5 years ( 58 , 61 ).…”