Clinical characteristics and outcomes of Richter transformation: experience of 204 patients from a single center

Abstract

The natural history, prognostication and optimal treatment of Richter transformation developed from chronic lymphocytic leukemia (CLL) are not well defined. We report the clinical characteristics and outcomes of a large series of biopsy-confirmed Richter transformation (diffuse large B-cell lymphoma or high grade B-cell lymphoma, n=204) cases diagnosed from 1993 to 2018. After a median follow up of 67.0 months, the median overall survival (OS) was 12.0 months. Patients who received no prior treatment for CLL had significantly better OS (median 46.3 vs. 7.8 months; P<0.001). Patients with elevated lactate dehydrogenase (median 6.2 vs. 39.9 months; P<0.0001) or TP53 disruption (median 8.3 vs. 12.8 months; P=0.046) had worse OS than those without. Immunoglobulin heavy chain variable region gene mutation, cell of origin, Myc/Bcl-2 double expression and MYC/BCL2/BCL6 double-/triple-hit status were not associated with OS. In multivariable Cox regression, elevated lactate dehydrogenase [Hazard ratio (HR) 2.3, 95% Confidence Interval (CI): 1.3-4.1; P=0.01], prior CLL treatment (HR 2.0, 95%CI: 1.2-3.5; P=0.01), and older age (HR 1.03, 95%CI: 1.01-1.05; P=0.01) were associated with worse OS. Twenty-four (12%) patients underwent stem cell transplant (20 autologous and 4 allogeneic), and had a median post-transplant survival of 55.4 months. In conclusion, the overall outcome of Richter transformation is poor. Richter transformation developed in patients with untreated CLL has significantly better survival. Stem cell transplant may benefit select patients.

Figure 1

Overall survival (OS) after Richter transformation (RT) diagnosis of the entire cohort and by prior chronic lymphocytic leukemia (CLL) treatment status. (A) OS for all patients. (B) OS by previous CLL treatment status. (C) OS by temporal relationship between CLL and RT in patients with previously untreated CLL. (D) OS by lines of therapy in patients with previously treated CLL. (E) OS by prior CLL treatment category.

Figure 2

Overall survival (OS) after Richter transformation (RT) diagnosis by clinical and molecular factors. (A) OS by age at RT diagnosis. (B) OS by lactate dehy-drogenase (LDH) at RT diagnosis. (C) OS by TP53 disruption status. (D) OS by Myc and Bcl-2 double expression status.

Figure 3

Survival outcomes of the 24 Richter transformation (RT) patients who underwent stem cell transplantation (SCT). (A) Swimmers plot showing time from RT diagnosis to SCT (blue) and post-SCT survival (red; numbers indicate post-SCT survival in months). (B) Post-SCT survival for all patients who underwent SCT. CI: Confidence Interval.