Richter's transformation to diffuse large B‐cell lymphoma: A retrospective study reporting clinical data, outcome, and the benefit of adding rituximab to chemotherapy, from the Israeli CLLStudy Group

Abstract

Richter's syndrome (RS) is the rare development of an aggressive lymphoid malignancy in a patient with pre-existing chronic lymphocytic leukemia (CLL). Data on RS is sparse and mostly derived from case reports or small series of patients and only a few larger cohorts have been published. The purpose of this large retrospective study was to summarize our national experience with RS in CLL, examine possible risk factors, and analyze relevant demographic, laboratory and clinical parameters, including results of therapy and outcome. We first evaluated data obtained from 119 patients with RS diagnosed during 1971-2010 from 12 medical centers in Israel. The final cohort summarized consisted of 81 patients with RS who developed only diffuse large B-cell lymphoma (DLBCL) after exclusion all cases with insufficient data and those who were not DLBCL. Median overall survival from time of diagnosis of RS was 8 months; after applying the Richter score, patients could be stratified into three prognostic groups, while all other clinical and laboratory parameters evaluated had no prognostic significance. Prior therapy for CLL had no impact on RS survival (P 5 0.8) and patients with therapy "na€ ıve" RS and those who had already received chemotherapy prior to developing RS, had the same survival. The addition of rituximab to chemotherapy for RS improved 2 years overall survival from 19% in the chemotherapy alone arm to 42% (P value of 0.001). Although prognosis of patients with RS remains dismal, this retrospective observation provides support for the use of chemoimmunotherapy in DLBCL-RS.

Richter transformation of CLL

“…Patients were assigned to one of the four risk groups on the basis of number of risk factors, with the median OS ranging from 13 months in the low-risk group to only 1 month in the high-risk group. This score was recently validated in a retrospective analysis conducted by the Mayo Clinic and Israel CLL study group [7,55]. Chigrinova and colleagues noted that the presence of TP53 and/or CDKN2A inactivation was associated with worse OS compared to other patients with RT (p = 0.01) [16].…”

“…Management algorithm for RT is shown in Figure 2. Chemoimmunotherapy (CIT) has been the standard therapy for patients with RT (Table 4), and addition of rituximab to standard chemotherapy has been shown to improve survival in patients with RT [55]. Unfortunately, none of the CIT regimens studied so far have been particularly effective, and the median survival after therapy is less than 1 year [65].…”

“…The prognosis after diagnosis of RT is very dismal with median OS of less than 1 year in most studies [5,55,56]. The MDACC group reported a large series of 148 patients with RT with a median OS of 8 months [5].…”

“…Given the rarity of the disease, there have not been any prospective randomized clinical trials for patients with RT, and most evidence is derived from single-arm phase I-II studies and retrospective analyses [55,[57][58][59][60][61][62][63][64]. Management algorithm for RT is shown in Figure 2.…”

Histologic transformation of chronic lymphocytic leukemia/small lymphocytic lymphoma

“…Most data for treatment for RS is derived from single-arm phase I-II studies, and retrospective analyses [13,[72][73][74][75][76][77][78][79]. The standard therapy for RS is chemoimmunotherapy with a median survival after therapy of less than 1 year [36].…”