Autologous and Allogeneic Stem Cell Transplantation for Richter's Transformation: A Retrospective Analysis From the Chronic Leukaemia Working Party and Lymphoma Working Party of the EBMT.

Richter's syndrome (RS) occurs in 2-8% of patients with chronic lymphocytic leukaemia (CLL). Clinical outcome has been generally poor after multiagent chemotherapy with median survival of less than 1 year. The aim of this retrospective study was to evaluate whether an autologous (AutoSCT) or an allogeneic stem cell transplantation (alloSCT) offers survival benefit. There are scant data addressing this issue.

As patients with RS are not identified separately in the current EBMT database a request was sent to all EBMT centres known to have performed SCT in patients with CLL, high-grade lymphoma or Hodgkin's lymphoma asking for RS transplants. Inclusion criteria included a diagnosis of RS prior to SCT, age > 18 years, and SCT performed 1997-2007. Centers who reported RS transplants received a questionnaire to collect detailed information on disease and transplant characteristics and outcome results. Data were analyzed by descriptive statistics and survival comparisons using log rank testing and Cox modelling. Fifty nine transplants for RS were reported by 25 centres, which is the largest cohort described.

Thirty nine patients (25 (64%) male) underwent AutoSCT (of whom 8 underwent a subsequent alloSCT). The median age was 56 years (range, 30-68 years) and 44% (n=17) of transplants were performed after 2003, with a TBI-containing regimen used in 5 patients. A minority (36% of cases with data known) of patients had received ≥3 lines of prior therapy. The majority of transplants (n=32; 84%) were performed within a year of diagnosis of RS, and 91% of patients (with data known) were in CR/PR at time of transplant.

With a median follow-up of 27 months, 15/39 (39%) patients were alive and 13 patients were disease-free, 21 (39%) had relapsed (19 died from relapse) and 5 (13%) died of treatment-related complications after ASCT. OS was 54% and 25% at 3 and 5 yrs respectively. Relapse incidence of 49%, NRM of 14% and PFS of 37% was observed at 3 yrs.

Twenty patients (12 (60%) male) underwent alloSCT from a matched sibling donor (n=10), VUD (n=8) or an alternative donor (n=2) with PBSC used in 90% of cases. The median age was 57 years (range, 42-70 years) and 70% (n=14) of transplants were performed after 2003. A majority (80%) of patients underwent alloSCT within 1 year of diagnosis of RS and had received ≥3 lines of prior therapy (71% of known cases). Conditioning was reduced-intensity (RIC) in 14 cases and myeloablative in 6 patients, with TBI used for 4 patients and T-cell depletion strategies in 13. At time of alloSCT 14 patients were in CR/PR and 5 had progressive disease (missing data in 1 case).

With a median follow-up of 15 months (range, 3-94 months) 11/20 (55%) patients were alive after alloSCT, of whom 7 were in CR/PR. Overall survival (OS) was 51% and 41% at three years and 5 years respectively. Conditioning (myeloablative vs RI-conditioning; P = 0.14) and source of donor (HLA-id sib vs VUD; P = 0.97) did not statistically influence outcome. OS was not statistically affected by the variables: prior lines of therapy < 3 or ≥3 lines (P = 0.72), CMV serostatus recipient/donor (P = 0.23), use of T-cell depletion (P = 0.88) or disease status at time of transplant. The 3 yr OS for patients transplanted in CR/PR was 51% compared to 27% for those transplanted with progressive disease (P = 0.18). Outcome was superior for patients < 60 yrs at alloSCT (p=0.04). Relapse incidence of 38%, NRM of 23% and PFS of 39% was observed at 3 yrs. Acute GVHD grade II to IV occurred in 30% of patients and there were no cases of extensive chronic GVHD within reported cases.

This is the largest study that has assessed the outcome after transplantation of patients with RS. In summary patients with RS who are chemosensitive to induction therapies may benefit from consolidation with transplantation strategies.

No relevant conflicts of interest to declare.