Allogeneic Hematopoietic Stem-Cell Transplantation for Patients with Richter's Syndrome:the SFGM-TC Experience
Authors: Bounaix Laura , Nguyen Stephanie , Blaise Didier , Michonneau David , Bourhis Jean-Henri , Maertens Johan , Poire Xavier , Chevallier Patrice , Maillard Natacha , Yakoub-Agha Ibrahim , Mannone Lionel , Bernard Marc , de Revel Thierry , Labussiere-Wallet Helene , Ceballos Patrice , Lemal Richard , Hermet Eric , Ravinet Aurélie , Tournilhac Olivier , Bay Jacques-Olivier , Guieze Romain 
Published: October 2019

Abstract
Introduction. Chronic lymphocytic leukemia (CLL) has typically an indolent course but can undergo transformation into a more aggressive lymphoma (mainly of diffuse large B-cell lymphoma histology) that is called Richter's syndrome. While the advent of novel therapies targeting the BCR signaling or the BCL-2 protein is transforming the management of patients with CLL, these drugs failed to prevent the risk of RS that is estimated to be 0.5-1% per year. RS is associated with a very poor outcome and is thus becoming the main obstacle to long term CLL cure. Allogeneic stem-cells transplantation (allo-SCT) has been recommended as the treatment of choice in eligible patients with clonally related RS (Rossi Blood 2018) but previous experience is still limited to less than 50 cases. We here aimed to investigate the safety and efficacy of allo-SCT for patients with RS.
Methods. We report on a retrospective study of consecutive patients with RS who underwent allo-HSCT between 2005 and 2016 in 15 French and Belgian centers from the Société Francophone de Greffe de Moelle et de Transplantation Cellulaire (SFGM-TC). Inclusion criteria were: age >18, confirmed RS diagnosis, allo-HCST from either sibling or unrelated donor. Data quality was ensured using computerized discrepancy errors and on-site data verification.
Results. A total of 24 patients (median age=59 years [19-69], M/F= 18/6) were included in the present study. Median time from CLL to RS diagnosis was 59 months [0-198]. The histology was DLBCL (86%) or HL (14%). The patients received a median of 1 [0-4] therapeutic line for CLL and 1 [0-3] for RS. Nine (38%) patients underwent auto-SCT prior to allo-HCT. At allo-HCT, 17 (71%) of patients were in complete and 7 (29%) in partial response. Most patients received reduced intensity conditioning (RIC) regimen (n= 18, 75%) and peripheral blood (76%) as source of stem-cells. Two (8%) patients received bone marrow stem cells and 4 (16%) cord blood stem cells. Donors were related (n=8) or unrelated (mismatched, n=8; matched, n=5; missing, n=3). A total of 15 patients (63%) received total body irradiation (TBI) within the conditioning.
With a median follow-up of 27 months, 2-year OS was 44% (figure 1). The 100-day non-relapse mortality was 25%. Cause of death was relapse (n=3), treatment toxicity (n=10; GVHd, n=3; infectious complications, n=6; pulmonary toxicity, n=1), infection complications (n=1) and cerebral stroke (n=1). 2-year OS was significantly shorter for older patients (20% if >59 years old vs 64% if ≤59,P = 0.031). The 2-year OS was influenced by presence of cGVHD (73% vs 25%,P = 0.006).
Neither donor type, prior auto-SCT, disease status prior to allo-HCT, use of antilymphocyte serum infusions nor the regimen conditioning significantly impact OS.
Conclusion. Our study suggests that allo-HCT is a strategy achieving prolonged survival but should be performed in young patients to limit the risk of NRM. The favorable impact of GVHd suggests an anti-RS allogenic effect.

Disclosures
Guieze: abbvie: Honoraria; janssen: Honoraria; gilead: Honoraria.