Long-term follow-up of patients receiving allogeneic stem cell transplant for chronic lymphocytic leukaemia: mixed T-cell chimerism is associated with high relapse risk and inferior survival.
There is limited information regarding the immunological predictors of post-allogeneic stem cell transplant (alloSCT) outcome in chronic lymphocytic leukaemia (CLL), such as mixed T-cell chimerism. We analysed 143 consecutive patients with relapsed/refractory CLL, transplanted between 2000 and 2012, to determine the prognostic relevance of mixed chimerism post-alloSCT and the ability of post-transplant immunomodulation to treat relapse. Mixed T-cell chimerism occurred in 50% of patients at 3 months and 43% at 6 months post-alloSCT; upon 3- and 6-month landmark analysis, this was associated with inferior progression-free survival (PFS) [Hazard ratio (HR) 1·93, P = 0·003 and HR 2·58, P < 0·001] and survival (HR 1·66, P = 0·05 and HR 2·17, P < 0·001), independent of baseline patient characteristics, and a lower rate of grade II-IV acute graft-versus-host disease (GHVD) (16% vs. 52%, P < 0·001). Thirty-three patients were treated with immunomodulation for relapse post-alloSCT (immunosuppression withdrawal, n = 6, donor lymphocyte infusion, n = 27); 17 achieved complete response (CR), which predicted superior PFS (53 months vs. 10 months, P < 0·001) and survival (117 months vs. 30 months, P = 0·006). Relapsed patients with mixed chimerism had inferior response to immunomodulation; conversion to full donor chimerism was highly correlated both with CR and with the development of severe acute GVHD, which was fatal in 3/8 patients. Novel therapeutic strategies are required for patients with mixed T-cell chimerism post-alloSCT for CLL.
['Thompson|Philip A|PA|', 'Stingo|Francesco|F|', 'Keating|Michael J|MJ|', 'Wierda|William G|WG|', "O'Brien|Susan M|SM|", 'Estrov|Zeev|Z|0000-0002-1623-3613', 'Ledesma|Celina|C|', 'Rezvani|Katayoun|K|', 'Qazilbash|Muzaffar|M|', 'Shah|Nina|N|', 'Parmar|Simrit|S|', 'Popat|Uday|U|', 'Anderlini|Paolo|P|', 'Yago|Nieto|N|', 'Ciurea|Stefan O|SO|', 'Kebriaei|Partow|P|', 'Champlin|Richard|R|', 'Shpall|Elizabeth J|EJ|', 'Hosing|Chitra M|CM|0000-0003-0409-5556']
D000328:Adult D000359:Aftercare D000368:Aged D046528:Chimerism D004812:Epidemiologic Methods D005260:Female D006085:Graft Survival D006086:Graft vs Host Disease D006801:Humans D007166:Immunosuppressive Agents D015451:Leukemia, Lymphocytic, Chronic, B-Cell D017710:Lymphocyte Transfusion D008297:Male D008875:Middle Aged D012008:Recurrence D033581:Stem Cell Transplantation D013601:T-Lymphocytes D014184:Transplantation, Homologous D016896:Treatment Outcome
transplant chronic lymphocytic leukaemia relapse survival mixed chimerism