TY - JOUR
T1 - Long-term follow-up of patients receiving allogeneic stem cell transplant for chronic lymphocytic leukaemia
T2 - mixed T-cell chimerism is associated with high relapse risk and inferior survival
AU - Thompson, Philip A.
AU - Stingo, Francesco
AU - Keating, Michael J.
AU - Wierda, William G.
AU - O'Brien, Susan M.
AU - Estrov, Zeev
AU - Ledesma, Celina
AU - Rezvani, Katayoun
AU - Qazilbash, Muzaffar
AU - Shah, Nina
AU - Parmar, Simrit
AU - Popat, Uday
AU - Anderlini, Paolo
AU - Yago, Nieto
AU - Ciurea, Stefan O.
AU - Kebriaei, Partow
AU - Champlin, Richard
AU - Shpall, Elizabeth J.
AU - Hosing, Chitra M.
N1 - Publisher Copyright:
© 2017 John Wiley & Sons Ltd
PY - 2017/5
Y1 - 2017/5
N2 - 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.
AB - 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.
KW - chronic lymphocytic leukaemia
KW - mixed chimerism
KW - relapse
KW - survival
KW - transplant
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U2 - 10.1111/bjh.14596
DO - 10.1111/bjh.14596
M3 - Article
C2 - 28295181
AN - SCOPUS:85015173218
SN - 0007-1048
VL - 177
SP - 567
EP - 577
JO - British Journal of Haematology
JF - British Journal of Haematology
IS - 4
ER -