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Risk‐stratified adoptive cellular therapy following allogeneic hematopoietic stem cell transplantation for advanced chronic lymphocytic leukaemia
Author(s) -
Richardson Simon E.,
Khan Iftekhar,
Rawstron Andrew,
Sudak Jagoda,
Edwards Noha,
Verfuerth Stephanie,
Fielding Adele K.,
Goldstone Anthony,
Kottaridis Panagiotis,
Morris Emma,
Benjamin Reuben,
Peggs Karl S.,
Thomson Kirsty J.,
Vandenberghe Elisabeth,
Mackin Stephen,
Chakraverty Ronjon
Publication year - 2013
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.12197
Subject(s) - medicine , alemtuzumab , cumulative incidence , donor lymphocyte infusion , transplantation , hematopoietic stem cell transplantation , graft versus host disease , minimal residual disease , chronic lymphocytic leukemia , incidence (geometry) , stem cell , hematology , oncology , gastroenterology , leukemia , genetics , physics , biology , optics
Summary Following reduced intensity‐conditioned allogeneic stem cell transplantation ( RIC allo‐ SCT ) for chronic lymphocytic leukaemia ( CLL ), there is an inverse relationship between relapse and extensive chronic graft‐versus‐host disease ( GVHD ). We evaluated outcomes in 50 consecutive patients with CLL using the approach of alemtuzumab‐based RIC allo‐ SCT and pre‐emptive donor lymphocyte infusions ( DLI ) for mixed chimerism or minimal residual disease ( MRD ), with the intention of reducing the risk of GVHD . Forty two patients had high‐risk disease, including 30% with 17p deletion (17p−). Of patients who were not in complete remission ( CR ) entering transplant, 83% subsequently achieved MRD ‐negative CR . Both MRD detection and uncorrected mixed chimerism were associated with greater risks of treatment failure. Nine of sixteen patients receiving DLI for persistent or relapsed disease subsequently attained MRD ‐negative CR . With a median follow‐up of 4·3 years, 4‐year current progression‐free survival was 65% and overall survival was 75% (60% and 61% in respectively, patients with 17p−). DLI was associated with a 29% cumulative incidence of severe GVHD and mortality of 6·4%. At last follow‐up, 83% of patients in CR were off all immunosuppressive treatment. In conclusion, the directed delivery of allogeneic cellular therapy has the potential to induce durable remissions in high‐risk CLL without incurring excessive GVHD .