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Donor‐derived CD 19‐targeted T cell infusion induces minimal residual disease‐negative remission in relapsed B‐cell acute lymphoblastic leukaemia with no response to donor lymphocyte infusions after haploidentical haematopoietic stem cell transplantation
Author(s) -
Chen Yuhong,
Cheng Yifei,
Suo Pan,
Yan Chenhua,
Wang Yu,
Chen Yao,
Han Wei,
Xu Lanping,
Zhang Xiaohui,
Liu Kaiyan,
Chang Lungji,
Xiao Lei,
Huang Xiaojun
Publication year - 2017
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.14923
Subject(s) - medicine , minimal residual disease , cytokine release syndrome , hematopoietic stem cell transplantation , tocilizumab , donor lymphocyte infusion , gastroenterology , sepsis , transplantation , immunology , chimeric antigen receptor , t cell , leukemia , disease , immune system
Summary Relapse is a common cause of failure in patients with B‐cell acute lymphoblastic leukaemia (B‐ ALL ) after haploidentical haematopoietic stem cell transplantation (haplo‐ HSCT ), and non‐responders to donor lymphoblastic infusion after HSCT have a very poor prognosis. Although donor‐derived CD 19‐directed chimeric antigen receptor‐modified ( CAR ) T cells can potentially cure leukaemia, their effectiveness and safety have not been confirmed in relapsed B‐ ALL cases after haplo‐ HSCT . Between January 2015 and January 2017, two and four patients each received one and two infusions of CAR T cells from haplo‐ HSCT donors. Five (83·33%) achieved minimal residual disease ( MRD )‐negative remission; one patient was discharged automatically without evaluation after developing severe thrombotic microangiopathies. Four of five responsive patients relapsed after 2–7 months, and one died of sepsis following MRD ‐negative remission after a second infusion. None of the other second infusion recipients achieved a second complete remission. Five patients (83·33%) experienced eight courses of grade 1–3 cytokine release syndrome; two were treated with tocilizumab. Two (33·3%) and one patient developed grade 2 and 3 acute graft‐ versus ‐host disease ( aGVHD ), respectively; the former was controlled with glucocorticoids. Donor‐derived CAR T‐cell infusion seems be effective and safe for relapsed B‐ ALL after haplo‐ HSCT , although larger clinical studies are needed.