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Pre‐ and post‐transplant minimal residual disease predicts relapse occurrence in children with acute lymphoblastic leukaemia
Author(s) -
Lovisa Federica,
Zecca Marco,
Rossi Bartolomeo,
Campeggio Mimma,
Magrin Elisa,
Giarin Emanuela,
Buldini Barbara,
Songia Simona,
Cazzaniga Giovanni,
Mina Tommaso,
Acquafredda Gloria,
Quarello Paola,
Locatelli Franco,
Fagioli Franca,
Basso Giuseppe
Publication year - 2018
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.15086
Subject(s) - medicine , cumulative incidence , minimal residual disease , hematopoietic stem cell transplantation , discontinuation , transplantation , incidence (geometry) , immunosuppression , oncology , pediatrics , bone marrow , physics , optics
Summary Relapse remains the leading cause of treatment failure in children with acute lymphoblastic leukaemia ( ALL ) undergoing allogeneic haematopoietic stem cell transplantation ( HSCT ). We retrospectively investigated the prognostic role of minimal residual disease ( MRD ) before and after HSCT in 119 children transplanted in complete remission ( CR ). MRD was measured by polymerase chain reaction in bone marrow samples collected pre‐ HSCT and during the first and third trimesters after HSCT (post‐ HSCT 1 and post‐ HSCT 3). The overall event‐free survival ( EFS ) was 50%. The cumulative incidence of relapse and non‐relapse mortality was 41% and 9%. Any degree of detectable pre‐ HSCT MRD was associated with poor outcome: EFS was 39% and 18% in patients with MRD positivity <1 × 10 −3 and ≥1 × 10 −3 , respectively, versus 73% in MRD ‐negative patients ( P < 0·001). This effect was maintained in different disease remissions, but low‐level MRD had a very strong negative impact only in patients transplanted in second or further CR . Also, MRD after HSCT enabled patients to be stratified, with increasing MRD between post‐ HSCT 1 and post‐ HSCT 3 clearly defining cohorts with a different outcome. MRD is an important prognostic factor both before and after transplantation. Given that MRD persistence after HSCT is associated with dismal outcome, these patients could benefit from early discontinuation of immunosuppression, or pre‐emptive immuno‐therapy.