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Br J Haematol. 2018 Mar;180(5):680-693. doi: 10.1111/bjh.15086. Epub 2018 Jan 23.

Pre- and post-transplant minimal residual disease predicts relapse occurrence in children with acute lymphoblastic leukaemia.

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Clinic of Paediatric Haemato-Oncology, Department of Women's and Children's Health, University of Padua, Padua, Italy.
Istituto di Ricerca Pediatrica Città della Speranza, Padua, Italy.
Paediatric Haematology/Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
Departments of Biotherapy, Necker Children's Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
Centro Ricerca Tettamanti, Paediatric Clinics, University of Milano-Bicocca, San Gerardo Hospital/Fondazione MBBM, Monza, Italy.
Paediatric Onco-Haematology, Stem Cell Transplantation and Cellular Therapy Division, Regina Margherita Children's Hospital, Turin, Italy.
Paediatric Haematology/Oncology, IRCCS Ospedale "Bambino Gesù", Roma, Italy.
Department of Paediatric Sciences, University of Pavia, Pavia, Italy.


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-HSCT1 and post-HSCT3). 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-HSCT1 and post-HSCT3 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.


acute lymphoblastic leukaemia; children; haematopoietic stem cell transplantation; leukaemia relapse; minimal residual disease

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