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

Federica Lovisa, Marco Zecca, Bartolomeo Rossi, Mimma Campeggio, Elisa Magrin, Emanuela Giarin, Barbara Buldini, Simona Songia, Giovanni Cazzaniga, Tommaso Mina, Gloria Acquafredda, Paola Quarello, Franco Locatelli, Franca Fagioli, Giuseppe Basso

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
JournalBritish Journal of Haematology
DOIs
Publication statusAccepted/In press - Jan 1 2018

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Keywords

  • Acute lymphoblastic leukaemia
  • Children
  • Haematopoietic stem cell transplantation
  • Leukaemia relapse
  • Minimal residual disease

ASJC Scopus subject areas

  • Hematology

Cite this

Lovisa, F., Zecca, M., Rossi, B., Campeggio, M., Magrin, E., Giarin, E., Buldini, B., Songia, S., Cazzaniga, G., Mina, T., Acquafredda, G., Quarello, P., Locatelli, F., Fagioli, F., & Basso, G. (Accepted/In press). Pre- and post-transplant minimal residual disease predicts relapse occurrence in children with acute lymphoblastic leukaemia. British Journal of Haematology. https://doi.org/10.1111/bjh.15086