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Follow-up of post-transplant minimal residual disease and chimerism in childhood lymphoblastic leukaemia: 90 d to react.

Cécile Pochon 1, 2 Emmanuel Oger 3, 4 Gérard Michel 5 Jean-Hugues Dalle 6 Alexandra Salmon 1 Brigitte Nelken 7 Yves Bertrand 8 Hélène Cavé 9 Jean-Michel Cayuela 10 Nathalie Grardel 11 Elizabeth Macintyre 12 Geneviève Margueritte 13 Françoise Méchinaud 14 Pierre Rohrlich 15 Catherine Paillard 16 François Demeocq 17 Pascale Schneider 18 Dominique Plantaz 19 Marilyne Poirée 20 Jean-François Eliaou 13, 21 Gilbert Semana 22 Séverine Drunat 23 Philippe Jonveaux 24 Pierre Bordigoni 25 Virginie Gandemer 26, 27 
Abstract : Relapse after transplantation is a major cause of treatment failure in paediatric acute lymphoblastic leukaemia (ALL). Here, we report the findings of a prospective national study designed to investigate the feasibility of immune intervention in children in first or subsequent remission following myeloablative conditioning. This study included 133 children who received a transplant for ALL between 2005 and 2008. Minimal Residual Disease (MRD) based on T cell receptor/immunoglobulin gene rearrangements was measured on days -30, 30, 90 and 150 post-transplantation. Ciclosporin treatment was rapidly discontinued and donor lymphocyte infusions (DLI) were programmed for patients with a pre- or post-transplant MRD status ≥10(-3) . Only nine patients received DLI. Pre- and post-transplant MRD status, and the duration of ciclosporin were independently associated with 5-year overall survival (OS), which was 62·07% for the whole cohort. OS was substantially higher in patients cleared of MRD than in those with persistent MRD (52·3% vs. 14·3%, respectively). Only pre-transplant MRD status (Hazard Ratio 2·57, P = 0·04) and duration of ciclosporin treatment (P < 0·001) were independently associated with relapse. The kinetics of chimerism were not useful for predicting relapse, whereas MRD monitoring up to 90 d post-transplantation was a valuable prognostic tool to guide therapeutic intervention.
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Contributor : Laurent Jonchère Connect in order to contact the contributor
Submitted on : Thursday, February 26, 2015 - 11:28:27 AM
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Cécile Pochon, Emmanuel Oger, Gérard Michel, Jean-Hugues Dalle, Alexandra Salmon, et al.. Follow-up of post-transplant minimal residual disease and chimerism in childhood lymphoblastic leukaemia: 90 d to react.. British Journal of Haematology, Wiley, 2015, 169 (2), pp.249-261. ⟨10.1111/bjh.13272⟩. ⟨hal-01120630⟩



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