title: Follow-up of post-transplant minimal residual disease and chimerism in childhood lymphoblastic leukaemia: 90 d to react.
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.
authors.affiliation: Department of Paediatric Haematology/oncology, University Hospital of Nancy, Nancy, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Pochon
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Oger
authors.forename: Gérard
authors.initials: G
authors.lastname: Michel
authors.forename: Jean-Hugues
authors.initials: JH
authors.lastname: Dalle
authors.forename: Alexandra
authors.initials: A
authors.lastname: Salmon
authors.forename: Brigitte
authors.initials: B
authors.lastname: Nelken
authors.forename: Yves
authors.initials: Y
authors.lastname: Bertrand
authors.forename: Hélène
authors.initials: H
authors.lastname: Cavé
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Cayuela
authors.forename: Nathalie
authors.initials: N
authors.lastname: Grardel
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Macintyre
authors.forename: Geneviève
authors.initials: G
authors.lastname: Margueritte
authors.forename: Françoise
authors.initials: F
authors.lastname: Méchinaud
authors.forename: Pierre
authors.initials: P
authors.lastname: Rohrlich
authors.forename: Catherine
authors.initials: C
authors.lastname: Paillard
authors.forename: François
authors.initials: F
authors.lastname: Demeocq
authors.forename: Pascale
authors.initials: P
authors.lastname: Schneider
authors.forename: Dominique
authors.initials: D
authors.lastname: Plantaz
authors.forename: Marilyne
authors.initials: M
authors.lastname: Poirée
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Eliaou
authors.forename: Gilbert
authors.initials: G
authors.lastname: Semana
authors.forename: Séverine
authors.initials: S
authors.lastname: Drunat
authors.forename: Philippe
authors.initials: P
authors.lastname: Jonveaux
authors.forename: Pierre
authors.initials: P
authors.lastname: Bordigoni
authors.forename: Virginie
authors.initials: V
authors.lastname: Gandemer
mesh_terms: D019264:Adoptive Transfer; D002648:Child; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D008214:Lymphocytes; D008297:Male; D018365:Neoplasm, Residual; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D011379:Prognosis; D016016:Proportional Hazards Models; D014019:Tissue Donors; D018183:Transplantation Chimera; D016896:Treatment Outcome
keywords: childhood leukaemia; chimerism; immunotherapy; minimal residual disease; stem cell transplantation