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: Cécile Pochon, Emmanuel Oger, Gérard Michel, Jean-Hugues Dalle, Alexandra Salmon, Brigitte Nelken, Yves Bertrand, Hélène Cavé, Jean-Michel Cayuela, Nathalie Grardel, Elizabeth Macintyre, Geneviève Margueritte, Françoise Méchinaud, Pierre Rohrlich, Catherine Paillard, François Demeocq, Pascale Schneider, Dominique Plantaz, Marilyne Poirée, Jean-François Eliaou, Gilbert Semana, Séverine Drunat, Philippe Jonveaux, Pierre Bordigoni, Virginie Gandemer
• Journal: British journal of haematology (Br J Haematol) Vol. 169 Issue 2 Pg. 249-61 (Apr 2015) ISSN: 1365-2141 [Electronic] England
• PMID: 25522886 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 John Wiley & Sons Ltd.

Topics

• Adoptive Transfer
• Child
• Female
• Follow-Up Studies
• Graft vs Host Disease (etiology)
• Hematopoietic Stem Cell Transplantation (adverse effects)
• Humans
• Lymphocytes
• Male
• Neoplasm, Residual
• Precursor Cell Lymphoblastic Leukemia-Lymphoma (mortality, pathology, therapy)
• Prognosis
• Proportional Hazards Models
• Tissue Donors
• Transplantation Chimera
• Treatment Outcome