Fiche publication
Date publication
juillet 2021
Journal
Haematologica
Auteurs
Membres identifiés du Cancéropôle Est :
Dr SIMAND Célestine
Tous les auteurs :
Tournilhac O, Le Garff-Tavernier M, Nguyen Quoc S, Forcade E, Chevallier P, Legrand-Izadifar F, Laurent Damaj G, Michonneau D, Tomowiak C, Borel C, Orvain C, Turlure P, Redjou R, Guillerm G, Vincent L, Simand C, Lemal R, Quiney C, Combes P, Pereira B, Calvet L, Cabrespine A, Bay JO, Leblond V, Dhédin N, Organization Filo FIL, De Moelle Et de Thérapie Cellulaire Sfgm-Tc SFG
Lien Pubmed
Résumé
Allogeneic hematopoietic stem cell transplantation (HSCT) remains a potentially curative and useful strategy in high-risk relapsing CLL. Minimal Residual Disease (MRD) assessment at 12 months post-HSCT is predictive of relapse. This phase 2 study aimed to achieve M12 MRD negativity (MRDneg) using MRD-driven immune-intervention (Md-PII) algorithm based on serial flow-cytometry blood MRD, involving cyclosporine tapering followed if failure by donor lymphocytes infusions. Patients had high-risk CLL according to 2006 EBMT consensus, in complete or partial response with lymphadenopathy < 5 cm and comorbidity score ≤ 2. Donors were HLA-matched sibling or matched unrelated (10/10). Forty-two enrolled patients with either 17p deletion (front-line, n=11; relapse n=16) or other high-risk relapse (n=15) received reduced intensity-conditioning regimen before HSCT and were submitted to Md-PII. M12-MRDneg status was achieved in 64% versus 14.2% before HSCT. With a median follow-up of 36 months (range, 19-53), 3-year overall survival, non-relapse mortality and cumulative incidence of relapse are 86.9% (95%CI, 70.8-94.4), 9.5% (95%CI, 3.7-23.4) and 29.6% (95%CI, 17.3-47.7). Incidence of 2-year limited and extensive chronic graft versus host disease (cGVHD) is 38% (95%CI, 23-53) and 23% (95%CI, 10-36) including 2 cases post Md-PII. Fifteen patients converted to MRDneg either after CsA withdrawal (n=12) or after cGVHD (n=3). As a time-dependent variable, MRDneg achievement at any time-point correlates with reduced relapse (HR=0.14 [0.04-0.53], p=0.004) and improvement of both progression free (HR=0.18 [0.06-0.6], p<0.005) and overall (HR: 0.18 [0.03-0.98], p=0.047) survival. These data highlight the value of MRD-driven immune-intervention to induce prompt MRD clearance in the therapy of CLL.
Mots clés
Graft vs Host Disease, etiology, Hematopoietic Stem Cell Transplantation, adverse effects, Humans, Leukemia, Lymphocytic, Chronic, B-Cell, diagnosis, Neoplasm, Residual, Prospective Studies, Retrospective Studies, Transplantation Conditioning
Référence
Haematologica. 2021 07 1;106(7):1867-1875
