Efficacy of minimal residual disease driven immune-intervention after allogeneic hematopoietic stem cell transplantation for high-risk chronic lymphocytic leukemia: results of a prospective multicenter trial - Université Clermont Auvergne Accéder directement au contenu
Article Dans Une Revue Haematologica Année : 2021

Efficacy of minimal residual disease driven immune-intervention after allogeneic hematopoietic stem cell transplantation for high-risk chronic lymphocytic leukemia: results of a prospective multicenter trial

Magali Le Garff-Tavernier
  • Fonction : Auteur
Stéphanie Nguyen Quoc
  • Fonction : Auteur
Edouard Forcade
  • Fonction : Auteur
Patrice Chevallier
  • Fonction : Auteur
Faezeh Legrand-Izadifar
  • Fonction : Auteur
Gandhi Laurent Damaj
  • Fonction : Auteur
David Michonneau
  • Fonction : Auteur
Cécile Tomowiak
  • Fonction : Auteur
Cécile Borel
  • Fonction : Auteur
Corentin Orvain
  • Fonction : Auteur
Pascal Turlure
  • Fonction : Auteur
Rabah Redjou
  • Fonction : Auteur
Gaëlle Guillerm
  • Fonction : Auteur
Laure Vincent
  • Fonction : Auteur
Celestine Simand
  • Fonction : Auteur
Claire Quiney
  • Fonction : Auteur
Patricia Combes
  • Fonction : Auteur
Bruno Pereira
Laure Calvet
  • Fonction : Auteur
Aurélie Cabrespine
  • Fonction : Auteur
Jacques-Olivier Bay
  • Fonction : Auteur
Véronique Leblond
  • Fonction : Auteur
Nathalie Dhédin
  • Fonction : Auteur

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.

Domaines

Hématologie

Dates et versions

hal-03440980 , version 1 (22-11-2021)

Identifiants

Citer

Olivier Tournilhac, Magali Le Garff-Tavernier, Stéphanie Nguyen Quoc, Edouard Forcade, Patrice Chevallier, et al.. Efficacy of minimal residual disease driven immune-intervention after allogeneic hematopoietic stem cell transplantation for high-risk chronic lymphocytic leukemia: results of a prospective multicenter trial. Haematologica, 2021, 106 (7), pp.1867-1875. ⟨10.3324/haematol.2019.239566⟩. ⟨hal-03440980⟩
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