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

• Published in: Haematologica (Roma) 2020-06
• Main Authors: Tournilhac, Olivier, Le Garff-Tavernier, Magali, Nguyen Quoc, Stéphanie, Forcade, Edouard, Chevallier, Patrice, Legrand-Izadifar, Faezeh, Damaj, Gandhi Laurent, Michonneau, David, Tomowiak, Cécile, Borel, Cécile, Orvain, Corentin, Turlure, Pascal, Redjou, Rabah, Guillerm, Gaëlle, Vincent, Laure, Simand, Celestine, Lemal, Richard, Quiney, Claire, Combes, Patricia, Pereira, Bruno, Calvet, Laure, Cabrespine, Aurélie, Bay, Jacques-Olivier, Leblond, Véronique, Dhédin, Nathalie
• Format: Article
• Language: English
• ISSN: 1592-8721

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