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Chronic Lymphocytic Leukemia
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
Ferrata Storti Foundation
Haematologica 2021 Volume 106(7):1867-1875
Olivier Tournilhac,1 Magali Le Garff-Tavernier,2 Stéphanie Nguyen Quoc,3 Edouard Forcade,4 Patrice Chevallier,5 Faezeh Legrand-Izadifar,6 Gandhi Laurent Damaj,7 David Michonneau,8 Cécile Tomowiak,9 Cécile Borel,10 Corentin Orvain,11 Pascal Turlure,12 Rabah Redjou,13 Gaëlle Guillerm,14 Laure Vincent,15 Celestine Simand,16 Richard Lemal,17 Claire Quiney,2 Patricia Combes,18 Bruno Pereira,19 Laure Calvet,20 Aurélie Cabrespine,1 Jacques-Olivier Bay,1 Véronique Leblond3 and Nathalie Dhédin21
1Service d’Hématologie Clinique et de Thérapie Cellulaire, CHU Estaing, Université Clermont Auvergne EA 7453 CIC1405, Clermont-Ferrand; 2Service d’Hématologie Biologique, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique - Hôpitaux de Paris, Paris; 3Service d’Hématologie Clinique, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique - Hôpitaux de Paris, Paris; 4Service d’Hématologie Clinique et de Thérapie cellulaire, CHU Bordeaux, Bordeaux; 5Service d’Hématologie Clinique, CHU Nantes Hôtel Dieu, Nantes; 6Service d’Hématologie Clinique, Département de Greffe de Moelle, CHU Nice, Nice; 7Hématologie Clinique, Institut d'Hématologie de Basse- Normandie, CHU Côte de Nacre, Caen; 8Service Hématologie Greffe, Hôpital Saint-Louis, Assistance Publique - Hôpitaux de Paris, Paris; Université Paris Diderot, Paris; 9Service Oncologie Hématologique et Thérapie Cellulaire, CHU Poitiers, Poitiers; 10Service d’Hématologie, Institut Universitaire du Cancer Toulouse - Oncopole, Toulouse; 11Service Maladies du Sang, CHU Angers, Angers; 12Service d’Hématologie Clinique, CHU Dupuytren, Limoges; 13Service d’Hématologie Clinique, Hôpital Henri Mondor, Assistance Publique - Hôpitaux de Paris, Créteil; 14Service d'Hématologie Clinique, Institut de Cancéro-Hématologie, Hôpital Augustin Morvan, Brest; 15Département Hématologie Clinique, Hôpital St Eloi, Montpellier; 16Service Hématologie, CHU de Strasbourg, Strasbourg; 17Service d’Histocompatibilité, CHU, Université Clermont Auvergne EA 7453 and CIC501, Clermont-Ferrand; 18Service Cytogénétique, CHU Estaing, Clermont-Ferrand; 19Unité de Biostatistiques, Direction de la Recherche Clinique (DRCI), CHU, Clermont-Ferrand; 20Service de Réanimation Médicale, Hôpital Gabriel Monpied, CHU de Clermont-Ferrand, Clermont-Ferrand and 21Unité Adolescents et Jeunes Adultes, Hôpital St Louis, Assistance Publique - Hôpitaux de Paris, Paris, France
ABSTRACT
Allogeneic hematopoietic stem cell transplantation (HSCT) remains a potentially curative and useful strategy in high-risk relapsing chronic lymphocytic leukemia (CLL). Minimal residual disease (MRD) assessment at 12 months (M12) post-HSCT is predictive of relapse. This phase II study aimed to achieve M12 MRD negativity (MRDneg) using an MRD-driven immune-intervention (Md-PII) algorithm based on serial flow-cytometry blood MRD, involving cyclosporine tapering followed in case of failure by donor lymphocytes infusions. Patients had high-risk CLL according to the 2006 European Society for Blood and Marrow Transplantation 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-condi- tioning regimen before HSCT and were submitted to Md-PII. M12- MRDneg status was achieved in 27 of 42 patients (64%) versus 6 of 42 (14.2%) before HSCT. With a median follow-up of 36 months (range, 19- 53), 3-year overall survival, non-relapse mortality and cumulative inci- dence of relapse are 86.9% (95% Confidence Interval [CI]: 70.8-94.4),
Correspondence:
OLIVIER TOURNILHAC
otournilhac@chu-clermontferrand.fr
Received: October 15 2019. Accepted: May 29, 2020. Pre-published: June 11, 2020.
https://doi.org/10.3324/haematol.2019.239566
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haematologica | 2021; 106(7)
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