Significance of Measurable Residual Disease in Adult Philadelphia Chromosome-Positive ALL: A GRAAPH-2014 Study.

Autor:	Kim R; Hematology Laboratory, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris Cité, Paris, France.; INSERM U944, CNRS UMR 7212 GenCellDis, Institut de Recherche Saint-Louis (IRSL), Paris, France., Chalandon Y; Division of Hematology, Department of Oncology, Geneva University Hospitals and Faculty of Medicine, University of Geneva, Geneva, Switzerland.; Swiss Group for Clinical Cancer Research (SAKK)., Rousselot P; Hematology Department, Centre Hospitalier de Versailles, Unité mixte de recherche 1184 Commissariat à l'Energie Atomique, University Paris-Saclay, Le Chesnay, France., Cayuela JM; Hematology Laboratory, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris Cité, Paris, France.; EA 3518, Institut de Recherche Saint-Louis (IRSL), Université Paris Cité, Paris, France., Huguet F; Hematology Department, Institut Universitaire de Cancer Toulouse-Oncopole, CHU de Toulouse, Toulouse, France., Balsat M; Hematology Department, Hospices Civils de Lyon, Hôpital Lyon Sud, Pierre Benite, France., Passet M; Hematology Laboratory, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris Cité, Paris, France.; INSERM U944, CNRS UMR 7212 GenCellDis, Institut de Recherche Saint-Louis (IRSL), Paris, France., Chevallier P; Hematology Department, Hôtel-Dieu-CHU de Nantes, Nantes, France., Hicheri Y; Hematology Department, Institut Paoli-Calmettes, Aix Marseille Univ, CNRS, Inserm, CRCM, Marseille, France., Raffoux E; Hematology Department, Hôpital Saint-Louis, AP-HP, Université Paris Cité, Paris, France., Leguay T; Hematology Department, CHU de Bordeaux, Hôpital du Haut-Levêque, Pessac, France., Chantepie S; Hematology Department, CHU Côte de Nacre, Caen, France., Maury S; Hematology Department, Hôpital Henri Mondor, AP-HP, Université Paris Est Créteil UPEC, Créteil, France., Hayette S; Hematology Laboratory, Hospices Civils de Lyon, Lyon-Sud Hospital, Pierre Benite, France., Solly F; Hematology Laboratory, CHUV, Lausanne, Suisse., Braun T; Hematology Department, Hôpital Avicenne, AP-HP, Bobigny, France., De Prijck B; Hematology Department, CHU de Liège, Liège, Belgium., Cacheux V; Hematology Department, CHU Estaing, Clermont-Ferrand, France., Salanoubat C; Hematology Department, CH Sud Francilien, Corbeil-Essonnes, France., Farnault L; Hematology Department, Hôpital Universitaire de Marseille Conception, Marseille, France., Guibaud I; Hematology Department, CH de Metz, Hôpital de Mercy, Metz, France., Lamarque M; Hematology Department, CH Emile Muller de Mulhouse, Mulhouse, France., Gastaud L; Hematology Department, Centre Antoine Lacassagne, Nice, France., Lemasle E; Hematology Department, Centre Henri Becquerel, Rouen, France., Brissot E; Hematology Department, Hôpital Saint-Antoine, AP-HP, Sorbonne Université, Paris, France., Tavernier E; Hematology Department, CHU de Saint-Etienne, Saint-Priest-en-Jarez, France., Bilger K; Hematology Department, CHU de Strasbourg, Hôpital Hautepierre, Strasbourg, France., Villate A; Hematology Department, CHU de Tours, Hôpital Bretonneau, Tours, France., Soulier J; Hematology Laboratory, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris Cité, Paris, France.; INSERM U944, CNRS UMR 7212 GenCellDis, Institut de Recherche Saint-Louis (IRSL), Paris, France., Graux C; Hematology Department, CHU UCL Namur Godinne, Yvoir, Belgium., Lhéritier V; Coordination du Groupe GRAALL, Member of the French institute Carnot OPALE (the Organisation for Partnership in Leukemia Consortium), Hospices Civils de Lyon, Hôpital Lyon Sud, Pierre Benite, France., Dombret H; Hematology Department, Hôpital Saint-Louis, AP-HP, Université Paris Cité, Paris, France., Boissel N; Hematology Department, Hôpital Saint-Louis, AP-HP, Université Paris Cité, Paris, France., Clappier E; Hematology Laboratory, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris Cité, Paris, France.; INSERM U944, CNRS UMR 7212 GenCellDis, Institut de Recherche Saint-Louis (IRSL), Paris, France.
Jazyk:	angličtina
Zdroj:	Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 2024 Sep 10; Vol. 42 (26), pp. 3140-3150. Date of Electronic Publication: 2024 Jul 19.
DOI:	10.1200/JCO.24.00108
Abstrakt:	Purpose: BCR::ABL1 quantification is widely regarded as the standard for monitoring measurable residual disease (MRD) in Philadelphia chromosome-positive (Ph+) ALL. However, recent evidence of BCR::ABL1 multilineage involvement questions the significance of BCR::ABL1 MRD. We aimed to define the prognostic role of MRD as assessed by BCR::ABL1 or lymphoid-specific immunoglobulin/T-cell receptor ( IG/TR ) gene markers. Patients and Methods: We conducted BCR::ABL1 and IG/TR quantification after each treatment cycle in 264 patients treated in the GRAAPH-2014 trial, which used four cycles of reduced-intensity chemotherapy with nilotinib, followed by hematopoietic stem-cell transplantation (HSCT). Results: Comparing BCR::ABL1 and IG/TR MRD revealed residual BCR::ABL1 -positive non-ALL cells in 98 (43%) of 228 patients, defining multilineage Ph+ ALL. Despite poorer BCR::ABL1 responses, patients with multilineage Ph+ ALL had similar disease-free survival (DFS; hazard ratio [HR], 0.83 [95% CI, 0.49 to 1.41]; P = .50). Although BCR::ABL1 response failed to predict outcomes, IG/TR positivity (≥0.01%) was strongly associated with lower DFS (after cycle 2, HR, 2.49 [95% CI, 1.40 to 4.40]; P = .002; after cycle 4, HR, 4.13 [95% CI, 1.82 to 9.38]; P = .001). In multivariable analysis, both IG/TR positivity after cycle 2 and initial WBC count ≥30 × 10 9 /L predicted poorer DFS, enabling to define a high-risk group having a 4-year DFS of 56.5% compared with 87.6% (HR, 3.72 [95% CI, 1.93 to 7.15]; P < .001). Moreover, allogeneic HSCT significantly improved DFS in the high-risk group (HR, 0.33 [95% CI, 0.18 to 0.60]; P < .001), whereas the standard-risk group had favorable outcomes regardless of allogeneic HSCT. Conclusion: Our findings challenge the significance of BCR::ABL1 monitoring in adult Ph+ ALL and demonstrate the prognostic role of IG/TR MRD. This study provides a framework for using MRD to guide treatment strategies in adults with Ph+ ALL.
Databáze:	MEDLINE
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