Minimal residual disease level predicts outcome in adults with Ph-negative Bprecursor acute lymphoblastic leukemia

Objectives: Detectable minimal residual disease (MRD) after therapy for acute lymphoblastic leukemia (ALL) is the strongest predictor of hematologic relapse. This study evaluated outcomes of patients with B-cell precursor ALL with MRD of ≥10-4. Methods: Study population was from ALL study groups in...

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Detalles Bibliográficos
Autores: Gökbuget, Nicola, Dombret, Hervé, Giebel, Sebastian, Bruggemann, Monika, Doubek, Michael|||0000-0002-1269-6282, Foà, Robin, Hoelzer, Dieter, Kim, Christopher, Martinelli, Giovanni|||0000-0002-1025-4210, Parovichnikova, Elena|||0000-0001-6177-3566, Rambaldi, Alessandro|||0000-0002-3739-7502, Ribera, Jose-Maria|||0000-0003-1042-6024, Schoonen, Marieke, Stieglmaier, Julia M., Zugmaier, Gerhard|||0000-0001-6879-2671, Bassan, Renato|||0000-0001-8214-2894
Tipo de recurso: artículo
Fecha de publicación:2019
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:203693
Acceso en línea:https://ddd.uab.cat/record/203693
https://dx.doi.org/urn:doi:10.1080/16078454.2019.1567654
Access Level:acceso abierto
Palabra clave:Acute lymphoblastic leukemia
Minimal residual disease
MRD
Allogeneic stem cell transplant
Descripción
Sumario:Objectives: Detectable minimal residual disease (MRD) after therapy for acute lymphoblastic leukemia (ALL) is the strongest predictor of hematologic relapse. This study evaluated outcomes of patients with B-cell precursor ALL with MRD of ≥10-4. Methods: Study population was from ALL study groups in Europe managed in national study protocols 2000-2014. MRD was measured by polymerase chain reaction or flow cytometry. Patients were age ≥15 years at initial ALL diagnosis. Patients were excluded if exposed to blinatumomab within 18 months of baseline or prior alloHSCT. Results: Of 272 patients in CR1, baseline MRD was ≥10-1, 10-2 to <10-1, 10-3 to <10-2, and 10-4 to <10-3 in 15 (6%), 71 (26%), 109 (40%), and 77 (28%) patients, respectively. Median duration of complete remission (DoR) was 18.5 months (95% confidence interval [CI], 11.9-27.2), median relapse-free survival (RFS) was 12.4 months (95% CI, 10.0-19.0) and median overall survival (OS) was 32.5 months (95% CI, 23.6-48.0). Lower baseline MRD level (P ≤ .0003) and white blood cell count <30,000/μL at diagnosis (P ≤ .0053) were strong predictors for better RFS and DoR. Allogeneic hematopoietic stem cell transplantation (alloHSCT) was associated with longer RFS (hazard ratio [HR], 0.59; 95% CI, 0.41-0.84) and DoR (HR, 0.43; 95% CI, 0.29-0.64); the association with OS was not significant (HR, 0.72; 95% CI, 0.50-1.05). Discussion: In conclusion, RFS, DoR, and OS are relatively short in patients with MRD-positive ALL, particularly at higher MRD levels. AlloHSCT may improve survival but has limitations. Alternative approaches are needed to improve outcomes in MRD-positive ALL.