1. Minimal residual disease level predicts outcome in adults with Ph-negative B-precursor acute lymphoblastic leukemia
- Author
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Gökbuget, Nicola, Dombret, Hervé, Giebel, Sebastian, Bruggemann, Monika, Doubek, Michael, Foà, Robin, Hoelzer, Dieter, Kim, Christopher, Martinelli, Giovanni, Parovichnikova, Elena, Rambaldi, Alessandro, Ribera, Jose-Maria, Schoonen, Marieke, Stieglmaier, Julia M., Zugmaier, Gerhard, Bassan, Renato, and Universitat Autònoma de Barcelona
- Subjects
Adult ,Male ,Oncology ,medicine.medical_specialty ,Adolescent ,Lymphoblastic Leukemia ,Acute lymphoblastic leukemia ,Disease-Free Survival ,03 medical and health sciences ,0302 clinical medicine ,Precursor B-Cell Lymphoblastic Leukemia-Lymphoma ,hemic and lymphatic diseases ,Internal medicine ,Ph Negative ,Humans ,Medicine ,Philadelphia Chromosome ,Aged ,business.industry ,Minimal residual disease ,Hematopoietic Stem Cell Transplantation ,hemic and immune systems ,Hematology ,Middle Aged ,Allografts ,Allogeneic stem cell transplant ,Europe ,Survival Rate ,body regions ,MRD ,030220 oncology & carcinogenesis ,Female ,business ,Follow-Up Studies ,030215 immunology - Abstract
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 −1, 10−3 to −2, and 10−4 to −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 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.
- Published
- 2019