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

Nicola Gökbuget, Hervé Dombret, Sebastian Giebel, Monika Bruggemann, Michael Doubek, Robin Foà, Dieter Hoelzer, Christopher Kim, Giovanni Martinelli, Elena Parovichnikova, Alessandro Rambaldi, Josep Maria Ribera, Marieke Schoonen, Julia M. Stieglmaier, Gerhard Zugmaier, Renato Bassan

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)337-348
Number of pages12
JournalHematology (United Kingdom)
Issue number1
Publication statusPublished - Jan 1 2019


  • Acute lymphoblastic leukemia
  • allogeneic stem cell transplant
  • minimal residual disease
  • MRD

ASJC Scopus subject areas

  • Hematology


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