Abstract
ABSTRACTObjectives: 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 ≥10−4Methods: 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.
Highlights
Outcomes for adult patients with acute lymphoblastic leukemia (ALL) have improved
This study evaluated outcomes of patients with B-cell precursor ALL with minimal residual disease (MRD) of ≥10−4 Methods: Study population was from ALL study groups in Europe managed in national study protocols 2000–2014
Of the 272 patients, time-to-event analyses for duration of complete remission (DoR), relapse-free survival (RFS), or overall survival (OS) included 270 patients and excluded 2 patients with quantifiable baseline MRD missing the date for MRD
Summary
Outcomes for adult patients with acute lymphoblastic leukemia (ALL) have improved. Some patients remain resistant to standard chemotherapy. Despite hematologic complete remission (CR) rates of 80–90% with intensive induction/consolidation chemotherapy, approximately 30–50% of adult and 10–20% of pediatric patients at CR1 exhibit minimal residual disease (MRD) [1,2,3,4,5,6,7,8]. MRD is defined as the presence of leukemic cells in patients with hematologic CR below 5%, which is the detection level of microscopy.
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