ABSTRACT
Current risk algorithms are primarily based on pre-treatment factors and imperfectly predict outcome in acute myeloid leukemia (AML). We introduce and validate a post-treatment approach of leukemic stem cell (LSC) assessment for prediction of outcome. LSC containing CD34+CD38- fractions were measured using flow cytometry in an add-on study of the HOVON102/SAKK trial. Predefined cut-off levels were prospectively evaluated to assess CD34+CD38-LSC levels at diagnosis (n = 594), and, to identify LSClow/LSChigh (n = 302) and MRDlow/MRDhigh patients (n = 305) in bone marrow in morphological complete remission (CR). In 242 CR patients combined MRD and LSC results were available. At diagnosis the CD34+CD38- LSC frequency independently predicts overall survival (OS). After achieving CR, combining LSC and MRD showed reduced survival in MRDhigh/LSChigh patients (hazard ratio [HR] 3.62 for OS and 5.89 for cumulative incidence of relapse [CIR]) compared to MRDlow/LSChigh, MRDhigh/LSClow, and especially MRDlow/LSClow patients. Moreover, in the NPM1mutant positive sub-group, prognostic value of golden standard NPM1-MRD by qPCR can be improved by addition of flow cytometric approaches. This is the first prospective study demonstrating that LSC strongly improves prognostic impact of MRD detection, identifying a patient subgroup with an almost 100% treatment failure probability, warranting consideration of LSC measurement incorporation in future AML risk schemes.
Subject(s)
Antigens, CD34/metabolism , Cell Count , Leukemia, Myeloid, Acute/diagnosis , Leukemia, Myeloid, Acute/mortality , Neoplastic Stem Cells/metabolism , ADP-ribosyl Cyclase 1/metabolism , Adolescent , Adult , Aged , Biomarkers , Female , Flow Cytometry , Humans , Immunophenotyping , Leukemia, Myeloid, Acute/etiology , Leukemia, Myeloid, Acute/therapy , Male , Middle Aged , Nucleophosmin , Prognosis , Recurrence , Reproducibility of Results , Survival Analysis , Young AdultABSTRACT
OBJECTIVES: To test whether, together with platelet count, platelet activity could be an important predictor of bleeding risk in immune thrombocytopenia (ITP) patients. METHODS: Platelet activity was tested by flow cytometric measurement of agonist induced P-selectin expression and compared between 23 adult ITP patients and 22 healthy volunteers. RESULTS: Platelet activity could be either increased or decreased in ITP patients, compared to healthy volunteers. In the lowest platelet count category, normal to low platelet activity was associated with the biggest increase in bleeding risk. Risk difference 80% (95% confidence interval: 45-115%) for <32 × 10(9) platelets/L. For higher platelet counts, there was no association of platelet activity with bleeding risk. DISCUSSION: Increased platelet activity was associated with decreased bleeding risk, but only in patients with low platelet counts. CONCLUSION: Platelet activity can be a predictor of bleeding risk in ITP patients with low platelet counts.
