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HbF induction in AML/MDS and outcome prediction
AB
CD
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Figure 2. HbF levels after two courses of decitabine treatment are associated with responses of different hematologic lineages after course 4, and with early platelet doubling. HbF values after treatment course 2 (x-axis) in patients with myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) who received at least two cycles of decitabine were plotted against (A) platelet counts (n=25) (y-axis), (B) absolute neutrophil counts (n=25), (C) hemoglobin levels (n=25), and (D) the percentage of bone marrow blasts (n=21), as determined after course 4. Linear regression equations are represented as lines and were estimated as (A) platelets=36+41*HbF, (B) absolute neutrophil count=1243+340*HbF, (C) hemoglobin=9.4+0.5*HbF, (D) percentage bone marrow blasts=25-6*HbF. (E) Box plot demonstrating significantly higher HbF values after the second course of decitabine treatment in MDS/AML patients who achieved platelet doubling already after one course of decitabine.
undergone hematopoietic stem cell transplantation at the time of their transplant, this difference lost statistical sig- nificance (P=0.098) (Online Supplementary Figure S6). The secondary endpoints, progression-free survival and AML- free survival were also investigated and showed a trend to a more favorable outcome for patients with elevated HbF: the median progression-free survival was 7.7 months ver- sus 2.4 months (HR=0.32; 95% CI: 0.10-1.10; P=0.07) (Figure 3B) and the median AML-free survival was 13.1 months versus 7.6 months (HR=0.42; 95% CI: 0.13-1.38; P=0.15) (Figure 3C).
In the AML cohort, 17 patients had HbF determinations available after two courses of treatment and could be included in a survival analysis. There was no significant difference in overall survival between those with elevated
HbF (n=9) and those with normal HbF (n=8): the median overall survival was 17.3 and 11.6 months, respectively (HR=0.68; 95% CI: 0.23-1.96; P=0.47) (Figure 3D).
Elevated HbF levels are observed in decitabine-treated patients with myelodysplastic syndrome/acute myeloid leukemia with bone marrow blast
clearance, and decline at relapse
To investigate whether malignant cells or normal, emerging erythroid precursors synthesize the elevated HbF in response to HMAs, linear regression analyses were performed (Figure 4A). This showed an association between HbF induction after four treatment courses and a decreasing percentage of blasts at this time point in 17 MDS/AML patients.
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