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W. Xiao et al.
Supplementary Table S3). The numbers of patients in the two groups were too low for statistical significance.
We further investigated if the MRD-pos patients with blast/PDC ratio <10 would have a higher rate of MRD clearance at a later post induction time point (post consol- idation and/or pre-HSCT). Excluding five patients (3 with a blast/PDC ratio <10 and 2 with a ratio >10) who did not have a follow-up MRD test, MRD-pos patients with blast/PDC ratio <10 had a four times higher MRD clear- ance rate than MRD-pos patients with a ratio >10 (6 of 12, 50% vs. 2 of 16, 12.5%; Fisher exact test, P=0.04).
Restoration of normal hematopoiesis in measurable residual disease-pos patients with blast/plasmacytoid dendritic cell ratio <10
To understand why the rate of MRD clearance was higher in the MRD-pos patients with blast/PDC ratio <10 (vs. >10), we reviewed the clinical characteristics and flow cytometric immunophenotype of these patients (Table 1 and Online Supplementary Table S4). We did not observe a correlation with WHO classification, CG risk, ELN risk and the rate of achieving CR, in accordance with prior observations of MRD positivity being the dominant pre- dictive factor post induction.9 In patients with a blast/PDC ratio >10, along with marked reduction of PDC, regener- ating HSCs (CD34+ cells) with normal immunophenotype were not seen (Figure 4A-D). In contrast, prominent PDC populations were present in all patients with a blast/PDC ratio <10 (Figure 4E-H). Moreover, 13 out of these 15 patients showed regenerating HSC with normal immunophenotype in addition to a distinct abnormal
myeloid blast population, indicating detectable normal hematopoietic regeneration alongside low-level persistent disease in these MRD-pos patients with normalized blast/PDC ratios (Online Supplementary Table S4).
Blast/plasmacytoid dendritic cell ratio >10 at late time points is associated with poor outcome
We examined the dynamics of blast/PDC ratio at later time points (post consolidation and/or pre-transplant): all the post-induction MRD-neg patients remained MRD-neg and the blast/PDC ratio remained <10. Among post- induction MRD-pos patients, 15 had post induction blast/PDC ratio <10: 13 remained <10 (2 died) and two patients converted >10 (both died). Eighteen patients had post induction blast/PDC ratio >10: nine remained >10 (7 died) and nine converted to <10 (none died). Although it is challenging to compare RFS and OS because of the rel- atively low number of subjects, these results suggest that patients with post induction blast/PDC ratio of >10 can convert to ratio <10, and these converted patients have a favorable outcome. Patients with post induction blast/PDC ratio <10 rarely convert to ratio >10 and if it does occur, these patients appear to have poor outcome.
We next evaluated if blast/PDC ratio can further risk stratify MRD-pos patients at late time points (prior to HSCT). Only patients receiving HSCT were included and the date of transplantation was chosen as a unifying start- ing point for outcome. Patients with relapsed disease (≥5% blasts by morphology) prior to HSCT were exclud- ed. We had 32 MRD-neg patients (all had blast/PDC ratio <10) and 16 MRD-pos patients (10 had blast/PDC ratio
ABCD
EFGH
Figure 4. Examples of abnormal blast immunophenotype in measurable residual disease (MRD)-pos patients with blast/plasmacytoid dendritic cell (PDC) ratio >10 (A-D) versus <10 (E-H). (A-D) PDC are markedly decreased (B) and the blasts have abnormal expression of CD11b (partial, C) and CD25 (D). (E-H) PDC are well preserved (F) and a subset of the blasts (highlighted in yellow) showed abnormal expression of CD38 (absent, data not shown), CD56 (G), and CD25 (H). Red: CD34- positive blasts; blue: PDC; purple: basophils; yellow: abnormal blasts gated on CD34-positive and CD38-negative expression (gates not shown).
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haematologica | 2019; 104(7)