Early peripheral clearance of leukemia-associated immunophenotypes in AML: centralized analysis of a randomized trial.

Although genetics is a relevant risk factor in acute myeloid leukemia (AML), it can be minimally informative and/or not readily available for the early identification of patients at risk for treatment failure. In a randomized trial comparing standard vs high-dose induction (ClinicalTrials.gov #NCT00495287), we studied early peripheral blast cell clearance (PBC) as a rapid predictive assay of chemotherapy response to determine whether it correlates with the achievement of complete remission (CR), as well as postremission outcome, according to induction intensity. Individual leukemia-associated immunophenotypes (LAIPs) identified pretherapy by flow cytometry were validated and quantified centrally after 3 days of treatment, expressing PBC on a logarithmic scale as the ratio of absolute LAIP+ cells on day 1 and day 4. Of 178 patients, 151 (84.8%) were evaluable. Patients in CR exhibited significantly higher median PBC (2.3 log) compared with chemoresistant patients (1.0 log; P < .0001). PBC < 1.0 predicted the worst outcome (CR, 28%). With 1.5 log established as the most accurate cutoff predicting CR, 87.5% of patients with PBC >1.5 (PBChigh, n = 96) and 43.6% of patients with PBC ≤1.5 (PBClow, n = 55) achieved CR after single-course induction (P < .0001). CR and PBChigh rates were increased in patients randomized to the high-dose induction arm (P = .04) and correlated strongly with genetic/cytogenetic risk. In multivariate analysis, PBC retained significant predictive power for CR, relapse risk, and survival. Thus, PBC analysis can provide a very early prediction of outcome, correlates with treatment intensity and disease subset, and may support studies of customized AML therapy.

The new reticulocyte parameter (RET-Y) of the Sysmex XE 2100: its use in the diagnosis and monitoring of posttreatment sideropenic anemia.

To verify their clinical usefulness in diagnosis and early response to therapy of sideropenic anemia, we compared the behavior of the reticulocyte parameter (RET-Y), a raw measure dependent on size and content of the cell, generated by the Sysmex XE 2100, with the mean reticulocyte volume (MCVr) and mean reticulocyte hemoglobin content (CHr) from the Bayer ADVIA 120 in healthy subjects and patients with iron deficiency anemia. Correlations were high (r = 0.88 and r = 0.94, respectively). All parameters varied significantly as early as 48 hours after the start of intravenous iron therapy (mean differences of 17.4% [RET-Y], 4.5% [MCVr], and 9.5% [CHr]). Sudden decreases in those parameters at interruption of therapy indicate the reappearance of sideropenic erythropoiesis. The receiver operating characteristic curve demonstrated a high degree of efficiency in differentiating moderate or severe iron deficiency anemia from the healthy state. The best association between sensitivity and specificity was at a cutoff of channel 1,624 for RET-Y and 104.5 fL for MCVr (negative and positive predictive values, respectively, of 99.6% and 96.5% for RET-Y and 98.7% and 93.3% for MCVr). RET-Y is correlated closely with CHr and is useful for diagnosis and early monitoring after the administration of intravenous iron.

Five fully automated methods for performing immature reticulocyte fraction: comparison in diagnosis of bone marrow aplasia.

We performed a parallel evaluation of 5 automated reticulocyte counters to produce the immature reticulocyte fraction (IRF). We analyzed 225 samples from healthy control subjects, 115 from patients with various diseases, 38 with advanced aplasia, and 22 in early erythropoietic recovery after chemotherapy or bone marrow transplantation. The reference intervals were different for each instrument (ADVIA 120, 0.04-0.25; CELL DYN 4000, 0.15-0.35; GEN-S, 0.20-0.37; SE 9500 RET 0.05-0.21; VEGA RETIC: 0.06-0.23). The imprecision, obtained by 1-way analysis of variance on duplicates, was satisfactory for clinical use for all methods (coefficient of variation, 7.6%-20.5% in healthy subjects), although it was higher than the analytic goal based on biologic variability within subjects. The comparison of different methods shows that agreement is good only between SE 9500 RET CELL DYN 4000, and VEGA RETIC (r2 = 0.72-0.78). The study of diagnostic performance in distinguishing aplasia from early bone marrow recovery shows slightly different results (area under the curve from 0.70 for ADVIA 120 to 0.96 for SE 9500 RET). Even with slight differences, the fluorescence-based methods seem to be more robust than other methods for IRF measurement.