Prognostic impact of discordant results from cytogenetics and flow cytometry in patients with acute myeloid leukemia undergoing hematopoietic cell transplantation

Abstract

Background: Cytogenetics and multicolor flow cytometry (MFC) are useful tools for monitoring outcome of treatment in acute myeloid leukemia (AML). However, no data are available regarding the meaning of results when the 2 tests do not agree.

Methods: The authors of this report analyzed 1464 pairs of concurrent cytogenetics and flow results from 424 patients, before and after hematopoietic cell transplantation, and compared the prognostic impact of discordant and concordant results.

Results: Informative discordant results were observed in 22% of patients. Compared with patients who had double-negative test results, either positive result had a significant impact on overall survival and relapse-free survival. The hazard ratios with either positive cytogenetic results or positive MFC results pretransplantation were 3.1 (P = .009) and 2.5 (P = .0008), respectively, for reduced overall survival and 2.7 (P = .01) and 4.1 (P < .0001), respectively, for decreased recurrence-free survival. Similar findings were obtained post-transplantation. Molecular cytogenetics, ie, fluorescence in situ hybridization (FISH), added value to the evaluation of discordant cases.

Conclusions: The detection of residual AML by either cytogenetics or flow cytometry in patients who underwent hematopoietic cell transplantation predicted early relapse and shortened survival.

Figure 1

Kaplan-Meier plots of overall survival (left) and relapse-free survival (right) by test results obtained pre-transplant (upper) and post-transplant (lower). Analysis was based on the last test result for the pre-transplant window (day −60 to −1) and the first test result for the post-transplant window (day 1 to 100). C+/F− represents the group of patients who had abnormal cytogenetic (including FISH) results but normal flow cytometry results. C−/F+ represents the group of patients who had normal cytogenetic results but abnormal flow cytometry results. C+/F+ represents those who had both abnormal cytogenetic and flow cytometry results. C−/F− represents those who had normal results for both cytogenetics and flow.

Figure 2

Impact of fluorescence in situ hybridization (FISH) testing results on overall survival (left) and relapse-free survival (right) when obtained pre-transplant (upper) and post-transplant (lower). Analysis was based on the last test result for the pre-transplant window (day −60 to −1) and the first test result for the post-transplant window (day 1 to 100). CF− represents patients with concordant negative results for both conventional G-banding cytogenetics and flow cytometry. CF+ represents patients with concordant positive results for both conventional cytogenetics and flow. CFDisc represents all patients with discordant results between conventional cytogenetics and flow, including either normal cytogenetics but abnormal flow or abnormal cytogenetics but normal flow. Additional FISH results are shown as abnormal (FISH+) or normal (FISH−).