PREDICTION OF RELAPSE OF PEDIATRIC ACUTE MYELOID-LEUKEMIA BY USE OF MULTIDIMENSIONAL FLOW-CYTOMETRY

Background: Most patients receiving therapy for acute myeloid leukemia (AML) enter an interval in which leukemic blast cells cannot be detec ted by light microscopy (i.e., morphologic remission). However, many o f these patients experience a subsequent relapse. Multidimensional flo w cytometry, which allows the discrimination of antigens expressed on normal and malignant cells, can detect small numbers of cancer cells i n bone marrow or peripheral blood specimens, This technique enables th e detection of one leukemic blast cell among 10(3) to 10(2) normal reg enerating hematopoietic cells, Purpose: We determined whether the pres ence of residual leukemic blast cells, identified in the bone marrow o f pediatric patients with AML by use of multidimensional flow cytometr y, would be predictive of subsequent leukemic relapse, Methods: Multid imensional flow cytometry was performed on 205 marrow specimens collec ted throughout the course of treatment from 39 patients who had achiev ed morphologic remission, The analyses employed monoclonal antibodies directed against CD45 in combination with mixed pairs of monoclonal an tibodies directed against 10 other antigens. A time-varying Cox regres sion analysis that controlled for sample time intervals, age, sex, mor phologic classification of disease, and white blood cell count at diag nosis was used to relate the multidimensional flow cytometric results to the risk of relapse after achieving remission. Reported P values ar e two-sided. Results: Thirty-five of the 39 patients had bone marrow s pecimens available from the time that first morphologic remission was achieved. Leukemic blast cells were detected in the specimens from 19 (54%) of these 35 patients. Twenty-five of the 35 patients did not rec eive an allogeneic (i.e. from a different genetic background) bone mar row transplant during first morphologic remission, and 13 of 14 with r esidual leukemic cells experienced a relapse at a median time of 153 d ays after diagnosis (range, 48-863 days). Nine of the 11 patients who did not receive an allogeneic bone marrow transplant and lacked eviden ce of leukemic blast cells at first morphologic remission relapsed at a median time of 413 days after diagnosis (range, 321-794 days). Among the 10 individuals who received an allogeneic bone marrow transplant during first morphologic remission, five were positive for leukemic bl ast cells and five were negative; one of these patients (positive for leukemic blast cells) experienced a relapse 265 days after diagnosis, and three others died of transplant-related complications. The estimat ed risk of relapse during intervals of multidimensional flow cytometri c positivity (i.e., intervals of remission for which the immediately p receding cytometry measurement was positive) was 2.8 times greater tha n that during negative intervals (95% confidence interval = 1.1-7.0; P = .02). Conclusions and Implications: Multi-dimensional flow cytometr y identifies residual leukemia in more than half of the patients with AML who ae in morphologic remission. The detection of leukemic blast c ells in these patients by multidimensional flow cytometry is predictiv e of a more rapid relapse.