caa a22 4500 397561857 CHVBK 20180308164818.0 cr unu---uuuuu 161202e19961016xx s 000 0 eng 10.1093/jnci/88.20.1483 doi (NATIONALLICENCE)oxford-10.1093/jnci/88.20.1483 Prediction of Relapse of Pediatric Acute Myeloid Leukemia by Use of Multidimensional Flow Cytometry [Elektronische Daten] [Eric L. Sievers, Beverly J. Lange, Jonathan D. Buckley, Franklin O. Smith, Denise A. Wells, Celeste A. Daigneault-Creech, Keith E. Shults, Irwin D. Bernstein, Michael R. Loken] Background: Most patients receiving therapy for acute myeloid leukemia (AML) enter an interval in which leukemic blast cells cannot be detected by light microscopy (i.e., morphologic remission). However, many of these patients experience a subsequent relapse. Multidimensional flow cytometry, which allows the discrimination of antigens expressed on normal and malignant cells, can detect small numbers of cancer cells in bone marrow or peripheral blood specimens. This technique enables the detection of one leukemic blast cell among 103 to 102 normal regenerating hematopoietic cells. Purpose: We determined whether the presence of residual leukemic blast cells, identified in the bone marrow of pediatric patients with AML by use of multidimensional flow cytometry, would be predictive of subsequent leukemic relapse. Methods: Multidimensional flow cytometry was performed on 205 marrow specimens collected throughout the course of treatment from 39 patients who had achieved morphologic remission. The analyses employed monoclonal antibodies directed against CD45 in combination with mixed pairs of monoclonal antibodies directed against 10 other antigens. A time-varying Cox regression analysis that controlled for sample time intervals, age, sex, morphologic classification of disease, and white blood cell count at diagnosis was used to relate the multidimensional flow cytometric results to the risk of relapse after achieving remission. Reported P values are two-sided. Results: Thirty-five of the 39 patients had bone marrow specimens 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 receive an allogeneic (i.e., from a different genetic background) bone marrow transplant during first morphologic remission, and 13 of 14 with residual leukemic cells experienced a relapse at a median time of 153 days after diagnosis (range, 48-863 days). Nine of the 11 patients who did not receive an allogeneic bone marrow transplant and lacked evidence 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 blast 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 estimated risk of relapse during intervals of multidimensional flow cytometric positivity (i.e., intervals of remission for which the immediately preceding cytometry measurement was positive) was 2.8 times greater than that during negative intervals (95% confidence interval = 1.1-7.0; P = .02). Conclusions and Implications: Multidimensional flow cytometry identifies residual leukemia in more than half of the patients with AML who are in morphologic remission. The detection of leukemic blast cells in these patients by multidimensional flow cytometry is predictive of a more rapid relapse. © Oxford University Press REPORTS nationallicence Sievers Eric L. Division of Pediatric Oncology, Fred Hutchinson Cancer Research Center Seattle, WA Division of Pediatric Hematology/Oncology, University of Washington, Seattle and Childrens Cancer Group Arcadia, CA aut Lange Beverly J. Division of Oncology, Children's Hospital of Philadelphia PA Childrens Cancer Group aut Buckley Jonathan D. Department of Preventive Medicine, University of Southern California Los Angeles Childrens Cancer Group aut Smith Franklin O. Division of Pediatric Hematology/Oncology, Indiana University Indianapolis Childrens Cancer Group aut Wells Denise A. Hematologics, Inc. Seattle, WA aut Daigneault-Creech Celeste A. Hematologics, Inc. Seattle, WA aut Shults Keith E. Cytometry Associates, Inc. Brentwood, TN aut Bernstein Irwin D. Division of Pediatric Oncology, Fred Hutchinson Cancer Research Center Seattle, WA Division of Pediatric Hematology/Oncology, University of Washington, Seattle and Childrens Cancer Group Arcadia, CA aut Loken Michael R. Hematologics, Inc. Seattle, WA aut JNCI: Journal of the National Cancer Institute Oxford University Press 88/20(1996-10-16), 1483-1488 0027-8874 88:20<1483 1996 88 jnci https://doi.org/10.1093/jnci/88.20.1483 text/html Onlinezugriff via DOI 1 other jats NATIONALLICENCE 856 40 https://doi.org/10.1093/jnci/88.20.1483 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Sievers Eric L. Division of Pediatric Oncology, Fred Hutchinson Cancer Research Center Seattle, WA Division of Pediatric Hematology/Oncology, University of Washington, Seattle and Childrens Cancer Group Arcadia, CA aut NATIONALLICENCE 700 1- Lange Beverly J. Division of Oncology, Children's Hospital of Philadelphia PA Childrens Cancer Group aut NATIONALLICENCE 700 1- Buckley Jonathan D. Department of Preventive Medicine, University of Southern California Los Angeles Childrens Cancer Group aut NATIONALLICENCE 700 1- Smith Franklin O. Division of Pediatric Hematology/Oncology, Indiana University Indianapolis Childrens Cancer Group aut NATIONALLICENCE 700 1- Wells Denise A. Hematologics, Inc. Seattle, WA aut NATIONALLICENCE 700 1- Daigneault-Creech Celeste A. Hematologics, Inc. Seattle, WA aut NATIONALLICENCE 700 1- Shults Keith E. Cytometry Associates, Inc. Brentwood, TN aut NATIONALLICENCE 700 1- Bernstein Irwin D. Division of Pediatric Oncology, Fred Hutchinson Cancer Research Center Seattle, WA Division of Pediatric Hematology/Oncology, University of Washington, Seattle and Childrens Cancer Group Arcadia, CA aut NATIONALLICENCE 700 1- Loken Michael R. Hematologics, Inc. Seattle, WA aut NATIONALLICENCE 773 0- JNCI: Journal of the National Cancer Institute Oxford University Press 88/20(1996-10-16), 1483-1488 0027-8874 88:20<1483 1996 88 jnci Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford