Relative impact of residual cytogenetic abnormalities and flow cytometric measurable residual disease on outcome after allogeneic hematopoietic cell transplantation in adult acute myeloid leukemia
Corentin Orvain,
Jacob A. Wilson,
Min Fang,
Brenda M. Sandmaier,
Eduardo Rodríguez-Arbolí,
Brent L. Wood,
Megan Othus,
Frederick R. Appelbaum,
Roland B. Walter
Affiliations
Corentin Orvain
Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, USA; Department of Medicine, Division of Hematology/Oncology, University of Washington, Seattle, WA, USA; Maladies du Sang, CHU d’Angers, Angers, France; Fédération Hospitalo-Universitaire Grand-Ouest Acute Leukemia, FHU-GOAL; Université d'Angers, Inserm UMR 1307, CNRS UMR 6075, Nantes Université, CRCI2NA, F-49000 Angers
Jacob A. Wilson
Cytogenetics Laboratory, Fred Hutchinson Cancer Center, Seattle, WA
Min Fang
Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, USA; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA
Brenda M. Sandmaier
Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, USA; Department of Medicine, Division of Hematology/Oncology, University of Washington, Seattle, WA
Eduardo Rodríguez-Arbolí
Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, USA; Department of Hematology, Hospital Universitario Virgen del Rocío, Instituto de Biomedicina de Sevilla (IBIS/CSIC/CIBERONC), University of Seville, Seville
Brent L. Wood
Department of Pathology and Laboratory Medicine, Children’s Hospital, Los Angeles, CA
Megan Othus
Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA
Frederick R. Appelbaum
Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, USA; Department of Medicine, Division of Hematology/Oncology, University of Washington, Seattle, WA
Roland B. Walter
Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, USA; Department of Medicine, Division of Hematology/Oncology, University of Washington, Seattle, WA, USA; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA; Department of Epidemiology, University of Washington, Seattle, WA
Measurable residual disease (MRD) before hematopoietic cell transplantation (HCT) is an independent established prognostic factor in patients with acute myeloid leukemia (AML). Several methods exist to evaluate the presence of residual leukemia cells, but how these are used best in combination is unclear. In order to examine how residual cytogenetic abnormalities and MRD testing by multiparameter flow cytometry (MFC) may refine risk assessment before HCT, we analyzed 506 adults with cytogenetically abnormal AML who underwent both routine karyotyping and MFC MRD testing before receiving a first allograft while in morphologic remission. Testing for residual cytogenetic abnormalities and MFC MRD identified four groups of patients with differential relapse-free survival (RFS) (hazard ratio [HR]=1.63 for Cytoabnormal/MFCnegative [P=0.01, n=63], HR=3.24 for Cytonormal/MFCpositive [P<0.001, n=60], and HR=5.50 for Cytoabnormal/MFCpositive [P<0.001, n=56] with Cytonormal/MFCnegative as reference [n=327]) and overall survival (OS) (HR=1.55 for Cytoabnormal/MFCnegative [P=0.03], HR=2.69 for Cytonormal/MFCpositive [P<0.001], and HR=4.15 for Cytoabnormal/MFCpositive [P<0.001] with Cytonormal/MFCnegative as reference). Results were similar for patients who received myeloablative or non-myeloablative conditioning. C-statistic values were higher, indicating higher accuracy, when using pre-HCT cytogenetic and MFC MRD information together for prediction of relapse, RFS, and OS, rather than using either test result alone. This study indicates that residual cytogenetic abnormalities and MFC MRD testing provide complementary prognostic information for post- HCT outcomes in patients with cytogenetically abnormal AML undergoing allogeneic HCT.
