title: Myeloablative, but not Reduced-Intensity, Conditioning Overcomes the Negative Effect of Flow-Cytometric Evidence of Leukemia in Acute Myeloid Leukemia.
abstract: Stringent complete remission (CR) in acute myeloid leukemia (AML) requires the absence of both morphologic and flow cytometric evidence of disease. We have previously shown that persistent AML detected by flow cytometry (FC+) before reduced-intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (alloHCT) was associated with significantly increased relapse, shorter disease-free survival (DFS), and poorer overall survival (OS), independent of morphologic blast count. We evaluated the effect of FC status on outcomes of alloHCT for AML after either myeloablative conditioning (MAC) or RIC regimens in 203 patients (MAC, n = 80, and RIC, n = 123) with no morphologic evidence of persistent AML pretransplant on marrow biopsy. The allografts included 130 umbilical cord blood (UCB) and 73 sibling donors. We performed central review of pretransplant standard sensitivity FC to identify detectable FC+. Twenty-five patients were FC+, including 15 (18.7%) receiving MAC and 10 (8.1%) RIC alloHCT. Among RIC patients FC+ was associated with significantly inferior relapse, DFS, and OS (multiple regression HR, 3.8; 95% CI, 1.7 to 8.7; P < .01 for relapse; HR, 2.9; 95% CI, 1.4 to 5.9; P < .01 for DFS; and HR, 3.4; 95% CI, 1.7 to 7; P < .01 for OS). In contrast, FC+ status was not associated with relapse or decreased OS after MAC. These data suggest that MAC, but not RIC, overcomes the negative effect of pretransplant FC+ after sibling or UCB alloHCT. Therefore, a deeper pretransplant leukemia-free state is preferred for those treated with RIC.
authors.affiliation: Division of Hematology, Oncology, and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, Minnesota. Electronic address: custun@umn.edu.
authors.forename: Celalettin
authors.initials: C
authors.lastname: Ustun
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Elizabeth L
authors.initials: EL
authors.lastname: Courville
authors.affiliation: Biostatistics and Bioinformatics, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Todd
authors.initials: T
authors.lastname: DeFor
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Michelle
authors.initials: M
authors.lastname: Dolan
authors.affiliation: Division of Hematology, Oncology, and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Nicole
authors.initials: N
authors.lastname: Randall
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Sophia
authors.initials: S
authors.lastname: Yohe
authors.affiliation: Division of Hematology, Oncology, and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Nelli
authors.initials: N
authors.lastname: Bejanyan
authors.affiliation: Division of Hematology, Oncology, and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Erica
authors.initials: E
authors.lastname: Warlick
authors.affiliation: Division of Hematology, Oncology, and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Claudio
authors.initials: C
authors.lastname: Brunstein
authors.affiliation: Division of Hematology, Oncology, and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Weisdorf
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Linden
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D036101:Cord Blood Stem Cell Transplantation; D005260:Female; D005434:Flow Cytometry; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D019653:Myeloablative Agonists; D012008:Recurrence; D035781:Siblings; D016019:Survival Analysis; D014019:Tissue Donors; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D019653:Myeloablative Agonists
keywords: AML; Allogeneic hematopoietic cell transplantation; Complete remission; Flow cytometry; Myeloablative conditioning; Reduced-intensity conditioning; Relapse; Survival