Relation of clinical response and minimal residual disease and their prognostic impact on outcome in acute myeloid leukemia.
OBJECTIVE
Both presence of minimal residual disease (MRD) and achievement of complete remission (CR) with incomplete platelet recovery (CRp) rather than CR after induction therapy predict relapse in acute myeloid leukemia (AML). These results suggest a correlation between response (peripheral count recovery) and MRD at the time of morphologic remission. Here we examine this hypothesis and whether MRD and response provide independent prognostic information after accounting for other relevant covariates.


METHODS
We retrospectively analyzed data from 245 adults with AML who achieved CR, CRp, or CR with incomplete blood count recovery (CRi) after induction therapy. Bone marrow samples were collected on or closest to the first date of blood count recovery, and MRD was determined by 10-color multiparameter flow cytometry.


RESULTS
The 71.0% of patients who achieved CR had MRD less frequently and had lower levels of MRD than the 19.6% of patients achieving CRp and 9.4% achieving CRi. Although pretreatment covariates such as cytogenetics, monosomal karyotype, relapsed or refractory rather than newly diagnosed AML, and FLT3 internal tandem duplication were associated with relapse, their prognostic effect was much lower once MRD and response were taken into account, the univariable statistical effect of which was not materially affected by inclusion of pretreatment covariates.


CONCLUSIONS
Our data indicate that post-therapy parameters including MRD status and response are important independent prognostic factors for outcome in patients with AML achieving remission. MRD status and type of response (CR v CRp or CRi) should play important, and perhaps dominant, roles in planning postinduction therapy.
Xueyan Chen, Brent L. Wood, Roland B. Walter, Pamela S. Becker, Janis L. Abkowitz, and Elihu H. Estey, University of Washington; and Hu Xie, Roland B. Walter, John M. Pagel, Pamela S. Becker, Vicky K. Sandhu, Frederick R. Appelbaum, and Elihu H. Estey, Fred Hutchinson Cancer Research Center, Seattle, WA. xchen1@uw.edu.
Xueyan
X
Chen
Xueyan Chen, Brent L. Wood, Roland B. Walter, Pamela S. Becker, Janis L. Abkowitz, and Elihu H. Estey, University of Washington; and Hu Xie, Roland B. Walter, John M. Pagel, Pamela S. Becker, Vicky K. Sandhu, Frederick R. Appelbaum, and Elihu H. Estey, Fred Hutchinson Cancer Research Center, Seattle, WA.
Hu
H
Xie
Xueyan Chen, Brent L. Wood, Roland B. Walter, Pamela S. Becker, Janis L. Abkowitz, and Elihu H. Estey, University of Washington; and Hu Xie, Roland B. Walter, John M. Pagel, Pamela S. Becker, Vicky K. Sandhu, Frederick R. Appelbaum, and Elihu H. Estey, Fred Hutchinson Cancer Research Center, Seattle, WA.
Brent L
BL
Wood
Xueyan Chen, Brent L. Wood, Roland B. Walter, Pamela S. Becker, Janis L. Abkowitz, and Elihu H. Estey, University of Washington; and Hu Xie, Roland B. Walter, John M. Pagel, Pamela S. Becker, Vicky K. Sandhu, Frederick R. Appelbaum, and Elihu H. Estey, Fred Hutchinson Cancer Research Center, Seattle, WA.
Roland B
RB
Walter
Xueyan Chen, Brent L. Wood, Roland B. Walter, Pamela S. Becker, Janis L. Abkowitz, and Elihu H. Estey, University of Washington; and Hu Xie, Roland B. Walter, John M. Pagel, Pamela S. Becker, Vicky K. Sandhu, Frederick R. Appelbaum, and Elihu H. Estey, Fred Hutchinson Cancer Research Center, Seattle, WA.
John M
JM
Pagel
Xueyan Chen, Brent L. Wood, Roland B. Walter, Pamela S. Becker, Janis L. Abkowitz, and Elihu H. Estey, University of Washington; and Hu Xie, Roland B. Walter, John M. Pagel, Pamela S. Becker, Vicky K. Sandhu, Frederick R. Appelbaum, and Elihu H. Estey, Fred Hutchinson Cancer Research Center, Seattle, WA.
Pamela S
PS
Becker
Xueyan Chen, Brent L. Wood, Roland B. Walter, Pamela S. Becker, Janis L. Abkowitz, and Elihu H. Estey, University of Washington; and Hu Xie, Roland B. Walter, John M. Pagel, Pamela S. Becker, Vicky K. Sandhu, Frederick R. Appelbaum, and Elihu H. Estey, Fred Hutchinson Cancer Research Center, Seattle, WA.
Vicky K
VK
Sandhu
Xueyan Chen, Brent L. Wood, Roland B. Walter, Pamela S. Becker, Janis L. Abkowitz, and Elihu H. Estey, University of Washington; and Hu Xie, Roland B. Walter, John M. Pagel, Pamela S. Becker, Vicky K. Sandhu, Frederick R. Appelbaum, and Elihu H. Estey, Fred Hutchinson Cancer Research Center, Seattle, WA.
Janis L
JL
Abkowitz
Xueyan Chen, Brent L. Wood, Roland B. Walter, Pamela S. Becker, Janis L. Abkowitz, and Elihu H. Estey, University of Washington; and Hu Xie, Roland B. Walter, John M. Pagel, Pamela S. Becker, Vicky K. Sandhu, Frederick R. Appelbaum, and Elihu H. Estey, Fred Hutchinson Cancer Research Center, Seattle, WA.
Frederick R
FR
Appelbaum
Xueyan Chen, Brent L. Wood, Roland B. Walter, Pamela S. Becker, Janis L. Abkowitz, and Elihu H. Estey, University of Washington; and Hu Xie, Roland B. Walter, John M. Pagel, Pamela S. Becker, Vicky K. Sandhu, Frederick R. Appelbaum, and Elihu H. Estey, Fred Hutchinson Cancer Research Center, Seattle, WA.
Elihu H
EH
Estey
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001792:Blood Platelets; D001856:Bone Marrow Examination; D018572:Disease-Free Survival; D005260:Female; D005434:Flow Cytometry; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D060828:Induction Chemotherapy / Q000009:adverse effects / Q000401:mortality; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual; D009504:Neutrophils; D010976:Platelet Count; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012008:Recurrence; D012074:Remission Induction; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult