Multigene Measurable Residual Disease Assessment Improves Acute Myeloid Leukemia Relapse Risk Stratification in Autologous Hematopoietic Cell Transplantation

•Largest study to date of measurable residual disease in autologous hematopoietic cell transplantation for acute myeloid leukemia•Autograft is suboptimal source for acute myeloid leukemia measurable residual disease detection•Granulocyte colony–stimulating factor administration can lead to false-pos...

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Bibliographic Details
Published in:Biology of blood and marrow transplantation 2016-11, Vol.22 (11), p.1974-1982
Main Authors: Mulé, Matthew P., Mannis, Gabriel N., Wood, Brent L., Radich, Jerald P., Hwang, Jimmy, Ramos, Nestor R., Andreadis, Charalambos, Damon, Lloyd, Logan, Aaron C., Martin, Thomas G., Hourigan, Christopher S.
Format: Article
Language:English
Subjects:
Acute myeloid leukemia
Adult
Aged
Autografts
Autologous hematopoietic cell transplantation
Female
Flow Cytometry
Genes, Wilms Tumor
Hematopoietic Stem Cell Transplantation - methods
Humans
Leukapheresis
Leukemia, Myeloid, Acute - diagnosis
Leukemia, Myeloid, Acute - therapy
Male
Measurable residual disease
Middle Aged
Neoplasm, Residual - diagnosis
Neoplasm, Residual - genetics
Polymerase Chain Reaction
Predictive Value of Tests
Recurrence
Retrospective Studies
Risk Assessment
Specimen Handling
Transplantation, Autologous
Young Adult
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Summary:•Largest study to date of measurable residual disease in autologous hematopoietic cell transplantation for acute myeloid leukemia•Autograft is suboptimal source for acute myeloid leukemia measurable residual disease detection•Granulocyte colony–stimulating factor administration can lead to false-positive Wilms tumor 1 measurable residual disease values.•Measurable residual disease detection by flow cytometry in post–granulocyte colony–stimulating factor autografts is challenging without leukemia-associated immunophenotype•Real-time quantitative PCR for somatic mutations and translocations can improve autograft measurable residual disease detection. We report here the largest study to date of adult patients with acute myeloid leukemia (AML) tested for measurable residual disease (MRD) at the time of autologous hematopoietic cell transplantation (auto-HCT). Seventy-two adult patients who underwent transplantation between 2004 and 2013 at a single academic medical center (University of California San Francisco) were eligible for this retrospective study based on availability of cryopreserved granulocyte colony–stimulating factor (GCSF)–mobilized autologous peripheral blood progenitor cell (PBPC) leukapheresis specimens (“autografts”). Autograft MRD was assessed by molecular methods (real-time quantitative PCR [RQ-PCR] for Wilms tumor 1 (WT1) alone or a multigene panel) and by multiparameter flow cytometry (MPFC). WT1 RQ-PCR testing of the autograft had low sensitivity for relapse prediction (14%) and a negative predictive value of 51%. MPFC failed to identify MRD in any of 34 autografts tested. Combinations of molecular MRD assays, however, improved prediction of post–auto-HCT relapse. In multivariate analysis of clinical variables, including age, gender, race, cytogenetic risk category, and CD34+ cell dose, only autograft multigene MRD as assessed by RQ-PCR was statistically significantly associated with relapse. One year after transplantation, only 28% patients with detectable autograft MRD were relapse free, compared with 67% in the MRD-negative cohort. Multigene MRD, while an improvement on other methods tested, was however suboptimal for relapse prediction in unselected patients, with specificity of 83% and sensitivity of 46%. In patients with known chromosomal abnormalities or mutations, however, better predictive value was observed with no relapses observed in MRD-negative patients in the first year after auto-HCT compared with 83% incidence of relapse
ISSN:1083-8791
1523-6536
DOI:10.1016/j.bbmt.2016.08.014