Proteomic Signature Associated With Clinical Response to Cytarabine Based Induction Therapy in Patients With AML 56 Years and Older
- Refinement and testing of a multiparameter flow cytometry-based cell-signaling
signature (FC classifier) associated with in vivo likelihood of complete response (CR)
to cytarabine-based induction chemotherapy in elderly patients (56 years and older)
newly diagnosed with non-M3 acute myeloid leukemia (AML).
- Identification of cell-signaling signature(s) associated with continuous CR to
cytarabine-based induction chemotherapy at one year (CCR1) in adult patients 56 years
and older with a newly diagnosed non-M3 AML.
- Identification of cell-signaling signature(s) associated with relapse-free survival at
one year (RFS1) in adult patients 56 years and older with a newly diagnosed non-M3 AML
who received cytarabine-based induction chemotherapy and achieved CR.
- To investigate changes in cell-signaling signature(s) between matched pre- and
post-treatment specimens of relapsed/refractory patients.
OUTLINE: This is a multicenter study.
Cryopreserved specimens are incubated with cytokines (e.g., interleukins), growth factors
(e.g., sargramostim or filgrastim), and chemotherapeutic agent (e.g., cytarabine, etoposide)
and other modulators. Cells are then fixed, permeabilized, and stained with antibodies that
recognize extracellular markers (for example, surface phenotypic markers such as clusters of
differentiation, drug transporters, and receptors) in conjunction with intracellular
activation-state-specific epitopes of designated signaling molecules. Subsequently, cell are
analyzed by phospho-flow cytometry (FC) in a random manner (without knowledge of clinical
variables and outcomes) to a training set (complete pre-specified FC) versus a testing set.
Cells are also analyzed by proteomic assays. Results are then compared with individual
patient scores, including predicted clinical outcomes.
Time Perspective: Retrospective
Response to induction chemotherapy: complete response (CR) vs non-complete response (NR)
Jerry Radich, MD
Fred Hutchinson Cancer Research Center
United States: Federal Government