S9031-S9333-S0112-S0301-A Biomarkers Associated With Response to Cytarabine in Samples From Older Patients With Acute Myeloid Leukemia

Proteomic Signature Associated With Clinical Response to Cytarabine Based Induction Therapy in Patients With AML 56 Years and Older

RATIONALE: Studying samples of blood and tissue from patients with cancer treated with cytarabine in the laboratory may help doctors learn more about the effects of cytarabine on cells. It may also help doctors understand how well patients respond to treatment.

PURPOSE: This research trial studies biomarkers associated with response to cytarabine in samples from older patients with acute myeloid leukemia.

OBJECTIVES:

• 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.

DISEASE CHARACTERISTICS:

• Newly diagnosed with non-M3 acute myeloid leukemia (AML)

• Pretreatment and relapse/refractory cryopreserved marrow and circulating mononuclear cells (MC) from patients who meet the following criteria:

  • Eligible and evaluable patients on study SWOG-9031, SWOG-9333 (Ara-C/DNR induction arm only), SWOG-S0112, or SWOG-S0301
  • Did not refuse consent for this use of specimens
  • Have 2+ vials of pretreatment marrow cells and/or 2+ vials of pretreatment peripheral blood cells in the Southwest Oncology Group (SWOG) AML/MDS Repository

PATIENT CHARACTERISTICS:

• See Disease Characteristics

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics