Multidrug Resistance Studies in Acute Myeloid Leukemia
- Determine Pgp antigen expression and Pgp-mediated functional multidrug resistance (MDR)
in pretreatment acute myeloid leukemia (AML) cells from adult patients enrolled on
CALGB clinical trials of PSC-833 Pgp modulation.
- Correlate Pgp-mediated MDR with patient pretreatment characteristics including age,
immunophenotype, and karyotype.
- Correlate Pgp expression, function, and in vitro modulation by PSC-833 with treatment
outcome in previously untreated AML patients treated on CALGB Pgp modulation trials.
- Determine Pgp expression and function in AML cells from patients with refractory or
relapsed leukemia following induction chemotherapy administered with or without
- Correlate acquisition of drug resistance with changes in expression of other antigens
and gain or loss of leukemic populations at relapse in these patients.
- Determine the role of other mediators, including multidrug resistance-associated
protein (MRP) and lung-resistance protein (LRP), in mediating MDR in these patients at
diagnosis and with relapsed or refractory disease after induction chemotherapy with or
- Determine the frequency of Pgp-, MRP-, and LRP- mediated MDR in adult acute
lymphoblastic leukemia cells and correlate this frequency with pretreatment
characteristics and treatment outcome in these patients.
OUTLINE: Samples are obtained: 1) pretreatment, 2) at the time of documentation of
refractory disease in acute myeloid leukemia (AML) patients who do not achieve complete
response (CR) after induction therapy, and 3) at the time of first relapse in patients who
Marrow cells are preferentially used for all samples, but peripheral blood is acceptable if
marrow is not available and the blood contains 20% or more blasts.
Pgp expression is measured using flow cytometry. AML samples are analyzed by immunoenzyme
techniques (IET) using antibodies to CD33, CD34, and MRK16. B-lineage acute lymphoblastic
leukemia (ALL) samples are analyzed by IET using antibodies to CD19, CD34, and MRK16. The
antibodies used to analyze T-cells include CD7 and CD34.
Pgp function is measured by growing cells in the presence of PSC-833 in vitro and then
measuring Pgp expression as above.
Multidrug resistance-associated protein (MRP) is measured using IET with the MRPm6 antibody.
Lung-resistance protein (LRP) is measured with IET and the LRP56 antibody. These results are
correlated with flow cytometry results.
PROJECTED ACCRUAL: Approximately 2034 patients will be accrued for this study over 5 years.
Expression and function of the multidrug resistance (MDR) mediators, other patient variables (immunophenotype, karyotype, demographic variables, and other characteristics), treatment, and outcome (CR rate, duration of CR, survival)
Maria R. Baer, MD
University of Maryland Greenebaum Cancer Center
United States: Federal Government
|Roswell Park Cancer Institute||Buffalo, New York 14263|
|Walter Reed Army Medical Center||Washington, District of Columbia 20307-5000|
|University of Chicago Cancer Research Center||Chicago, Illinois 60637|
|CCOP - Kansas City||Kansas City, Missouri 64131|
|CCOP - Christiana Care Health Services||Wilmington, Delaware 19899|
|CCOP - North Shore University Hospital||Manhasset, New York 11030|
|Holden Comprehensive Cancer Center at University of Iowa||Iowa City, Iowa 52242-1002|
|Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center||Lebanon, New Hampshire 03756-0002|
|Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill||Chapel Hill, North Carolina 27599-7570|
|Naval Medical Center - San Diego||San Diego, California 92134-3202|
|Queens Cancer Center of Queens Hospital||Jamaica, New York 11432|
|Blumenthal Cancer Center at Carolinas Medical Center||Charlotte, North Carolina 28232-2861|
|Long Island Jewish Medical Center||New Hyde Park, New York 11040|
|Mount Sinai Medical Center||New York, New York 10029|
|SUNY Upstate Medical University Hospital||Syracuse, New York 13210|
|Wake Forest University Comprehensive Cancer Center||Winston-Salem, North Carolina 27157-1096|
|CCOP - Hematology-Oncology Associates of Central New York||East Syracuse, New York 13057|
|Wayne Memorial Hospital, Incorporated||Goldsboro, North Carolina 27534|
|University of Illinois Cancer Center||Chicago, Illinois 60612-7243|
|CancerCare of Maine at Eastern Maine Medical Center||Bangor, Maine 04401|
|Masonic Cancer Center at University of Minnesota||Minneapolis, Minnesota 55455|
|CCOP - Nevada Cancer Research Foundation||Las Vegas, Nevada 89109-2306|
|Don Monti Comprehensive Cancer Center at North Shore University Hospital||Manhasset, New York 11030|
|Methodist Estabrook Cancer Center||Omaha, Nebraska 68114-4199|
|University Medical Center of Southern Nevada||Las Vegas, Nevada 89102|
|Fort Wayne Medical Oncology and Hematology||Fort Wayne, Indiana 46815|
|Cancer Institute of New Jersey at Cooper - Voorhees||Voorhees, New Jersey 08043|
|Tunnell Cancer Center at Beebe Medical Center||Lewes, Delaware 19958|
|Menorah Medical Center||Overland Park, Kansas 66209|
|Saint Luke's Hospital - South||Overland Park, Kansas 66213|
|Shawnee Mission Medical Center||Shawnee Mission, Kansas 66204|
|Union Hospital Cancer Program at Union Hospital||Elkton MD, Maryland 21921|
|Truman Medical Center - Hospital Hill||Kansas City, Missouri 64108|
|St. Joseph Medical Center||Kansas City, Missouri 64114|
|Heartland Hematology Oncology Associates, Incorporated||Kansas City, Missouri 64118|
|North Kansas City Hospital||Kansas City, Missouri 64116|
|Saint Luke's Cancer Institute at Saint Luke's Hospital||Kansas City, Missouri 64111|
|Research Medical Center||Kansas City, Missouri 64132|
|Saint Luke's East - Lee's Summit||Lee's Summit, Missouri 64086|
|Liberty Hospital||Liberty, Missouri 64068|
|Heartland Regional Medical Center||Saint Joseph, Missouri 64506|
|Saint Joseph Oncology, Incorporated||Saint Joseph, Missouri 64507|
|Monter Cancer Center of the North Shore-LIJ Health System||Lake Success, New York 11042|
|Memorial Hospital of Rhode Island||Pawtucket, Rhode Island 02860|
|Kinston Medical Specialists||Kinston, North Carolina 28501|
|McLeod Regional Medical Center||Florence, South Carolina 29501|