Hematologic malignancies are important causes of morbidity and mortality in adults. These diseases affect primarily patients over the age of 50, and results of conventional therapy are unsatisfactory. Allogeneic stem cell transplantation has been effective in obtaining long-term disease control in many patients with these disorders including those in whom initial therapy has failed. Allografting has traditionally been limited to younger patients in good medical condition because of the high rates of graft versus host disease (GVHD) and non-relapse mortality associated with increasing age and decreasing performance status. Strategies to decrease morbidity and mortality related to allografting in older patients have included reductions in the intensity of the preparative regimens. In this grant application we propose to determine whether unrelated donor transplantation using a reduced intensity conditioning will result in lower rates of acute GVHD and non relapse mortality and better outcomes in older patients (45 to 65 years of age) with myeloid leukemias when compared to a conventional myeloablative protocol, and whether this reduction in non relapse mortality is secondary to lower levels of inflammatory cytokines (IL-1,IL-2,IFN-gamma, TNF-alpha, IL-6, IL-10, and IL12) in patients receiving a reduced intensity conditioning than in patients receiving conventional myeloablative transplants. Within this application we will also determine the relevance of lineage specific chimerism using existing cell sorting and chimerism determination techniques, and correlate degree of chimerism of specific myeloid, lymphoid, and stem cell subsets with engraftment, relapse, and GVHD. The ultimate goal of this study is to optimize transplant strategies for each patient population by defining the best preparative regimen associated with the lowest toxicities and best long term outcomes.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01HL069334-03
Application #
6794002
Study Section
Special Emphasis Panel (ZHL1-CSR-F (S1))
Program Officer
Henslee-Downey, Jean
Project Start
2002-06-05
Project End
2007-05-31
Budget Start
2004-07-10
Budget End
2005-05-31
Support Year
3
Fiscal Year
2004
Total Cost
$405,000
Indirect Cost
Name
University of Texas MD Anderson Cancer Center
Department
Internal Medicine/Medicine
Type
Other Domestic Higher Education
DUNS #
800772139
City
Houston
State
TX
Country
United States
Zip Code
77030