The success of autologous marrow transplantation (AMT) for the treatment of patients with hematologic malignancy is limited largely by a high incidence of disease recurrence after AMT. IL-2 with or without adoptive immunotherapy in the form of ex vivo-generated lymphokine-activated killer (LAK) cells, has induced regression of advanced cancer in some patients, including, primarily, some with hematologic malignancies. This approach could potentially represent a treatment modality which would be non-cross- resistant with chemoradiotherapy conditioning regimens for AMT. IL-2+LAK cells has been used mostly in the presence of large tumor burdens. Our goal is to test the hypothesis that this approach, if used early after AMT in a setting of minimal residual disease, may reduce the posttransplant relapse rate. We have demonstrated that IL-2-responsive LAK precursor cells appear in the circulation early after AMT. We have identified an IL- 2 regimen which is tolerable when administered early after AMT and induces immunomodulatory effects. We have begun to test the feasibility of administering IL-2 plus LAK cells early after AMT. The goals of the studies proposed are to establish a treatment regimen of IL-2 and autologous LAK cells which can be applied to the majority of patients early after AMT for acute leukemia and malignant lymphoma and then to determine the effect of such a regimen on posttransplant relapse rates. Accordingly, the specific aims of this proposal are as follows: 1) to establish the feasibility of administering a regimen of IL-2 and autologous LAK cells early to the majority of patients undergoing AMT for hematologic malignancies, and to compare the relapse rates in patients so treated with appropriate historical controls, and 2) based on the above trial, to conduct a randomized controlled trial of IL-2 and LAK cells versus no consolidative therapy after AMT in patients at high risk for relapse for hematologic malignancies to determine the effect, if any, on the relapse rate.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA047748-05
Application #
3773350
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Fred Hutchinson Cancer Research Center
Department
Type
DUNS #
075524595
City
Seattle
State
WA
Country
United States
Zip Code
98109
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Bensinger, William I (2007) Is there still a role for allogeneic stem-cell transplantation in multiple myeloma? Best Pract Res Clin Haematol 20:783-95
Bensinger, William I (2007) Reduced intensity allogeneic stem cell transplantation in multiple myeloma. Front Biosci 12:4384-92
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Bensinger, W I (2006) The current status of reduced-intensity allogeneic hematopoietic stem cell transplantation for multiple myeloma. Leukemia 20:1683-9
Bensinger, William I (2004) The role of hematopoietic stem cell transplantation in the treatment of multiple myeloma. J Natl Compr Canc Netw 2:371-8
Bensinger, William I (2004) The current status of hematopoietic stem cell transplantation for multiple myeloma. Clin Adv Hematol Oncol 2:46-52
Yusuf, U; Frangoul, H A; Gooley, T A et al. (2004) Allogeneic bone marrow transplantation in children with myelodysplastic syndrome or juvenile myelomonocytic leukemia: the Seattle experience. Bone Marrow Transplant 33:805-14
Einsele, H; Bamberg, M; Budach, W et al. (2003) A new conditioning regimen involving total marrow irradiation, busulfan and cyclophosphamide followed by autologous PBSCT in patients with advanced multiple myeloma. Bone Marrow Transplant 32:593-9

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