Manipulation of the stem cell as a target for hematologic malignancies.
Hematologic malignancies affect more than 80,000 patients in the United States each year. Some patients with lymphoma and leukemia are cured with conventional chemotherapy treatments. For others, autologous or allogeneic bone marrow transplantation may be the best therapeutic option. This chapter will explore novel therapies for the hematologic malignancies, using the stem cell as a target. We review work in the murine model looking at (1) the phenotype of the engrafting cells, (2) stem cell competition and host stem cells, (3) allochimerism with low-dose total body irradiation, and (4) the tolerance approach with costimulator blockade. Human data, including stem cell migration, adhesion receptor expression, and manipulations for gene therapy, are reviewed. The NOD/scid mouse model serves as a bridge between the basic bench work and human clinical trials, and we discuss applications related to umbilical cord blood and gene therapy, as well as discuss the inherent variability of this system. Finally, we address unique clinical applications in gene therapy, high-dose cell transplants, minimal myeloablation, and cellular immune therapy as approaches to treatment of for patients with hematologic malignancies.
Ballen
K K
KK
University of Massachusetts Cancer Center, Worcester, USA.
Becker
P S
PS
Stewart
F M
FM
Quesenberry
P J
PJ
D000818:Animals; D005312:Fetal Blood; D015316:Genetic Therapy / Q000379:methods; D019337:Hematologic Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D051379:Mice; D023421:Models, Animal; D013234:Stem Cells; D019172:Transplantation Conditioning; D014916:Whole-Body Irradiation