CHRONIC MYELOGENOUS LEUKEMIA - IN SEARCH OF THE BENIGN HEMATOPOIETIC STEM-CELL

Donor marrow transplantation can cure chronic myelogenous leukemia (CM L). Unfortunately, the procedure is associated with severe complicatio ns and is limited to the minority of potential recipients with suitabl y matched donors. Autologous marrow transplantation using negative sel ection approaches such as incubation with gamma interferon (IFN-gamma) can produce cytogenetic and clinical remissions, but they are often a ssociated with recurrent evidence of leukemia. A primitive progenitor population can be separated from normal human marrow on the basis of m orphologic characteristics and cell surface antigen expression. Cell p opulations with similar morphologic and phenotypic characteristics obt ained by positive selection from the marrow of patients with CML appea r to be benign. Benign primitive and committed progenitors selected in this fashion can be expanded ex vivo when cultured in a ''Transwell'' system which physically separates hematopoietic cells from stromal fe eder layers. Positive selection and ex vivo cultivation of benign prog enitors from CML marrow may provide a source of hematopoietic stem cel ls suitable for autologous marrow transplantation. Autologous natural killer (NK) cells obtained from the peripheral blood of patients with CML are of benign origin and have antileukemia activity. Interleukin 2 (IL-2) activated autologous NK cells may be used in post-transplant c ellular therapy to prevent recurrence of CML.