Bone marrow stem cell protection from chemotherapy by low-molecular-weightcompounds

The stem cells of the bone marrow have the capacity for both self-renewal a nd derivation of all the blood cell lineages. Consequently, toxicity to the se cells can result in neutropenia, agranulocytosis, thrombocytopenia, panc ytopenia, or aplastic anemia. Many anticancer drugs adversely affect the bo ne marrow, and neutropenia is a common limiting factor in dose escalation. In this review, we discuss agents that appear to have potential as bone mar row sparing agents. Computerized catalogs of the National Library of Medici ne and Medline were searched for reports on low-molecular-weight compounds that detailed effects on the hematopoietic progenitor cells. The most promi sing agents are the endogenous peptides p-glutamic acid-glutamic acid-aspar tic acid-cysteine-lysine and acetyl-serine-aspartic acid-lysine-praline, an d the exogenous compounds amifostine and ammonium trichloro[dioxoethylene-O ,O']tellurate, but several others are also discussed. These compounds prese rve stem cell function in the presence of antineoplastic drugs of diverse p harmacological classes, and they do so by various mechanisms of action. The ir present status in clinical practice is also detailed. More needs to be l earned about their mechanisms of action and therapeutic potential, but the results are encouraging For some of these compounds and more clinical trial s should be expected. (C) 2001 International Society for Experimental Hemat ology. Published by Elsevier Science Inc.