EFFECT OF RECOMBINANT HUMAN HEMOGLOBIN ON HUMAN BONE-MARROW PROGENITOR CELLS - PROTECTION AND REVERSAL OF 3'-AZIDO-3'-DEOXYTHYMIDINE-INDUCED TOXICITY

Long-term therapy of AIDS patients with 3'-azido-3'-deoxythymidine (AZ T) is limited by hematopoietic toxicity. While the mechanism(s) of thi s toxicity remain elusive, various strategies are being developed to r educe these toxic effects including combination therapy with non-myelo toxic anti-human immunodeficiency virus (HIV) drugs and/or administrat ion of protective or rescue agents, such as cytokines and growth facto rs. Using a physiologically relevant human CD34+ bone marrow cell liqu id culture system, a crosslinked human recombinant hemoglobin (rHb), c urrently in Phase II clinical trials, was investigated for effects on hematopoiesis and for its potential in protecting or reversing AZT-ind uced hematopoietic toxicity. These investigations demonstrated that 0. 01, 0.1, or 1 mu M human rHb did not affect the proliferation of eryth roid or myeloid lineage cells. A concentration of 1 mu M rHb partially protected erythroid lineage cells from an inhibition of proliferation induced by 0.1 and 1 mu M AZT. Inhibition of proliferation of cells p reviously exposed to AZT was not reversed at this concentration. These data suggest that human rHb may be of benefit in reducing the toxic e ffects of AZT in the bone marrow of AIDS patients.