Biological safety considerations in the production of health care products from recombinant organisms

Severe intravascular hemolysis associated with interferon treatment for chronic myeloid leukemia

“…This symptomatic group was also severely immunologically compromised ( Table I). The 8.9% incidence of HIV-I seropositivity in thalassemic children seen here is much higher than the incidence of I % reported in similar studies [4]. .…”

“…Furthermore, it is difficult to explain hemolysis with interferon-w2a, but not a-2b, on an immunogenic basis when the biochemical difference between the two is confined to a single amino acid at position 22 121. Interferon-a-2a is cloned in an Eschercchia coli strain, with a final purity >99% [3,4]. While it is theoretically possible that our patient reacted to a "contaminating" E. coli protein, we are not aware of reports of intravascular hemolysis associated with biological substances cloned in this way [5].…”

“…We also tend to believe that the resolution of acrocyanosis and the disappearance of cryoagglutinins following surgery rule out a chance association among the three. Indeed, cryoagglutinins and acrocyanosis are known to be causally linked 131, and the development of autoimmune hemolytic anemia is a well-known paraneoplastic sign [4] in a variety of cancers (lymphomas, lung, ovary, tumors of the gastrointestinal tract, etc.). The absence of hemolyrnphopoietic tissue in the pathological specimen fits with the hypothesis that benign teratoma is not a site of direct cryoagglutinin production but that it serves as a stimulus for such production to occur in normal lymphoid tissue of the host.…”