THE EFFECT OF HUMAN CORD-BLOOD ON SJL J MICE AFTER CHEMOABLATION AND IRRADIATION AND ITS POSSIBLE CLINICAL-SIGNIFICANCE/

There is evidence from the existing published literature that human um bilical cord blood, when used for purposes of bone marrow transplantat ion, does not necessarily have to be HLA matched in order to be effica cious. These reports include experimental observations on the ability of human umbilical cord blood to rescue lethally irradiated mice and c linical observations from China wherein HLA mismatched umbilical cord blood has been engrafted successfully in children with malignant disea se. The study reported herein describes an experimental immunocompeten t murine model to determine if human umbilical cord blood can be used to improve survival after chemoablation and irradiation. The animals r eceived chemoablation followed by irradiation, and irradiation alone. The presence of human DNA in these mice following injection of human u mbilical cord blood cells was determined, and the immunological status of the animals was evaluated. Animals receiving human umbilical cord blood cells after chemoablation and irradiation had a better mean surv ival at day 50 than animals receiving syngeneic marrow. Human DNR coul d be found in various organs, particularly the lung, spleen and liver of the mice for the first 30 days. Thereafter, human DNA became more d ifficult to detect but trace amounts of human DNA could be found up to one year later. The results of mixed lymphocyte reactions and phenoty pe analyses for murine T cell markers performed after injection of HUC B cells both indicated endogenous repopulation, and relatively intact immune systems in these mice. Since human umbilical cord blood allowed mice to survive the lethal effects of chemoablation plus irradiation, or irradiation alone, with reconstitution of the animals' own, relati vely intact, immune systems, it would appear that HLA mismatched human umbilical cord blood could potentially be used as an adjuvant treatme nt for patients with advanced malignancies or other diseases for which hematopoietic reconstitution is indicated.