REDUCTION IN THE DURATION OF MYELOTOXICITY ASSOCIATED WITH RADIOIMMUNOTHERAPY WITH INFUSIONS OF THE HEMOREGULATORY PEPTIDE, HP5B IN MICE

The hemoregulatory peptide, pGlu-Glu-Asp-Cys-Lys (pEEDCK or HP5b), has been shown to reversibly inhibit the proliferation of bone-marrow pro genitor cells, and has been reported to protect mice from the myelotox icity associated with ara-C, a chemotherapeutic agent. We undertook to use this reagent to reduce radioimmunotherapy(RAIT)-associated bone-m arrow toxicity by suppressing hematopoiesis during the critical period when bone marrow is exposed to radiation. The reported studies optimi ze the use of HP5b to reduce the duration of neutropenia and thrombocy topenia. We found that 3.6 mu g/day of HP5b administered through a con tinuous 7d mini-osmotic pump, together with a bolus dose of 3.6 mu g 3 hours before the radioantibody dose, gave the best effect, as measure d by neutrophil counts on day 28 post RAIT. With sub-lethal doses of R AIT, the period of neutropenia was reduced by 2 weeks, and there appea red to be more rapid recovery of morphologically mature myeloid cells. The peptide, however, does not appear to alleviate the lymphotoxicity associated with RAIT. No adverse effects have been noted from continu ous infusions of the peptide. In the past, we reported that cytokines (IL-I/GM-CSF) are not marrow-restorative when given after RAIT. Howeve r, an additive effect is observed when HP5b infusions are combined wit h post-RAIT cytokine administration, suggesting that a significant poo l of bone-marrow progeniter cells remains when HP5b is co-administered with RAIT. Thus, HP5b is an alternate approach to reducing myelotoxic ity, and may be used in combination with cytokines to further reduce t he duration of myelosuppression. (C) 1997 Wiley-Liss, Inc.