A PHASE-I STUDY OF INTERLEUKIN-6 AFTER AUTOLOGOUS BONE-MARROW TRANSPLANTATION FOR PATIENTS WITH POOR-PROGNOSIS HODGKINS-DISEASE

We performed a pilot study of human recombinant IL-6 (SDZ ILs 969) in 6 patients with poor prognosis Hodgkin's disease following autologous bone marrow transplantation (ABMT) to determine its safety and tolerab ility. IL-6 was administered the day following bone marrow infusion by subcutaneous injection once daily at a dose of 1 mu/kg/day to 3 patie nts and 2.5 mu g/kg/day to 3 patients and was continued for 6 weeks or until platelet engraftment (>50 x 10(9)/L independent of transfusion) . No severe or life threatening toxicities were seen at either dose le vel. A reversible elevation in alkaline phosphatase occurred in 4 pati ents and all patients complained of headache, myalgias, and fever. Gas trointestinal toxicity was low, grade 3-4 mucositis occured less frequ ently than in similarly-treated historical controls receiving GM-CSF. Serum concentrations of other cytokines such as IL-3 and G-CSF after A BMT differed from results obtained in transplant recipients given GM-C SF. The median time to an ANC >0.5 x 10(9)/L was 25.5 days and to a pl atelet count of >20 x 10(9)/L independat of transfusion was 35.5 days. Engraftment was no different from controls. Five patients relapsed at a median of 5 months post-ABMT and four remain alive at a median of 1 2 months post-ABMT. We conclude that IL-6 administration is safe and w ell tolerated in patients following ABMT. Further efforts to evaluate its effect on hematopietic recovery as well as relapse following trans plantation in a larger patient series are warranted.