A phase I study of interleukin-6 after autologous bone marrow transplantation for patients with poor prognosis Hodgkin's 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 tolerability. IL-6 was administered the day following bone marrow infusion by subcutaneous injection once daily at a dose of 1 micro/kg/day to 3 patients and 2.5 microg/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 level. A reversible elevation in alkaline phosphatase occurred in 4 patients and all patients complained of headache, myalgias, and fever. Gastrointestinal toxicity was low, grade 3-4 mucositis occured less frequently than in similarly-treated historical controls receiving GM-CSF. Serum concentrations of other cytokines such as IL-3 and G-CSF after ABMT differed from results obtained in transplant recipients given GM-CSF. The median time to an ANC >0.5 x 10(9)/L was 25.5 days and to a platelet 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 12 months post-ABMT. We conclude that IL-6 administration is safe and well tolerated in patients following ABMT. Further efforts to evaluate its effect on hematopietic recovery as well as relapse following transplantation in a larger patient series are warranted.
Imrie
K R
KR
The University of Toronto Autologous Blood and Marrow Transplant Program, Canada. 72103.3667@COMPUSERVE.COM
Sheridan
B
B
Colwill
R
R
Crump
M
M
Stewart
A K
AK
McCrae
J
J
Danish
R
R
Sutton
D
D
Romeyer
F
F
Keating
A
A
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001761:Bleomycin / Q000008:administration & dosage; D016026:Bone Marrow Transplantation; D003131:Combined Modality Therapy; D016207:Cytokines / Q000097:blood; D003606:Dacarbazine / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006689:Hodgkin Disease / Q000097:blood / Q000188:drug therapy* / Q000628:therapy*; D006801:Humans; D015850:Interleukin-6 / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008466:Mechlorethamine / Q000008:administration & dosage; D010865:Pilot Projects; D011241:Prednisone / Q000008:administration & dosage; D011344:Procarbazine / Q000008:administration & dosage; D011379:Prognosis; D011994:Recombinant Proteins / Q000627:therapeutic use; D014182:Transplantation, Autologous; D014747:Vinblastine / Q000008:administration & dosage; D014750:Vincristine / Q000008:administration & dosage
D016207:Cytokines; D015850:Interleukin-6; D011994:Recombinant Proteins; D001761:Bleomycin; D011344:Procarbazine; D008466:Mechlorethamine; D014750:Vincristine; D014747:Vinblastine; D003606:Dacarbazine; D004317:Doxorubicin; D011241:Prednisone