PHASE-I TRIAL OF SEQUENTIAL CYCLOPHOSPHAMIDE, CYCLOSPORINE-A, AND INTERFERON-ALPHA IN PATIENTS WITH CANCER - ATTEMPT TO INDUCE AUTOLOGOUS GRAFT-VERSUS-HOST REACTION TO ELICIT AN ANTITUMOR RESPONSE
Bg. Redman et al., PHASE-I TRIAL OF SEQUENTIAL CYCLOPHOSPHAMIDE, CYCLOSPORINE-A, AND INTERFERON-ALPHA IN PATIENTS WITH CANCER - ATTEMPT TO INDUCE AUTOLOGOUS GRAFT-VERSUS-HOST REACTION TO ELICIT AN ANTITUMOR RESPONSE, Journal of immunotherapy with emphasis on tumor immunology, 18(2), 1995, pp. 115-118
Citations number
16
Categorie Soggetti
Immunology,Oncology,"Medicine, Research & Experimental
Previous reports of autologous bone marrow transplant (auto-BMT) have
demonstrated that myeloablative therapy followed by cyclosporin A (CsA
), with and without interferon (IFN), can generate autoreactive cytoto
xic T lymphocytes (auto-CTL) with potential therapeutic benefit. This
is the first report of an attempt to generate auto-CTL using CsA and I
FN after a non-myeloablative regimen. Cyclophosphamide (CTX) 1,200 mg/
m(2) i.v. day 1 was followed by CsA and IFN-alpha days 2-28, administe
red in a sequential three-step Phase I dose-escalation scheme. Patient
s were evaluated twice weekly for clinical evidence of graft-versus-ho
st (GVH) reaction. Peripheral blood mononuclear cells (PBMCs) were obt
ained before treatment, at time of clinical GVH reaction, and days 21
and 28, and analyzed for auto-CTL, natural killer (NK) cell, and lymph
okine-activated killer (LAK) cell activity. Patients also underwent pu
nch skin biopsy at the time of clinical GVH reaction or day 21 to iden
tify histologic evidence of GVH. Fourteen patients completed therapy a
nd were evaluable for immunologic studies and anti-tumor response. No
increase in auto-CTL, NK cell, or LAK cell activity was seen. Clinical
or histologic evidence of GVH reaction did not occur. We conclude tha
t this myelosuppressive dose of CTX combined with CsA and IFN is unabl
e to generate clinical or immunologic evidence of an auto-GVH reaction
. Further efforts are warranted to evaluate other therapeutic attempts
to generate auto-CTL with anti-tumor activity based on preliminary re
sults of clinical benefit in auto-BMT.