Do the immunosuppressive drugs used as treatment for graft-versus-host disease directly inhibit lymphoid tumor cell growth?
Hematopoietic stem cell transplantation (HSCT) is a curative treatment for certain leukemias and lymphomas that prove resistant to standard chemotherapy. The immunosuppressive drugs prednisone and cyclosporin A (CsA) are routinely used during HSCT to prevent or treat graft-versus-host disease (GVHD) or to inhibit antibody-mediated inflammation. However, little is known about the direct impact of prednisone and CsA on the growth of malignant lymphoid cells in the setting of HSCT. To address this issue, we measured tumor cell growth in vitro and in vivo after treatment with prednisone and CsA, used separately, together, and in combination with irradiation. Our results showed that: (i) combinations of CsA and prednisone inhibited the growth of a variety of lymphoid tumors in vitro, particularly in combination with irradiation, and (ii) tumor size was significantly reduced in a mouse B-lymphoid tumor model following CsA or CsA plus prednisone treatments, with or without HSCT.
D'Costa
Sybil
S
Department of Immunology, St. Jude Children's Research Hospital, 332 N. Lauderdale, Memphis, TN 38105, USA.
Slobod
Karen S
KS
Hurwitz
Julia L
JL
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D016572:Cyclosporine / Q000494:pharmacology / Q000627:therapeutic use; D006086:Graft vs Host Disease / Q000188:drug therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D008223:Lymphoma / Q000150:complications / Q000473:pathology* / Q000628:therapy*; D051379:Mice; D016513:Mice, SCID; D011241:Prednisone / Q000494:pharmacology / Q000627:therapeutic use; D014407:Tumor Cells, Cultured
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D011241:Prednisone