Enhancement of cyclosporin A-induced autologous graft-versus-host disease after peripheral blood stem cell transplantation by utilizing selected CD34(+) cells.
Although autologous graft-versus-host disease (GVHD) can be induced by administration of cyclosporin A (CsA) after peripheral blood stem cell transplantation (PBSCT), the incidence appears to be remarkably lower compared to the incidence after bone marrow transplantation. The reduced incidence of autologous GVHD after PBSCT may be attributed to peripheral regulatory cells that are transferred with the stem cell inoculum. To determine whether transplantation of CD34-selected peripheral blood stem cells (PBSCs) leads to potentiation of autologous GVHD, five patients with malignant lymphoma were transplanted with CD34-selected PBSCs, followed by administration of CsA and interferon (IFN)-gamma. Inducibility of autologous GVHD and autocytotoxic activities of peripheral blood mononuclear cells (PBMCs) after transplantation were assessed. All patients demonstrated prompt hematologic recovery. Cytotoxic activity of PBMCs against autologous lymphocytes was detectable in four of four patients analyzed during a limited period from days 14 to 34 post-transplant. An erythematous rash compatible with GVHD, confirmed by skin biopsy, developed in three of five patients. One of the three patients developed not only skin, but also gut and liver GVHD. Transplantation of the CD34-selected stem cell graft that does not accompany transfusion of regulatory cells may potentiate the inducibility of autologous GVHD by the administration of CsA and IFN-gamma.
Miura
Y
Y
The Sidney Kimmel Cancer Research Center at Johns Hopkins University, Baltimore, MD 21231, USA. ymiura@jhmi.edu
Ueda
M
M
Takami
A
A
Shiobara
S
S
Nakao
S
S
Hess
A D
AD
D018952:Antigens, CD34 / Q000032:analysis; D000970:Antineoplastic Agents / Q000009:adverse effects; D002469:Cell Separation; D016572:Cyclosporine / Q000009:adverse effects*; D005260:Female; D006086:Graft vs Host Disease / Q000139:chemically induced* / Q000401:mortality; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects* / Q000401:mortality; D006412:Hematopoietic Stem Cells / Q000737:chemistry / Q000166:cytology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D007371:Interferon-gamma / Q000009:adverse effects; D008297:Male; D008875:Middle Aged
D018952:Antigens, CD34; D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D007371:Interferon-gamma; D016572:Cyclosporine