Current and novel therapies in acute GVHD.
Despite improvements in our understanding of transplant immunology and clinical and supportive care, acute graft-versus-host disease (GVHD) remains a clinical challenge and a major cause of morbidity and mortality for patients after allogeneic hematopoietic stem-cell transplantation. While systemic corticosteroid is standard primary therapy for acute GVHD, there is no established standard treatment in the steroid-refractory setting. New generations of monoclonal antibodies, biologics, and chemotherapeutics with immunomodulatory effects have been developed over the past decade, and are being tested as novel therapies in this disease. Many of these agents - including, among others, mycophenolate mofetil, anti-tumor necrosis factor-alpha antibodies, denileukin diftitox, and anti-interleukin-2Ralpha-chain antibodies - have demonstrated promising activity in steroid-refractory acute GVHD. Despite the high response rates, however, long-term survival remains poor due to a high incidence of infections. The key to improving acute GVHD outcomes may, in fact, rest upon successful initial therapy, and timely taper of corticosteroids to promote healthier immune reconstitution. Clinical trials combining these newer agents with systemic corticosteroids as initial treatment are under way, and will determine whether fortifying initial therapy will indeed reduce the development of steroid-refractory GVHD and improve long-term outcomes. In this article, we review current and novel agents available for acute GVHD, and discuss newer investigational approaches - such as phototherapy and cellular therapies - in the management of this common transplant complication.
Ho
Vincent T
VT
Department of Adult Oncology, Center for Hematologic Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, 44 Binney Street, D1B06, Boston, MA 02115, USA. vincent_ho@dfci.harvard.edu
Cutler
Corey
C
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D004359:Drug Therapy, Combination; D006086:Graft vs Host Disease / Q000188:drug therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D016219:Immunotherapy, Adoptive; D010789:Phototherapy
D000305:Adrenal Cortex Hormones; D000911:Antibodies, Monoclonal; D007155:Immunologic Factors