Pulse cyclophosphamide for corticosteroid-refractory graft-versus-host disease.
Corticosteroid-resistant GVHD is difficult to manage and is associated with high morbidity and mortality. Cyclophosphamide (Cy) is an established immunosuppressive and cytotoxic drug widely used as part of pretransplant conditioning regimens. In a retrospective study of 15 patients who had not responded to corticosteroids (nine with acute GVHD, three with GVHD after donor leukocyte infusion, and three progressive chronic GVHD), pulse Cy at a median dose of 1 g/m(2) was very effective in the treatment of skin (100% response), liver (70% response), and the oral cavity (100% response). Severe intestinal GVHD responded poorly. The toxicity profile was acceptable, with manageable, short-term myelosuppression in some patients. The risk of opportunistic infections, mixed chimerism, relapses, or post-transplant lymphoproliferative disease was not increased. Overall survival was 57%, with median and maximum follow-up of 9 and 37 months, respectively. The cost of the drug was negligible, especially when compared to monoclonal antibodies. Pulse Cy requires further investigation in corticosteroid-resistant GVHD.
Mayer
J
J
Department of Internal Medicine--Hemato-oncology, University Hospital Brno, Brno, Czech Republic. jmayer@fnbrno.cz
Krejcí
M
M
Doubek
M
M
Pospísil
Z
Z
Brychtová
Y
Y
Tomíska
M
M
Rácil
Z
Z
D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015551:Autoimmunity; D003520:Cyclophosphamide / Q000008:administration & dosage*; D004341:Drug Evaluation; D004351:Drug Resistance; D006086:Graft vs Host Disease / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D008107:Liver Diseases / Q000188:drug therapy; D008875:Middle Aged; D009059:Mouth Diseases / Q000188:drug therapy; D012189:Retrospective Studies; D012871:Skin Diseases / Q000188:drug therapy; D016019:Survival Analysis
D000305:Adrenal Cortex Hormones; D003520:Cyclophosphamide