title: Transfusion-associated GVHD after fludarabine therapy in a patient with systemic lupus erythematosus.
abstract: BACKGROUND
  Fludarabine, a purine antimetabolite with potent immunosuppressive properties, has previously been associated with the development of transfusion-associated GVHD (TA-GVHD) in patients with hematologic malignancies. Its role as a risk factor for TA-GVHD in patients without underlying leukemia or lymphoma is uncertain.
  
  
  METHODS
  A 42-year-old female with refractory lupus nephritis received three monthly cycles of fludarabine (30 mg/m2/day on Days 1-3) and cyclophosphamide (500 mg/m2 on Day 1). Three months after the last dose of fludarabine, she received 2 units of packed RBCs and 6 units of pooled random platelets, none of which were irradiated. Two weeks later, fever, rash, aminotransferase elevations, hyperbilirubinemia, and pancytopenia developed.
  
  
  RESULTS
  Marrow biopsy showed severe aplasia and skin biopsy was consistent with GVHD. Allele-level HLA typing on circulating lymphocytes revealed extra HLA alleles not present in her pretreatment sample, but identical to the HLA haplotypes of an unrelated platelet donor. Treatment with antithymocyte globulin, cyclosporine, and prednisone was followed by preparatory conditioning for a PBPC transplant from an HLA-identical sibling, but the patient died of disseminated candidiasis before transplant.
  
  
  CONCLUSIONS
  Fludarabine and other purine analogs are increasingly used in the treatment of disorders other than hematologic malignancy, such as autoimmune disease. The occurence of TA-GVHD after fludarabine therapy in a patient with lupus strongly suggests that this drug is sufficiently immunoablative to be an independent risk factor for TA-GVHD. Irradiation of blood components should be considered in all patients who receive fludarabine therapy.
authors.affiliation: Department of Transfusion Medicine, National Institute of Muscuoloskeletal and Skin Disease, National Institute of Health, Bethesda, MD 20892, USA. sleitman@mail.cc.nih.gov
authors.forename: Susan F
authors.initials: SF
authors.lastname: Leitman
authors.forename: John F
authors.initials: JF
authors.lastname: Tisdale
authors.forename: Charles D
authors.initials: CD
authors.lastname: Bolan
authors.forename: Mark A
authors.initials: MA
authors.lastname: Popovsky
authors.forename: John H
authors.initials: JH
authors.lastname: Klippel
authors.forename: James E
authors.initials: JE
authors.lastname: Balow
authors.forename: Dimitrios T
authors.initials: DT
authors.lastname: Boumpas
authors.forename: Gabor G
authors.initials: GG
authors.lastname: Illei
mesh_terms: D000328:Adult; D003520:Cyclophosphamide / Q000009:adverse effects; D004359:Drug Therapy, Combination; D017707:Erythrocyte Transfusion / Q000009:adverse effects*; D017809:Fatal Outcome; D005260:Female; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000209:etiology*; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy*; D017713:Platelet Transfusion / Q000009:adverse effects*; D012307:Risk Factors; D014740:Vidarabine / Q000009:adverse effects* / Q000031:analogs & derivatives*
chemical_list: D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine