Transfusion-associated GVHD after fludarabine therapy in a patient with systemic lupus erythematosus.
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.
Leitman
Susan F
SF
Department of Transfusion Medicine, National Institute of Muscuoloskeletal and Skin Disease, National Institute of Health, Bethesda, MD 20892, USA. sleitman@mail.cc.nih.gov
Tisdale
John F
JF
Bolan
Charles D
CD
Popovsky
Mark A
MA
Klippel
John H
JH
Balow
James E
JE
Boumpas
Dimitrios T
DT
Illei
Gabor G
GG
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*
D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine