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Matched and Mismatched Allogeneic Stem-Cell Transplantation From Unrelated Donors Using Combined Graft-Versus-Host Disease Prophylaxis Including Rabbit Anti–T Lymphocyte Globulin

From the Departments of Hematology & Oncology, Institute for Medical Statistics, Transfusion Medicine, Albert-Ludwigs University Medical Center, Freiburg, Germany.

Address reprint requests to Jürgen Finke, MD, Department of Hematology & Oncology, Albert-Ludwigs University Freiburg Medical Center, Hugstetter Str 55, D-79106 Freiburg, Germany; email: Finke{at}mm11.ukl.uni-freiburg.de.

Purpose: With improved HLA-typing techniques, it is presently unclear what degree of identity is necessary for successful unrelated-donor stem-cell transplantation (UD SCT). Here, we describe the outcome after matched and mismatched UD SCT using a graft-versus-host disease (GVHD) prophylaxis including high-dose rabbit anti–T lymphocyte globulin (ATG).

Patients and Methods: One hundred adult patients (median age, 37 years; range, 17 to 65 years) with hematologic malignancies underwent transplantation in early disease (first complete remission [CR1] or first chronic phase [CP1]; n = 34) or in advanced disease (second complete remission or second chronic phase, no remission, refractory; n = 66) with nondepleted bone marrow (n = 87) or peripheral-blood–derived (n = 13) stem cells from an HLA-A, HLA-B, HLA-DRB1*, or HLA-DQB1* identical (n = 75) or mismatched (one antigen, n = 21; two to three antigens, n = 4) unrelated donor. GVHD prophylaxis consisted of rabbit ATG before transplantation in addition to cyclosporine and short-course methotrexate.

Results: The cumulative incidence of acute GVHD °II-°IV was 21% (95% confidence interval [CI], 14% to 33%) and 20% (95% CI, 9% to 44%) and acute GVHD °III–°IV was 5.3% (95% CI, 2% to 14%) and 4% (95% CI, 0.6% to 28%) in HLA-matched and HLA-mismatched transplantations, respectively. The risk for extensive chronic GVHD was 43% (95% CI, 32% to 59%) and 44% (95% CI, 26% to 75%) for HLA-matched and HLA-mismatched patients, respectively. The risk of relapse at 4 years was 17% (95% CI, 7% to 43%) and 43% (95% CI, 31% to 60%) for CR1/CP1 and advanced disease patients, respectively. With a median follow-up of 1,068 days (range, 12 to 1,958 days), 3-year disease-free and overall survival for patients who underwent transplantation in CR1/CP1 was 63% (95% CI, 46% to 81%) and 75% (95% CI, 59% to 90%), respectively; and for patients with advanced disease, it was 34% (95% CI, 22% to 46%) and 39% (95% CI, 25% to 53%), respectively.

Conclusion: A certain degree of one antigen mismatching may not compromise the outcome after UD SCT when using this rabbit ATG in addition to standard GVHD prophylaxis regimen.

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