0041-1337/98/6605-620$03.00/0 TRANSPLANTATION Vol. 66, 620 – 625, No. 5, September 15, 1998 Copyright © 1998 by Williams & Wilkins Printed in U.S.A. LOW INCIDENCE OF ACUTE GRAFT-VERSUS-HOST DISEASE, USING UNRELATED HLA-A-, HLA-B-, AND HLA-DR-COMPATIBLE DONORS AND CONDITIONING, INCLUDING ANTI-T-CELL ANTIBODIES 1 O. RINGD ´ EN, 2,3,4,5 M. REMBERGER, 3 S. CARLENS, 2,4 H. HA ¨ GGLUND, 2,4 J. MATTSSON, 2,4 J. ASCHAN, 2,6 B. L ¨ ONNQVIST, 2,6 S. KLAESSON, 7 J. WINIARSKI, 7 T. DALIANIS, 3 O. OLERUP, 3 E. SPARRELID, 8 A. ELMHORN-ROSENBORG, 9 B-M. SVAHN, 2 AND P. LJUNGMAN 2,6 Bone Marrow Transplant Unit, Departments of Clinical Immunology, Transplantation Surgery, Haematology, Paediatrics, Infectious Diseases, and Pathology, Karolinska Institute, Huddinge Hospital, Huddinge, S-141 86 Huddinge, Sweden Background. Using unrelated bone marrow, there is an increased risk of graft-versus-host disease (GVHD). Methods. HLA-A-, HLA-B-, and HLA-DR-compatible unrelated bone marrow was given to 132 patients. The diagnoses included chronic myeloid leukemia (n43), acute lymphoblastic leukemia (n29), acute myeloid leukemia (n27), myelodysplastic syndrome (n4), lymphoma (n3), myeloma (n1), myelofibrosis (n1), severe aplastic anemia (n12), and metabolic disor- ders (n12). The median age was 25 years (range 1–55 years). HLA class I was typed serologically, and class II was typed by polymerase chain reaction using se- quence-specific primer pairs. Immunosuppression consisted of antithymocyte globulin or OKT3 for 5 days before transplantation and methotrexate com- bined with cyclosporine. Results. Engraftment was seen in 127 of 132 patients (96%). Bacteremia occurred in 47%, cytomegalovirus (CMV) infection in 49%, and CMV disease in 8%. The cumulative incidences of acute GVHD > grade II and of chronic GVHD were 23% and 50%, respectively. The 5-year transplant-related mortality rate was 39%. The overall 5-year patient survival rate was 49%; in patients with metabolic disorders and severe aplastic anemia, it was 61% and 48%, respectively. The disease-free survival rate was 47% in patients with hematological malignan- cies in first remission or first chronic phase and 38% in patients with more advanced disease (P0.04). Acute GVHD was associated with early engraftment of white blood count (P0.02). Poor outcome in multivariate analysis was associated with acute myeloid leukemia (P0.01) and CMV disease (P0.04). Conclusion. Using HLA-A-, HLA-B-, and HLA-DR- compatible unrelated bone marrow and immunosup- pression with antithymocyte globulin, methotrexate, and cyclosporine, the probability of GVHD was low and survival was favorable. The first successful bone marrow transplantation (BMT*) using an unrelated donor was performed in 1980 (1). Since then, unrelated donors have been used increasingly, because only one third of patients have an HLA-identical sibling (2–9). Large registries with volunteer donors are now estab- lished all over the world. The largest is the American Na- tional Marrow Donor Program (NMDP), with around 3 mil- lion volunteer donors. The Tobias Register at Huddinge Hospital has 40,000 donors. Today, at our center, we have more unrelated than related donors. However, there are sev- eral obstacles to unrelated BMT versus transplantation with HLA-identical sibling donors (5). These obstacles arise be- cause the unrelated donors are not as well HLA matched, which may pave the way for rejection, graft-versus-host dis- ease (GVHD), prolonged immune reconstitution, and infec- tions. In particular, the incidence of severe GVHD has been markedly higher than that seen among HLA-identical sib- lings (2, 3). By matching recipients and donors by genomic typing for HLA class II antigens, the incidence of acute GVHD and the outcome have improved, compared with transplantation using serological typing alone (6–8). Fur- thermore, the use of T-cell depletion in vitro or in vivo also reduces the risk of acute GVHD (7, 9). We here report our experience with 132 recipients of HLA-A-, HLA-B-, and HLA- DR-compatible unrelated bone marrow who were given anti- T-cell antibodies. 1 This study was supported by grants from the Swedish Cancer Foundation (0070-B96 –10XAC), the Children’s Cancer Foundation (199 4 – 060), the Swedish Medical Research Council (K97– 06X- 05971–17A), the FRF Foundation, the Cancer-och Trafikskadades Riksfo ¨rbund, the Tobias Foundation, and the Ellen Bachrach Foun- dation. 2 Bone Marrow Transplant Unit. 3 Department of Clinical Immunology. 4 Department of Transplantation Surgery. 5 Address correspondence to: O. Ringde ´n, MD, PhD, Karolinska Institute, Department of Clinical Immunology, Huddinge Hospital, F79, SE-141 86 Huddinge, Sweden. E-mail: olle.ringden@immunlab.hs. sll.se. 6 Department of Haematology. 7 Department of Pediatrics. 8 Department of Infectious Diseases. 9 Department of Pathology. * Abbreviations: ALL, acute lymphoblastic leukemia; AML, acute myeloid leukemia; ATG, antithymocyte globulin; BMT, bone marrow transplantation; CML, chronic myeloid leukemia; CMV, cytomegalo- virus; CR, complete remission; CsA, cyclosporine; Cy, cyclophospha- mide; GVHD, graft-versus-host disease; MTX, methotrexate; MUD, matched unrelated donors; NMDP, National Marrow Donor Pro- gram; PBPC, peripheral blood progenitor cells; PCR, polymerase chain reaction; PUVA, psoralen and ultraviolet light; SAA, severe aplastic anemia; TRM, transplant-related mortality; WBC, white blood count. 620