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.
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 disorders (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 sequence-specific primer pairs. Immunosuppression consisted of antithymocyte globulin or OKT3 for 5 days before transplantation and methotrexate combined 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 > or = 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 malignancies 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).


CONCLUSIONS
Using HLA-A-, HLA-B-, and HLA-DR-compatible unrelated bone marrow and immunosuppression with antithymocyte globulin, methotrexate, and cyclosporine, the probability of GVHD was low and survival was favorable.
Ringdén
O
O
Department of Clinical Immunology, Karolinska Institute, Huddinge Hospital, Sweden. olle.ringden@immunlab.hs.sll.se
Remberger
M
M
Carlens
S
S
Hagglund
H
H
Mattsson
J
J
Aschan
J
J
Lönnqvist
B
B
Klaesson
S
S
Winiarski
J
J
Dalianis
T
T
Olerup
O
O
Sparrelid
E
E
Elmhorn-Rosenborg
A
A
Svahn
B M
BM
Ljungman
P
P
D000293:Adolescent; D000328:Adult; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D016470:Bacteremia / Q000150:complications; D016026:Bone Marrow Transplantation / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D003586:Cytomegalovirus Infections / Q000150:complications; D018572:Disease-Free Survival; D005260:Female; D006085:Graft Survival / Q000276:immunology; D006086:Graft vs Host Disease / Q000209:etiology*; D015234:HLA-A Antigens / Q000032:analysis*; D015235:HLA-B Antigens / Q000032:analysis*; D006684:HLA-DR Antigens / Q000032:analysis*; D006650:Histocompatibility Testing; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods; D007223:Infant; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology*; D019172:Transplantation Conditioning; D016896:Treatment Outcome
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D006684:HLA-DR Antigens