A comparison of nonmyeloablative and reduced-intensity conditioning for allogeneic stem-cell transplantation.
BACKGROUND
Nonmyeloablative (NM) conditioning and reduced-intensity conditioning (RIC) are increasingly used for allogeneic hematopoietic stem-cell transplantation. Such regimens have not been compared.


METHODS
The primary endpoint was graft-versus-host disease (GVHD). Secondary endpoints included transfusions, engraftment, and transplant-related mortality (TRM). NM conditioning (n=24) consisted of fludarabine and 2-Gy total-body irradiation followed by immunosuppression with cyclosporine A (CsA) combined with mycophenolate mofetil (MMF). The RIC (n=34) protocol consisted of fludarabine combined with busulfan or cyclophosphamide, antithymocyte globulin, and posttransplant immunosuppression CsA plus methotrexate. Diagnoses included hematologic malignancies and solid tumors. Donors were 34 human leukocyte antigen-identical siblings and 24 unrelated donors. Chimerism was analyzed by polymerase chain reaction of minisatellites.


RESULTS
Graft failure occurred in 6 of 24 in the NM group and in 1 of 34 in the RIC group, which was a significant difference (odds ratio [OR], 22.6; P=0.02). The NM group also had less leukopenia and required fewer erythrocyte and platelet transfusions than the RIC group. The time to and proportion of CD3, CD19, and CD45 donor chimerism were similar in both groups. The cumulative incidence of grades II to IV acute GVHD was higher in the NM group (59% vs. 12%; OR, 26.9; P<0.001), but we found no difference in the cumulative incidence of chronic GVHD (41% vs. 61%). TRM was 42% in the NM group and 20% in the RIC patients (relative hazard, 11.6; P=0.03).


CONCLUSIONS
NM conditioning with posttransplant immunosuppression using CsA and MMF resulted in less leukopenia and fewer transfusions, but resulted in more cases of graft failure, acute GVHD, and TRM than in RIC patients.
Centre for Allogeneic Stem Cell Transplantation and Division of Clinical Immunology, Huddinge University Hospital, Karolinska Institutet, Stockholm, Sweden.
Katarina
K
Le Blanc
Mats
M
Remberger
Mehmet
M
Uzunel
Jonas
J
Mattsson
Lisbeth
L
Barkholt
Olle
O
Ringdén
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D005260:Female; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation / Q000401:mortality; D006801:Humans; D007165:Immunosuppression Therapy; D015994:Incidence; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D018183:Transplantation Chimera; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous