Antithymocyteglobulin as prophylaxis of graft failure and graft-versus-host disease in recipients of partially T-cell-depleted grafts from matched unrelated donors: a dose-finding study.
OBJECTIVE
In this study, we set out to evaluate the effect of three different antithymocyteglobulin (ATG) doses on graft failure and incidence of graft-vs-host disease (GVHD) among recipients of partially T-cell-depleted (TCD) grafts from matched unrelated donors (MUDs).


METHODS
Data of 74 consecutively treated MUD recipients were analyzed. Fifty-two, 13, and 9 MUD patients were treated with ATG in a total dose of 8 mg/kg, 6 mg/kg, and 4 mg/kg (given from days -8 until -4), respectively.


RESULTS
Granulocyte and platelet engraftment were not different between the groups, while graft failure was observed in two patients only (receiving 8 mg/kg and 4 mg/kg ATG, respectively). The cumulative incidence of severe (grade III-IV) acute GVHD and extensive chronic GVHD was 4%, 0%, 44% and 11%, 8%, 44% in groups receiving ATG in a dose of 8 mg/kg, 6 mg/kg, and 4 mg/kg, respectively (severe acute GVHD: p<0.001; extensive chronic GVHD: p=0.05).


CONCLUSIONS
Based on these findings, we recommend when ATG is used in the setting of stem cell transplantation with (partially) TCD grafts from MUDs, to give a total dose of 6 to 8 mg/kg. A further decrease in dosage resulted in a highly significant increased incidence of severe acute and extensive chronic GVHD.
Department of Hematology, University Medical Center Utrecht, Utrecht, The Netherlands. emeijer@digd.azu.nl
Ellen
E
Meijer
Jan J
JJ
Cornelissen
Bob
B
Löwenberg
Leo F
LF
Verdonck
D000293:Adolescent; D000328:Adult; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006086:Graft vs Host Disease / Q000453:epidemiology*; D018380:Hematopoietic Stem Cell Transplantation / Q000401:mortality*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D015994:Incidence; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology*; D014019:Tissue Donors
D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents