High rabbit-antihuman thymocyte globulin levels are associated with low likelihood of graft-vs-host disease and high likelihood of posttransplant lymphoproliferative disorder.
Rabbit-antithymocyte globulin (ATG) given with conditioning has the potential to decrease the likelihood of graft-versus-host disease (GVHD) or graft failure and to increase the likelihood of relapse or infections. After a given ATG dose, serum ATG levels are variable. Here we determined ATG levels on days 7 and 28 in 153 patients whose conditioning included 4.5 mg/kg ATG (thymoglobulin). Median follow-up was 547 days (range: 14-1519, minimum for patients who have not died, relapsed, developed second malignancy, or had graft failure, 365). Both high day 7 levels and high day 28 levels were associated with low likelihoods of grade II-IV acute GVHD and chronic GVHD needing systemic immunosuppressive therapy, and a high likelihood of posttransplant lymphoproliferative disorder (PTLD). Patients with day 7 ATG levels above 0.803 mg/L had 0.52-fold risk of developing chronic GVHD needing systemic therapy (P = 0.012) and patients with day 7 ATG levels above 1.436 mg/L had 5.84-fold risk of developing PTLD (P = 0.001) compared to patients with lower ATG levels. There was no association of ATG levels with relapse, death, or non-PTLD infections. Association with graft failure could not be evaluated due to only 4 graft failures in the cohort. In conclusion, patients with slow clearance of ATG have a low risk of GVHD, but a high risk of PTLD. The clearance of this relatively low dose of ATG does not impact the likelihood of relapse, death, or non-PTLD infections.
The University of Calgary and Alberta Health Services, Calgary, Alberta, Canada. pjpodgor@ucalgary.ca
Peter J
PJ
Podgorny
Alejandra
A
Ugarte-Torres
Yiping
Y
Liu
Tyler S
TS
Williamson
James A
JA
Russell
Jan
J
Storek
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000961:Antilymphocyte Serum / Q000008:administration & dosage / Q000097:blood* / Q000276:immunology; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000097:blood* / Q000276:immunology; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008232:Lymphoproliferative Disorders / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011817:Rabbits; D033581:Stem Cell Transplantation / Q000009:adverse effects*; D016019:Survival Analysis; D020858:Tissue and Organ Harvesting / Q000379:methods*; D016896:Treatment Outcome; D055815:Young Adult
D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents