Standard antithymocyte globulin dosing results in poorer outcomes in overexposed patients after ex vivo CD34(+) selected allogeneic hematopoietic cell transplantation Journal Article


Authors: Scordo, M.; Bhatt, V.; Hilden, P.; Smith, M.; Thoren, K.; Cho, C.; Shah, G. L.; Maloy, M. A.; Papadopoulos, E. B.; Jakubowski, A. A.; Avecilla, S. T.; O'Reilly, R. J.; Castro-Malaspina, H.; Tamari, R.; Shaffer, B. C.; Boelens, J. J.; Perales, M. A.; Giralt, S. A.
Article Title: Standard antithymocyte globulin dosing results in poorer outcomes in overexposed patients after ex vivo CD34(+) selected allogeneic hematopoietic cell transplantation
Abstract: Antithymocyte globulin (ATG) use mitigates the risk of graft rejection and graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (allo-HCT), but ATG overexposure in the setting of lymphopenia negatively affects immune recovery. We hypothesized that standard empiric weight-based dosing of ATG, used to prevent graft rejection in ex vivo CD34-selected allo-HCT, may lead to serious adverse consequences on outcomes in certain patients. We evaluated 304 patients undergoing myeloablative-conditioned ex vivo CD34-selected allo-HCT with HLA-matched donors for the treatment of hematologic malignancies. Patients received rabbit ATG at a dose of 2.5 mg/kg/day i.v. on days -3 and/or -2. An ATG dosing cutoff of 450 mg was used for statistical analyses to assess the relationship between ATG and overall survival (OS). Among all patients, median total ATG dose was 360 mg (range, 130 to 510 mg); 279 (92%) received a total dose of ATG ≤450 mg, and 25 (8%) received a total dose >450 mg. On the first day of ATG administration (day -3), the median absolute lymphocyte count was.0 K/μL. For patients who received a total dose of ATG >450 mg or ≤450 mg, the incidences of acute and late-acute GVHD grade II-IV were statistically similar. At 3 years post-HCT, for patients who received a total dose of ATG >450 mg or ≤450 mg, nonrelapse mortality (NRM) rates were 35% and 18%, respectively (P =.029), disease-free survival (DFS) rates were 37% and 61%, respectively (P =.003), and OS rates were 40% and 67%, respectively (P =.001). Among all patient and HCT characteristics in multivariable analyses, receipt of a total dose of ATG >450 mg was associated with an increased risk of NRM (hazard ratio [HR], 2.9; P =.01), shorter DFS (HR, 2.0; P =.03), and inferior OS (HR, 2.1; P =.01). In summary, the use of weight-based ATG at a time of relative lymphopenia before ex vivo CD34-selected allo-HCT results in overdosing in heavier patients, leading to higher NRM and lower DFS and OS. Further pharmacokinetic investigation in this setting is critical to determining the optimal dosing strategy for ATG. © 2019 American Society for Blood and Marrow Transplantation
Keywords: allogeneic hematopoietic cell transplantation; antithymocyte globulin; ex vivo cd34 selection
Journal Title: Biology of Blood and Marrow Transplantation
Volume: 25
Issue: 8
ISSN: 1083-8791
Publisher: Elsevier Inc.  
Date Published: 2019-08-01
Start Page: 1526
End Page: 1535
Language: English
DOI: 10.1016/j.bbmt.2019.02.021
PUBMED: 30831208
PROVIDER: scopus
PMCID: PMC7302932
DOI/URL:
Notes: Article -- Export Date: 30 August 2019 -- Source: Scopus
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
  1. Sergio Andres Giralt
    1066 Giralt
  2. Miguel-Angel Perales
    938 Perales
  3. Richard O'Reilly
    748 O'Reilly
  4. Molly Anna Maloy
    269 Maloy
  5. Valkal Bhatt
    61 Bhatt
  6. Christina Cho
    134 Cho
  7. Roni Tamari
    213 Tamari
  8. Michael Scordo
    382 Scordo
  9. Melody Smith
    33 Smith
  10. Patrick Dale Hilden
    108 Hilden
  11. Gunjan Lalitchandra Shah
    440 Shah
  12. Katie Lynn Thoren
    37 Thoren
  13. Brian Carl Shaffer
    173 Shaffer
  14. Jaap Jan Boelens
    213 Boelens