Impact of rabbit anti-thymocyte globulin (ATG) exposure on outcomes after ex vivo T-cell–depleted hematopoietic cell transplantation in pediatric and young adult patients Journal Article
| Authors: | Lakkaraja, M.; Mauguen, A.; Boulad, F.; Cancio, M. I.; Curran, K. J.; Harris, A. C.; Kernan, N. A.; Klein, E.; Kung, A. L.; Oved, J.; Prockop, S.; Scaradavou, A.; Spitzer, B.; O'Reilly, R. J.; Boelens, J. J. |
| Article Title: | Impact of rabbit anti-thymocyte globulin (ATG) exposure on outcomes after ex vivo T-cell–depleted hematopoietic cell transplantation in pediatric and young adult patients |
| Abstract: | Background aims: Traditional weight-based dosing of rabbit anti-thymocyte globulin (rATG) used in allogeneic hematopoietic cell transplantation (HCT) to prevent graft-versus-host disease (GVHD) and graft rejection leads to variable exposures. High exposures induce delayed CD4+immune reconstitution (CD4+IR) and greater mortality. We sought to determine the impact of rATG exposure in children and young adults receiving various types of EX-VIVO T-cell–depleted (EX-VIVO-TCD) HCT. Methods: Patients receiving their first EX-VIVO-TCD HCT (CliniMACS CD34+, Isolex or soybean lectin agglutination), with removal of residual T cells by E-rosette depletion (E-) between 2008 and 2018 at Memorial Sloan Kettering Cancer Center were retrospectively analyzed. rATG exposure post-HCT was estimated (AU*d/L) using a validated population pharmacokinetic model. Previously defined rATG-exposures, <30, 30–55, ≥55 AU*d/L, were related with outcomes of interest. Cox proportional hazard and cause-specific models were used for analyses. Results: In total, 180 patients (median age 11 years; range 0.1–44 years) were included, malignant 124 (69%) and nonmalignant 56 (31%). Median post-HCT rATG exposure was 32 (0–104) AU*d/L. Exposure <30 AU*d/L was associated with a 3-fold greater probability of CD4+IR (P < 0.001); 2- to 4-fold lower risk of death (P = 0.002); and 3- to 4-fold lower risk of non-relapse mortality (NRM) (P = 0.02). Cumulative incidence of NRM was 8-fold lower in patients who attained CD4+IR compared with those who did not (P < 0.0001). There was no relation between rATG exposure and aGVHD (P = 0.33) or relapse (P = 0.23). Effect of rATG exposure on outcomes was similar in three EX-VIVO-TCD methods. Conclusions: Individualizing rATG dosing to target a low rATG exposure post-HCT while maintaining total cumulative exposure may better predict CD4+IR, reduce NRM and increase overall survival, independent of the EX-VIVO-TCD method. © 2024 International Society for Cell & Gene Therapy |
| Keywords: | child; retrospective studies; young adult; t lymphocyte; t-lymphocytes; hematopoietic stem cell transplantation; retrospective study; pediatric; graft versus host reaction; transplantation conditioning; graft vs host disease; lymphocyte antibody; t-cell depletion; hematopoietic stem cell transplant; antilymphocyte serum; humans; human; adolescent and young adult; individualized dosing; rabbit anti-thymocyte globulin |
| Journal Title: | Cytotherapy |
| Volume: | 26 |
| Issue: | 4 |
| ISSN: | 1465-3249 |
| Publisher: | Elsevier Science Ltd. |
| Date Published: | 2024-04-01 |
| Start Page: | 351 |
| End Page: | 359 |
| Language: | English |
| DOI: | 10.1016/j.jcyt.2024.01.004 |
| PUBMED: | 38349310 |
| PROVIDER: | scopus |
| PMCID: | PMC10997457 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF -- Corresponding author is MSK author: Jaap Jan Boelens -- Source: Scopus |
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