The adverse event landscape of stem cell transplant: Evidence for AGVHD driving early transplant associated toxicities Journal Article
| Authors: | Takahashi, T.; Watkins, B.; Bratrude, B.; Neuberg, D.; Hebert, K.; Betz, K.; Yu, A.; Choi, S. W.; Davis, J.; Duncan, C.; Giller, R.; Grimley, M.; Harris, A. C.; Jacobsohn, D.; Lalefar, N.; Farhadfar, N.; Pulsipher, M. A.; Shenoy, S.; Petrovic, A.; Schultz, K. R.; Yanik, G. A.; Blazar, B. R.; Horan, J. T.; Langston, A.; Kean, L. S.; Qayed, M. |
| Article Title: | The adverse event landscape of stem cell transplant: Evidence for AGVHD driving early transplant associated toxicities |
| Abstract: | Although unrelated-donor (URD) hematopoietic cell transplantation (HCT) is associated with many toxicities, a detailed analysis of adverse events, as defined by the Common Terminology Criteria for Adverse Events (CTCAE), has not previously been curated. This represents a major unmet need, especially as it relates to assessing the safety of novel agents. We analyzed a detailed AE database from the “ABA2” randomized, double-blind, placebo-controlled clinical trial of abatacept for acute graft-versus-host disease (AGVHD) prevention, for which the FDA mandated a detailed AE assessment through Day +180, and weekly neutrophil and platelet counts through Day +100. These were analyzed for their relationship to key transplant outcomes, with a major focus on the impact of AGVHD on the development/severity of AEs. A total of 2102 AEs and 1816 neutrophil/platelet counts were analyzed from 142 8/8-HLA-matched URD HCT recipients on ABA2 (placebo cohort, n = 69, abatacept cohort, n = 73). This analysis resulted in 2 major observations. (1) Among graft source, conditioning intensity, age, and Grade 2 to 4 AGVHD, only AGVHD impacted Grade 3 to 5 AE acquisition after the first month post-transplant. (2) The development of Grade 3 to 4 AGVHD was associated with thrombocytopenia. We have created a detailed resource for the transplant community by which to contextualize clinical toxicities after transplant. It has identified AGVHD as a major driver of post-HCT Grade 3 to 5 AEs, and underscored a link between AGVHD and thrombocytopenia. This establishes a critical safety framework upon which the impact of novel post-transplant AGVHD therapeutics should be evaluated. This trial was registered at www.clinicaltrials.gov (#NCT01743131). © 2024 |
| Keywords: | adolescent; adult; child; controlled study; aged; middle aged; young adult; major clinical study; busulfan; fludarabine; placebo; systemic therapy; methotrexate; neutrophil count; phase 2 clinical trial; randomized controlled trial; thrombocytopenia; cohort analysis; cyclophosphamide; melphalan; steroid; stem cell transplantation; hematopoietic stem cell transplantation; food and drug administration; acute graft versus host disease; disease severity; myeloablative conditioning; neutrophil; multicenter study; prophylaxis; patient safety; graft versus host reaction; neutrophils; age distribution; toxicity; graft vs host disease; double blind procedure; double-blind method; cytomegalovirus infection; graft recipient; platelet count; abatacept; steroid therapy; adverse event; unrelated donor; unrelated donors; epstein barr virus infection; Common Terminology Criteria for Adverse Events; humans; human; male; female; article; leukocyte differential count; organ distribution; aba2 |
| Journal Title: | Transplantation and Cellular Therapy |
| Volume: | 31 |
| Issue: | 2 |
| ISSN: | 2666-6375 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2025-02-01 |
| Start Page: | 109.e1 |
| End Page: | 109.e13 |
| Language: | English |
| DOI: | 10.1016/j.jtct.2024.03.030 |
| PUBMED: | 38583802 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Source: Scopus |
