Details

Autor(en) / Beteiligte

• Takahashi, Takuto
• Watkins, Benjamin
• Bratrude, Brandi
• Neuberg, Donna
• Hebert, Kyle
• Betz, Kayla
• Yu, Alison
• Choi, Sung W
• Davis, Jeffrey
• Duncan, Christine
• Giller, Roger
• Grimley, Michael
• Harris, Andrew C.
• Jacobsohn, David
• Lalefar, Nahal
• Farhadfar, Nosha
• Pulsipher, Michael A.
• Shenoy, Shalini
• Petrovic, Aleksandra
• Schultz, Kirk R.
• Yanik, Gregory A.
• Blazar, Bruce R.
• Horan, John T.
• Langston, Amelia
• Kean, Leslie S.
• Qayed, Muna

Titel

The Adverse Event Landscape of Stem Cell Transplant: Evidence for aGVHD Driving Early Transplant Associated Toxicities

Ist Teil von

• Transplantation and cellular therapy, 2024-04

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2024

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• •Acute GVHD independently impacts Grade 3 to 5 AE incidence post-transplant.•Acute GVHD onset and severity are correlated with thrombocytopenia.•This database will be a critical resource for contextualizing novel HCT strategies. 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).