PMID- 34521106 OWN - NLM STAT- MEDLINE DCOM- 20211129 LR - 20211129 IS - 2473-9537 (Electronic) IS - 2473-9529 (Print) IS - 2473-9529 (Linking) VI - 5 IP - 21 DP - 2021 Nov 9 TI - Incidence and risk factors associated with bleeding and thrombosis following chimeric antigen receptor T-cell therapy. PG - 4465-4475 LID - 10.1182/bloodadvances.2021004716 [doi] AB - Bleeding and thrombotic events are an emerging toxicity associated with chimeric antigen receptor (CAR) therapies. To determine their incidence, we retrospectively analyzed consecutive adult patients (N = 127) with large B-cell lymphoma (LBCL) or B-cell acute lymphoblastic leukemia (B-ALL) treated from 2017 through 2020 with axicabtagene ciloleucel (axi-cel; n = 89) or a bispecific CD19/CD22 CAR (n = 38). Twelve (9.4%) and 8 (6.3%) patients developed bleeding and thrombosis within the first 3 months, respectively. In the axi-cel subgroup, these occurred in 11.2% and 6.7%, respectively. Bleeding occurred between days 8 and 30 (median, 17.5) and thrombosis between days 2 and 91 (median, 29). Bleeding sites included genitourinary, soft tissue, intracranial, gastrointestinal, and pulmonary and were associated with features of consumptive coagulopathy. On univariate analysis, patients with bleeding were older, had lower baseline platelets (86 x 103/muL vs 178 x 103/muL; P < .01), lower platelet and fibrinogen nadirs , and elevated lactate dehydrogenase. Immune effector cell (IEC)-associated neurotoxicity syndrome (ICANS) grade >/=3 was associated with increased bleeding (50% vs 15%; P = .01), thrombosis (50% vs 16%; P = .04), prothrombin time prolongation, hypofibrinogenemia, and elevated D-dimer. Low pretreatment platelet counts were associated with bleeding in a multivariate logistic regression model. Patients with thrombocytopenia or severe ICANS are at increased risk of bleeding and should be closely monitored, particularly within the first month after CAR therapy. Future studies in larger cohorts should assess risk factors for systemic coagulopathies in CAR T therapy, including their association with neurotoxicity. CI - (c) 2021 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved. FAU - Johnsrud, Andrew AU - Johnsrud A AUID- ORCID: 0000-0003-3928-4787 AD - Division of Blood and Marrow Transplantation and Cellular Therapy; and. FAU - Craig, Juliana AU - Craig J AUID- ORCID: 0000-0002-5644-2292 AD - Division of Blood and Marrow Transplantation and Cellular Therapy; and. FAU - Baird, John AU - Baird J AUID- ORCID: 0000-0001-8291-6546 AD - Division of Blood and Marrow Transplantation and Cellular Therapy; and. FAU - Spiegel, Jay AU - Spiegel J AD - Division of Blood and Marrow Transplantation and Cellular Therapy; and. FAU - Muffly, Lori AU - Muffly L AUID- ORCID: 0000-0002-9887-6136 AD - Division of Blood and Marrow Transplantation and Cellular Therapy; and. FAU - Zehnder, James AU - Zehnder J AD - Department of Molecular Pathology; and. FAU - Tamaresis, John AU - Tamaresis J AUID- ORCID: 0000-0002-9868-2366 AD - Department of Biomedical Data Science, Stanford University, Stanford, CA. FAU - Negrin, Robert AU - Negrin R AD - Division of Blood and Marrow Transplantation and Cellular Therapy; and. FAU - Johnston, Laura AU - Johnston L AD - Division of Blood and Marrow Transplantation and Cellular Therapy; and. FAU - Arai, Sally AU - Arai S AUID- ORCID: 0000-0003-1993-4172 AD - Division of Blood and Marrow Transplantation and Cellular Therapy; and. FAU - Shizuru, Judith AU - Shizuru J AD - Division of Blood and Marrow Transplantation and Cellular Therapy; and. FAU - Lowsky, Robert AU - Lowsky R AD - Division of Blood and Marrow Transplantation and Cellular Therapy; and. FAU - Meyer, Everett AU - Meyer E AD - Division of Blood and Marrow Transplantation and Cellular Therapy; and. FAU - Weng, Wen-Kai AU - Weng WK AD - Division of Blood and Marrow Transplantation and Cellular Therapy; and. FAU - Shiraz, Parveen AU - Shiraz P AUID- ORCID: 0000-0002-6721-0358 AD - Division of Blood and Marrow Transplantation and Cellular Therapy; and. FAU - Rezvani, Andrew AU - Rezvani A AD - Division of Blood and Marrow Transplantation and Cellular Therapy; and. FAU - Latchford, Theresa AU - Latchford T AD - Division of Blood and Marrow Transplantation and Cellular Therapy; and. FAU - Mackall, Crystal AU - Mackall C AUID- ORCID: 0000-0003-0359-9023 AD - Division of Blood and Marrow Transplantation and Cellular Therapy; and. FAU - Miklos, David AU - Miklos D AUID- ORCID: 0000-0003-0717-4305 AD - Division of Blood and Marrow Transplantation and Cellular Therapy; and. FAU - Frank, Matthew AU - Frank M AD - Division of Blood and Marrow Transplantation and Cellular Therapy; and. FAU - Sidana, Surbhi AU - Sidana S AUID- ORCID: 0000-0003-3288-7614 AD - Division of Blood and Marrow Transplantation and Cellular Therapy; and. LA - eng GR - K08 CA248968/CA/NCI NIH HHS/United States GR - KL2 TR003143/TR/NCATS NIH HHS/United States GR - P01 CA049605/CA/NCI NIH HHS/United States GR - T32 HL007952/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PL - United States TA - Blood Adv JT - Blood advances JID - 101698425 RN - 0 (Receptors, Chimeric Antigen) SB - IM MH - Cell- and Tissue-Based Therapy MH - Humans MH - Incidence MH - *Receptors, Chimeric Antigen MH - Retrospective Studies MH - Risk Factors MH - *Thrombosis/epidemiology/etiology PMC - PMC8579267 EDAT- 2021/09/15 06:00 MHDA- 2021/11/30 06:00 PMCR- 2021/11/08 CRDT- 2021/09/14 20:26 PHST- 2021/03/15 00:00 [received] PHST- 2021/06/22 00:00 [accepted] PHST- 2021/09/15 06:00 [pubmed] PHST- 2021/11/30 06:00 [medline] PHST- 2021/09/14 20:26 [entrez] PHST- 2021/11/08 00:00 [pmc-release] AID - 476900 [pii] AID - 2021/ADV2021004716 [pii] AID - 10.1182/bloodadvances.2021004716 [doi] PST - ppublish SO - Blood Adv. 2021 Nov 9;5(21):4465-4475. doi: 10.1182/bloodadvances.2021004716.