PMID- 36895292 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230311 IS - 1927-1220 (Electronic) IS - 1927-1212 (Print) IS - 1927-1212 (Linking) VI - 12 IP - 1 DP - 2023 Feb TI - The Impact of Graft CD3(+) T-Cell Dose on the Outcome of T-Cell Replete Human Leukocyte Antigen-Mismatched Allogeneic Hematopoietic Peripheral Blood Stem Cells Transplantation. PG - 27-36 LID - 10.14740/jh1071 [doi] AB - BACKGROUND: Data on whether the graft CD3-positive (CD3(+)) T-cell dose in T-cell-replete human leukocyte antigen (HLA)-mismatched allogeneic hematopoietic peripheral blood stem cells transplantation (PBSCT) influences post-transplant outcomes are controversial. METHODS: Using King Hussein Cancer Center (KHCC) Blood and Marrow Transplantation (BMT) Registry database, 52 adult subjects, receiving the first T-cell-replete HLA-mismatched allogeneic hematopoietic PBSCT for acute leukemias or myelodysplastic syndrome, were identified, from January 2017 to December 2020. The cutoff value of graft CD3(+) T-cell dose was identified using the receiver operating characteristic (ROC) formula and Youden's analysis. Subjects were divided into two cohorts: cohort 1 with low CD3(+) T-cell dose (n = 34) and cohort 2 with high CD3(+) T-cell dose (n = 18). Correlative analyses were performed between CD3(+) T-cell dose and the risk of graft-versus-host disease (GvHD), relapse, relapse-free survival (RFS), and overall survival (OS). P-values were two-sided and considered significant when P < 0.05. RESULTS: Subject covariates were displayed. Subject's characteristics were comparable, except for higher nucleated cells and more female donors in the high CD3(+) T-cell cohort. The 100-day cumulative incidence of acute GvHD (aGvHD) was 45+/-7% and 3-year cumulative incidence of chronic GvHD (cGvHD) was 28+/-6.7%. There was no statistically significant difference between the two cohorts in aGvHD (50% vs. 39%, P = 0.4) or cGvHD (29% vs. 22%, P = 0.7). The 2-year cumulative incidence of relapse (CIR) was 67.5+/-16.3% for low compared with 14.3+/-6.8% for high CD3(+) T-cell cohort (P = 0.018). Fifteen subjects relapsed and 24 have died, 13 due to disease relapse. There was an improvement in 2-year RFS (94% vs. 83%; P = 0.0022) and 2-year OS (91% vs. 89%; P = 0.025) in low CD3(+) T-cell cohort compared with high CD3(+) T-cell cohort. Graft CD3(+) T-cell dose is the only significant risk factor for relapse (P = 002), and OS (P = 0.030) in univariate analysis which was maintained in multivariate for relapse (P = 0.003), but not for OS (P = 0.050). CONCLUSIONS: Our data suggest that high graft CD3(+) T-cell dose is associated with lower risk of relapse, and might improve long-term survival, but has no influence on the risk of developing aGvHD or cGvHD. CI - Copyright 2023, Halahleh et al. FAU - Halahleh, Khalid AU - Halahleh K AD - Hematology Oncology and Bone Marrow Transplantation, King Hussein Cancer Center, Amman, Jordan. FAU - Mustafa, Rawan AU - Mustafa R AD - Department of Internal Medicine, Hematology Oncology Section, King Hussein Cancer Center, Amman, Jordan. FAU - Sarhan, Dania AU - Sarhan D AD - Cell Therapy and Applied Genomics (CTAG Lab) laboratory, King Hussein Cancer Center, Amman, Jordan. FAU - Al Rimawi, Dalia AU - Al Rimawi D AD - Biostatistics Unit, Research Office, King Hussein Cancer Center, Amman, Jordan. FAU - Abdelkhaleq, Hadeel AU - Abdelkhaleq H AD - Biostatistics Unit, Research Office, King Hussein Cancer Center, Amman, Jordan. FAU - Muradi, Isra AU - Muradi I AD - Department of Internal Medicine, University of Tripoli, Tripoli, Libya Jamahiriya. FAU - Sultan, Iyad AU - Sultan I AD - Department of Pediatrics, Hematology and Medical Oncology, King Hussein Cancer Center, Amman, Jordan. LA - eng PT - Journal Article DEP - 20230225 PL - Canada TA - J Hematol JT - Journal of hematology JID - 101635099 PMC - PMC9990716 OTO - NOTNLM OT - Allogeneic hematopoietic cell transplantation OT - Graft CD3+ T-cell dose OT - GvHD OT - Overall survival OT - PBSC OT - Relapse-free survival COIS- The authors declare that they have no conflict of interest. EDAT- 2023/03/11 06:00 MHDA- 2023/03/11 06:01 PMCR- 2023/02/25 CRDT- 2023/03/10 02:25 PHST- 2022/10/24 00:00 [received] PHST- 2022/12/16 00:00 [accepted] PHST- 2023/03/10 02:25 [entrez] PHST- 2023/03/11 06:00 [pubmed] PHST- 2023/03/11 06:01 [medline] PHST- 2023/02/25 00:00 [pmc-release] AID - 10.14740/jh1071 [doi] PST - ppublish SO - J Hematol. 2023 Feb;12(1):27-36. doi: 10.14740/jh1071. Epub 2023 Feb 25.