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High proportions of CD3+ T cells in grafts delayed lymphocyte recovery and reduced overall survival in haploidentical peripheral blood stem cell transplantation.

ABSTRACT: T cells in grafts serve an important role in the pathogenesis of graft versus host disease (GVHD) and immune recovery during HLA matched allogeneic stem cell transplantation. However, the role of T cells in the haploidentical peripheral blood stem cell transplantation (Haplo-PBSCT) is yet to be determined. In the present study, the role of CD3+ T cells in grafts and impact on hematopoietic and immune recovery, cytomegalovirus (CMV) reactivation, GVHD, relapse, progress free survival and overall survival (OS) were evaluated and analyzed. A total of 30 patients who underwent haplo-PBSCT were included in the present study. CD3+ T cells accounted for a median of 23.1% (range 8-47.4%) with a median dose of 299.7x106/kg (range 104-623.4). Patients were divided into two groups according to the CD3+ T cell count: Above the median (high T cell group) and below the median CD3+ T cell (low T cell group). No significant difference was identified between neutrophil and platelet recovery time between two groups (P>0.05). The mean lymphocyte recovery time of high T cell group and low T cell group were 107.07 days (95% CI 79.88-134.25), and 50.4 days (95% CI 41.42-59.38), respectively. The lymphocyte recovery time of high T cell group was higher that of low T cell group (P<0.05). No significant difference between CMV reactivation, chronic GVHD and primary disease relapse rates was observed between two groups (P>0.05). The cumulative incidence of grade II or above acute GVHD was higher in the high T groups compared with low T groups (P<0.05). The overall survival and progress free survival rates were higher in the low T cell group compared with the high T cell group (P<0.05). In conclusion, high levels of CD3+ T cells in the grafts were associated with delayed lymphocyte recovery and an increased risk of acute GVHD and decreased overall survival.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC7179384 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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High proportions of CD3<sup>+</sup> T cells in grafts delayed lymphocyte recovery and reduced overall survival in haploidentical peripheral blood stem cell transplantation.

Zhang Ying Y Guo Caili C Sun Chunhong C Chen Ying Y Zhu Huachao H Xi Jieying J Zhang Mei M He Pengcheng P Wang Xiaoning X

Molecular and clinical oncology 20200402 6

T cells in grafts serve an important role in the pathogenesis of graft versus host disease (GVHD) and immune recovery during HLA matched allogeneic stem cell transplantation. However, the role of T cells in the haploidentical peripheral blood stem cell transplantation (Haplo-PBSCT) is yet to be determined. In the present study, the role of CD3<sup>+</sup> T cells in grafts and impact on hematopoietic and immune recovery, cytomegalovirus (CMV) reactivation, GVHD, relapse, progress free survival a ...[more]

PMID: 32337040

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Project description:In the coronavirus disease 19 (COVID-19) pandemic era, the number of haploidentical hematopoietic cell transplantations (HCTs) with peripheral blood (PB) grafts increased significantly compared with HCTs with bone marrow (BM) grafts, which may be associated with adverse outcomes. We compared outcomes of HCT in BM graft and PB graft recipients age ≥18 years with hematologic malignancies who underwent T cell- replete haploidentical HCT and received graft-versus-host disease (GVHD) prophylaxis with post-transplantation cyclophosphamide, tacrolimus, and mycophenolate mofetil. Among the 264 patients, 180 (68%) received a BM graft and 84 (32%) received a PB graft. The median patient age was 50 years in both groups. The majority (n = 199; 75%) received reduced-intensity conditioning. The rate of acute leukemia or myelodysplastic syndrome was higher in the BM graft recipients compared with the PB graft recipients (85% [n = 152] versus 55% [n = 46]; P < .01). The median times to neutrophil and platelet engraftment and the incidence of grade II-IV and grade III-IV acute GVHD (aGVHD) were comparable in the 2 groups. Among the patients with grade II-IV aGVHD, the rate of steroid-refractory aGVHD was 9% (95% confidence interval [CI], 5% to 18%) in the BM group versus 32% (95% CI, 19% to 54%) in the PB group (hazard ratio [HR], 3.7, 95% CI, 1.5 to 9.3; P = .006). At 1 year post-HCT, the rate of chronic GVHD (cGVHD) was 8% (95% CI, 4% to 13%) in the BM group versus 22% (95% CI, 14% to 36%) in the PB group (HR, 3.0; 95% CI, 1.4-6.6; P = .005), and the rate of systemic therapy-requiring cGVHD was 2.5% (95% CI, 1% to 7%) versus 14% (95% CI, 7% to 27%), respectively (HR, 5.6; 95% CI, 1.7 to 18; P = .004). The PB group had a significantly higher risk of bacterial and viral infections, with no appreciable advantage in the duration of hospitalization, immune reconstitution, relapse, nonrelapse mortality, or survival. Our data suggest a benefit of the use of BM grafts over PB grafts for haplo-HCT.

Project description:BackgroundT-cell depleted (TCD) haploidentical transplantation using CD3+/CD19+ and TCRαβ+/CD19+ depletion techniques has been increasingly used in children with hematological malignancies. We present a retrospective study aimed to compare transplant outcomes in children with leukemia receiving a TCD haploidentical transplant using either CD3+/CD19+ or TCRαβ+/CD19+ platforms.MethodsA total of 159 children with leukemia (ALL=80) (AML=79) that received a TCD haploidentical transplantation using either CD3+/CD19+ (n=79) or TCRαβ+/CD19+ (n=80) platforms between 2005 and 2020 were included. Median age was 9 years in both groups. There were no differences in patient, donor, and transplant characteristics between groups except for donor KIR B genotype more frequent in the TCRαβ+/CD19+ group (91%) than in the CD3+/CD19+ group (76%) (p=0.009) and a high number of NK+ cells and lower CD19+ cells infused in the TCRαβ+/CD19+ group (35.32x106/kg and 0.06 x106/Kg) than in the CD3+/CD19 group (24.6x106/Kg and 0.25 x106/Kg) (p=0.04 and p=0.0001), respectively. Conditioning was based on TBF. Median follow-up for survivors was 11 years (range; 8-16 y) in CD3+/CD19+ group and 5 years (range; 2-9 y) in the TCRαβ+/CD19+ group.ResultsEngraftment kinetics were similar in both groups (13 days for neutrophils and 10 days for platelets). There was no difference in the incidence of acute GvHD II-IV (29 ± 5% in the CD3+/CD19+ group vs 38 ± 5% in the TCRαβ+/CD19+ group) and chronic GvHD (32 ± 5% vs 23 ± 4%, respectively). NRM was 23 ± 5% in the CD3+/CD19+group vs 21 ± 4% in the TCRαβ+/CD19+group. Relapse incidence was also similar, 32 ± 5% vs 34 ± 6%, respectively. DFS and OS were not different (45 ± 5% vs 45 ± 6% and 53 ± 6% vs 58 ± 6% respectively). As there were no differences on transplant outcomes between groups, we further analyzed all patients together for risk factors associated with transplant outcomes. On multivariate analysis, we identified that early disease status at transplant (HR: 0.16; 95%CI (0.07-0.35) (p=0.0001), presence of cGvHD (HR: 0.38; 95%CI (0.20-0.70) (p= 0.002), and donor KIR-B genotype (HR: 0.50; 95%CI (0.32-0.90) (p=0.04) were associated with better DFS.ConclusionsOur data suggest that there are no advantages in transplant outcomes between TCD platforms. Risk factors for survival are dependent on disease characteristic, donor KIR genotype, and chronic GvHD rather than the TCD platform used.

Dataset Information

High proportions of CD3+ T cells in grafts delayed lymphocyte recovery and reduced overall survival in haploidentical peripheral blood stem cell transplantation.

Publications

High proportions of CD3<sup>+</sup> T cells in grafts delayed lymphocyte recovery and reduced overall survival in haploidentical peripheral blood stem cell transplantation.

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