Dataset Information

Robust CD4+ T-cell recovery in adults transplanted with cord blood and no antithymocyte globulin.

ABSTRACT: Quality of immune reconstitution after cord blood transplantation (CBT) without antithymocyte globulin (ATG) in adults is not established. We analyzed immune recovery in 106 engrafted adult CBT recipients (median age 50 years [range 22-70]) transplanted for hematologic malignancies with cyclosporine/mycophenolate mofetil immunoprophylaxis and no ATG. Patients were treated predominantly for acute leukemia (66%), and almost all (96%) underwent myeloablation. Recovery of CD4+ T cells was faster than CD8+ T cells with median CD4+ T-cell counts exceeding 200/mm3 at 4 months. Early post-CBT, effector memory (EM), and central memory cells were the most common CD4+ subsets, whereas effector and EM were the most common CD8+ T-cell subsets. Naive T-cell subsets increased gradually after 6 to 9 months post-CBT. A higher engrafting CB unit infused viable CD3+ cell dose was associated with improved CD4+ and CD4+CD45RA+ T-cell recovery. Cytomegalovirus reactivation by day 60 was associated with an expansion of total, EM, and effector CD8+ T cells, but lower CD4+ T-cell counts. Acute graft-versus-host disease (aGVHD) did not significantly compromise T-cell reconstitution. In serial landmark analyses, higher CD4+ T-cell counts and phytohemagglutinin responses were associated with reduced overall mortality. In contrast, CD8+ T-cell counts were not significant. Recovery of natural killer and B cells was prompt, reaching medians of 252/mm3 and 150/mm3 by 4 months, respectively, although B-cell recovery was delayed by aGVHD. Neither subset was significantly associated with mortality. ATG-free adult CBT is associated with robust thymus-independent CD4+ T-cell recovery, and CD4+ recovery reduced mortality risk.

SUBMITTER: Politikos I

PROVIDER: S-EPMC6960461 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Robust CD4+ T-cell recovery in adults transplanted with cord blood and no antithymocyte globulin.

Politikos Ioannis I Lavery Jessica A JA Hilden Patrick P Cho Christina C Borrill Taylor T Maloy Molly A MA Giralt Sergio A SA van den Brink Marcel R M MRM Perales Miguel-Angel MA Barker Juliet N JN

Blood advances 20200101 1

Quality of immune reconstitution after cord blood transplantation (CBT) without antithymocyte globulin (ATG) in adults is not established. We analyzed immune recovery in 106 engrafted adult CBT recipients (median age 50 years [range 22-70]) transplanted for hematologic malignancies with cyclosporine/mycophenolate mofetil immunoprophylaxis and no ATG. Patients were treated predominantly for acute leukemia (66%), and almost all (96%) underwent myeloablation. Recovery of CD4+ T cells was faster tha ...[more]

PMID: 31935291

Similar Datasets

Project description:Traditional weight-based dosing results in variable rabbit antithymocyte globulin (rATG) clearance that can delay CD4+ T-cell immune reconstitution (CD4+ IR) leading to higher mortality. In a retrospective pharmacokinetic/pharmacodynamic (PK/PD) analysis of patients undergoing their first CD34+ T-cell-depleted (TCD) allogeneic hematopoietic cell transplantation (HCT) after myeloablative conditioning with rATG, we estimated post-HCT rATG exposure as area under the curve (arbitrary unit per day/milliliter [AU × day/mL]) using a validated population PK model. We related rATG exposure to nonrelapse mortality (NRM), CD4+ IR (CD4+ ≥50 cells per µL at 2 consecutive measures within 100 days after HCT), overall survival, relapse, and acute graft-versus-host disease (aGVHD) to define an optimal rATG exposure. We used Cox proportional hazard models and multistate competing risk models for analysis. In all, 554 patients were included (age range, 0.1-73 years). Median post-HCT rATG exposure was 47 AU × day/mL (range, 0-101 AU × day/mL). Low post-HCT area under the curve (<30 AU × day/mL) was associated with lower risk of NRM (P < .01) and higher probability of achieving CD4+ IR (P < .001). Patients who attained CD4+ IR had a sevenfold lower 5-year NRM (P < .0001). The probability of achieving CD4+ IR was 2.5-fold higher in the <30 AU × day/mL group compared with 30-55 AU × day/mL and threefold higher in the <30 AU × day/mL group compared with the ≥55 AU × day/mL group. In multivariable analyses, post-HCT rATG exposure ≥55 AU × day/mL was associated with an increased risk of NRM (hazard ratio, 3.42; 95% confidence interval, 1.26-9.30). In the malignancy subgroup (n = 515), a tenfold increased NRM was observed in the ≥55 AU × day/mL group, and a sevenfold increased NRM was observed in the 30-55 AU × day/mL group compared with the <30 AU × day/mL group. Post-HCT rATG exposure ≥55 AU × day/mL was associated with higher risk of a GVHD (hazard ratio, 2.28; 95% confidence interval, 1.01-5.16). High post-HCT rATG exposure is associated with higher NRM secondary to poor CD4+ IR after TCD HCT. Using personalized PK-directed rATG dosing to achieve optimal exposure may improve survival after HCT.

Dataset Information

Robust CD4+ T-cell recovery in adults transplanted with cord blood and no antithymocyte globulin.

Publications

Robust CD4+ T-cell recovery in adults transplanted with cord blood and no antithymocyte globulin.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets