Dynamical System Modeling of Immune Reconstitution after Allogeneic Stem Cell Transplantation Identifies Patients at Risk for Adverse Outcomes

被引：19

作者：

Toor, Amir A. ^{[1
]}

Sabo, Roy T. ^{[2
]}

Roberts, Catherine H. ^{[1
]}

Moore, Bonny L. ^{[1
]}

Salman, Salman R. ^{[1
]}

Scalora, Allison F. ^{[1
]}

Aziz, May T. ^{[3
]}

Alil, Ali S. Shubar ^{[1
]}

Hall, Charles E. ^{[1
]}

Meier, Jeremy ^{[1
]}

Thorn, Radhika M. ^{[1
]}

Wang, Elaine ^{[1
]}

Song, Shiyu ^{[4
]}

Miller, Kristin ^{[5
]}

Rizzo, Kathryn ^{[6
]}

Clark, William B. ^{[1
]}

McCarty, John M. ^{[1
]}

Chung, Harold M. ^{[1
]}

Manjili, Masoud H. ^{[7
]}

Neale, Michael C. ^{[8
,9
]}

机构：

[1] Virginia Commonwealth Univ, Bone Marrow Transplant Program, Massey Canc Ctr, Dept Internal Med, Richmond, VA 23298 USA

[2] Virginia Commonwealth Univ, Dept Biostat, Richmond, VA 23298 USA

[3] Virginia Commonwealth Univ, Dept Pharm & Therapeut, Richmond, VA 23298 USA

[4] Virginia Commonwealth Univ, Dept Radiat Oncol, Richmond, VA 23298 USA

[5] Virginia Commonwealth Univ, Dept Internal Med, Richmond, VA 23298 USA

[6] Virginia Commonwealth Univ, Dept Pathol, Richmond, VA 23298 USA

[7] Virginia Commonwealth Univ, Dept Microbiol & Immunol, Richmond, VA 23298 USA

[8] Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA 23298 USA

[9] Virginia Commonwealth Univ, Dept Human Genet, Richmond, VA 23298 USA

来源：

BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION | 2015年 / 21卷 / 07期

关键词：

Stem cell transplant; Dynamical system; Immune reconstitution; T cells; Graft-versus-host disease; VERSUS-HOST-DISEASE; BONE-MARROW-TRANSPLANTATION; MINOR HISTOCOMPATIBILITY ANTIGENS; MATCHED UNRELATED DONOR; TOTAL-BODY IRRADIATION; ACUTE MYELOID-LEUKEMIA; ANTITHYMOCYTE GLOBULIN; INTRAVENOUS BUSULFAN; GRAFT; RECIPIENTS;

D O I：

10.1016/j.bbmt.2015.03.011

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Systems that evolve over time and follow mathematical laws as they evolve are called dynamical systems. Lymphocyte recovery and clinical outcomes in 41 allograft recipients conditioned using antithymocyte globulin (ATG) and 4.5-Gy total body irradiation were studied to determine if immune reconstitution could be described as a dynamical system. Survival, relapse, and graft-versus-host disease (GVHD) were not significantly different in 2 cohorts of patients receiving different doses of ATG. However, donor-derived CD3+ cell reconstitution was superior in the lower ATG dose cohort, and there were fewer instances of donor lymphocyte infusion (DLI). Lymphoid recovery was plotted in each individual over time and demonstrated 1 of 3 sigmoid growth patterns: Pattern A (n = 15) had rapid growth with high lymphocyte counts, pattern B (n = 14) had slower growth with intermediate recovery, and pattern C (n = 10) had poor lymphocyte reconstitution. There was a significant association between lymphocyte recovery patterns and both the rate of change of donor-derived CD3+ at day 30 after stem cell transplantation (SCT) and clinical outcomes. GVHD was observed more frequently with pattern A, relapse and DLI more so with pattern C, with a consequent survival advantage in patients with patterns A and B. We conclude that evaluating immune reconstitution after SCT as a dynamical system may differentiate patients at risk of adverse outcomes and allow early intervention to modulate that risk. (C) 2015 American Society for Blood and Marrow Transplantation.

引用

页码：1237 / 1245

页数：9

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