Assessment of thymic output in adults after haematopoietic stem-cell transplantation and prediction of T-cell reconstitution

Lancet. 2000 May 27;355(9218):1875-81. doi: 10.1016/S0140-6736(00)02293-5.


Background: The potential benefits of haematopoietic stem-cell transplantation are tempered by the depletion of T-cells accompanying this procedure. We used a new technique which quantifies the excisional DNA products of T-cell-receptor (TCR) gene rearrangement to measure thymic output directly in patients with multiple myeloma, and thus assessed the contribution of the thymus to immune recovery after transplantation.

Methods: We studied 40 patients, 34-66 years of age, who had been randomly assigned myeloablative chemotherapy and autologous peripheral-blood haematopoietic stem-cell transplantation with unmanipulated grafts or grafts enriched for CD34 stem cells. CD4 and CD8 T-cell counts were measured, thymic output was estimated serially until 2 years after transplantation, and percentages of naive T-cells were measured.

Findings: The production of substantial numbers of new naive T cells by the thymus could be detected by 100 days post-transplant; there was a significant inverse relation between age and recovery of new T cells. In the CD34-unselected group, numbers of TCR-rearrangement excision circles returned to baseline after 2 years, whereas in the CD34-selected group, numbers at 2 years were significantly higher than both baseline numbers (p=0.004), and 2-year numbers in the unselected group (p=0.046). Increased thymic output correlated with, and was predictive of, increased naive T-cell numbers and broader T-cell-receptor repertoires.

Interpretation: Our results provide evidence that the adult thymus contributes more substantially to immune reconstitution after haematopoietic stem-cell transplantation than was previously thought, and therefore could be a target for therapeutic intervention.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Antigens, CD / immunology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Gene Rearrangement, T-Lymphocyte
  • Granulocyte Colony-Stimulating Factor / administration & dosage
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Lymphocyte Count
  • Middle Aged
  • Multiple Myeloma / drug therapy
  • Multiple Myeloma / immunology
  • Multiple Myeloma / therapy*
  • Myeloablative Agonists / administration & dosage
  • Receptors, Antigen, T-Cell / immunology*
  • T-Lymphocytes*
  • Thymus Gland / immunology*
  • Transplantation Conditioning


  • Antigens, CD
  • Myeloablative Agonists
  • Receptors, Antigen, T-Cell
  • Granulocyte Colony-Stimulating Factor