Rapid establishment of long-term culture-initiating cells of donor origin after nonmyeloablative allogeneic hematopoietic stem-cell transplantation, and significant prognostic impact of donor T-cell chimerism on stable engraftment and progression-free survival

Transplantation. 2003 Jul 15;76(1):230-6. doi: 10.1097/01.TP.0000071862.42835.76.

Abstract

Background: Nonmyeloablative allogeneic hematopoietic stem-cell transplantation (NST) allows establishment of donor hematopoiesis without eradication of recipient stem cells by chemoradiotherapy. Quantification of donor chimerism may predict graft failure and relapse.

Methods: We quantified donor long-term culture-initiating cells (LTC-IC) in nine patients during the early phase after NST and lineage-specific donor cells of myeloid (CD33+, CD34+, granulocytes) and lymphoid lineage (CD3+, CD4+, CD8+, CD56+) in 38 patients with a median follow-up of 40 weeks after NST. Conditioning therapy consisted of fludarabine 90 mg/m2 followed by total body irradiation of 2 Gy.

Results: Only rapid establishment of donor T-cell chimerism was essential for stable donor engraftment. Patients with less than 90% of donor T cells 4 weeks after NST had a significantly higher risk of relapse, graft rejection, or both (14 of 18 patients) than patients with donor T-cell chimerism of 90% and higher (3 of 20 patients). Although conditioning therapy was nonmyeloablative, a significant decrease of repopulating stem cells defined as LTC-IC was seen after 2 weeks followed by rapid recovery of LTC-IC to pretransplant values. Interestingly, all LTC-IC were from donor origin 2 and 4 weeks after NST, but rapid establishment of donor LTC-IC was not predictive for progression-free survival.

Conclusions: Rapid establishment of lymphoid but not myeloid donor chimerism is a prognostic factor for stable donor engraftment after NST. It seems that an immunologic shield of alloreactive donor T cells is essential for early hematopoietic progenitors.

MeSH terms

  • ABO Blood-Group System
  • Adolescent
  • Adult
  • Aged
  • Antigens, CD / blood
  • Blood Group Incompatibility
  • Cell Culture Techniques / methods
  • Disease-Free Survival
  • Female
  • Graft vs Host Disease / prevention & control
  • Hematopoietic Stem Cells / cytology*
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • In Situ Hybridization, Fluorescence
  • Leukemia / therapy
  • Male
  • Middle Aged
  • Neoplasms / therapy
  • Prognosis
  • Stem Cell Transplantation / methods*
  • T-Lymphocytes / immunology*
  • Tissue Donors
  • Transplantation Chimera / immunology*
  • Transplantation, Autologous
  • Transplantation, Homologous
  • Treatment Outcome

Substances

  • ABO Blood-Group System
  • Antigens, CD
  • Immunosuppressive Agents