Impaired lymphocyte reconstitution after autologous transplant is associated with apoptosis of CD8+ T cells and adverse clinical outcome

Leuk Lymphoma. 2019 Sep;60(9):2264-2270. doi: 10.1080/10428194.2018.1563696. Epub 2019 Jan 18.

Abstract

We noticed that the lymphocyte counts, after autologous hematopoietic stem cell transplantation, oscillated during the first 4 post-transplant months. Thereafter, the lymphocyte counts stabilized and segregated the patients into two groups, those who normalized their lymphocyte counts and those with prolonged lymphopenia. In both groups, the CD4 counts remained low for at least 6 months. However, in approximately half of the patient, the CD8 counts increased to normal or above normal values. Patients with prolonged lymphopenia had higher rates of lymphocytes' spontaneous apoptosis and the lymphocytes in patients who restored their counts expressed the intracellular CD14-derived MO2 epitope that protects the cells from apoptosis. These findings were translated to longer disease-free survival and overall survival in patients who restored the CD8 counts. Collectively, our data show that post-transplant lymphocytes that express intracellular CD14-MO2 epitope have survival advantage.

Keywords: Lymphocytes; basic biology; cell cycle and apoptosis changes.

MeSH terms

  • Adult
  • Aged
  • Apoptosis / immunology
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Disease-Free Survival
  • Epitopes, T-Lymphocyte / analysis
  • Epitopes, T-Lymphocyte / immunology
  • Epitopes, T-Lymphocyte / metabolism
  • Female
  • Follow-Up Studies
  • Hematopoietic Stem Cell Transplantation / adverse effects*
  • Hodgkin Disease / immunology
  • Hodgkin Disease / mortality
  • Hodgkin Disease / surgery*
  • Humans
  • Kaplan-Meier Estimate
  • Lymphocyte Count
  • Lymphoma, Non-Hodgkin / immunology
  • Lymphoma, Non-Hodgkin / mortality
  • Lymphoma, Non-Hodgkin / surgery*
  • Lymphopenia / blood
  • Lymphopenia / diagnosis*
  • Lymphopenia / immunology
  • Lymphopenia / mortality
  • Male
  • Middle Aged
  • Multiple Myeloma / immunology
  • Multiple Myeloma / mortality
  • Multiple Myeloma / surgery*
  • Postoperative Complications / blood
  • Postoperative Complications / diagnosis*
  • Postoperative Complications / immunology
  • Postoperative Complications / mortality
  • Prognosis
  • Risk Assessment
  • Time Factors
  • Transplantation, Autologous / adverse effects
  • Young Adult

Substances

  • Epitopes, T-Lymphocyte