The number of donor CD3(+) cells is the most important factor for graft failure after allogeneic transplantation of CD34(+) selected cells from peripheral blood from HLA-identical siblings

Blood. 2001 Jan 15;97(2):383-7. doi: 10.1182/blood.v97.2.383.

Abstract

This study analyzed the characteristics of 257 HLA-identical sibling transplants of granulocyte colony-stimulating factor-mobilized peripheral blood progenitor cells depleted of T cells by CD34(+) positive selection (allo-PBT/CD34(+)) for their effect on the incidence of graft failure. Twenty-four patients developed graft failure (actuarial probability, 11%; 95% confidence interval, 7.1-14. 9). Prognostic factors considered were sex and age of donor and recipient, donor-recipient blood group compatibility, diagnosis, disease status at transplant, conditioning regimen, cytomegalovirus serology, number of CD34(+) and CD3(+) cells infused, and cryopreservation. The major factor associated with graft failure was the number of CD3(+) cells in the inoculum. Twenty-three of 155 patients receiving a T-cell dose in the graft less than or equal to 0.2 x 10(6)/kg experienced graft failure, compared with only one of 102 patients receiving more than 0.2 x 10(6)/kg (actuarial probability 18% vs 1%, respectively; P =.0001). The actuarial probability of graft failure progressively increased as the number of CD3(+) cells in the graft decreased, which was determined by grouping the number of CD3(+) cells in quartiles (log-rank P =.03; log-rank for trend P =.003). In the multivariate analysis by the proportional hazard method, 2 covariates entered into regression at a significant level: CD3(+) cells less than or equal to 0.2 x 10(6)/kg (risk ratio = 17; P <.0001), and patients with chronic myelogenous leukemia (CML) conditioned with busulphan-based regimens (risk ratio = 4.8; P =.001). From these results it appears that the number of CD3(+) cells in the inoculum-with a threshold of 0.2 x 10(6)/kg or less-is the most critical factor in maintaining a sustained engraftment in allo-PBT/CD34(+) from HLA-identical siblings. In addition, for patients with CML receiving 0.2 x 10(6)/kg or less CD3(+) cells, total body irradiation might be better than busulphan-based regimens.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actuarial Analysis
  • Adolescent
  • Adult
  • Antigens, CD34 / blood*
  • Blood Donors
  • CD3 Complex / blood*
  • Cell Count
  • Female
  • Follow-Up Studies
  • Graft Rejection / blood
  • Graft Rejection / etiology*
  • Graft Rejection / immunology
  • Hematologic Neoplasms / complications
  • Hematologic Neoplasms / diagnosis
  • Hematologic Neoplasms / therapy
  • Hematopoietic Stem Cell Transplantation / adverse effects*
  • Hematopoietic Stem Cell Transplantation / standards
  • Histocompatibility
  • Humans
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / complications
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / diagnosis
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / therapy
  • Lymphocyte Depletion / standards
  • Lymphocytes / immunology*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Nuclear Family
  • Prognosis
  • Transplantation, Homologous / adverse effects
  • Transplantation, Homologous / immunology

Substances

  • Antigens, CD34
  • CD3 Complex