Higher doses of CD34+ peripheral blood stem cells are associated with increased mortality from chronic graft-versus-host disease after allogeneic HLA-identical sibling transplantation

Leukemia. 2003 May;17(5):869-75. doi: 10.1038/sj.leu.2402909.

Abstract

Allogeneic peripheral blood stem cell transplantation (PBSCT) has emerged as an alternative to bone marrow transplantation. PBSCT can be associated with a higher incidence of chronic graft-versus-host disease (cGVHD). In this study, we investigated whether there was a correlation between the composition of PBSC grafts (CD34+ and CD3+ cells) and hematological recovery, GVHD, relapse, and relapse-free survival (RFS) after myeloablative HLA-identical sibling PBSCT. The evolution of 100 acute or chronic leukemia patients was analyzed. Neither hematological recovery, acute or cGVHD, nor relapse, was significantly associated with CD3+ cell dose. Increasing CD34+ stem cells was associated with faster neutrophil (P=0.03) and platelet (P=0.007) recovery. Moreover, 47 of the 78 patients evaluable for cGVHD (60%; 95% CI, 49-71%) developed extensive cGVHD. The probability of extensive cGVHD at 4 years was 34% (95% CI, 21-47%) in patients receiving a 'low' CD34+ cell dose (<8.3 x 10(6)/kg), as compared to 62% (95% CI, 48-76%) in patients receiving a 'high' CD34+ cell dose (>8.3 x 10(6)/kg) (P=0.01). At a median follow-up of 59 months, this has not translated into a difference in relapse. In patients evaluable for cGVHD, RFS was significantly higher in patients receiving a 'low' CD34+ cell dose as compared to those receiving a 'high' CD34+ cell dose (P=0.04). This difference was mainly because of a significantly higher cGVHD-associated mortality (P=0.01). Efforts to accelerate engraftment by increasing CD34+ cell dose must be counterbalanced with the risk of detrimental cGVHD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adolescent
  • Adult
  • Antigens, CD34 / metabolism*
  • Female
  • Graft vs Host Disease / mortality*
  • Graft vs Host Disease / prevention & control
  • Granulocyte Colony-Stimulating Factor / pharmacology
  • HLA Antigens / metabolism
  • Hematopoietic Stem Cell Mobilization
  • Histocompatibility Testing
  • Humans
  • Infections / etiology
  • Infections / immunology
  • Leukemia, Myeloid / diagnosis
  • Leukemia, Myeloid / mortality*
  • Leukemia, Myeloid / therapy
  • Male
  • Middle Aged
  • Myelodysplastic Syndromes / diagnosis
  • Myelodysplastic Syndromes / mortality*
  • Myelodysplastic Syndromes / therapy
  • Neoplasm Recurrence, Local / mortality
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Recurrence, Local / therapy
  • Peripheral Blood Stem Cell Transplantation / mortality*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / diagnosis
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / mortality*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy
  • Siblings
  • Survival Rate
  • Tissue Donors
  • Transplantation, Isogeneic / immunology
  • Transplantation, Isogeneic / mortality
  • Treatment Outcome

Substances

  • Antigens, CD34
  • HLA Antigens
  • Granulocyte Colony-Stimulating Factor