Clonogenic hemopoietic precursors in bone marrow transplantation

Abstract

Multilineage and single-lineage hemopoietic precursors were studied in 102 bone marrow transplant recipients and their respective donors to determine their contribution to clinical outcome as measured by time to engraftment and survival. The patient population was heterogenous with respect to diagnosis and disease status. They included individuals with acute myeloid leukemia (AML), chronic myeloid leukemia (CML), acute lymphoblastic leukemia (ALL), aplastic anemia, and a few other hematopoietic malignancies. The frequency of various clonogenic precursors in the normal donor population varied considerably. The data yielded a symmetrical distribution. In contrast, most bone marrow transplant recipients presented with significantly reduced numbers of clonogenic cells before transplantation, resulting in skewed distribution profiles. Serial studies of recipients demonstrated a significantly lower than normal level of clonogenic precursors even 3 and 4 years after transplantation. The median values and distribution profiles approximated those observed before transplantation but did not return to measurements obtained for normal donors. Patients with ALL deviated from this pattern. The median values and distribution profiles of clonogenic precursors before transplantation approximated the pattern of normal donors. The frequency of clonogenic progenitors after transplantation, however, remained significantly lower than that of their respective donor or pretransplant values. Cell cycle studies performed after normalization of peripheral blood hematopoietic parameters demonstrated for most recipients that a higher than normal proportion of multipotent cells was in S-phase (P = .011). By univariate and multivariate approaches, clonogenic precursors and clinical parameters were assessed for their contributions to clinical outcome as measured by time to engraftment and survival time. The number of nucleated cells in the transplant inoculum contributed to survival independent of other risk factors. Patients with a higher cell load had a higher probability of surviving than did patients with a lower cell concentration in the transplant inoculum (P = .042). The frequency of clonogenic precursors in the transplant inoculum altered neither survival nor time to engraftment. The time to engraftment was significantly influenced by the frequency of clonogenic megakaryocyte precursors (CFU-M) observed in recipients prior to transplantation (P = .003). Patients with high values engrafted faster than did patients with a low frequency of CFU-M. This was independent of both diagnosis and disease status of the patients at time of transplantation.