Bone marrow reconstitution after high-dose chemotherapy and autologous peripheral blood progenitor cell transplantation: Effect of graft size

Background: Peripheral blood progenitor cell transplantation is rapidly replacing autologous bone marrow transplantation as hematological support after high-dose chemotherapy for lymphoma or solid tumors. Controversy exists concerning the number of progenitor cells required for rapid and sustained bone marrow recovery, and as to which of the widely available methods for estimating this number should be employed. Methods: Forty consecutive patients with solid tumors or lymphomas received high-dose chemotherapy followed by autologous peripheral stem cell reinfusion. All stem cell harvests had been performed after mobilization with standard-dose chemotherapy followed by 300 μg G-CSF daily. Hematopoietic reconstitution was studied in relation to pertinent patient characteristics, to the size of the graft (in terms of the total number of mononuclear cells (MNC), the number of granulocyte/macrophage colony-forming units (CFU-GM) and the number of CD34⁺ cells, and to the use of G-CSF after stem cell reinfusion. Results: Both the numbers of CFU-GM and CD34⁺ cells reinfused, but not those of the MNC, correlated with granu-locyte and platelet recovery. Patients who received at least 5 × 10⁶ CD34⁺ cells/kg body weight achieved platelet transfusion independence on day 12 after reinfusion (range: day 7-37), significantly earlier than patients who had received less (p{box drawings light horizontal}0.001). Thirty patients who received G-CSF (300 ng s.c. daily) after reinfusion achieved granulocyte recovery (>500 × 10⁶/l) on day 9 (range: day 8-12), while this took a median of 15 days (range: day 10-28) in 10 consecutive patients not receiving G-CSF (p{box drawings light horizontal}0.0003). In one patient who had received 1.4 × 10⁶ CD34⁺ cells/kg, secondary bone marrow failure developed 3 months after transplantation. Reinfusion of cryopreserved autologous bone marrow was followed by prompt recovery. Conclusions: Peripheral stem cells, mobilized by moderate-dose chemotherapy and G-CSF, lead to rapid and durable engraftment after high-dose chemotherapy when at least 3-5 × 10⁶ CD34⁺ cells/kg are reinfused. Lower numbers may also be satisfactory, but are associated with slower granulocyte and platelet recoveries. A moderate dose of G-CSF after reinfusion significantly hastens granulocyte recovery without interfering with platelet recovery.