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 rapidl y replacing autologous bone marrow transplantation as hematological su pport after high-dose chemotherapy for lymphoma or solid tumors. Contr oversy exists concerning the number of progenitor cells required for r apid and sustained bone marrow recovery, and as to which of the widely available methods for estimating this number should be employed. Meth ods: Forty consecutive patients with solid tumors or lymphomas receive d high-dose chemotherapy followed by autologous peripheral stem cell r einfusion. Ah stem cell harvests had been performed after mobilization with standard-dose chemotherapy followed by 300 mu g G-CSF daily. Hem atopoietic reconstitution was studied in relation to pertinent patient characteristics, to the size of the graft (in terms of the total numb er of mononuclear cells (MNC), the number of granulocyte/macrophage co lony-forming units (CFU-GM) and the number of CD34(+) cells, and to th e use of G-CSF after stem cell reinfusion. Results: Both the numbers o f CFU-GM and CD34(+) cells reinfused, but not those of the MNC, correl ated with granu locyte and platelet recovery. Patients who received at least 5 x 10(6) CD34(+) cells/kg body weight achieved platelet transf usion independence on day 12 after reinfusion (range: day 7-37), signi ficantly earlier than patients who had received less (p = 0.001). Thir ty patients who received G-CSF (300 mu g s.c. daily) after reinfusion achieved granulocyte recovery (greater than or equal to 500 x 10(6)/l) on day 9 (range: day 8-12), while this took a median of 15 days (rang e: day 10-28) in 10 consecutive patients not receiving G-CSF (p = 0.00 03). In one patient who had received 1.4 x 10(6) CD34(+) cells/kg, sec ondary bone marrow failure developed 3 months after transplantation. R einfusion of cryopreserved autologous bone marrow was followed by prom pt recovery. Conclusion: Peripheral stem cells, mobilized by moderate- dose chemotherapy and G-CSF, lead to rapid and durable engraftment aft er high-dose chemotherapy when at least 3-5 x 10(6) CD34(+) cells/kg a re reinfused. Lower numbers may also be satisfactory, but are associat ed with slower granulocyte and platelet recoveries. A moderate dose of G-CSF after reinfusion significantly hastens granulocyte recovery wit hout interfering with platelet recovery.