Delayed G-CSF after autologous progenitor cell transplantation: a prospective randomized trial.

G-CSF is given after autologous progenitor cell transplantation to accelerate neutrophil engraftment. Historically, G-CSF has been started on the day of progenitor cell infusion. To study the timing of the initiation of G-CSF after autologous peripheral blood progenitor cell (PBPC) transplantation, we conducted a prospective, randomized trial comparing the initiation of G-CSF therapy on day 0, day +3 or day +5 after autologous PBPC transplantation. Seventy patients with diagnoses of breast cancer, non-Hodgkin's lymphoma, Hodgkin's disease, or multiple myeloma were prospectively randomized to one of the three treatment arms. All patients were treated with a chemotherapy (only) preparative regimen. The source of hematopoietic reconstitution was PBPC alone (without autologous marrow), and all patients yielded a minimum of 2 x 10(6) CD34+ cells per kilogram. Times to neutrophil engraftment and platelet engraftment were identical in the three treatment groups, with neutrophil engraftment occurring at a median of 10, 11 and 11 days when starting G-CSF on day 0, day 3 or day 5, respectively. Time to platelet transfusion independence was 14, 11 and 14 days by treatment group. We conclude that delaying the initiation of G-CSF from day 0 to day +5 does not affect engraftment and results in cost savings.

A randomized study of multi-day infusion of autologous peripheral blood progenitor cells.

Peripheral blood progenitor cells (PBPC) are increasingly used as the source of stem cells in both the autologous and allogeneic settings. Based on previous early non-randomized studies reporting enhanced engraftment following fractionated autologous PBPC infusion, some centers and study groups infuse PBPC over 3 days. To study the possible benefit of multiple day PBPC infusion, 60 patients receiving high-dose chemotherapy and autologous progenitor cell transplantation (ABMT) were randomized to receive their PBPC divided over 1, 2 or 3 days. Stem cells were mobilized with G-CSF 5 microg/kg for 7 days and PBPC were collected on days 5-7. Patients received daily G-CSF 5 microg/kg i.v. over 30 min beginning 4 h after the infusion of the first aliquot of PBPCs. Toxicity was similar for the 1, 2 and 3 day infusion groups. The median time to achieve 500 neutrophils/mm3 was 10, 11 and 11 days in the groups receiving PBPCs over 1, 2 or 3 days, respectively. The median time to achieve a platelet count of 20 x 10(9)/l was 11 days for the group receiving their cells as a single infusion and 12 days in the other two groups. We conclude that expanding PBPC infusion over 2 or 3 days does not enhance engraftment or reduce toxicity.

G-CSF post-autologous progenitor cell transplantation: a randomized study of 5, 10, and 16 micrograms/kg/day.

G-CSF is routinely administered after autologous bone marrow or peripheral blood progenitor cell transplantation to enhance neutrophil engraftment. However, many different doses of G-CSF have been described with no clear consensus on the most cost-effective dose. We performed a prospective randomized trial examining the efficacy of three different doses of G-CSF post-autologous transplant (5, 10, or 16 micrograms/kg/day). Fifty-seven consecutive patients with breast cancer (n = 30), non-Hodgkin's lymphoma (n = 16), Hodgkin's disease (n = 6), multiple myeloma (n = 2), acute leukemia (n = 2), and testicular cancer (n = 1) were randomized, with 19 patients enrolled in each of the three treatment groups. All patients underwent a high-dose chemotherapy preparative regimen and received an autologous peripheral blood progenitor cell (PBPC) transplant (without bone marrow), with G-CSF beginning on day 0. There was no difference in time to neutrophil engraftment among the three treatment groups (mean 10.2 to 10.8 days). There is a trend towards earlier platelet engraftment in the patient group receiving 5 microgram/kg/day of G-CSF. The total cost of G-CSF by dose group was $2900, $4400, and $6500 per patient. We conclude that there was no advantage to the use of higher doses of G-CSF after autologous transplantation, and that lower doses are associated with lower costs.

Progressive disease after ABMT for Hodgkin's disease.

A major limitation of ABMT for relapsed/refractory Hodgkin's disease is disease recurrence post-transplantation. We retrospectively reviewed 68 patients undergoing ABMT from January 1987 to June 1993. All received a uniform preparatory regimen (CBV). The median patient age was 30; 75% received prior radiation therapy and all patients received prior chemotherapy. Thirty-one percent presented at the time of transplantation with tumor masses larger than 10 cm. Sixty-two percent received autologous marrow alone and 38% PBPC with or without autologous bone marrow. Overall and progression-free survival are 43 and 36% at 5 years. Median follow-up for survivors is 59 months. Multivariate analysis revealed that tumor bulk was the most powerful poor prognostic factor for both survival and progression-free survival. Those transplanted with non-bulky tumors had an overall survival and progression-free survival of 52 and 44%, respectively, compared to those transplanted with bulky tumors who had an overall survival and progression-free survival of 22 and 16% (P = 0.03 and P = 0.04, respectively). Twenty-seven patients have relapsed. Four relapsed more than 2 years after ABMT. Four of the 27 patients who have relapsed remain alive, two without evidence of disease. The time after transplant to relapse was prognostically important, with no patients who relapsed within 6 months of ABMT still being alive, compared with 25% of patients who relapsed 7 or more months after ABMT who are still alive. We conclude that salvage therapy for relapse after ABMT is appropriate, as some patients may achieve prolonged survival. The time from transplant to relapse is an important survival predictor.

Outpatient bone marrow harvest: the Cleveland Clinic experience.

Patients undergoing a bone marrow harvest have traditionally been hospitalized for several days. Recently, the feasibility of outpatient bone marrow harvesting has been reported. We retrospectively examined the results of 485 patients undergoing an outpatient bone marrow harvest from 1989 to 1993. One hundred and eleven patients were normal donors and the remaining patients were undergoing a bone marrow harvest for autologous transplants. Four hundred and eighty one patients (99%) were discharged within 12 h of the harvest and none have developed long-term complications from the procedure. We additionally analyzed harvest yield with respect to time under anesthesia and underlying diagnosis. Surprisingly, time under anesthesia correlated negatively with harvest yield (P = 0.0001). After adjusting for volume harvested and time under anesthesia, harvest yield was higher in normal donors and patients with breast cancer than for patients with non-Hodgkin's lymphoma and Hodgkin's disease. We conclude that outpatient harvesting is safe. The negative correlation of time under anesthesia with harvest yield may be a result of variables which are difficult to quantify, such as bone marrow microenvironment.

Comparison of G-CSF with GM-CSF for mobilizing peripheral blood progenitor cells and for enhancing marrow recovery after autologous bone marrow transplant.

Primed peripheral blood progenitor cells (PBPC) with hematopoietic growth factors enhance marrow engraftment after autologous bone marrow transplantation (BMT). G-CSF and GM-CSF stimulate the production of PBPC; both cytokines alone also stimulate neutrophil recovery after autologous BMT. Little data exist comparing these two cytokines. We prospectively studied G-CSF and GM-CSF in autologous BMT. Forty-four consecutive patients with either Hodgkin's disease or non-Hodgkin's lymphoma underwent autologous BMT using both PBPC and autologous marrow. The autologous BMT preparative regimen was CBV (VP-16 2400 mg/m2, CY 1800 mg/m2 i.v. four times daily for 4 days, BCNU 600 mg/m2). Sixteen patients received G-CSF 5 micrograms/kg sc daily for 8 days for mobilization of PBPC and received G-CSF 16 micrograms/kg i.v. four times daily after autologous BMT. Twenty-eight patients received GM-CSF to mobilize PBPC (14 patients received 250 micrograms/m2 sc daily for 8 days; 14 patients received 125 micrograms/m2 sc twice daily for 8 days) and GM-CSF (250 micrograms/m2 i.v. four times daily) after autologous BMT. Patients underwent three to five pheresis procedures to harvest at least 3 x 10(8) nucleated cells/kg. Patients receiving G-CSF had higher peripheral WBC counts than did those receiving GM-CSF. Total numbers of mononuclear cells, total CD34+ cells and total CD34+/33-negative cells were similar in the two treatment groups. The patients receiving G-CSF after autologous BMT experienced a more rapid engraftment of both neutrophils (9 days vs 13 days, p = 0.0001) and platelets (14 days vs 18 days, p = 0.027) than did patients receiving GM-CSF after transplant.(ABSTRACT TRUNCATED AT 250 WORDS)