Hematopoietic rescue after high-dose chemotherapy using autologous peripheral-blood progenitor cells or bone marrow: a randomized comparison.

1995 ◽  
Vol 13 (6) ◽  
pp. 1328-1335 ◽  
Author(s):  
J Beyer ◽  
N Schwella ◽  
J Zingsem ◽  
I Strohscheer ◽  
I Schwaner ◽  
...  

PURPOSE To compare autologous bone marrow (BM) with peripheral-blood progenitor cells (PBPC) as hematopoietic rescue after high-dose chemotherapy (HDCT). PATIENTS AND METHODS From January 1991 until April 1993, 47 consecutive patients with relapsed or refractory germ cell tumors were randomized to either BM harvest or collection of PBPC mobilized by chemotherapy plus granulocyte colony-stimulating factor (G-CSF). After additional conventional-dose salvage treatment, all patients received HDCT with carboplatin 1,500 mg/m2, etoposide 2,400 mg/m2, and ifosfamide 10 g/m2 with either BM or PBPC rescue. RESULTS Forty-six patients were assessable for hematologic reconstitution, and one patient died on day +4 before engraftment. Rescue using PBPC resulted in a significantly shorter recovery time to neutrophil counts more than 500/microL (10.0 v 11.0 days, P < .01), neutrophil counts more than 1,000/microL (10.0 v 12.0 days, P = .001), and platelet counts more than 20,000/microL (10.0 v 17.0 days, P < .01), as well as in fewer days to transfusion independence from RBCs (8.0 v 12.0, P < .05) and platelets (9.0 v 12.0, P < .01) and fewer days of intravenous (IV) antibiotics (9.0 v 11.0, P < .05). However, no statistical differences in transfusion requirements or in other clinical outcome variables were observed. Overall survival and event-free survival also were not different in the two study arms. CONCLUSION We conclude that the use of PBPC mobilized by chemotherapy plus G-CSF results in sustained trilineage reconstitution after HDCT, which occurs more rapidly as compared with BM. The earlier hematologic reconstitution in patients with PBPC rescue significantly reduces the time to transfusion independence.

Blood ◽  
2000 ◽  
Vol 96 (9) ◽  
pp. 3001-3007 ◽  
Author(s):  
Ian McNiece ◽  
Roy Jones ◽  
Scott I. Bearman ◽  
Pablo Cagnoni ◽  
Yago Nieto ◽  
...  

Abstract Ex vivo expanded peripheral blood progenitor cells (PBPCs) have been proposed as a source of hematopoietic support to decrease or eliminate the period of neutropenia after high-dose chemotherapy. CD34 cells were selected from rhG-CSF mobilized PBPCs from patients with breast cancer and were cultured for 10 days in defined media containing 100 ng/mL each of rhSCF, rhG-CSF, and PEG-rhMGDF in 1 L Teflon bags at 20 000 cells/mL. After culture the cells were washed and reinfused on day 0 of transplantation. On day +1, cohort 1 patients (n = 10) also received an unexpanded CD34-selected PBPC product. These patients engrafted neutrophils (absolute neutrophil count, &gt;500/μL) in a median of 6 (range, 5-14) days. Cohort 2 patients (n = 11), who received expanded PBPCs only, engrafted neutrophils in a median of 8 (range, 4-16) days. In comparison, the median time to neutrophil engraftment in a historical control group of patients (n = 100) was 9 days (range, 7-30 days). All surviving patients are now past the 15-month posttransplantation stage with no evidence of late graft failure. The total number of nucleated cells harvested after expansion culture was shown to be the best predictor of time to neutrophil engraftment, with all patients receiving more than 4 × 107 cells/kg, engrafting neutrophils by day 8. No significant effect on platelet recovery was observed in any patient. These data demonstrate that PBPCs expanded under the conditions defined can shorten the time to engraftment of neutrophils compared with historical controls and that the rate of engraftment is related to the dose of expanded cells transplanted.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2999-2999 ◽  
Author(s):  
Tara Seshadri ◽  
Khalil Al-Farsi ◽  
Julie Stakiw ◽  
Clement Ma ◽  
Ronnie Saragosa ◽  
...  

Abstract Introduction: Most autologous hematopoietic cell transplants (AHCT) are performed using peripheral blood mobilized progenitor cells (PBSC). However a small but significant proportion of patients (pts) are unable to mobilize adequate numbers of PBSC. The use of G-CSF-stimulated bone marrow (BM) derived progenitor cells is one method to circumvent this problem and enable AHCT to be performed. However, the long and short-term ability to engraft and the impact of this method on overall and progression free survival (OS and PFS) have not been established. Methods: We reviewed 52 pts (17 AML, 24 NHL, 11 HL) who failed PBSC collection between Jan 1999-Dec 2006 (<2×5106 CD34+cells/kg) and underwent G-CSF stimulated BM harvest to permit high dose therapy (etoposide 60 mg/kg + melphalan 160–180 mg/m2, + TBI 500 or 1200 cGy for pts with AML). 23 pts were supported by harvested BM (44%) and 29 (56%) with a mixture (Mx) of BM and PBSC. Overall and PFS was compared to pts undergoing AHCT using chemotherapy-mobilized PBSCs (n=440) in the same time period (AML n=32, NHL n=273, HL=135) who had a similar median age, pre-transplant induction, salvage therapy and intensive therapy regimens. Kaplan-Meier curves and the Log-rank test were used to compare the OS and PFS between cases and controls. Due to skewed data, the non-parametric Wilcoxon Rank Test was used for simple comparisons of clinical factors. Results: Median age of the cohort at AHCT was 43 years (range 24–68, 67% females). Status prior to AHCT was CR 44%, PR 54%, and SD 2%. Number of chemotherapy regimens (median):AML: 3; NHL: 3; HL: 2. Median BM CFU-GM infused was 4.4×104/kg and median PBSC infused was 0.1×106/kg (n=29). Median follow up times for AML/NHL/HL was 20, 18 and 50 months respectively. Twenty-three pts died:18 from disease progression, 4 treatment-related (TRM) and one of second cancer. Median engraftment time for neutrophils (>0.5×109/L) was 14 days and platelets (>20×109/L) was 27 days and was significantly longer compared to pts who received PBSC alone (10 and 11 days, respectively, p<0.0001). Pts receiving Mx grafts had significantly faster engraftment vs those receiving BM alone (p<0.001). Transfusion requirements (median) during the ASCT admission were 4 units for RBC and 25 units for platelets. Median 12 month Hb, platelet and neutrophil counts were 116 g/L (70–149), 113×109/L (21–238) and 2.4×109/L (0.3–6.2). Two year OS of patients who received harvested BM versus PBSC alone was: 63%/71% (AML, p=0.51), 57%/70% (NHL, p=0.04) and 71%/94% (HL, p=0.04). There was no significant difference in PFS between BM recipients and controls. Non relapse mortality was 5/52 (9.6%) for pts receiving BM compared to 18/440 (4%) supported by PBSCs. Conclusion: Performing an AHCT with BM in patients failing PBSC collection is feasible. Although engraftment is significantly delayed it appears sustained at 12 months post AHCT. Overall survival is inferior compared with patients receiving PBSC alone. Reasons for inferior disease-specific outcomes for pts with lymphoma receiving BM need to be determined.


Blood ◽  
2000 ◽  
Vol 96 (9) ◽  
pp. 3001-3007 ◽  
Author(s):  
Ian McNiece ◽  
Roy Jones ◽  
Scott I. Bearman ◽  
Pablo Cagnoni ◽  
Yago Nieto ◽  
...  

Ex vivo expanded peripheral blood progenitor cells (PBPCs) have been proposed as a source of hematopoietic support to decrease or eliminate the period of neutropenia after high-dose chemotherapy. CD34 cells were selected from rhG-CSF mobilized PBPCs from patients with breast cancer and were cultured for 10 days in defined media containing 100 ng/mL each of rhSCF, rhG-CSF, and PEG-rhMGDF in 1 L Teflon bags at 20 000 cells/mL. After culture the cells were washed and reinfused on day 0 of transplantation. On day +1, cohort 1 patients (n = 10) also received an unexpanded CD34-selected PBPC product. These patients engrafted neutrophils (absolute neutrophil count, >500/μL) in a median of 6 (range, 5-14) days. Cohort 2 patients (n = 11), who received expanded PBPCs only, engrafted neutrophils in a median of 8 (range, 4-16) days. In comparison, the median time to neutrophil engraftment in a historical control group of patients (n = 100) was 9 days (range, 7-30 days). All surviving patients are now past the 15-month posttransplantation stage with no evidence of late graft failure. The total number of nucleated cells harvested after expansion culture was shown to be the best predictor of time to neutrophil engraftment, with all patients receiving more than 4 × 107 cells/kg, engrafting neutrophils by day 8. No significant effect on platelet recovery was observed in any patient. These data demonstrate that PBPCs expanded under the conditions defined can shorten the time to engraftment of neutrophils compared with historical controls and that the rate of engraftment is related to the dose of expanded cells transplanted.


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