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Randomized Trial of Filgrastim, Sargramostim, or Sequential Sargramostim and Filgrastim After Myelosuppressive Chemotherapy for the Harvesting of Peripheral-Blood Stem Cells

From the Clinical Research Division, Response Oncology, Inc, Memphis, TN, and the Clinical Economics Research Unit, Georgetown University Medical Center, Washington, DC.

Address reprint requests to C. Dean Buckner, MD, 540, 30th Ave S, Seattle, WA 98144; email dbuckner{at}jetcity.com

	ABSTRACT

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION APPENDIX REFERENCES

 
PURPOSE: The purpose of this study was to compare the effects of filgrastim, sargramostim, or sequential sargramostim and filgrastim on CD34⁺ cell yields and morbidity after myelosuppressive mobilization chemotherapy (MC).

PATIENTS AND METHODS: One hundred fifty-six patients were randomized to receive filgrastim (n = 51), sargramostim (n = 52), or sargramostim for 5 days followed by filgrastim (n = 53) after MC with either cyclophosphamide and etoposide (n = 75) or paclitaxel and cyclophosphamide (n = 81).

RESULTS: Compared with those who received sargramostim, patients who received filgrastim had faster recovery of an absolute neutrophil count of 0.5 x 10⁹/L or greater (a median of 11 v 14 days; P = .0001), with fewer patients requiring RBC transfusions (P = .008), fewer patients with fever (18% v 52%; P = 0.001), fewer hospital admissions (20% v 42%; P = .013), and less intravenous antibiotic therapy (24% v 69%; P = .001). Patients who received filgrastim yielded more CD34⁺ cells (median, 7.1 v 2.0 x 10⁶/kg/apheresis; P = .0001), and a higher fraction achieved 2.5 x 10⁶ (94% v 78%; P = .021) and 5 x 10⁶ (88% v 53%; P = .001) or more CD34⁺ cells/kg with fewer aphereses (median, 2 v 3; P = .002) and fewer days of growth-factor treatment (median, 12 v 14; P = .0001). There were no major differences in outcomes between the filgrastim alone and the sequential regimens. After high-dose chemotherapy, patients who had peripheral-blood stem cells (PBSCs) mobilized with filgrastim or the sequential regimen received higher numbers of CD34⁺ cells and had faster platelet recovery (P = .015), with fewer patients (P = .014) receiving fewer platelet transfusions (P = .001) than patients receiving sargramostim-mobilized PBSCs.

CONCLUSION: It was concluded that filgrastim alone or sequential sargramostim and filgrastim were superior to sargramostim alone for the mobilization of CD34⁺ cells and reduction of toxicities after MC.

	INTRODUCTION

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION APPENDIX REFERENCES

 
AUTOLOGOUS peripheral-blood stem cells (PBSCs) are the preferred source of hematopoietic stem cells for the support of patients receiving high-dose chemotherapy (HDC).¹ PBSCs can be collected after the administration of a myeloid growth factor alone^1-4 or after the administration of myelosuppressive mobilization chemotherapy (MC) and a myeloid growth factor.^5-9 More PBSCs, as measured by CD34⁺ cell content, are collected after the administration of MC and a growth factor than after treatment with a growth factor alone.¹ It is currently common practice to administer disease-specific MC and a myeloid growth factor to facilitate the harvest of PBSCs and to treat the underlying malignancy.¹

The two most commonly used myeloid growth factors for the facilitation of PBSC harvests in the United States are recombinant human granulocyte colony-stimulating factor (filgrastim)^2-11 and recombinant human granulocyte-macrophage colony-stimulating factor (rHuGM-CSF). Sargramostim is a glycosylated form of rHuGM-CSF derived from yeast and marketed in the United States,^12-15 and molgramostim is an unglycosylated form of rHuGM-CSF derived from Escherichia coli and only available for experimental use in the United States.^16-24

The administration of MC and a myeloid growth factor is associated with variable CD34⁺ cell yields and morbidity.¹ It has not been determined in randomized prospective trials whether there are major differences between myeloid growth factor regimens and CD34⁺ cell yields and morbidity after MC. There are reports of PBSCs being harvested with MC followed by the administration of filgrastim,^4-11,25 sargramostim,^14,15,26 or the combination of sargramostim and filgrastim,¹² but there have been no prospective, randomized studies comparing the relative effectiveness of these regimens.

A prospective randomized trial was performed to compare the effects of filgrastim alone, sargramostim alone, or the sequential administration of sargramostim and filgrastim on CD34⁺ cell yields, hematologic recovery, morbidity, and resource utilization after the administration of MC.

	PATIENTS AND METHODS

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION APPENDIX REFERENCES

 
Study Design
This was a randomized, open-label trial of three schedules of myeloid growth factors administered after MC for the collection of CD34⁺ PBSCs. The MC regimen, cyclophosphamide and etoposide (CE) or paclitaxel and cyclophosphamide (PC), was determined by the primary treatment protocol. The primary treatment protocols for patients with multiple myeloma and malignant lymphoma included only the CE regimen, whereas the protocols for patients with breast cancer included both CE and PC. Patients were stratified by disease, extent of prior therapy, and MC regimen. Patients were randomized in strata and forced to balance in blocks of six. The following three groups of patients were evaluated:

1. Filgrastim alone: daily administration until PBSC harvests were completed.

2. Sargramostim alone: daily administration until PBSC harvests were completed.

3. Sargramostim followed by filgrastim: daily administration of sargramostim for 5 days, followed by daily filgrastim until PBSC harvests were completed.

Patient Selection
Between September 1997 and July 31, 1998, 158 patients with breast cancer, malignant lymphoma, or multiple myeloma who met the protocol eligibility criteria for treatment with HDC with PBSC support were enrolled. Eligibility criteria included an Eastern Cooperative Oncology Group performance status of 0 to 2; age less than 66 years; and evidence of adequate hepatic, renal, and cardiac function. Patients who had undergone a prior mobilization procedure or who had previously received HDC with PBSC support were excluded. All patients signed a protocol-specific informed consent form that had been approved by the institutional review board of the hospital where the therapy was administered.

Two of the 158 patients were excluded from the sargramostim group because they erroneously received either filgrastim alone or sargramostim and filgrastim. Thus 156 patients were assessable for toxicity of MC. Six of the 156 randomized patients received CE or PC but did not have PBSC harvested because of early treatment-related death (n = 4) or poor clinical condition (n = 2) from infection or congestive heart failure. Thus 150 patients were assessable for efficiency of PBSC harvests.

Nine of the 150 patients who had PBSCs harvested did not proceed to HDC because of inadequate CD34⁺ cell collections (n = 5) or refusal of further treatment (n = 4). Twenty patients received sequential HDC treatments with the infusion of a fraction of their collected PBSCs after each course of chemotherapy and were not included in the analyses of hematopoietic recovery. Thus 126 patients were assessable for engraftment parameters after a single course of HDC and PBSC infusion.

Treatment Centers
Patients were treated in one of 39 medical centers in the United States under the care of 88 medical oncologists affiliated with the Clinical Trials Division of Response Oncology Inc (ROI; Memphis, TN) listed in the Appendix. Chemotherapy for all phases of treatment was administered, and the PBSCs were harvested in an outpatient facility²⁷. Patients who required hospital admission were admitted to hospitals that met the criteria of the American Society of Clinical Oncology/American Society of Hematology guidelines for stem-cell transplantation.²⁸

Administration of MC and Myeloid Growth Factors
MC consisted of cyclophosphamide 4 g/m² on day 1 and etoposide 200 mg/m² on days 1 to 3 (CE; n = 75)⁷ or paclitaxel 200 mg/m² on day 1 and cyclophosphamide 3 g/m² on day 2 (PC; n = 81).⁹

Myeloid growth factor administration was administered subcutaneously beginning on the day after the completion of MC. The regimens evaluated were filgrastim 6 µg/kg/d (Amgen, Thousand Oaks, CA); sargramostim 250 µg/m²/day (Immunex, Seattle, WA); or sargramostim 250 µg/m²/d for 5 days, followed by filgrastim 6 µg/kg/d. All myeloid growth factors were administered daily until the final day of apheresis.

Collection, Cryopreservation, and Infusion of PBSCs
Patients had complete blood counts measured daily and began apheresis after the WBC count recovered to 3 x 10⁹/L, irrespective of the day of the week. PBSCs were collected and cryopreserved as previously described.^5,29 CD34⁺ cell enumeration was performed in a single laboratory, as previously described.²⁹ PBSCs were thawed and infused 24 to 48 hours after the last dose of HDC, which was designated day 0.

Several criteria were used to determine the number of apheresis procedures. Patients would undergo a minimum of four aphereses unless (1) the cumulative yield of CD34⁺ cells on any day was 5 x 10⁶ cells/kg or more, in which case aphereses were discontinued, or (2) the cumulative yield of CD34⁺ cells was more than 2.5 x 10⁶ cells/kg but fewer than 5 x 10⁶ cells/kg, in which case one additional apheresis was performed.

High-Dose Chemotherapy
The following HDC regimens were administered to 126 patients: cyclophosphamide, thiotepa, and carboplatin (n = 87),²⁷ carmustine, etoposide, cytarabine, and cyclophosphamide (n = 25),³⁰ busulfan, melphalan, and thiotepa (n = 13),³¹ or a single high dose of melphalan (n = 1).³²

Cell-Dose Criteria for Support of HDC
The optimal dose for support of HDC was considered to be 5.0 x 10⁶ CD34⁺ cells/kg or more, and the minimal dose to proceed with HDC was 1.0 x 10⁶ CD34⁺ cells/kg.³³ Patients who yielded fewer than 1.0 x 10⁶ CD34⁺ cells/kg were offered a second attempt to mobilize PBSCs or were not treated with HDC.³⁴ Patients who yielded fewer than 2.5 but 1.0 x 10⁶ or more CD34⁺ cells/kg could elect to have HDC supported by less than optimal CD34⁺ cell numbers or to undergo a second mobilization procedure.³⁴

Supportive Care During MC and HDC With PBSC Support
Patients received MC and HDC in an outpatient treatment facility, with daily surveillance for complications warranting hospital admission, including fever with signs and symptoms of infection, documented bacteremia, inadequate caloric and/or fluid intake, severe mucositis, or severe diarrhea.³⁵ All patients received filgrastim 6 µg/kg/d beginning on day 1 after PBSC infusion and continued until the absolute neutrophil count (ANC) was 0.5 x 10⁹/L or greater for 3 consecutive days. Patients received prophylactic ciprofloxacin orally after they completed chemotherapy until their ANC was 0.5 x 10⁹/L or greater for 3 consecutive days after the nadir. Febrile patients were treated with intravenous broad-spectrum antibiotics, usually with admission to the hospital. RBC and platelet transfusions were administered empirically for patients with hemoglobin levels less than 8.0 mg/dL and platelet counts of 20 x 10⁹/L or lower, respectively.

Definitions
After MC, hematopoietic recovery was measured from the first day of chemotherapy administration (day 0). After HDC, hematopoietic recovery was measured from the day of PBSC infusion (day 0). Fever was defined as a body temperature of 38.5°C (101°F) or higher on one or more determinations.³⁶ Neutrophil recovery after MC or HDC was defined as the first of 2 consecutive days on which the ANC was 0.5 x 10⁹/L or higher after the nadir. Platelet recovery after MC or HDC was defined as the first of 2 consecutive days on which the platelet count was 20 x 10⁹/L or higher after the nadir without transfusions.

Statistical Analyses
All data were collected using a custom-designed distributed data system, reviewed at a central clinical trials center (ROI), and analyzed using ^TMSAS system software (SAS Institute, Cary, NC). The number of CD34⁺ cells collected x 10⁶/kg/apheresis was calculated by dividing the total number of CD34⁺ cells collected per patient by the number of daily aphereses. All continuous variables were analyzed using the Wilcoxon rank sum test. Proportions were compared using a ² statistic or Fisher’s exact test, as appropriate. Neutrophil and platelet recovery rates after HDC were estimated using the product-limit method according to Kaplan-Meier³⁷ and were compared using the log-rank test.³⁸

	RESULTS

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION APPENDIX REFERENCES

 
Patient Characteristics
Characteristics of the 156 assessable patients who received MC are listed in Table 1. There were no statistically significant differences between the three groups.

More patients who received filgrastim alone had a temperature of 38.5°C or higher on 1 or more days, compared with sargramostim-treated patients (P = .001). Twenty percent of patients in the filgrastim-alone group were admitted to hospitals, compared with 42% in the sargramostim group (P = .001). The incidence of intravenous (IV) antibiotic use was 24% in the filgrastim group and 69% in the sargramostim group (P = .001). The fraction of patients who received RBC transfusions was 22% in the filgrastim-alone group and 46% in the sargramostim group (P = .008). Twenty-five percent of patients in the filgrastim group received platelet transfusions, compared with 42% in the sargramostim group (P = .072).

Sargramostim versus sequential sargramostim and filgrastim. The median number of days to recovery of an ANC of 0.5 x 10⁹/L or greater was 14 for patients who received sargramostim and 12 for patients who received the sequential regimen (P = .0001). There was no difference in the proportion of patients with a platelet-count nadir of 20 x 10⁹/L or lower between the two groups. The proportion of patients with a hemoglobin nadir of 8.0 mg/dL was 54% for patients who received sargramostim and 35% for patients who received the sequential regimen (P = .040).

A temperature of 38.5°C was observed in 52% of sargramostim-treated patients and 15% of sargramostim and filgrastim–treated patients (P = .001). Forty-two percent of patients in the sargramostim-alone group were admitted to hospitals, compared with 21% in the sequential group (P = .017). The incidence of IV antibiotic use was 69% in the sargramostim group and 25% in the sequential group (P = .001). Forty-two percent of patients in the sargramostim group received platelet transfusions, compared with 26% in the sequential group (P = .086).

Filgrastim versus sequential sargramostim and filgrastim. Patients who received sequential sargramostim and filgrastim recovered an ANC of 0.5 x 10⁹/L or greater on a median day of day 12, compared with day 11 for patients who received filgrastim alone (P = .001). There were no other statistically significant differences between patients who received filgrastim or the sequential regimen for any of the end points listed in Table 2.

Toxicities and Hematopoietic Recovery After PC or CE Treatment
Measurements and rates for the following parameters were higher in more patients who received CE, compared with patients who received PC (respectively): fever, 36% versus 21% (P = .037); incidence of bacteremia, 9% versus 0% (P = .005); IV antibiotic usage, 51% versus 28% (P = .004); admissions to hospital, 39% versus 17% (P = .003); median days in hospital, 6 versus 4 (P = .020); fraction who received platelet transfusions, 48% versus 16% (P = .001); and the fraction who received RBC transfusions, 44% versus 23% (P = .007). The median day on which an ANC of 0.5 x 10⁹/L or greater occurred was day 13 for patients who received CE and day 12 for patients who received PC (P = .0001). Forty-one percent of the patients in the CE group and 19% in the PC group had platelet-count nadirs of 20 x 10⁹/L or lower (P = .001). Forty-nine percent of the patients in the CE group and 33% in the PC group had hemoglobin nadirs of 8.0 mg/dL or lower (P = 0.042). Five of the six patients who did not proceed to apheresis received CE, including all four who died of treatment-related causes.

CD34⁺ Cell Harvests and Growth-Factor Administration
One hundred fifty (96%) patients underwent one or more apheresis procedures. The median number of CD34⁺ cells collected for all 150 patients was 8.5 x 10⁶/kg (range, 0.02 to 96) in a median number of two apheresis procedures (range, one to nine) with a median of 13 days of growth-factor administration (range, 9 to 22). Eighty-nine percent of patients achieved a level of 2.5 x 10⁶ CD34⁺ cells/kg or higher, and 74% achieved 5 x 10⁶ CD34⁺ cells/kg or higher. Seven (5%) patients yielded fewer than 1 x 10⁶ CD34⁺ cells/kg, and five of these seven underwent second mobilization procedures. The results of CD34⁺ cell yields for the three groups of patients are listed in Table 3.

Filgrastim versus sequential sargramostim and filgrastim. The only significant difference between these two groups was that the first day of apheresis was on day 12 for the filgrastim group and day 13 for the sequential sargramostim and filgrastim group (P = .008).

Sargramostim versus sequential sargramostim and filgrastim. For most end points (listed in Table 3), the sequential administration of sargramostim and filgrastim was significantly superior to sargramostim alone. Second mobilizations were not performed in any patient in the sequential sargramostim and filgrastim group, compared whereas they were performed in five patients in the sargramostim-alone group (P = .018).

CD34⁺ Cell Yields After PC or CE
Tables 4 and 5 summarize the differences observed in CD34⁺ cell harvests between patients who received PC or CE. Patients who received PC yielded a median of 5.75 x 10⁶ CD34⁺ cells/kg, compared with 11.83 x 10⁶ CD34⁺ cells/kg for patients who received CE (P = .0003). Patients who received PC yielded 2.78 x 10⁶ CD34⁺ cells/kg/apheresis, compared with 6.44 x 10⁶ CD34⁺ cells/kg for patients who received CE (P = .0002). As a generality, the statistically significant differences observed between the three cytokine regimens for the entire population were confirmed in subgroup analyses by mobilization regimen. However, for patients who received CE, there were no differences in the proportion of patients who achieved levels of 2.5 or 5.0 x 10⁶ CD34⁺ cells/kg or higher for patients who received filgrastim (91% and 86%, respectively), sargramostim (82% and 77%, respectively), or sequential sargramostim and filgrastim (95% and 85%, respectively), all with P values of .180 or greater.

Filgrastim versus sequential sargramostim and filgrastim. Patients who received filgrastim–mobilized PBSCs recovered platelets to a level of 20 x 10⁹/L on day 9, compared with day 11 for patients who received sargramostim and filgrastim–mobilized PBSCs (P = .101). Twenty-nine percent of the patients who received the sequential regimen were infused with fewer than 5.0 x 10⁶ CD34⁺ cells/kg, compared with 14% for patients who received filgrastim alone (P = .087).

Sargramostim versus sequential sargramostim and filgrastim. Patients who received sargramostim-mobilized PBSCs were infused with fewer CD34⁺ cells/kg than were patients who received the sequential regimen (P = .001). Patients who received sargramostim-mobilized PBSCs had slower recovery of platelets, but this difference was not statistically significant (P = .294). Patients who received the sequential regimen were transfused with platelets a median of 1 day less (P = .006).

	DISCUSSION

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION APPENDIX REFERENCES

 
In this study, one major finding was that patients who received filgrastim after MC yielded more CD34⁺ cells than did patients who received sargramostim. There were differences in CD34⁺ cell yields between the two MC regimens, as shown in Tables 4 and 5. Twice as many CD34⁺ cells were collected after CE as after PC. For patients who received CE, more CD34⁺ cells were collected after filgrastim or sequential sargramostim and filgrastim than after sargramostim alone. However, 82% of the patients who received sargramostim yielded 2.5 x 10⁶ CD34⁺ cells/kg or more, and 77% yielded 5.0 x 10⁶ CD34⁺ cells/kg or more, which were not significantly different from those in patients who received filgrastim alone or sequential sargramostim and filgrastim (Table 4). Thus sargramostim and filgrastim after CE were equally effective for achieving target CD34⁺ cell numbers. The major differences in achieving target CD34⁺ cell yields were observed in patients who received PC (Table 5). In general, PC was associated with fewer toxicities and more rapid hematologic recovery than CE. It has previously been observed that more intensive chemotherapy regimens are associated with a better CD34⁺ cell yield than less intensive regimens, this would probably explain the current observations.^1,5,39

There have been no previous randomized trials comparing the prophylactic administration of filgrastim with sargramostim after MC. However, one randomized trial compared filgrastim with molgramostim in 26 patients with Hodgkin’s disease who received MC.¹⁶ Twenty-one patients completed PBSC collections, and there were no differences in CD34⁺ cell yields or toxicities between the two treatment groups.¹⁶ Bregni et al,¹⁸ in a nonrandomized trial, compared filgrastim with molgramostim, administered by continuous IV infusion, in 49 patients with malignant lymphoma who received cyclophosphamide 7 g/m². They found more rapid recovery of neutrophils after filgrastim treatment (P = .01), more rapid recovery of platelets after molgramostim treatment (P = .01), and more CD34⁺ cells/kg/apheresis after molgramostim treatment, but these differences were not statistically significant (P = .132). They also found no differences in the yields of undifferentiated hematopoietic progenitors as defined by the CD34⁺/CD33^- surface phenotype. Differences between these two studies and the study presented here could be due to differences in the rHuGM-CSF molecule, the myelosuppressive regimens, the dose and schedule of growth-factor administration, or the relatively small number of patients evaluated.

Filgrastim has been compared with sargramostim or the combination of sargramostim and filgrastim in healthy individuals.^13,40-42 These studies demonstrated that the use of filgrastim alone or sequential sargramostim and filgrastim mobilized more CD34⁺ cells than did sargramostim alone in healthy persons. These studies also suggested that the use of sequential sargramostim and filgrastim mobilized more primitive hematopoietic cells (CD23⁺/CD38^-/HLA-DR⁺) than did treatment with either drug alone. The practical significance of these observations for PBSC transplantation is unknown. However, the lack of reports of late graft failure after autologous or allogeneic transplantation with filgrastim-mobilized PBSCs would suggest that the infusion of inadequate quantities of more primitive stem cells is not a major clinical problem.

Spitzer et al¹² randomized patients to receive filgrastim 10 µg/kg/d or the combination of filgrastim 10 µg/kg/d plus sargramostim 5 µg/kg/d without prior chemotherapy and found no increase in CD34⁺ cell yields after the combination growth factor administration. These observations are consistent with those of the study presented here, although the schedule of growth-factor administration was concurrent rather than sequential, as in this study.

In this study, hematopoietic recovery after a single course of HDC and PBSC infusion was evaluated in 126 patients (Table 6). Patients who had PBSCs mobilized with CE or PC and sargramostim alone received 50% fewer CD34⁺ cells, compared with patients who received cells harvested after filgrastim or sequential sargramostim and filgrastim mobilization. There was a 3-day faster recovery of platelets in patients who received filgrastim-mobilized PBSCs than in patients who received sargramostim-mobilized PBSCs (day 9 v day 12; P = .015), which was probably due to the large difference in median CD34⁺ cell dose. This finding lends further support to a number of studies which have shown that infusing 5.0 x 10⁶ CD34⁺ cells/kg or more is associated with a reduction in time to platelet recovery, with fewer supportive-care requirements.^6,29,43,44 Patients who received sequential sargramostim- and filgrastim-mobilized PBSCs did not recover platelets until a median of day 11, compared with day 9 for patients who received comparable median numbers of filgrastim-mobilized CD34⁺ cells (P = .101). However, this was probably due to the fact that 29% of patients infused with PBSCs mobilized by sequential sargramostim and filgrastim were transfused with fewer than 5 x 10⁶ CD34⁺ cells/kg, compared with 14% for patients infused with PBSCs mobilized by filgrastim alone (P = .087).

As shown in Table 2, patients who received filgrastim or the sequential regimen had a faster recovery of neutrophils to a level of 0.5 x 10⁹/L, compared with patients who received sargramostim alone (P = .0001 and .0001, respectively). The increased incidence of fever in patients who received sargramostim probably accounts for the increased frequency of hospital admissions and IV antibiotic usage. Fever in the sargramostim group was most likely due to the drug itself and not to infection, because the incidence of documented bacteremia was the same for all three groups.

The higher incidence of anemia and more frequent RBC transfusions in the sargramostim group was an unexpected finding because neither filgrastim nor sargramostim has a known effect on RBC production. The mechanism by which sargramostim-treated patients were more likely to develop anemia than were patients who received filgrastim or the sequential regimen was not investigated and could only be speculated upon. There were no differences in the frequency of patients with a platelet-count nadir of 20 x 10⁹/L or higher among the three groups. More patients in the sargramostim group received platelet transfusions than did patients who received filgrastim or the sequential regimen, but these differences did not reach statistical significance.

There are no randomized trials comparing the effects of prophylactic administration of filgrastim or sargramostim on toxicities and hematologic recovery after MC. However, in one study, filgrastim has been compared with sargramostim in patients with chemotherapy-induced myelosuppression.⁴⁵ In that study, 181 afebrile patients with an ANC lower than 0.5 x 10⁹/L were randomized to receive filgrastim or sargramostim until neutrophil recovery occurred. There was no statistical difference in the mean number of days it took to reach an ANC of 0.5, but the mean number of days to reach 1.0 or 1.5 x 10⁹/L was 1 day less for the filgrastim group, with the administration of 1 less day of growth factor. There were no statistically significant differences in hospitalization time, mean duration of fever, or mean duration of IV antibiotic usage between patients receiving filgrastim or sargramostim.

Only two chemotherapy mobilization regimens, PC and CE, were administered in this study. Because there were differences between the two regimens in terms of toxicity and CD34⁺ cell yields, these findings may need to be confirmed for other mobilization regimens used to facilitate PBSC harvests. However, the current findings are, in general, consistent with the studies of myeloid growth factors alone, without chemotherapy, for the mobilization of PBSCs.^12,13,40-42 If the goal is to harvest large quantities of CD34⁺ cells with the least morbidity and resource utilization, filgrastim alone administered after MC would appear to be the best currently available myeloid growth factor regimen. Other potential benefits of mobilizing PBSCs with sargramostim or sequential sargramostim and filgrastim, ie, the possible mobilization of more primitive stem cells or dendritic cells,^13,40-42 were not addressed in this study.

	APPENDIX

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION APPENDIX REFERENCES

 
The following physicians participated in this study (all are affiliated with the Response Oncology Network in the cities listed): Albany, GA: J. Tongol; Albuquerque, NM: B. McAneny, J. Liebmann, V. Vigil; Asheville, NC: J. Puckett; Atlanta, GA: M. Moore, R. Leff; Bayonne, NJ: D. Iyengar; Billings, MT: B. Whittenberger, G. Midence, P. Cobb, R. Santala; Boca Raton, FL: I. Sysel; Clearwater, FL: G. Stanton, J. Hajdenberg, L. Ziegler, T. McLaughlin; Columbia, SC: R. Smith, Jr, W. Babcock; Columbia, MO: D. Schlossman, M. Muscato; Corpus Christi, TX: M. Nash; El Paso, TX: J. Gomez, R. Rivera, R. Portillo; Ft. Smith, AR: J. Wells; Ft Wayne, IN: G.T. Gabrys; Glendale, CA: K. Ucar; Grand Rapids, MI: K. Yost, L. Pawl; Hollywood, FL: A. Rosenberg, F. Wittlin, I. Sysel, R. Cano, W. Rymer; Houma, LA: R. Doria; Houston, TX: E. Rogg; Jackson, MI: G. Shumaker; Kansas City, KS: K. Pendergrass, S. Ethirajan; Knoxville, TN: A. Grossman, J. Foster, R.B. Avery; Lafayette, LA: L. Meza; Little Rock, AR: B. Baltz, L. Mendelsohn; Macon, GA: J. Smith, Jr., K. Deaton, M. Mangum; Memphis, TN: A. Weir, III, E. Weeks, K. Tauer, L. Schwartzberg; Miami, FL: A. Feinberg, A. Larcada, H. Lessner, H. Wallach, M. Troner, P. Kaywin; Mobile, AL: T. Beeker; Nashville, TN: A. Cohen, A. Greco, A. Meluch, C. Penley, J. Hainsworth, J. Strupp, R. Lamar, S. Spigel; Northside (Atlanta), GA: C. Franco; Richmond, VA: D. Trent, L. Lewkow, M. Shwarz; Savannah, GA: A. Bala, J. West, L.E. Robertson; Scranton, PA: F. Laluna, W. Heim; St. Louis, MO: L. White, S. Allen; Syracuse, NY: A. Scalzo, D. Churchill, H. Puc; Tampa, FL: R. Blanco, R. Altemose; Treasure Coast, FL: M. Wertheim, N. Iannotti; Washington, DC: V. Malkovska; Worcester, MA: S. Donohue.

	ACKNOWLEDGMENTS

 
Supported in part by the Community Cancer Research Foundation, Seattle, WA, and the Josep Steiner Foundation, Bern, Switzerland.

	REFERENCES

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION APPENDIX REFERENCES

 
1. Demirer T, Buckner CD, Bensinger WI: Optimization of peripheral blood stem cell mobilization. Cells (Dayt) 14:106-116, 1996

2. Bensinger WI, Singer J, Appelbaum F, et al: Autologous transplantation with peripheral blood mononuclear cells collected after administration of recombinant granulocyte stimulating factor. Blood 81:3158-3163, 1993[Abstract/Free Full Text]

3. Bensinger WI, Longin K, Appelbaum F, et al: Peripheral blood stem cells (PBSCs) collected after recombinant granulocyte colony stimulating factor (rhG-CSF): An analysis of factors correlating with the tempo of engraftment after transplantation. Haematol 87:825-831, 1994

4. Weaver CH, Birch R, Greco FA, et al: Mobilization and harvesting of peripheral blood stem cells: A randomized dose escalation trial of filgrastim. Br J Haematol 100:338-347, 1998[Medline]

5. Schwartzberg L, Birch R, Hazelton B, et al: Peripheral blood stem cell mobilization by chemotherapy with and without recombinant human granulocyte colony-stimulating factor. J Hematother 1:317-327, 1992[Medline]

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Submitted May 13, 1999; accepted August 11, 1999.

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