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Effect of CD34⁺ Cell Dose on Resource Utilization in Patients After High-Dose Chemotherapy With Peripheral-Blood Stem-Cell Support

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

Address reprint requests to Kevin A. Schulman, MD, Clinical Economics Research Unit, 2233 Wisconsin Ave NW, Suite 440, Washington, DC 20007; email schulmak{at}gunet.georgetown.edu

	ABSTRACT

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

 
PURPOSE: The mean time to neutrophil and platelet recovery for patients receiving high-dose chemotherapy (HDC) supported with peripheral-blood stem cells (PBSCs) is related to the dose of CD34⁺ cells infused. The effect of cell dose on resource utilization after transplantation has not been previously reported.

MATERIALS AND METHODS: We assessed CD34⁺ cell dose and resource utilization for 1,317 patients undergoing transplantation with PBSCs from April 1991 to June 1997. PBSCs were collected after mobilization with chemotherapy and recombinant human granulocyte colony-stimulating factor (rhG-CSF). Daily measurement of the CD34⁺ content of the PBSC collection was performed by a central laboratory using a single CD34⁺ analysis technique. Resource utilization included engraftment parameters, length of stay, and transfusion requirements for 100 days posttransplantation. Analysis included descriptive statistics and multiple regression.

RESULTS: Mean patient age was 47 years, and 86% of patients were female. Median cell dose was 3.6 x 10⁶/kg and 13.2 x 10⁶/kg for patients receiving less than 5.0 x 10⁶ CD34⁺ cells/kg and 5.0 x 10⁶ or more CD34⁺ cells/kg, respectively. Patients receiving less than 5.0 x 10⁶ CD34⁺ cells/kg were more likely to have metastatic breast cancer or non-Hodgkin's lymphoma and required more platelet and RBC transfusions, 3.3 more hospital days, and increased antibiotic and antifungal use. In univariate analysis, the cost of care was $41,516 (±$20,876 SD) and $32,382 (±$16,353 SD) for patients with less than 5.0 x 10⁶ CD34⁺ cells/kg and 5.0 x 10⁶ or more CD34⁺ cells/kg, respectively. In multivariate analysis, patients with less than 5.0 x 10⁶ CD34⁺ cells/kg had an increase in costs of $5,062 (± $1,262 SE).

CONCLUSION: Infusion of more than 5.0 x 10⁶ CD34⁺ cells/kg was associated with a reduction in resource utilization. Achieving a target of 5.0 x 10⁶ CD34⁺ cells/kg should have important clinical and economic benefits for patients.

	INTRODUCTION

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

 
HEMATOPOIETIC RECOVERY after the administration of myeloablative therapy remains a significant clinical issue for oncologists. Autologous peripheral-blood stem cells (PBSCs) have been used increasingly for hematopoietic recovery after administration of high-dose chemotherapy (HDC) with or without total-body irradiation for patients with malignant diseases. Several studies suggest that autologous PBSCs alone are superior to autologous bone marrow transplantation (ABMT) with regard to the rate of hematopoietic recovery achieved after administration of myeloablative therapy.^1-6 Recently, the association between CD34⁺ cell dose and hematopoietic recovery has been investigated. A previous study in a subset of this population has shown that CD34⁺ cell content is related to engraftment kinetics in patients receiving PBSCs after myeloablative HDC.⁷ That study demonstrated that patients who receive a cell dose of more than 5.0 x 10⁶ cells/kg have optimal engraftment after PBSC transplantation. An optimal cell dose of at least 5.0 x 10⁶ cells/kg has been confirmed by others.^8,9

Although the clinical superiority of this dose of CD34⁺ cells has been established, the resource-use implications of cell dose for transplantation patients has not been fully examined. In this study, we assess resource utilization for patients receiving PBSC transplants for a period of up to 100 days after PBSC infusion. This analysis directly assesses the relationship between CD34⁺ cell count and resource utilization for patients undergoing PBSC transplantation.

	MATERIALS AND METHODS

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

 
Patient Selection
Between April 1991 and June 1997, data were collected on 1,317 consecutive patients undergoing PBSC transplantation, including CD34⁺ cell dose and subsequent resource utilization. Patients were entered onto protocols administering HDC supported by PBSCs. The PBSCs were collected after cyclophosphamide-based mobilization chemotherapy with recombinant human granulocyte colony-stimulating factor (rhG-CSF). Patients were eligible for the study if they had relapsed Hodgkin's disease (HD), non-Hodgkin's lymphoma (NHL), stage II breast cancer with four or more lymph nodes involved with tumor, stage III breast cancer with one or more positive nodes, stage IV breast cancer, ovarian cancer, relapsed sarcoma, or multiple myeloma. Additional inclusion criteria included patient age of 18 to 65 years, Eastern Cooperative Oncology Group performance status of 0 to 1, and evidence of adequate hepatic, renal, and cardiac function. All patients signed a statement of informed consent approved by the institutional review board of the hospital where therapy was administered.

Mobilization of PBSCs
Patients were enrolled onto one of three protocols using cyclophosphamide and rhG-CSF for mobilization of PBSCs. Seven-hundred forty patients received cyclophosphamide and etoposide (CE) plus rhG-CSF. Three-hundred fifty-two patients had PBSCs mobilized with cyclophosphamide, etoposide, and cisplatin plus rhG-CSF. Two-hundred twenty-five patients received a cyclophosphamide and paclitaxel plus rhG-CSF regimen. For patients receiving CE, cyclophosphamide 4 g/m² was administered on day 1, and etoposide 200 mg/m² was administered on days 1 through 3. Cyclophosphamide was diluted in 500 mL of normal saline and infused over 2 to 3 hours. Patients received uroprotection with mesna administered as a 600-mg/m² bolus immediately before and after cyclophosphamide and for 24 hours as a continuous infusion of 2,400 mg/m². Etoposide was diluted in 500 mL of normal saline and administered over 1 to 2 hours. Patients receiving cyclophosphamide, etoposide, and cisplatin plus rhG-CSF were given cisplatin 35 mg/m² diluted in 250 mL of normal saline and administered over 1 hour with 25 to 50 g of mannitol on days 1 through 3. For patients receiving the cyclophosphamide and paclitaxel plus rhG-CSF regimen, paclitaxel 170 to 200 mg/m² was infused over 3 hours on day 1, and cyclophosphamide 3 g/m² was infused over 2 to 3 hours on day 2.

All patients received rhG-CSF 6 µg/kg/d (Amgen, Thousand Oaks, CA), administered subcutaneously from the day after the end of mobilization until completion of leukapheresis. All patients underwent analysis of PBSCs concurrent with leukapheresis.

A previous analysis recommended collection of a minimum level of 1.0 x 10⁶ CD34⁺ cells/kg before proceeding to HDC.³ Therefore, 44 of 1,317 patients required a second course of mobilization therapy, which was accomplished through chemotherapy and rhG-CSF (n = 38) or rhG-CSF alone (n = 6).

Collection and Cryopreservation of PBSCs
After the administration of chemotherapy, complete blood cell counts were obtained daily, and patients began leukapheresis when the total WBC count recovered to 1,000 to 5,000/µL. Leukapheresis was performed daily with a Fenwal CS-3000 Plus blood cell separator (Baxter, Deerfield, IL) for 3- to 4-hour sessions, processing 10 L of whole blood per session until analysis of the product confirmed collection of more than 2.5 x 10⁶ CD34⁺ cells/kg patient weight. The final product containing 10% dimethyl sulfoxide in autologous platelet-deficient plasma was frozen in a liquid nitrogen–dependent Gordenier controlled-rate freezer (Gordenier Electronics, Roseville, MI) and was maintained in the vapor phase of liquid nitrogen below -130°C.

Measurement of Stem-Cell Content
Measurement of the CD34⁺ content of the PBSC collection was performed daily by a central reference laboratory using a single technique of CD34⁺ analysis. The methods for this analysis have been reported previously.¹⁰ A specific quality-control protocol was meticulously followed during the study period to assure accuracy of the clinical data.

Treatment Regimens
One-hundred fifty-three patients with NHL and 29 patients with HD were treated with carmustine 300 mg/m² intravenously (IV) on day -5, etoposide 150 mg/m² IV every 12 hours on days -4 to -1, cytarabine 100 mg/m² IV every 12 hours on days -4 to -1, and cyclophosphamide 35 mg/kg/d IV on days -4 to -1.¹¹ Three-hundred fifteen patients with metastatic breast cancer, 522 patients with high-risk stage II or III breast cancer, and 31 patients with ovarian cancer were treated with high-dose cyclophosphamide, thiotepa, and carboplatin. Patients received thiotepa 167 mg/m², cyclophosphamide 2 g/m², and carboplatin 267 mg/m² in equal bolus doses on days -5, -4, and -3. Eight patients with multiple myeloma and 18 patients with low-grade NHL were treated with busulfan 1.0 mg/kg orally every 6 hours on days -7 to -4 and cyclophosphamide 75 mg/kg/d IV on days -3 and -2. One-hundred eighty-three patients (metastatic breast cancer, 118 patients; HD, 19 patients; NHL, 46 patients) were given busulfan 12 mg/kg, melphalan 100 mg/m², and thiotepa 500 mg/m² (BuMelT), as previously described.¹² Thirty-nine ovarian cancer patients and five breast cancer patients received melphalan 160 mg/m² IV over 30 to 60 minutes on day -4, mitoxantrone 25 mg/m² over 50 minutes on days -4 and -3, and carboplatin 1,400 mg/m² IV over 45 to 60 minutes on day -3. Fourteen sarcoma patients were treated with ifosfamide (10 g/m²), 2.5 g/m² as a 24-hour continuous infusion on days -6 to -3, etoposide (1,400 mg/m²), 350 mg/m²/d IV over 3 hours, and carboplatin (1,200 mg/m²), 300 mg/m²/d IV over 2 hours on days -6 to -3. Cryopreserved PBSCs were thawed and infused 24 to 48 hours after the last dose of chemotherapy, as previously described.³ The day of PBSC infusion was designated day 0 in all treatment regimens.

Supportive Care
Patients analyzed for this report were treated in 40 United States medical centers under the care of 230 community medical oncologists. Outpatient care was delivered through specialty centers committed to administering HDC. Outpatient support staff of each center underwent identical primary training and continuing education and followed standardized protocols, standing orders, and supportive care guidelines.

Patients received mobilization chemotherapy and HDC in an outpatient treatment facility with daily surveillance for complications warranting hospital admission, such as febrile neutropenia or inadequate oral intake. Patients who were serologically positive for herpes simplex virus received prophylactic acyclovir. Patients received prophylactic tobramycin, ceftriaxone, and vancomycin when appropriate during neutropenia. Indwelling catheters were instilled with a solution containing heparin 5,000 U/mL and vancomycin 25 mg/mL, with the solution aspirated and discarded at each change. RBC and platelet transfusions were given empirically for a hematocrit of less than 24% (old, hemoglobin < 8.5 mg/dL) and a platelet count of less than 20 x 10⁹/L, respectively. All blood products were irradiated to 25 Gy before administration. All patients received rhG-CSF administered within 24 hours of PBSC infusion until the absolute neutrophil count reached at least 0.5 x 10⁹/L for 3 consecutive days.

Clinical Assessment
Time to neutrophil engraftment was calculated from the day of PBSC infusion to the first of 3 consecutive days on which the absolute neutrophil count was at least 0.5 x 10⁹/L after the nadir. Time to platelet engraftment was calculated from the day of PBSC infusion to the first of 7 consecutive days on which the platelet count exceeded 20 x 10⁹/L unsupported by platelet transfusions.

Resource Utilization and Costs
Direct medical resource utilization data, which included initial hospital stay and any readmissions and related costs, were collected on the basis of chart review for a period of up to 100 days after PBSC transplantation. Resource use was collected for the following resource categories: hospital days, days of rhG-CSF use, days of IV antibiotics, days of IV antifungal agents, RBC transfusions, platelet transfusions, and outpatient center costs (defined as costs of supportive care for patients after PBSC transplantation on an outpatient basis, whether or not hospitalization was required). Physician professional services were not included in this assessment.

Resource costs were developed for both inpatient and outpatient services from the provider perspective. For this assessment, we attempted to develop measures of these resource costs rather than rely upon charges appearing on patient bills.¹³ Costs of inpatient days were based on the mean costs of 52 patients undergoing PBSC transplantation or ABMT at one university hospital and were based on an internal cost-accounting system at the medical center. These costs included inpatient radiology and operating room costs. Since data on pharmaceutical and blood products were collected separately for our study patients, these costs were subtracted from the average inpatient cost per day for hospitalized patients.

Costs for pharmaceutical products were calculated according to average daily doses for a 70-kg person with normal renal function and on established dosing schedules. Costs were based on average wholesale price, using generic when possible, for each product,¹⁴ plus an administration cost for each dose. Administration costs included costs of materials and nursing time for administering the medication. Calculation of costs for blood products was based on an estimate of average acquisition costs per unit of blood product. Outpatient center costs were based on estimates of the marginal costs of nursing time, equipment costs, and supplies for a patient immediately after PBSC transplantation. Calculated costs, in 1996 dollars, are listed in Table 1. Costs for the 100 days post-PBSC transplantation were taken as the product of the resource utilization for individual patients and the costs of those resources during this period.

Statistical Analysis
All data were collected using a custom-designed distributed data system reviewed at a central clinical trials center (Response Oncology, Inc, Memphis, TN) and analyzed using the SAS system (SAS Institute, Cary, NC). Analysis involved descriptive statistics on baseline patient characteristics. Proportions were compared using the ² test or Fisher's exact method. Continuous variables were analyzed using Student's t test or analysis of variance. Median neutrophil and platelet engraftment were estimated using the Kaplan-Meier method and compared between groups categorized by CD34⁺ cell count using the log-rank test.

Primary analysis was based on dichotomous cell dose as an independent variable. The dependent variable was the cost per patient for the period up to 100 days after PBSC infusion. Candidate independent variables include age, sex, performance status, disease, mobilization regimen, intensification regimen, prior chemotherapy, prior radiation therapy, number of phereses, and CD34⁺ cell dose. A stepwise regression model was used in the multivariate analysis to correlate the dependent variable (cost per patient for the period up to 100 days after PBPC infusion) with significant independent variables from the univariate analysis. Interactions that made biologic sense were investigated. A secondary analysis included cell dose as a categorical variable (< 5.0 x 10⁶ cells/kg; 5.0 x 10⁶ to 10.0 x 10⁶ cells/kg; 10.0 x 10⁶ to 20.0 x 10⁶ cells/kg; and > 20.0 x 10⁶ cells/kg), with the same predictor variables used in the multivariate analysis.

In a sensitivity analysis, we varied the cost of a hospital day by 50%, because other providers may have different cost standards. Differences were considered significant if P values were .05 in the univariate analysis and .10 in the multivariate analysis.

	RESULTS

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

 
Patient Characteristics
Table 2 presents patient characteristics both overall and by differing cell dose. Patients are presented by age, performance status, cancer type, sex, myeloablative regimen, and amount of prior chemotherapy and radiation therapy. Overall, the mean patient age was 47 years (range, 15 to 71 years). Eighty-six percent of all patients were female. Patients were more likely to have adjuvant or metastatic breast cancer than any other type. Seventy-seven percent of all patients had only one prior cycle of chemotherapy, whereas 18% had prior radiation therapy.

Patients who received a cell dose of less than 5.0 x 10⁶ cells/kg tended to have poorer performance status and were more likely to have metastatic breast cancer or NHL (Table 2). Patients receiving less than 5.0 x 10⁶ cells/kg were also more likely to have received more than one regimen of prior chemotherapy and prior radiation therapy. These patients were also more likely to have received BuMelT.

A median of 10.3 x 10⁶ CD34⁺ cells/kg (range, 1.1 to 165) was infused. Thirty-two of 1,317 patients (2.4%) were infused with less than 2.5 x 10⁶ CD34⁺ cells/kg. Median cell dose was 3.6 x 10⁶/kg and 13.2 x 10⁶/kg for less than 5.0 x 10⁶ CD34⁺ cells/kg and 5.0 x 10⁶ or more CD34⁺ cells/kg, respectively. Time to engraftment was improved in the group receiving 5.0 x 10⁶ or more CD34⁺ cells/kg (median days to recovery of absolute neutrophil count 0.5 x 10⁹/L were 10 v 9 days, P < .0001; median days to recovery of platelet count 20 x 10⁹/L were 12 v 9 days, P < .001). Mortality within 100 days was 5.9% in patients who received less than 5.0 x 10⁶ CD34⁺ cells/kg and was 2.7% in patients who received 5.0 x 10⁶ or more CD34⁺ cells/kg (P = .009). Relapse or disease progression within 100 days was 11.4% in patients who received less than 5.0 x 10⁶ CD34⁺ cells/kg and was 6.6% in patients who received 5.0 x 10⁶ or more CD34⁺ cells/kg (P = .008).

Resource Counts
Table 3 presents resource counts as a function of CD34⁺ cell dose. Patients who received less than 5.0 x 10⁶ cells/kg required more platelet and RBC transfusions, approximately 3.3 days greater length of stay, slightly more than 3 additional days of IV antibiotic use, and 0.75 days of additional IV antifungal use. In addition, patients who received less than 5.0 x 10⁶ cells/kg required almost 2 more days of rhG-CSF use.

Cost
The univariate analysis of cost is presented in Table 4. Transplantation was more expensive in patients who were 50 years of age or older and in patients who received a cell dose of less than 5.0 x 10⁶ cells/kg. Transplantation was less expensive for patients receiving adjuvant treatment for breast cancer (in comparison to all other patients) and for patients who had better Eastern Cooperative Oncology Group status but was more expensive for patients who required two or more PBSC mobilizations. Transplantation was also more expensive for patients who had received prior chemotherapy and for patients who had three or more phereses or prior radiation therapy. Transplantation was less expensive for patients who had CE plus rhG-CSF mobilization and for patients who received carmustine, etoposide, cytarabine, and cyclophosphamide or high-dose cyclophosphamide, thiotepa, and carboplatin as HDC regimens. Transplantation was also less expensive for patients who received transplants after 1994.

In a multivariate analysis, patient age, nonadjuvant breast treatment, number of phereses, cell dose, and chemotherapy regimen were important predictors of resource use (Table 5). Even after controlling for other variables, a cell dose of less than 5.0 x 10⁶ CD34⁺ cells/kg was associated with an additional $5,000 in resource costs per patient (P = .0001). To assess whether this result was consistent across diagnoses, we assessed the interaction between disease and cell dose. This interaction term was nonsignificant (P = .51), suggesting that the effect of cell dose is homogeneous across all patients in this population.

In Table 6, we examine the effect of cell dose as a predictor of cost in a multivariate analysis across a range of CD34⁺ cell doses. In terms of treatment effect, greater cell dose is associated with lower costs across our four categories of cell dose. Patients who received more than 20.0 x 10⁶ CD34⁺ cells/kg had $7,854 lower costs than patients who received less than 5.0 x 10⁶ CD34⁺ cells/kg.

In our sensitivity analysis, we found that a cell dose of 5.0 x 10⁶ or more CD34⁺ cells/kg was associated with a reduction in cost of $6,782 if the cost of a hospital day was increased by 50% and was associated with a reduction in cost of $3,336 if the cost of a hospital day was decreased by 50%.

	DISCUSSION

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

 
In this study, we found that CD34⁺ cell dose for patients undergoing PBSC transplantation after HDC is inversely related to resource utilization for patients up to 100 days after initial therapy. Patients who received a cell dose of less than 5.0 x 10⁶ CD34⁺ cells/kg required increased transfusions, antibiotic and antifungal treatment, growth factor support, and longer inpatient length of stay. Examining cell dose as a categorical variable between 5.0 x 10⁶ CD34⁺ cells/kg and more than 20.0 x 10⁶ CD34⁺ cells/kg, we found a dose-response relationship between cell dose and costs, with increased cell dose being associated with a reduction in costs for individual patients.

Currently, the concept of cell dose as an important treatment parameter remains a major focus of research. An earlier study from a subset of the same population suggested that increased cell dose was associated with more rapid platelet and neutrophil recovery for patients undergoing HDC and PBSC support.⁷ In our study, we have found that in addition to faster hematologic recovery, cell dose is inversely related to resource consumption of individual patients for a period of up to 100 days after PBSC transplantation. These data are among the first to explore this relationship.^10,15

Patients receiving a cell dose of less than 5.0 x 10⁶ CD34⁺ cells/kg included a higher proportion of patients with metastatic breast cancer and NHL when compared with patients receiving a cell dose of 5.0 x 10⁶ or more CD34⁺ cells/kg. Furthermore, patients receiving a lower cell dose were more likely to have received more than one regimen of prior chemotherapy or radiation therapy and were more likely to be treated with BuMelT. Our analysis suggests that this difference in severity of illness accounts for almost 50% of the differences in costs by cell dose in our univariate analysis. Still, there is a significant difference in resource utilization by cell dose after adjusting for the treatment differences in our multiple regression analysis.

Economic analyses of PBSC transplantation compared with ABMT have demonstrated an effect of PBSC on time to neutrophil recovery and overall patient length of stay.^4,6,16,17 However, although several investigators reported that cell dose was associated with PBSC transplantation,^17-20 none examined the impact of cell dose as a predictor of resource utilization. Furthermore, cell dose was not collected in a uniform fashion across these studies (the studies collected cell doses as colony-forming unit granulocyte-macrophages or as mononuclear cell count). Only one economic report collected data on CD34⁺ cell count, but that study did not use the cell count information in its analysis.⁶ One study examining outpatient autologous transplantation did investigate the uses of CD34⁺ cell count as a predictor of resource utilization for patients undergoing treatment for multiple myeloma.²¹ However, cell dose was not the major focus of the study. Furthermore, the investigators did not report differences in resource utilization associated with cell dose. Rather, they used cell dose as a matching variable to compare patients undergoing inpatient and outpatient autotransplantation.

Our data provide strong support for the hypothesis that cell dose is related to resource utilization and time of engraftment for patients receiving HDC and PBSC. Given the observational nature of the data set used for this analysis, however, further direct assessment of the effect of cell dose on resource use and engraftment parameters is merited. A randomized trial could adjust for several potential biases in this analysis. First, for patients receiving transplants before 1995, 2.5 x 10⁶ CD34⁺ cells/kg was assumed to be the target cell dose for patients undergoing PBSC support. Thus, it is possible that transplantation with an even greater cell dose in patients may result in additional resource savings, approaching those reported in Table 6. Alternatively, it is possible that the additional harvesting in patients with low initial CD34⁺ yield may not result in either substantial additional cell collection or significant changes in resource utilization, because CD34⁺ cell yield may be a surrogate marker for heavily pretreated patients. However, cell dose is still a significant predictor of cost in our multivariate analysis, which controlled for patient characteristics and treatment. Other unmeasured factors may also contribute to resource utilization and may not be appropriately considered in our multivariate regression model.

In our analysis, we did not consider the effect of mortality or relapse/progression on the post-PBSC transplantation costs for the period up to 100 days after PBSC infusion, because these outcomes may be directly related to cell dose and treatment and are intrinsic to our analysis. However, we did perform a separate analysis to investigate the potential impact of mortality and relapse/progression on our assessment of resource utilization. We found that our estimate of the cost savings associated with infusion of more than 5.0 x 10⁶ CD34⁺ cells/kg was robust with respect to the small differences in these outcomes across cell dose based on several different analyses incorporating mortality and relapse/progression.

Finally, economic evaluation based on resource utilization for a limited set of resource items, the method used for this study, may underestimate resource costs for study patients. Thus, our assessment of the relationship between cell dose and resource utilization may be a conservative estimate of the true difference in costs for patients receiving PBSC transplantation. In addition, because this study was based on chart review, we were unable to assess patient out-of-pocket costs. Again, our assessment of the difference in resource costs by CD34⁺ cell dose is a conservative estimate of the true difference in cost to providers and patients.

In conclusion, as shown in this study, infusion of more than 5.0 x 10⁶ CD34⁺ cells/kg after HDC was associated with a reduction in length of hospitalization, antibiotic use, number of transfusions, and transplantation costs of up to $5,062 per patient. Strategies that enable more patients to achieve the target of 5.0 x 10⁶ CD34⁺ cells/kg should have important clinical and economic benefits for patients.

	ACKNOWLEDGMENTS

 
Supported by an educational grant from Amgen, Inc.

We acknowledge Kevin P. Weinfurt, Ph.D., for his assistance in developing the analytic framework for assessing the mortality effect on cost.

	REFERENCES

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

 
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5. Duncan N, Hewetson M, Powles R, et al: An economic evaluation of peripheral blood stem cell transplantation as an alternative to autologous bone marrow transplantation in multiple myeloma. Bone Marrow Transplant 18:1175-1178, 1996[Medline]

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16. Bennett CL, Armitage JL, Armitage GO, et al: Costs of care and outcomes for high-dose therapy and autologous transplantation for lymphoid malignancies: 1987 through 1991. J Clin Oncol 13:969-973, 1995[Abstract]

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Submitted July 9, 1998; accepted December 9, 1998.

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