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© 1999 American Society for Clinical Oncology Outpatient-Based Bone Marrow Transplantation for Hematologic Malignancies: Cost Saving or Cost Shifting?From the School of Medicine, School of Nursing, Oncology Center, and Program for Medical Technology and Practice Assessment, Johns Hopkins University, Baltimore, MD. Address reprint requests to J. Douglas Rizzo, MD, International Bone Marrow Transplant Registry/Autologous Blood and Marrow Transplant Registry Statistical Center, 8701 Watertown Plank Rd, Milwaukee, WI 53226; email rizzo{at}mcw.edu
PURPOSE: To determine whether a shift in care from an inpatient-based to an outpatient-based bone marrow transplantation (BMT) program decreased charges to payers without increasing clinical complications or out-of-pocket costs to patients. PATIENTS AND METHODS: This nonrandomized prospective cohort study compared clinical and economic outcomes for 132 consecutive BMT patients with hematologic malignancies who received either inpatient- or outpatient-based BMT care. RESULTS: Seventeen of 132 BMT patients underwent outpatient-based BMT. Compared with the inpatient-based group, the outpatient-based group had a markedly lower mean number of inpatient hospital days (22 v 47; P < .001) and decreased mean inpatient facility charges ($61,059 less per patient; P < .0001) but had higher mean outpatient facility charges ($49,732 higher; P < .0001). Total professional fees were similar for the groups. The mean total charge to payers was only 7% less ($12,652; P = .21) for outpatient-based BMT than for inpatient-based BMT, but total charge was 34% less for outpatient compared with inpatient BMT ($54,240; P = 0.056) in a subset of patients who had a standard rather than high risk of treatment failure. There was no significant difference between groups in out-of-pocket costs for transportation, lodging, meals, home nursing, household assistance, child care, medication expenses, or unreimbursed medical bills. There also was no significant difference between groups in reported income lost, involuntary unemployment, or months of disability. The two groups had similar rates of major complications, including death, significant acute graft-versus-host disease, and veno-occlusive disease of the liver. CONCLUSION: Increased use of outpatient-based BMT should produce substantial cost savings for payers without adverse effects on patients for those patients who do not have a high risk of treatment failure.
BONE MARROW transplantation (BMT) is an intensive treatment modality that has been used with increasing frequency in the treatment of malignant and nonmalignant diseases in the last decade.1,2 Complications may be life-threatening, with 100-day mortality rates ranging from 5% to more than 50%, depending on the type of transplant. Typically, complications associated with BMT have mandated inpatient delivery of care, with lengthy inpatient stays. Reported average costs of BMT for hematologic malignancies have been as high as $193,000 per case.3 With increasing penetrance of managed care, as well as concerns regarding appropriate use of health care resources, strategies to reduce the hospital length of stay and costs associated with BMT have been explored. Although cost of BMT has become an important concern in transplantation centers, relatively few cost analyses have been reported.4-22 One strategy attempted by some BMT centers has been to perform outpatient-based BMT.9 Results from these centers have shown that outpatient-based BMT can be performed safely, with reduced inpatient length-of-stay and reduced hospital charges. However, these outpatient-based BMT programs have been largely confined to autologous marrow or peripheral-blood stem-cell (PBSC) transplantation and have used growth factors to enhance hematologic recovery.9,17,18 Furthermore, it is unclear whether the reduction in hospital charges achieved by these programs is offset by an increase in other types of costs. Our cancer center began to perform outpatient-based BMT using an inpatient-outpatient (IPOP) continuum-of-care model in late 1995. We designed a new clinical area adjacent to the inpatient facility capable of providing intensive ambulatory care to transplantation patients. Allogeneic and autologous transplant recipients with hematologic malignancies were eligible for IPOP care, regardless of whether they had a standard or high risk of treatment failure. The main objective of this study was to determine whether patients with hematologic malignancies who receive outpatient-based BMT care rather than traditional inpatient-based BMT care have a significant reduction in total direct medical charges to payers (for both inpatient and outpatient services), without an increase in adverse clinical outcomes or out-of-pocket costs to patients.
Study Design This study was performed as a nonrandomized prospective cohort study comparing clinical and economic outcomes for consecutive patients with hematologic malignancies who received either outpatient-based BMT care or traditional inpatient-based BMT care.
Patient Eligibility Patients undergoing BMT in our hospital were required to meet standard eligibility criteria. These included age younger than 70 years for autologous BMT and age younger than 65 years for allogeneic transplantation, Eastern Cooperative Oncology Group (ECOG) performance status of less than 2 (out-of-bed activity more than 50% of daytime hours), left ventricular ejection fraction greater than 45%, forced expiratory volume in 1 second and forced ventilatory capacity greater than 50% of predicted value (75% if prior chest irradiation), bilirubin less than 2.0 mg/dL, serum creatinine less than 2.0 mg/dL, human immunodeficiency virus–negative, and no evidence of pregnancy. Patients eligible for BMT were encouraged to participate in the IPOP program by the BMT staff. Those willing to receive outpatient-based BMT care through the IPOP program also had to meet the following additional eligibility criteria: patients had to be ambulatory, English-speaking, of normal hearing capacity (to facilitate communication), and have no severe medical comorbidities that precluded safe outpatient care. In addition, patients had to have family member(s) or friend(s) who were willing and available to stay with them in the local hotel facility from 10 days before transplantation to 40 to 70 days after the transplantation. Because outpatient-based procedures are often not reimbursed as well by third-party payers than inpatient procedures, patients had to receive approval from their insurance carrier to receive care through the IPOP program, including approval of a small daily living allowance to cover the cost of the local hotel room. Randomization was not performed because of concerns regarding patient willingness, caregiver availability, and insurance approval.
Treatment Description Patients who received outpatient-based BMT care through the IPOP program were not admitted to the hospital at any time between receipt of the myeloablative regimen and count recovery unless a complication precluding outpatient care occurred (eg, febrile neutropenia, severe pain requiring intravenous narcotics, inability to maintain oral intake, and so on). Patients in the IPOP program were seen daily in a newly constructed intensive ambulatory clinic and resided in local hotel facilities with their designated caregiver each evening. The duration of each daily outpatient visit was dependent on the care objectives of the day. Intravenous medications for IPOP patients were generally given in the ambulatory clinic, although some were administered by home infusion. Febrile neutropenic IPOP patients were admitted to the inpatient service for initial evaluation and management and were discharged to the ambulatory clinic once they were afebrile for more than 24 hours and clinically stable on intravenous antibiotics. Each new febrile episode was treated similarly. Likewise, IPOP patients who experienced complications (mucositis, reduced oral intake) were admitted only when they could not be managed safely as an outpatient; IPOP patients were then discharged when clinically stable. Caregivers received a special care instruction course taught by transplantation nursing staff. For billing purposes, days on which care was received were divided into three categories: inpatient days, intensive outpatient days (IPOP days), and routine outpatient days. Intensive outpatient days included all daily visits to the intensive ambulatory transplantation clinic between initiation of the preparative regimen and recovery of neutrophils to more than 500 x 109 cells/L. Outpatient days for patients enrolled in the IPOP program were billed in the "routine" fashion once they had established neutrophil counts of more than 500 x 109 cells/L. All outpatient days for patients who underwent transplantation in the traditional setting were billed in the "routine" fashion. Protocols for the delivery of myeloablative regimens, hydration, antiemetics, antibiotics, antiviral medications, and graft-versus-host disease (GVHD) prophylaxis were identical in both care delivery settings with one exception. Mesna was used routinely in the IPOP patients, but not in the other patients, to decrease the risk of urothelial bleeding in outpatients who were not receiving the daily volume of intravenous fluids typically given to inpatients. Growth factors were not routinely used in our transplantation protocols. All patients considered for this analysis received bone marrow as their source of stem cells. The transplantation treatment protocols, as well as the comparative study of the outcomes of the intervention, were approved by our institutional review board.
Outcome Measures Patients who underwent transplantation for treatment of multiple myeloma, chronic myelogenous leukemia in accelerated or blast phase, and acute lymphocytic leukemia were considered to have high risk of disease recurrence. Patients with acute myelogenous leukemia in first relapse, second remission, or subsequent relapse were designated as high risk. Non-Hodgkin's lymphoma or Hodgkin's disease patients who never achieved an initial complete response or whose response to conventional chemotherapy for recurrence was less than a partial response were also considered to have high-risk disease. All others were considered to be at standard risk of disease recurrence. Significant ganciclovir usage was defined as treatment with ganciclovir for more than 7 days and was used as an estimate of cytomegalovirus infection rates. Total medical charges to payers. The economic perspective for the analysis of hospital charges was that of the third-party payer, and all consecutive patients who underwent transplantation as described above were considered in the analysis of total hospital charges. The total medical charges to payers included inpatient and outpatient facility charges and all professional fees generated between 12 days before transplantation until 100 days after transplantation for each patient. Essentially, all patient care for these patients in this window period occurred at the transplantation center. Charge data were gathered into a working data set from the larger, prospectively collected database that is maintained by the hospital and used for mandatory state reporting. Inpatient and outpatient facility charges are recorded to the level of revenue and procedure codes and can be categorized by service areas. Inpatient and outpatient facility charge structures must be identical by state law. Professional-fee charge data were maintained prospectively by the university and included level of service as well as associated professional work units for each patient. The number and length of admissions and certain clinical complications associated with billable procedures that were recorded in the charge database were gathered into our working data set. Charge review was performed on a randomly selected 10% sample of bills to confirm relevant charge capture and lack of duplicate billing. The state of Maryland administers an all-payer hospital rate setting system to provide cost containment and an equitable payment system. Through this system, all hospital-based inpatient and outpatient services are rate-regulated, such that rates reflect "reasonable costs" compared with other similar providers in the state, with generally low mark-up, and rates for identical inpatient and outpatient procedures are identical at the same hospital. Hospitals report cost-to-charge ratios for each department, which must be approved by state regulators yearly. Charges reported in this analysis all conform with these regulations. Survey of out-of-pocket costs. All patients who underwent transplantation in either setting between July 1995 and October 1996 who survived 1 year or longer became eligible for analysis of out-of-pocket costs related to the transplantation procedure. All survivors were contacted at their 1-year transplantation anniversary and asked to complete a questionnaire about the costs of their care that they themselves paid. The questionnaire assessing out-of-pocket costs was developed for this study with the assistance of physicians, nurses, and social workers who care for transplant recipients. It was piloted on a small group of surviving transplant recipients for face and content validity. Results have been reproducible when compared with a similar instrument given prospectively at 3, 6, and 12 months after transplantation in a small group of patients. Categorical response options were given for each question to facilitate easy completion by the patients. Direct nonmedical costs covered by the survey included transportation, lodging and meals, telephone, child care, and household assistance expenses while undergoing BMT. Indirect costs assessed in the survey included employment status and occupation changes, changes in productivity and length of usual work week, disability history, and lost income. The questionnaire also included questions about unreimbursed direct medical costs and the perceived financial impact of BMT-related care. Reminders were sent to all survivors on at least two occasions to increase the survey response rates. Statistical analysis. Analyses were performed to compare costs and clinical outcomes between those patients who underwent transplantation in the traditional inpatient setting and those in the IPOP program. Total medical charges to payers was a continuous variable and was transformed using natural log transformation to achieve a normal distribution for comparison with a two-sample t test. Results were also compared for the two groups using the median untransformed charges and the nonparametric two-sample Wilcoxon rank-sum (Mann-Whitney) test. Results are presented as means, with associated P values generated from the log-transformed t test. Because the confidence intervals generated from the log-transformed comparison of means cannot be back-transformed to dollar amounts for reporting in a valid way, medians with 95% confidence intervals (CI) are also presented for the charge outcomes. Stratified analyses were performed to explore the relationship between hospital charges and major independent clinical variables such as age, sex, race, transplantation type (allogeneic or autologous), myeloablative regimen, disease risk status, and treatment of autologous marrow with 4-hydroxycyclophosphamide. Stepwise multiple regression was also used to identify confounders in the relationship between hospital charges and type of transplantation. Each of the major independent clinical variables was added in stepwise fashion to a linear regression model to test their effect on the relationship between BMT setting (inpatient or outpatient) and the natural log of total hospital charges. Small numbers of patients in the study limited the number of major variables placed in the model. Those variables with significant regression coefficients were considered to be confounders. Secondary analyses were performed to compare specific charge categories between groups.
Means of clinical variables that were continuous (age, length of stay) were compared using a one-way analysis of variance. Dichotomous clinical variables were compared using a Out-of-pocket costs reported by patients were considered categorical variables. Comparison of medians for each group was performed using the two-sample Wilcoxon rank-sum (Mann-Whitney) test, and P values were reported. Patients were enrolled in the study for a fixed period of time during the first 15 months of the program. Final power calculations reveal an 80% power to detect a 40% difference in total charges to payers between the inpatient- and outpatient-based transplantation groups. This study has an 80% power to detect an absolute difference of 35% in the proportion of total clinical events between the two groups. All analyses were performed using STATA software (Version 5.0; STATA Corp, College Station, TX; Computing Resource Center, Santa Monica, CA).
Patient Characteristics One hundred thirty-two consecutive patients with hematologic malignancies underwent allogeneic or autologous BMT at our center between July 1995 and October 1996. Of these patients, 115 had a BMT performed in the traditional inpatient setting, with the remaining 17 participating in the outpatient-based IPOP program. Enrollment in the IPOP program was less than anticipated. Although most patients were eligible for IPOP, the most frequent limitation to enrollment was refusal by insurers to approve the outpatient-based BMT procedure. Anecdotal evidence suggests that this may have been due to the structure of payer billing systems regarding major outpatient procedures. Characteristics of the enrolled patients are listed in Table 1. Patients participating in the IPOP program were significantly younger than those in the traditional transplantation group (36 v 44 years; P = .01). There was a difference in the distribution of diagnoses between the two groups, but there was no significant difference in the type of transplantation or the percentage of patients with high-risk disease.
Clinical Complications
Clinical complication rates were measured within the first 100 days after transplantation in both groups (Table 2). Rates of significant acute GVHD (grade
Length of Stay in Inpatient and Outpatient Settings
Total Medical Charges to Payers
Mean pharmacy charges were approximately $6,000 higher in the IPOP group than in the traditional inpatient group; this difference may be largely explained by the use of mesna in all IPOP patients but not in any of the patients undergoing traditional inpatient BMT. Charges for mesna averaged approximately $4,000 per patient. Mean charges related to transfusions of platelets and RBCs were also $8,370 higher on average in the IPOP group than in the traditional inpatient group. Mean total laboratory charges were nearly identical. Under our outpatient charge structure, intravenous infusion of each medication or transfusion was associated with a charge related to its administration by the nursing staff, regardless of whether it was administered concurrently with other intravenous medications. Because IPOP patients spent a greater period of time in the outpatient setting, where infusions are billed in an unbundled fashion, they incurred nearly twice the mean infusion administration charges of patients in the traditional group, a difference of $4,369. Stratified analysis and stepwise multiple regression were performed to determine the impact of important patient characteristics on the relationship between transplantation setting and total charges. Only disease risk status significantly influenced the relationship between total hospital charges and transplantation setting. For those patients with standard risk of recurrence (as defined in Patients and Methods, under Outcome Measures, Clinical Outcomes), transplantations performed in the IPOP program were associated with mean hospital charges that, on average, were $54,240 lower than those in the traditional inpatient group ($104,540 v $158,780, respectively; P = .056), representing a difference of 34%. Median charges in the low-risk group were $95,568 (95% CI, $73,599 to $153,427) and $139,508 (95% CI, $119,179 to $162,560), respectively; P = .04. Patients in the high-risk category constituted 67% of all patients and had mean total charges that were quite similar between the outpatient (IPOP) and inpatient settings ($182,946 v $186,576, respectively; P > .10). Median charges in this risk group were $120,414 (95% CI, $86,133 to $310,373) and $162,792 (95% CI, $139,803 to $189,820), respectively; this difference was not significant.
Out-of-Pocket Costs The survey of out-of-pocket costs showed no significant difference between the outpatient-based IPOP group and the inpatient group in unreimbursed medical bills (median of $5,000 or less for patients in both groups for inpatient care and outpatient care; P > .10 by Wilcoxon rank-sum). In addition, there was no significant difference in reported unreimbursed medical expenses for the pretransplantation evaluation (median $2,500 or less in both groups; P > .10 by Wilcoxon rank-sum) or unreimbursed costs for transplantation-related medications (median of $0 in IPOP group and $1 to $500 in the inpatient group; P > .10 by Wilcoxon rank-sum). There was no significant difference between patients in the IPOP group and the inpatient group for length of disability (median, 4 to 6 months in each group; P > .10 by Wilcoxon rank-sum), level of productivity among those returning to work within the first year (productivity was considered to be the "same" as pretransplantation productivity for both groups; P > .10 by Wilcoxon rank-sum), and those changing occupation because of illness or transplantation (18% v 17%; P > .10). The median income lost during the first year after BMT was less than $5,000 for the IPOP group and $5,000 to $10,000 for the inpatient group (P > .10). Outpatient-based BMT patients were very similar to inpatient-based BMT patients in the reported direct nonmedical costs for lodging (median of $1 to $500 in both groups; P = .54), meals (median of $1 to $500 in both groups; P = .84), child care (median of $0 in both groups; P = .14), nursing care (median of $0 in both groups; P = .86), transportation (median, $1 to $500 for outpatients v $0 for inpatients; P = .18), household assistance (median of $0 in both groups; P = .44), and personal care (median of $0 in both groups; P = .67). Anecdotally, many patients in both groups wrote in comments suggesting that substantial nonfinancial assistance was provided to them by friends and community groups during their posttransplantation course. Patients were asked to rank the adverse affects of out-of-pocket costs of BMT on their total financial debt, living situation, career plans, and retirement plans. A discrete 7-point Likert scale was used, with 1 representing no adverse affect and 7 representing severe adverse affect. There was no statistically significant difference for IPOP patients compared with traditional inpatients for adverse affect on total financial debt (median of 3 both groups; P = .12), living situation (median of 1 for IPOP patients v 3 for inpatients; P = .07), career plans (median of 4 v 3; P = .97), and retirement plans (median of 3 v 2.5; P = .55).
Our results indicate that the outpatient-based BMT program (IPOP) was able to significantly reduce inpatient length of stay by 47% compared with the traditional inpatient program, without causing an increase in clinical complications. Patients who underwent transplantation in the outpatient IPOP group also had almost 50% lower mean inpatient hospital charges when compared with traditional inpatients. However, increased mean outpatient charges for the IPOP patients offset much of the inpatient savings, such that unadjusted average total hospital charges from 12 days before transplantation until 100 days after transplantation were only 7% lower in the IPOP group compared with those of the traditional inpatients. By demonstrating that there was no significant increase in clinical complications in the outpatient BMT group, this study has confirmed the feasibility and safety of performing outpatient-based BMT for patients with hematologic malignancies requiring autologous or allogeneic BMT. Previous reports in the literature have demonstrated the feasibility of outpatient-based BMT care, but these have been confined to breast cancer9 or autologous PBSC with granulocyte colony-stimulating factor support for hematologic malignancies.17,18 In each of these previous studies, growth factors played an integral part in recovery after BMT.9,17,18 Aside from the current study, one other group has reported giving the myeloablative regimen on a wholly outpatient basis.17 In our IPOP program, outpatient-based BMT care did not increase clinical complications. Indeed, 100-day and 1-year mortality rates slightly favored the IPOP group, and the incidence of significant acute GVHD, VOD, mechanical ventilation, renal failure, and cytomegalovirus infection (as measured by ganciclovir usage) were very similar in the two groups. However, our power to detect small differences in clinical outcomes was low. These results should provide reassurance to clinicians and insurers that this type of outpatient-based BMT does not expose patients to more frequent or severe transplantation-related complications. This study also demonstrated that decreasing initial inpatient hospital days does not necessarily translate into decreased costs to third-party payers for all groups of patients. Peters et al9 reported a 40% to 50% reduction over a 5-year period in total hospital charges for autologous (PBSC) BMT for breast cancer patients compared with historical controls. However, this reported savings most likely was due to a combination of factors, including secular trends in transplantation and supportive care as well as increased use of growth factors. Whereas Jagannath et al17 demonstrated a 26% average reduction in risk-adjusted total charges for myeloma patients who underwent transplantation with autologous PBSC in the outpatient setting compared with the inpatient setting, we were only able to show an average savings of 7% for hematologic malignancy patients undergoing autologous and allogeneic BMT in the outpatient-based IPOP BMT program, and this difference was not statistically significant. However, stratification by important patient characteristics revealed that disease risk status influenced the relationship between total hospital charges and BMT setting. Patients with standard-risk disease in the IPOP group incurred total hospital charges that were 34% lower than those of patients in the traditional group (P = .056), whereas patients with high-risk disease had very similar total charges, regardless of whether they received the BMT in the inpatient or the outpatient setting. Although this important finding occurred in only a small group of patients, it suggests that selection of patients with standard-risk hematologic malignancies for outpatient-based BMT may lead to substantial cost savings. If this reduction in charges can be broadened to a significant proportion of the approximately 15,000 patients who receive stem-cell transplants in the United States each year (International Bone Marrow Transplant Registry/Autologous Blood and Marrow Transplant Registry, data on file), then the impact on overall charges could be quite large. Although Jagannath et al17 included estimates of indirect costs to patients in the analysis of their outpatient BMT program for myeloma patients, these costs were not directly measured. In our study, we asked patients who survived treatment about the out-of-pocket expenses they incurred for changes in employment and disability, transportation and lodging, meals, child and nursing care, household assistance, medications, and medical bills not reimbursed by insurers, and we found no significant difference between the outpatient-based and inpatient-based BMT groups. Of note, the out-of-pocket cost burden to patients receiving BMT in either setting was lower than anticipated. Patients who may be asked to consider having BMT on an outpatient basis should be reassured that costs of care will not be shifted from their insurer to their own pockets. Patients were not randomized in this study, and the small numbers of patients in the IPOP group limited our ability to fully adjust for differences in characteristics between the study groups. Therefore, it remains possible that some degree of selection bias occurred, with less ill patients enrolling in the outpatient-based treatment group. However, stratified analyses indicated that patient age, sex, race, type of transplantation, and preparative regimen did not significantly confound the relationship between charges and BMT setting. A second limitation of this study relates to the use of charge data rather than more direct measures of resource utilization. However, in Maryland, charges provide a reasonable proxy for costs, because charges are regulated by the state. Furthermore, we chose the perspective of the third-party payer for this analysis because third-party payers are generally the most concerned about the costs of major procedures like BMT. A third limitation is that we did not have data on all potentially important clinical complications that may occur after BMT, but we were able to evaluate a number of the most important clinical complications of BMT. A fourth limitation is that we may not have captured all out-of-pocket costs, because patients may not have remembered or kept track of all their expenses and because we did not collect this information from patients who died. Nevertheless, it is unlikely that recall would be significantly different between the inpatient and outpatient treatment groups. As well, the results reported among the retrospective group seem reproducible compared with a small group of patients completing questionnaires prospectively. This study confirms that outpatient-based BMT is feasible with regard to outpatient delivery of the preparative regimen and management of clinical complications. Despite a substantial reduction in inpatient care days, our study also shows that significant reductions in unadjusted total medical charges to payers may not result from simply shifting care to the outpatient setting for all BMT patients. Our results suggest that a select group of patients (ie, those with standard risk of recurrent disease) may derive substantial cost savings from an outpatient-based BMT program, although this important finding occurred in a small group of patients and should be confirmed in a larger group. If such a program is replicated and extended to more of the approximately 10,000 patients receiving BMT in the United States each year for hematologic malignancies, then substantial savings could be appreciated. Our data should begin to assure providers, managed care organizations, and insurers about the potential benefits of offering outpatient-based BMT to selected patients who have a standard risk of treatment failure.
We gratefully acknowledge the assistance of Mollie Jenckes, MS, for assistance in preparing questionnaires, and Claro Pio Roda for assistance with data set preparation.
This work was supported by National Cancer Institute grant no. P01CA15396 and by the Johns Hopkins Hospital, Baltimore, MD. J.D.R. was supported by a research fellowship from the Robert Wood Johnson Clinical Scholars Program during the conduct of this project.
1. Appelbaum FR: The use of bone marrow and peripheral blood stem cell transplantation in the treatment of cancer. CA Cancer J Clin 46:142-164, 1996[Abstract] 2. Bortin MM, Horowitz MM, Rimm AA: Increasing utilization of allogeneic bone marrow transplantation: Results of the 1988-1990 survey. Ann Intern Med 116:505-512, 1992 3. Westerman IL, Bennett CL: A review of the costs, cost-effectiveness and third-party charges of bone marrow transplantation. Stem Cells 14:312-319, 1996[Abstract] 4. Beard ME, Inder AB, Allen JR, et al: The costs and benefits of bone marrow transplantation. N Z Med J 104:303-305, 1991[Medline] 5. Dufoir T, Saux MC, Terraza B, et al: Comparative cost of allogeneic or autologous bone marrow transplantation and chemotherapy in patients with acute myeloid leukaemia in first remission. Bone Marrow Transplant 10:323-329, 1992[Medline]
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Hillner BE, Smith TJ, Desch CE: Efficacy and cost-effectiveness of autologous bone marrow transplantation in metastatic breast cancer: Estimates using decision analysis while awaiting clinical trial results. J Am Med Assoc 267:2055-2061, 1992 7. Griffiths RI, Bass EB, Powe NR, et al: Factors influencing third party payer costs for allogeneic BMT. Bone Marrow Transplant 12:43-48, 1993[Medline] 8. Faucher C, Le Corroller AG, Blaise D, et al: Comparison of G-CSF-primed peripheral blood progenitor cells and bone marrow auto transplantation: Clinical assessment and cost-effectiveness. Bone Marrow Transplant 14:895-901, 1994[Medline] 9. Peters WP, Ross M, Vredenburgh JJ, et al: The use of intensive clinic support to permit outpatient autologous bone marrow transplantation for breast cancer. Semin Oncol 21:25-31, 1994 10. Bennett CL, Armitage JL, Armitage GO, et al: Costs of care and outcomes for high-dose therapy and autologous transplantation for lymphoid malignancies: Results from the University of Nebraska 1987 through 1991. J Clin Oncol 13:969-973, 1995[Abstract] 11. Lawless GD: Cost-effectiveness of autologous bone marrow transplantation. Am J Health Syst Pharm 52:S11-S14, 1995 12. Uyl-de Groot CA, Hagenbeek A, Verdonck LF, et al: Cost-effectiveness of ABMT in comparison with CHOP chemotherapy in patients with intermediate- and high-grade malignant non-Hodgkin's lymphoma (NHL). Bone Marrow Transplant 16:463-470, 1995[Medline] 13. Uyl-de Groot CA, Okhuijsen SY, Hagenbeek A, et al: Costs of introducing autologous BMT in the treatment of lymphoma and acute leukaemia in The Netherlands. Bone Marrow Transplant 15:605-610, 1995[Medline]
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Barr R, Furlong W, Henwood J, et al: Economic evaluation of allogeneic bone marrow transplantation: A rudimentary model to generate estimates for the timely formulation of clinical policy. J Clin Oncol 14:1413-1420, 1996 15. Bredeson C, Malcolm J, Davis M, et al: Cost analysis of the introduction of PBPC for autologous transplantation: Effect of switching from bone marrow (BM) to peripheral blood progenitor cells (PBPC). Bone Marrow Transplant 20:889-896, 1997[Medline]
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Hartmann O, Le Corroller AG, Blaise D, et al: Peripheral blood stem cell and bone marrow transplantation for solid tumors and lymphomas: Hematologic recovery and costs—A randomized, controlled trial. Ann Intern Med 126:600-607, 1997 17. Jagannath S, Vesole DH, Zhang M, et al: Feasibility and cost-effectiveness of outpatient autotransplants in multiple myeloma. Bone Marrow Transplant 20:445-450, 1997[Medline]
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Meisenberg BR, Miller WE, McMillan R, et al: Outpatient high-dose chemotherapy with autologous stem-cell rescue for hematologic and nonhematologic malignancies. J Clin Oncol 15:11-17, 1997 19. Messori A, Bonistalli L, Costantini M, et al: Cost-effectiveness of autologous bone marrow transplantation in patients with relapsed non-Hodgkin's lymphoma. Bone Marrow Transplant 19:275-281, 1997[Medline]
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Smith TJ, Hillner BE, Schmitz N, et al: Economic analysis of a randomized clinical trial to compare filgrastim-mobilized peripheral-blood progenitor-cell transplantation and autologous bone marrow transplantation in patients with Hodgkin's and non-Hodgkin's lymphoma. J Clin Oncol 15:5-10, 1997 21. Weeks FM, Yee GC, Bartfield AA, et al: The true cost of bone marrow transplantation. Am J Med Sci 314:101-112, 1997[Medline] 22. Woronoff-Lemsi MC, Arveux P, Limat S, et al: Cost comparative study of autologous peripheral blood progenitor cells (PBPC) and bone marrow (ABM) transplantations for non-Hodgkin's lymphoma patients. Bone Marrow Transplant 20:975-982, 1997[Medline] Submitted September 15, 1998; accepted April 27, 1999.
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Copyright © 1999 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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ABSTRACT
INTRODUCTION
2 test or Fisher's exact test when samples were particularly small. The two-sample Wilcoxon rank-sum (Mann-Whitney) test was used to compare medians for all categorical clinical variables. Kaplan-Meier estimates for survival were performed and were compared using the log-rank test. Stratified analyses were performed to explore the relationship between various independent clinical variables and clinical outcomes. 
2), VOD of the liver, mechanical ventilation for respiratory failure, and dialysis for renal failure were not significantly different in the IPOP group compared with the inpatient group. Maximum ECOG scores for pulmonary toxicity reported during the first 100 days after transplantation were similar in the two groups, whereas maximum reported renal toxicity was lower in the IPOP group compared with the inpatient group. Rates of vancomycin-resistant enterococcus were similar in the two groups. No patient in the IPOP group had significant ganciclovir usage, whereas six patients in the inpatient group required its use. One patient in the inpatient group experienced graft failure. Stratified analyses using the major independent variables (age, race, sex, transplantation type, preparative regimen, disease risk, and purging for autologous BMT) did not alter the relationship between transplantation group and clinical complications. 
