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Logo of nihpaAbout Author manuscriptsSubmit a manuscriptNIH Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
 
Biol Blood Marrow Transplant. Author manuscript; available in PMC Sep 1, 2011.
Published in final edited form as:
PMCID: PMC2919628
NIHMSID: NIHMS207886
The Costs and Cost-Effectiveness of Allogeneic Peripheral Blood Stem Cell Transplantation versus Bone Marrow Transplantation in Pediatric Patients with Acute Leukemia
Yu-Feng Lin, DrPH,1,2 David R. Lairson, PhD,2 Wenyaw Chan, PhD,2 Xianglin L. Du, PhD,2 Kathryn S. Leung, MD,1 Alana A. Kennedy-Nasser, MD,1 Caridad A. Martinez, MD,1 Stephen M. Gottschalk, MD,1 Catherine M. Bollard, MD,1 Helen E. Heslop, MD,1 Malcolm K. Brenner, MD, PhD,1 and Robert A. Krance, MD1
1 Center for Cell and Gene Therapy, Department of Pediatrics, Baylor College of Medicine, Houston, USA
2 School of Public Health, University of Texas Health Science Center at Houston, Houston, USA
Correspondence and reprint requests: Yu-Feng Lin, DrPH, Center for Cell and Gene Therapy, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA (yufengl/at/bcm.edu)
In a retrospective study, we evaluated the cost and cost-effectiveness of allogeneic peripheral blood stem cell transplantation (PBSCT) (n=30) compared with bone marrow transplantation (BMT) (n=110) in children with acute leukemia at 1 year of follow up. Treatment success was defined as disease free survival at one year post transplant. For standard risk disease patients the treatment success rate was 57.1% for PBSCT patients and 80.3% for recipients of BMT (P=NS). The average total cost per treatment success at 1 year in the standard risk disease group was $512,294 for the PBSCT group and $352,885 for the BMT group (P=NS). For patients with high risk disease, the treatment success rate was 18.8% for PBSCT patients and 23.5% for BMT (P=NS). The cumulative average cost for patients in the BMT group was $457,078 compared to $377,316 for PBSCT (P=NS). Point estimates of the incremental cost-effectiveness ratio (ICER) indicate that allogeneic transplantation of bone marrow grafts is dominant over PBSCT for its lower costs and higher effectiveness in patients with standard risk disease (ICER = −$687,108; 95% CI = $2.4 million to dominated). For patients with high risk disease, BMT was more effective and more costly and the ICER was $1.69 million (95% CI = $29.7 million to dominated) per additional treatment success. The comparative economic evaluation provides support for BMT for standard risk patients, but a great degree of uncertainty limits the clear advantage for either treatment option in patients with high risk disease. Further research using larger and randomized controlled trials will be required to confirm the long term cost-effectiveness of each procedure.
Keywords: children, acute leukemia, allogeneic stem cell transplantation
Advances in stem cell transplantation (SCT) technology have improved the outcome and increased the availability of the technique, encouraging its use as a front-line treatment for many serious malignant and non-malignant disorders. Although bone marrow (BM) was initially, the exclusive source of stem cells, peripheral blood stem cells (PBSC) have become an increasingly favored alternative. Indeed, they have now largely superseded bone marrow as the source of cells in autologous transplantation, due to preferable clinical outcomes, such as faster engraftment kinetics, and shorter hospitalization [13]. While allogeneic PBSC produce similar benefits in the allogeneic setting, these are partially offset by the association of this source of stem cells with an increased risk of graft-versus-host disease (GvHD), which occurs even after recent improvements in GvHD prophylaxis and in molecular techniques for establishing donor-recipient histocompatibility [410]. Consequently it is uncertain whether PBSC are preferable to BM cells overall for use as allografts. In practice, bone marrow continues to be the main stem cell source for matched sibling donor and matched unrelated donor transplantations, while PBSC is more widely used for haploidential transplantation, since this permits an increased dose of stem cells to be given, with apparently beneficial effects on engraftment [1113]. Umbilical cord blood is a third source of stem cells for allogeneic SCT and may reduce the incidence of severe GvHD compared to the alternatives [14]. The limitations of umbilical cord blood are, however, significant, including greatly delayed time to hematological recovery and increased risk of infection, both of which lead to higher overall costs [15].
Although allogeneic SCT with blood or marrow stem cells offers the prospect of a permanent cure, few studies have addressed the overall costs and cost-effectiveness of the procedure or compared the cost effectiveness of these stem cell sources. Previous adult studies have compared the cost-effectiveness of each source, but little is known about cost comparisons in the pediatric population [1620]. This is a significant deficiency, since the disease mix in the pediatric versus the adult population (e.g. ALL>AML), the biology of the diseases, and the risks of severe GvHD are all strikingly different from adult cohorts. This may result in different predisposition to post transplant complications and different overall outcomes and hence cost effectiveness assessments. We now compare the costs and cost-effectiveness of allogeneic peripheral blood stem cell transplantation (PBSCT) and bone marrow transplantation (BMT) in pediatric patients with acute leukemia. We examined the one-year post transplant economic implications of PBSCT versus BMT treatment by stratifying patients’ disease status in a retrospective study derived from a single institution in which patients received their primary transplant from 2001 to 2006.
Patients
We studied children (range 0 years – 18 years) with acute leukemia, who received allogeneic PBSCT or BMT between January 1st, 2001 and September 30th, 2006 in the Stem Cell Transplant Unit at Texas Children’s Hospital (TCH, Houston TX). We analyzed patients who received a primary transplant and also had acute leukemia as their primary disease. Standard disease risk was defined as ALL or AML in first or second remission, and the high risk category was ALL or AML in third or subsequent remission or in relapse or patients with secondary AML [21]. The study protocol was approved by the institutional review board at Baylor College of Medicine and Texas Children’s Hospital (Houston, TX).
Study Design
The data collection time period consisted of the transplantation phase (admitted for initiation of pre-transplant chemotherapy until hospital discharge), short-term follow-up (after initial hospitalization to 100 days post transplant), and long-term follow-up (post transplant, 100 days to 1 year). Medical records were retrospectively reviewed for patients’ demographic data, date of engraftment, duration of hospital stay, onset of acute and chronic GvHD, incidence of infectious complications and duration of disease-free survival. Data were obtained from the electronic medical record system of the Center for Cell and Gene Therapy in TCH using the StemSoft and Logician software to ensure thorough and consistent counting of resource use.
The source of the stem cells for the allograft was determined by physicians and based on availability. The HLA typing method varied by year of transplant with high resolution of both class I (HLA-A, B, C) and class II (DRB1) antigens used from June 1st 2005. When the potential transplant candidates lacked an HLA-genotypically identical sibling donor or there was insufficient time to search for a suitable donor, stem cell grafts from haploidentical related donors were considered. Prior to year 2003, 93% of the patients received BMT. After 2003, 30% of patients received PBSCT. The collection of marrow and peripheral blood stem cells was based on institutional standard operating procedures. Myeloid engraftment and grading of acute or chronic GvHD were examined and evaluated by standard criteria [22].
Cost Analysis
Cost data were retrospectively acquired from administrative records and cost estimates were based on micro-cost information from the internal accounting system. At TCH, the decision support system is populated with patient demographic and utilization data and combines with the general ledger accounting and payroll data to allow financial analysis of each hospital encounter. The general ledger and payroll expenses are input into the system. These costs, along with relative value units (RVU) or cost weights assigned at the product level, create a cost per procedure, and these data are accumulated and further summarized to create a total cost per visit. The database only comprised cost data from October 1st 2003 to September 30th, 2007. Data beyond October 1st 2007 were not validated at the time the data was requested. Among the 140 patients recruited for the study, we initially acquired the actual costs on 57 patients in the BMT group and 19 patients receiving PBSCT. All costs were adjusted to 2008 dollars according to the medical care component of the consumer price index [23].
The components of costs include: days in hospital, outpatient visits, intravenous treatments, nuclear medicine, laboratory and diagnostic services, radiotherapeutic and surgical procedures, blood products, medications, and emergency room visits. The costs for stem cell collection before transplantation were not included in the analysis as the costs for bone marrow harvest and peripheral blood stem cell apheresis were essentially identical ($9,164.40 for harvest and $9,285.32 for apheresis, respectively). Of the 30 patients who received PBSCT, two had more than one PBSC collection. The procurement costs listed above included the laboratory tests and donor collection fees but did not incorporate the costs of processing stem cell products in the laboratory. Indirect costs were excluded because the perspective of this study was the healthcare providers and policy makers.
Since cost data were only available for patients receiving transplantation after September 30th 2003, we developed a regression model with the available cost data, to predict the total cost for those patients admitted for transplantation from January 1st 2001 to September 30th 2003. Our regression equation included gender, ethnicity, and patients’ prognostic factors and length of hospital stay, and its quadratic term, along with short-term and long-term study endpoints (see appendix for the regression model and table for coefficients). For the transplant phase, we included the donor type, donor or recipient CMV serostatus, patient’s disease risk, and their length of stay into the equation. During the short term follow up, patient’s disease risk, occurrence of acute GvHD, and duration of inpatient stay were included in the computation. In the long term follow up, the disease risk, occurrence of chronic GvHD, infection or relapse, and hospitalization were included in the equation. The equation was used to predict the total costs by each phase of treatment, and the imputation procedure was used separately on marrow and blood groups. The prediction method assumed that the hospital cost allocation method after September 30, 2003 was also applicable to the prior period for which cost data were not available. Stability during the study period in the institutional allocation of expenses in the transplant unit was confirmed by the accounting department. In addition, we examined the cost distribution for outlier cases by normal probability plot. Outliers were then excluded from the estimation of the cost prediction model [24].
Effectiveness Analysis
The BMT group served as the reference population for the cost-effectiveness comparison for the PBSCT group. Cost-effectiveness was measured at 1 year after the transplant procedure. Treatment outcome was defined as treatment success during the 1 year follow up period up to the last date of contact as of December 31st, 2007. Treatment was considered a success if patients survived disease free for 1 year. Cost and survival information was censored at the time of patient’s disease relapse or death during this one year follow up. Incremental effectiveness was measured by the one year post transplant differences in the percentage of cases with treatment success (PBSCT minus BMT). Incremental cost was measured by the one year post transplant differences in the average cost (PBSCT minus BMT). Incremental Cost-effectiveness ratios (ICER) were expressed as the incremental effect divided by the incremental cost.
Descriptive Statistical Analyses
Descriptive statistics were used to summarize the distribution of each variable and to compare baseline characteristics between patients enrolled in the PBSCT group and those enrolled in the BMT group, using SPSS 15.0 and SAS 9.2. Although the nature of the population surveyed provided unequal group numbers, we allowed for the effects of these discrepancies and used Mann-Whitney U-test to compare these two groups on all continuous variables and itemized costs in patients who had actual costs. The discrete variables, such as the frequency of acute and chronic GvHD and infectious complications, were compared by means of a frequency table using the Fisher’s exact test. For all statistical tests, we used 0.05 as the level of significance.
Uncertainty Analyses
Uncertainty was examined with standard sensitivity analysis and probabilistic sensitivity analysis. Standard one-way sensitivity analysis was used to examine the effect of imputing cost data for cases treated prior to October 1st 2003, estimating the mean cost with and without the imputed data. We considered using bootstrap simulation to examine statistical uncertainty. However, bootstrapping heavily relies on the tails of the estimated sampling distribution, and the smaller the sample, the less likely all of the relevant characteristics of the population would be represented [25]. Probabilistic sensitivity analysis on the cost variables therefore used 1000 Monte Carlo simulations to estimate the 95% confidence intervals (TreeAge Pro 2009 Suite, TreeAge Software Inc., Williamstown, MA, USA) [2628].
Patient and Transplant Characteristics
A total of 140 patients were consecutively recruited during the study period, of whom 110 received BMT and 30 a PBSCT. Patient and transplantation characteristics are summarized in Table 1. Fourteen (46.7%) patients who received PBSCT were standard disease risk cases as compared to 76 (69.1%) of the BMT patients. Of the peripheral blood stem cell recipients, there were 14 (46.7%) ALL patients vs. 16 (53.3%) AML patients. Seventy-four (67.3%) ALL patients received marrow transplantation as compared to one third (n=36, 32.7%) of AML patients. For the PBSCT group, fifteen (50.0%) of patients underwent an HLA mismatched related transplantation and 4 (13.3%) patients received an HLA matched related stem cell transplantation. Nine (30.0%) PBSCT patients had an HLA matched unrelated donor and 2 (6.7%) patients received mismatched unrelated stem cell transplantation. In the BMT group, the stem cell source was an HLA matched related donor in 38 (34.5%) patients; HLA matched unrelated donor in 49 (44.6%) patients; and HLA mismatched related or unrelated donor in 23 (20.9%) patients. A significantly higher percentage of PBSCT patients received CD34 selected allografts than patients treated with bone marrow. This variable was taken into account during multivariate analyses and was not a significant risk factor for acute or chronic GvHD (data not shown). There were no statistically significant differences in terms of patients’ age, gender, ethnicity or insurance coverage between PBSCT and BMT groups.
Table 1
Table 1
Patient Characteristics
Clinical Outcomes
As anticipated, subjects who received PBSCT had significantly faster neutrophil and platelet engraftment than patients in the BMT group (P<0.001 for neutrophils; P=0.034 for platelets) (Table 2). The frequency of acute or chronic GvHD was not statistically significantly different between groups. However, the incidence of infectious complications in patients receiving PBSCT was significantly higher than recipients of BMT (P=0.028). At 1 year of follow up, sixty-one (80.3%) of the standard disease risk BMT patients were disease free as compared with 8 (57.1%) of the PBSCT patients (P= NS). There were 8 (23.5%) high risk BMT patients and 3 high risk PBSCT (18.8%) patients that remained disease free after 1 year post transplant.
Table 2
Table 2
Clinical Outcomes at 1 Year of Follow Up
Cost Data
The average costs of treatment and follow up per category are presented in Table 3. The mean total cost for the initial hospitalization in the PBSCT group was higher than in the BMT group, but the difference was not statistically significant. Room and board accounted for 50% of total costs, followed by pharmacy (≈28.0% of total costs). Other major cost items during this initial phase were blood products, laboratory and radiology services. The average hospitalization time was 42.9 days for patients in the PBSCT group versus 36. 8 days in BMT recipients. The total costs over this time period were $282,577 (SD $272,344) for PBSCT and $208,987 (SD $169,554) for BMT. These differences are not significant. Three outlier cases (1 PBSCT patient and 2 BMT patients) accumulated over 1 million dollars in costs per patient and all subsequently died of progressive diseases during this first hospitalization period, leading to a large variation of costs and length of stay for both groups.
Table 3
Table 3
Treatment and follow up costs per patient in the BMT and PBSCT group*
The costs of the short-term follow up period (after initial hospitalization to 100 days post transplant) were higher for PBSCT recipients than for BMT patients ($147,907 for PBSCT versus $103, 428 for BMT). PBSCT patients on average had 25 days of inpatient stay compared to 19 days in patients receiving BMT. Room and board were identified as the most costly category. During short-term follow up, PBSCT recipients had more blood product and pharmacy usage, consistent with their longer inpatient stay.
We determined costs over the longer-term follow up period from patients who survived from 100 days post transplant to the 1 year follow up. The average total costs were similar in both groups, $106,683 (SD $76,577) for PBSCT patients versus $124,578 (SD $147,207) for the BMT group, while the average inpatient days were 14 days and 25 days, respectively. During this longer-term follow up, the costs of pharmacy and room and board accounted for about 60% of total costs for both groups.
The subgroup of patients with standard risk disease experienced an average total cost per successfully treated PBSC recipient of $367,511 (SD $164, 382) compared to $327,170 (SD $156,654) for successfully treated BM recipients (P=NS) (Table 4). In the subgroup of patients with high risk disease, the average cost per successfully treated PBSC patient was $263,392 (SD $129,239) compared to $438,473 (SD $256,150) for successfully treated BM patients (P=NS). For patients who relapsed or died before the 1 year follow up, the cumulative costs of their treatment intervention were greater than those who remained disease free at 1 year. For these failing patients, the average total costs in the standard risk group were $705,338 (SD $297,292) after PBSCT versus $457,459 (SD $357,503) after BMT (P=0.029). For the high risk group, the average total costs of failed therapy were $403,606 (SD $311,868) in the PBSCT group versus $462,803 (SD $304,924) in the BMT group (P=NS).
Table 4
Table 4
Total costs per patient in the BMT and PBSCT group at 1 year post transplant*
After one year of follow up, the initial hospitalization costs for transplantation accounted for approximately 50% of total costs, followed by short-term (26%) and long-term follow up costs (24%). In the subgroup of patients with standard disease risk, the increase in total costs was 40% – 92% for patients who did not achieve disease free survival at 1 year of follow up compared with those who had been treated successfully. In the subgroup of patients with high risk disease, the increase in average total costs was approximately 6% – 53% in patients who may have relapsed or died within 1 year post transplant of follow up as compared with those patients who were disease free.
Fourteen patients had additional transplants if they relapsed from their primary SCT. Among those patients, three had BM as their stem cell grafts while 11 patients had PBSCT. The average total costs for the PBSCT patients were $383,017 (SD $143,513) versus $262,299 (SD $65,776) for the BMT group (data not shown). The median survival time for PBSCT was 199 days (range 10 – >1700 days) compared with 150 days (range 49 – 391 days) for BMT patients.
Cost-Effectiveness Analysis
BMT served as the reference when computing the ICERs for standard and high risk patients (Tables 5). For patients with standard disease risk, the total mean cost per PBSCT patient was $512,294 (SD $280,433) compared with $352,885 (SD $214,976) for BMT patients. The treatment success rate was 57.1% in patients receiving PBSCT versus 80.3% for patients receiving BMT. The bone marrow transplantation was dominant compared to PBSCT, as its effectiveness was higher and its costs lower (ICER = −$687,108). For high risk patients, the average costs were $377,316 (SD $288,498) for the PBSCT group and $457,078 (SD $290,630) for the BMT group, respectively. The probability of treatment success was 18.8% for PBSCT and 23.5% for BMT; three patients in the PBSCT group were treated successfully, compared to eight patients receiving BMT during 1 year follow up. The ICER for the high risk group was approximately $1.69 million per additional treatment success if the transplants using BM rather than PBSC.
Table 5
Table 5
Cost-Effectiveness Analysis of Stem Cell Transplantation (SCT) for Acute Leukemia in Children*
Uncertainty Analysis
The ICERs were recomputed to exclude imputed costs to gauge the effect of the cost imputation process on the underlying data (Table 6). Among patients with standard risk disease, BMT remained dominant over PBSCT (ICER = −$969,453). The ICER was reduced to $1.41 million in the analysis of high risk patients, with BMT more expensive and more effective than the PBSCT.
Table 6
Table 6
Uncertainty Analysis of Cost-Effectiveness Analysis on Actual Cost Data
The results of the probabilistic sensitivity analyses are shown in Figures 1 and and22 for standard risk and high risk disease groups, respectively. The mean costs were $515,540 (SD $162,969; 95% confidence interval $258,867 to −$890,989) for the standard risk PBSCT patients and $357,748 (SD $146,874; 95% confidence interval $132,581 to −$699,985) for the standard risk BMT patients. The 95% confidence ellipse showed BMT was dominant over PBSCT, and the 95% confidence limits for the ICER ranged from $2.4 million to −$5.5 million. Most points (76.7%) fell in quadrant II, indicating a higher probability that PBSCT was less effective and more costly (Fig. 1). There was a 19% probability for PBSCT being less costly but also being less effective (quadrant III).
Figure 1
Figure 1
Incremental Cost-Effectiveness (ICE) of Peripheral Blood Stem Cell Transplantation (A) and Bone Marrow Transplantation (B) – Standard Risk Group
Figure 2
Figure 2
Incremental Cost-Effectiveness (ICE) of Peripheral Blood Stem Cell Transplantation (A) and Bone Marrow Transplantation (B) – High Risk Group
For high risk patients who received PBSCT as their treatment, the mean costs were $386,193 (SD $255,691; 95% confidence interval $70,297 to $1,026,887) while the mean costs of BMT were $468,244 (SD $243,771; 95% confidence interval $128,543 to $1,030,401). The 95% confidence limits for the ICER ranged from $29.7 million to −$35.2 million. There is a 36.8% probability that PBSCT would be less costly but also less effective compared to BMT (quadrant III) as shown in Figure 2. Furthermore, PBSCT has an equivalent opportunity (24%) of being the dominant option (quadrant IV) or being the dominated choice (quadrant II) over BMT. Overall there is no clear preference for either treatment method due to the large degree of uncertainty in the results.
We report a cost-effectiveness analysis comparing PBSCT and BMT in a cohort of pediatric patients. Cost benefit analyses measure both the costs and the effectiveness of alternative treatments in monetary units and thereby determine the net (social) benefit. Our study measures effectiveness in terms of clinical indicators/health outcomes and is the first to include such cost-effectiveness end point analyses out to 1 year of follow up. The clinical outcomes indicate that faster engraftment was observed in patients receiving PBSCT compared to recipients receiving BMT, but the frequency of infectious complications was higher in PBSCT recipients. Inpatient days and hospital costs were not statistically significantly different between the two transplant groups. At one year of follow up, patients in the BMT group had a higher treatment success rate and lower costs than the recipients of the PBSCT within the standard but not the high risk disease group, where the treatment success rate and the cumulative costs were lower in the PBSCT group compared to the BMT group.
Previous cost-effectiveness analyses of stem cell transplantation versus chemotherapy or no transplantation have largely studied adult populations with heterogeneous diseases [2935]. Several of these studies found SCT was cost-effective, as the intervention cost less than $50,000 per quality-adjusted life year (QALY) [3235]. Comparisons of the cost-effectiveness of PBSC versus and BM have been limited. Only one exclusively pediatric study analyzing cost-effectiveness of each stem cell source in children with hematological malignancy has been reported. This single institution study (Hospital Nino Jesus, Spain) of 25 patients accrued over 9 years found that overall costs at 100 days post transplant was lower for PBSCT than for BMT [36]. Although more adult cost-effectiveness analyses have been published, only the acute costs were investigated [20,29,31,33].
In a separate study, we analyzed the impact of stem cell source cells on disease-free survival in the pediatric transplant population at 1 year and 3 years of follow up, respectively. Our series showed there was a significant difference in the cumulative probabilities of disease-free survival between patients receiving BMT versus PBSCT by Kaplan-Meier method. However, multivariate Cox regression analysis showed no effect for the source of stem cells on treatment-related mortality, relapse or treatment failure overall whereas the HLA typing, disease status at transplant, the impact of CD34 selection and occurrence of acute or chronic GvHD were also included as independent variables. In the subgroups of patients with standard risk or high risk disease, the estimated probabilities of survival did not retain statistically significant differences between those receiving PBSCT compared to those receiving BMT. Of note, it was mostly stem cells from haploidentical donors that were CD34 selected, while non-selected PBSC were mainly used for matched unrelated donors. We subsequently performed multivariate analysis to adjust for independent effect of potential risk factors and found that CD34 selection was not associated with overall outcomes. Moreover, we analyzed the effects of age on the outcome observed with each stem cell source and found no significant correlation between graft type and age distribution. Ultimately, only the pre-transplant CMV seropositivity and differences in severity of underlying disease remained significant risk factors for disease-free survival.
By separating patients into those with standard and high risk disease, we found that despite the faster hematopoietic recovery observed in PBSCT recipients during initial transplant, there was no difference from BMT recipients in the time of hospitalization or costs incurred. In addition, during initial (short-term) follow up after hospital discharge to 100 days post transplant, the PBSCT group had higher costs and experienced a longer length of stay compared with BMT, although these differences did not reach statistical significance. Our results also showed a large difference in mean costs depending on the disease risk groups, a measure not available to the previous pediatric report [36]. We analyzed the incremental cost-effectiveness ratio and showed that the treatment success rate was significantly different between disease risk groups. Although there was great variability in costs and the group sizes were relatively small, our results appeared to be robust in sensitivity analyses of the observed difference between each group.
We developed a cost prediction model from detailed accounting data to estimate costs for patients transplanted between January 2001 and September 2003. We also confirmed that during the study period there was no alteration in institutional allocation of expenses for the transplant unit. Hence, we have no reason to believe that any changes that may have occurred in hospital accounting practices would bias the cost comparisons between study groups. Based on the regression model we developed to impute cost data, the adjusted R2 were all well above .90 where less than 10% of variance would be explained by other additional variables, including those possibly outcome relevant variables. It was noted that the HLA-matched related donors (donor 2) have a lower negative coefficient compared to HLA-mismatched sibling donors (donor 1) as the latter have been perceived as being more costly. This internal inconsistency is likely due to the small numbers in this study, providing an idiosyncratic outcome that results from random effects in a small data set.
During the first year of follow up post transplant, patients mainly returned to the primary transplant clinic for standard of care. Inclusion of outpatient costs outside of the institution and homecare utilization would be expected to raise the total costs of follow up. One study examined the contribution of costs occurring between 3 to 6 months when patients returned to the care of their local physicians after 100 days, and found that they represented 3.8% of total costs [29]. Although these data were not available at our institution, we would not expect the exclusion of those relatively minor cost estimates to result in significant differential increase in costs. Since the intent of our study was to analyze the total direct costs from the perspective of healthcare providers, we did not include the costs resulting from the time loss of patients or their families entered into the transplant program.
Although differences between institutions, and differing health care structures and pricing make direct comparisons with our study difficult, these data can be adjusted to factor in such distinctions. It is important to have precise estimates of hospital costs if the evaluation is to be accurate and so our study used micro-costing to measure all the direct medical costs of allogeneic transplantation for up to 1 year. These resource intensive transplant services may vary at regional and even local levels and our results may not be representative of other areas, even within the United States. Nonetheless, our detailed micro-costing and consistent cost categories allowed valid comparisons of resource requirements for the alternative therapies.
We investigated the total direct costs up to 1 year in all patients who received their primary transplant at our institution. Fourteen patients in our study had multiple transplants and were excluded from our primary analysis since these additional treatments are one of several salvage options for primary treatment failure and carry different, and non-comparable, expectations of cost and complexity irrespective of the stem cell source. For those patients who had multiple transplants after they relapsed from their initial transplant, the costs and outcomes information were subsequently measured in separate analyses. Since this was a retrospective observational study, accrual was subject to selection bias. However, treatment groups were similar in terms of their age, gender, ethnicity, and insurance coverage. We appreciate that fewer PBSCT than BMT recipients were studied, a difference that reflects clinical practice in pediatric SCT during the study period. It will certainly be helpful to reanalyze the data with a larger, more balanced cohort, since this would likely increase the confidence of our conclusions. Similarly, we followed the children for one year, an intermediate health care outcome, and a longer term study will be valuable to compare the longer term cost-effectiveness of each procedure.
The above limitations notwithstanding, cost-effectiveness analyses will likely become increasingly important as healthcare policies change. Our current incremental cost-effectiveness ratio and analysis of uncertainty suggest that allogeneic transplantation of bone marrow grafts was a more cost-effective treatment option compared to peripheral blood stem cells in patients with standard risk childhood acute leukemia disease. For high risk disease our data are less prescriptive, since the differences were more limited and the range of costs much larger. The comparative economic evaluation provides support for BMT for standard risk patients, but a great degree of uncertainty limits the clear advantage for either treatment option in patients with high risk disease. A larger and randomized controlled trial, especially in high risk patients, is essential to definitively demonstrate the long term cost-effectiveness of blood stem cells and bone marrow grafts for allogeneic transplantation of children.
Acknowledgments
HEH is supported by a Dan L. Duncan chair and MKB by a Fayez S. Sarofim chair. We thank the nursing staff of the Bone Marrow Transplant Unit at the Texas Children’s Hospital for their excellent children’s care; Myrlena Lee, Carolyn Smith, Bernadette Burttchell, Bonnie Byrne and James Arce for their assistance in data collections. We gratefully acknowledge critical reading of the manuscript from Dr. Jonathan S. Boomer. This work was supported by NIH grant P30 CA 125123.
Appendix: Regression Model Cost Equation
  • Total Costs (Initial hospitalization for SCT) = β0 + β1*Gender (male/female) + β2*Ethnicity (Hispanic/non-Hispanic) + β3*Donor1 (HLA-mismatched sibling/Other) + β4*Donor2 (HLA-matched related/Other) + β5*Donor3 (HLA-matched unrelated/Other) + β6*CMV (D-R positive/Other) + β7*Disease risk (standard/high risk) + β8*LOS + β9*(LOS)2 + error
  • Total Costs (After discharged to Day +100 post SCT: short-term follow up) = β0 + β1*Gender (male/female) + β2*Ethnicity (Hispanic/non-Hispanic) + β3*aGvHD (yes/no) + β4*Disease risk (standard/high risk) + β5*LOS + β6*(LOS)2 + error
  • Total Costs (From Day +100 to 1 year post SCT: long-term follow up) = β0 + β1*Gender (male/female) + β2*Ethnicity (Hispanic/non-Hispanic) + β3*cGvHD (yes/no) + β4*Infection (yes/no) +β5*Relapse (yes/no) + β6*Disease risk (standard/high risk) + β7*LOS + β9*(LOS)2 + error
Table 1
Parameter coefficients and standard errors of the independent variables included in the cost regression model
VariableParameter CoefficientStandard ErrorAdjusted R2
Marrow group; BMT phase 1 (N = 53)0.9626
Gender (Ref* = Male)3235.9411059
Ethnicity (Ref* = Hispanic)5049.7010891
Disease Risk (Ref* = Standard Risk)−447.5512343
CMV (Ref* = Positive)8798.9311436
Donor1 (Ref* = HLA-mismatched sibling)−5294830414
Donor2 (Ref* = HLA-matched related)−3462019353
Donor3 (Ref* = HLA-matched unrelated)−7407.0618045
LOS4828.421137.41
LOS218.5017.11
Blood group; BMT phase 1 (N = 11)0.9705
Gender (Ref* = Male)−3561.9919307
Ethnicity (Ref* = Hispanic)1444017264
Disease Risk (Ref* = Standard Risk)−1282818028
CMV (Ref* = Positive)00
Donor1 (Ref* = HLA-mismatched sibling)−5615536035
Donor2 (Ref* = HLA-matched related)−13627860466
Donor3 (Ref* = HLA-matched unrelated)−1558838287
LOS7209.481718.96
LOS2−2.1820.24
Marrow group; BMT phase 2 (N = 53)0.9813
Gender (Ref* = Male)6606.495811.76
Ethnicity (Ref* = Hispanic)215925393.42
Disease Risk (Ref* = Standard Risk)5476.395865.31
aGvHD (Ref* = Yes)136705296.64
LOS2868.65378.52
LOS275.536.29
Blood group; BMT phase 2 (N = 11)0.9335
Gender (Ref* = Male)−1321721027
Ethnicity (Ref* = Hispanic)3878217468
Disease Risk (Ref* = Standard Risk)1197619088
aGvHD (Ref* = Yes)−5465.6518231
LOS5502.201577.93
LOS25.5625.60
Marrow group; BMT phase 3 (N = 41)0.9118
Gender (Ref* = Male)−2858918293
Ethnicity (Ref* = Hispanic)2843418366
Disease Risk (Ref* = Standard Risk)3023820998
cGvHD (Ref* = Yes)4358.6934508
Relapse (Ref* = Yes)2303038049
Infection (Ref* = Yes)528.2321988
LOS6507.701012.9
LOS2−7.0912.82
Blood group; BMT phase 3 (N = 8)0.9429
Gender (Ref* = Male)−1790534883
Ethnicity (Ref* = Hispanic)−2560423423
Disease Risk (Ref* = Standard Risk)2250616518
cGvHD (Ref* = Yes)−4689.5822303
Relapse (Ref* = Yes)2381219970
Infection (Ref* = Yes)00
LOS7761.362719.7
LOS2−31.2762.19
Ref*: Reference group; BMT phase 1 = Initial hospitalization for SCT; BMT phase 2 = After discharged to Day +100 post SCT: short-term follow up; BMT phase 3 = From Day +100 to 1 year post SCT: long-term follow up
Footnotes
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The authors declare no financial conflict of interest.
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