One-stop autologous breast reconstruction: A safe and effective cost-saving pathway.

INTRODUCTION: Patients undergoing autologous breast reconstruction usually require further operations as part of their reconstructive journey. This involves contralateral breast symmetrization and nipple-areola complex (NAC) reconstruction. Restrained access to elective operating space led us to implement a one-stop breast reconstruction pathway. METHODS: Patients undergoing contemporaneous contralateral breast symmetrization and immediate NAC reconstruction with free nipple grafts between July 2020 and June 2021 were identified. A retrospective review of our prospectively maintained database was conducted, to retrieve surgical notes, postoperative complications, and length of inpatient stay. A cost analysis was performed considering savings from contralateral symmetrization. RESULTS: A total of 50 eligible cases were identified, which had unilateral one-stop breast reconstructions. Complication rates and length of stay were not affected by this approach, with only one free flap being lost for this cohort. This approach resulted in £181,000 being saved for our service over a calendar year. DISCUSSION: A one-stop breast reconstruction pathway has proven to be safe and effective in our unit. During these uncertain times, it has streamlined the management of eligible patients, while releasing capacity for other elective operations. Patients avoid having to wait for secondary procedures, finishing their reconstructive pathway earlier. We plan to continue providing this service which has shown to be beneficial clinically and financially.

The cost of multiple myeloma and its complications: A single-center study from Oran, Algeria.

BACKGROUND: The expenses of multiple myeloma (MM) represent a real economic and societal burden for patients and health authorities. However, very little is known about the situation in Algeria. Therefore, the aim of this study is to evaluate the costs generated by the management of MM and its complications in Algerian patients. MATERIALS AND METHODS: An observational retrospective study conducted on patients diagnosed with MM, from January 1st, 2019 to April 31st, 2023, at the Establishment Hospitalier Universitaire November 1st, Oran. A bottom-up costing methodology was used to assess the phase-specific cost and the complication burden. RESULTS: In total, 249 qualified for the study. For autologous stem cell transplantation (ASCT) eligible patients, the mean per patient cost of treating myeloma was estimated at: induction regimen ($4072); ASCT ($2899); consolidation ($1538); and maintenance ($355.76). The mean drug cost for ASCT-ineligible patients was $1421. The use of generic bortezomib and generic melphalan has led to a reduction in expenses of $1,075,181 ($5,024 per patient; 55.35%) and $10,864 ($487 per patient; 15.07%), respectively. Another cost-saving adaptation was ASCT using non-cryopreserved (NC) stem cells. The cost of managing MM complications was $177,782 per year. CONCLUSION: A number of adjustments have been implemented to the management of MM over time to improve clinical efficacy and reduce costs in Algeria. However, this may have come with a startlingly high cost of complications.

Cost and effectiveness of autologous haematopoietic stem cell transplantation and high-efficacy disease-modifying therapies in relapsing-remitting multiple sclerosis.

BACKGROUND: Autologous haematopoietic stem cell transplantation (AHSCT) is a highly effective one-off treatment for relapsing-remitting multiple sclerosis (RR-MS), potentially representing an optimal front-loading strategy for costs. OBJECTIVE: Exploring cost/effectiveness of AHSCT and high-efficacy disease-modifying treatments (HE-DMTs) in RR-MS, estimating costs at our centre in Italy, where National Health Service (NHS) provides universal health coverage. METHODS: Costs (including drugs, inpatient/outpatient management) for treatment with AHSCT and HE-DMTs were calculated as NHS expenditures over 2- and 5-year periods. Cost-effectiveness for each treatment was estimated as "cost needed to treat" (CNT), i.e. expense to prevent relapses, progression, or disease activity (NEDA) in one patient over n-years, retrieving outcomes from published studies. RESULTS: Costs of AHSCT and HE-DMTs were similar over 2 years, whereas AHSCT was cheaper than most HE-DMTs over 5 years (€46 600 vs €93 800, respectively). When estimating cost-effectiveness of treatments, over 2 years, mean CNT of HE-DMTs for NEDA was twofold that of AHSCT, whereas it was similar for relapses and disability. Differences in CNT were remarkable over 5 years, especially for NEDA, being mean CNT of HE-DMTs €382 800 vs €74 900 for AHSCT. CONCLUSIONS: AHSCT may be highly cost-effective in selected aggressive RR-MS. Besides priceless benefits for treated individuals, cost-savings generated by AHSCT may contribute to improving healthcare assistance at a population level.

Efficacy and cost of G-CSF derivatives for prophylaxis of febrile neutropenia in lymphoma and multiple myeloma patients underwent autologous hematopoietic stem cell transplantation.

OBJECTIVES: To compare the efficacies and costs between pegfilgrastim and filgrastim prophylaxis for FN post-ASCT for lymphoma and multiple myeloma patients. METHODS: 43 patients who received pegfilgrastim (6 mg) were compared to a retrospective cohort of 129 patients that had received filgrastim post-ASCT. Hematopoietic recovery time, FN incidence and treatment costs were assessed and compared. RESULTS: The mean time to absolute neutrophil count engraftment was 8.72 ± 2.38 days for the prospective pegfilgrastim group and 9.87 ± 3.13 days for the retrospective filgrastim group (P = 0.027). The incidence of FN was 18.60% and 50.39% in prospective pegfilgrastim and retrospective filgrastim groups, respectively (P = 0.000). The mean cost of filgrastim was $617.22 ± 37.87, compared with $525.78 for pegfilgrastim (P = 0.032). DISCUSSION: Convenience, effectiveness, and safety of prophylaxis for FN in the prospective pegfilgrastim group were significantly improved compared to the retrospective filgrastim group in ASCT patients. CONCLUSION: Pegfilgrastim prophylaxis was more effective and convenient than filgrastim for FN prophylaxis in patients post-ASCT, especially for MM patients.

Factors Associated With State-Specific Medicaid Expansion and Receipt of Autologous Breast Reconstruction Among Patients Undergoing Mastectomy.

Importance: Despite demonstrated psychosocial benefits, autologous breast reconstruction remains underutilized. An analysis of the association between Medicaid expansion and autologous breast reconstruction has yet to be performed. Objective: To compare autologous breast reconstruction rates and determine the association between Medicaid expansion and breast reconstruction. Design, Setting, and Participants: A retrospective cross-sectional study was performed using the State Inpatient Database from January 1, 2012, through September 30, 2015, and included 51 340 patients. Patients were identified using the International Classification of Diseases, Ninth Revision, codes for breast cancer, mastectomy, and autologous breast reconstruction. Data from states that expanded Medicaid (New Jersey, New York, and Washington) were compared with states that did not expand Medicaid (Florida, North Carolina, and Wisconsin). Data were analyzed from June 1, 2020, through February 28, 2021. Exposures: The Patient Protection and Affordable Care Act's Medicaid expansion was implemented in 2014; the preexpansion period ranged from 2012 to 2013 (2 years), whereas the postexpansion period ranged from 2014 to 2015 quarter 3 (1.75 years). Main Outcomes and Measures: Primary outcomes included use of autologous breast reconstruction before and after expansion. Independent covariates included patient demographics, comorbidities, and state of residence. Results: Among 45 850 patients who underwent mastectomy and 9215 patients who received autologous breast reconstruction, 36 777 (67%) were White and 32 205 (59%) had private insurance. The use of immediate or delayed autologous reconstruction increased from 18.1% (4951 of 27 290) to 23.0% (4264 of 18 560) throughout the study period. Compared with 2012, the odds of reconstruction were 64% higher in 2015 (odds ratio [OR], 1.64; 95% CI, 1.48-1.80; P < .001). African American (OR, 1.43; 95% CI, 1.33-1.55; P < .001) and Hispanic (OR, 1.44; 95% CI, 1.31-1.60; P < .001) patients had higher odds of reconstruction compared with White patients regardless of state of residence. However, Medicaid expansion was associated with a 28% decrease in the odds of reconstruction (OR, 0.72; 95% CI, 0.61-0.87; P < .001) for African American patients, a 40% decrease (OR, 0.60; 95% CI, 0.50-0.74; P < .001) for Hispanic patients, and 20% decrease (OR, 0.80; 95% CI, 0.67-0.96; P = .01) for patients with Asian, Native American, or other minority race/ethnicity. Medicaid expansion was not associated with changes in the odds of reconstruction for White patients. Conclusions and Relevance: In this cross-sectional study, although the odds of receiving autologous breast reconstruction increased annually, Medicaid expansion was associated with decreased odds of reconstruction for African American patients, Hispanic patients, and other patients of color.

Cost-utility analysis of four common surgical treatment pathways for breast cancer.

BACKGROUND: The aim was to evaluate the cost-utility of four common surgical treatment pathways for breast cancer: mastectomy, breast-conserving therapy (BCT), implant breast reconstruction (BR) and autologous-BR. METHODS: Patient-level healthcare consumption data and results of a large quality of life (QoL) study from five Dutch hospitals were combined. The cost-effectiveness was assessed in terms of incremental costs and quality adjusted life years (QALYs) over a 10-year follow-up period. Costs were assessed from a healthcare provider perspective. RESULTS: BCT resulted in comparable QoL with lower costs compared to implant-BR and autologous-BR and showed better QoL with higher costs than mastectomy (€17,246/QALY). QoL outcomes and costs of especially autologous-BR were affected by the relatively high occurrence of complications. If reconstruction following mastectomy was performed, implant-BR was more cost-effective than autologous-BR. CONCLUSION: The occurrence of complications had a substantial effect on costs and QoL outcomes of different surgical pathways for breast cancer. When this was taken into account, BCT was most the cost-effective treatment. Even with higher costs and a higher risk of complications, implant-BR and autologous-BR remained cost-effective over mastectomy. This pleas for adapting surgical pathways to individual patient preferences in the trade-off between the risks of complications and expected outcomes.

The Costs of Breast Reconstruction and Implications for Episode-Based Bundled Payment Models.

BACKGROUND: Implementation of payment reform for breast reconstruction following mastectomy demands a comprehensive understanding of costs related to the complex process of reconstruction. Bundled payments for services to women with breast cancer may profoundly impact reimbursement and access to breast reconstruction. The authors' objectives were to determine the contribution of cancer therapies, comorbidities, revisions, and complications to costs following immediate reconstruction and the optimal duration of episodes to incentivize cost containment for bundled payment models. METHODS: The cohort was composed of women who underwent immediate breast reconstruction between 2009 and 2016 from the MarketScan Commercial Claims and Encounters database. Continuous enrollment for 3 months before and 24 months after reconstruction was required. Total costs were calculated within predefined episodes (30 days, 90 days, 1 year, and 2 years). Multivariable models assessed predictors of costs. RESULTS: Among 15,377 women in the analytic cohort, 11,592 (75 percent) underwent tissue expander, 1279 (8 percent) underwent direct-to-implant, and 2506 (16 percent) underwent autologous reconstruction. Adjuvant therapies increased costs at 1 year [tissue expander, $39,978 (p < 0.001); direct-to-implant, $34,365 (p < 0.001); and autologous, $29,226 (p < 0.001)]. At 1 year, most patients had undergone tissue expander exchange (76 percent) and revisions (81 percent), and a majority of complications had occurred (87 percent). Comorbidities, revisions, and complications increased costs for all episode scenarios. CONCLUSIONS: Episode-based bundling should consider separate bundles for medical and surgical care with adjustment for procedure type, cancer therapies, and comorbidities to limit the adverse impact on access to reconstruction. The authors' findings suggest that a 1-year time horizon may optimally capture reconstruction events and complications.

Pegfilgrastim improves the outcomes of mobilization and engraftment in autologous hematopoietic stem cell transplantation for the treatment of multiple myeloma.

Autologous stem cell transplantation (ASCT) is the only curable therapy for multiple myeloma (MM), while its success primarily relies on mobilization to obtain sufficient hematopoietic stem/progenitor cells (HPC). Although the role of Pegfilgrastim (PEG), a novel PEGylated form of the recombinant G-CSF filgrastim (FIL), in mobilization has been demonstrated, it remains unclear whether this approach is cost-effective in MM treatment. Here, we performed a real-world analysis to evaluate the efficacy and cost of PEG for mobilization in a cohort of MM patients, of which 53% carried high-risk cytogenetic abnormalities. A total of 91 patients who received either a single dose of PEG (6 or 12 mg, n = 42) or multiple dosing of 10 µg/kg/day FIL (n = 49) after chemotherapy for HPC mobilization were included. The yield of MNCs and CD34+ cells per milliliter of blood collected via apheresis was significantly greater in the PEG group than that in the FIL group (P = 0.014 and P = 0.038). Mobilization with PEG yielded significantly higher median number of collected CD34+ cells than FIL (5.56 vs. 4.82 × 106/kg; P = 0.038). Moreover, the average time-to-recovery of leukocytes and platelets after transplantation was markedly shorter in the PEG group than that in the FIL group (leukocyte, 11.59 ± 1.98 vs 12.93 ± 2.83 days, P = 0.019; platelet, 12.86 ± 2.62 vs 14.80 ± 5.47, P = 0.085). However, the total cost of mobilization and apheresis using PEG or FIL was comparable (P = 0.486). Of note, mobilization with 12 mg PEG further shortened time-to-recovery of leukocytes (10.64 ± 0.51 vs. 12.04 ± 2.26 days, P = 0.05) and platelets (10.60 ± 2.89 vs. 13.33 ± 2.35 days, P = 0.031) compared with 6 mg PEG. Our results support a notion that PEG (especially 12 mg) combined with chemotherapy is a cost-effective and convenient regimen of mobilization, which might improve the outcome of ASCT in MM.

Autologous Breast Reconstruction versus Implant-Based Reconstruction: How Do Long-Term Costs and Health Care Use Compare?

BACKGROUND: The authors compared long-term health care use and cost in women undergoing immediate autologous breast reconstruction and implant-based breast reconstruction. METHODS: This study was conducted using the OptumLabs Data Warehouse, which contains deidentified retrospective administrative claims data, including medical claims and eligibility information from a large U.S. health insurance plan. Women who underwent autologous or implant-based breast reconstruction between January of 2004 and December of 2014 were included. The authors compared 2-year use rates and predicted costs of care. Comparisons were tested using the t test. RESULTS: Overall, 12,296 women with immediate breast reconstruction were identified; 4257 with autologous (35 percent) and 8039 with implant-based (65 percent) breast reconstruction. The proportion of autologous breast reconstruction decreased from 47.2 percent in 2004 to 32.7 percent in 2014. The mean predicted reconstruction cost of autologous reconstruction was higher than that of implant-based reconstruction in both unilateral and bilateral surgery. Similar results for mean predicted 2-year cost of care were seen in bilateral procedures. However, in unilateral procedures, the 2-year total costs were higher for implant-based than for autologous reconstruction. Two-year health care use rates were higher for implant-based reconstruction than for autologous reconstruction for both unilateral and bilateral procedures. Women undergoing unilateral implant-based reconstruction had higher rates of hospital admissions (30.3 versus 23.1 per 100; p < 0.01) and office visits (2445.1 versus 2283.6 per 100; p < 0.01) than those who underwent autologous reconstruction. Emergency room visit rates were similar between the two methods. Bilateral procedures yielded similar results. CONCLUSION: Although implant-based breast reconstruction is a less expensive index operation than autologous breast reconstruction, it was associated with higher health care use, resulting in similar total cost of care over 2 years.

Impact of Physician Payments on Microvascular Breast Reconstruction: An All-Payer Claim Database Analysis.

BACKGROUND: Rates of autologous breast reconstruction are stagnant compared with prosthetic techniques. Insufficient physician payment for microsurgical autologous breast reconstruction is one possible explanation. The payment difference between governmental and commercial payers creates a natural experiment to evaluate its impact on method of reconstruction. This study assessed the influence of physician payment differences for microsurgical autologous breast reconstruction and implants by insurance type on the likelihood of undergoing microsurgical reconstruction. METHODS: The Massachusetts All-Payer Claims Database was queried for women undergoing immediate autologous or implant breast reconstruction from 2010 to 2014. Univariate analyses compared demographic and clinical characteristics between different reconstructive approaches. Logistic regression explored the relative impact of insurance type and physician payments on breast reconstruction modality. RESULTS: Of the women in this study, 82.7 percent had commercial and 17.3 percent had governmental insurance. Implants were performed in 80 percent of women, whereas 20 percent underwent microsurgical autologous reconstruction. Women with Medicaid versus commercial insurance were less likely to undergo microsurgical reconstruction (16.4 percent versus 20.3 percent; p = 0.063). Commercial insurance, older age, and obesity independently increased the odds of microsurgical reconstruction (p < 0.01). When comparing median physician payments, governmental payers reimbursed 78 percent and 63 percent less than commercial payers for microsurgical reconstruction ($1831 versus $8435) and implants ($1249 versus $3359, respectively). Stratified analysis demonstrated that as physician payment increased, the likelihood of undergoing microsurgical reconstruction increased, independent of insurance type (p < 0.001). CONCLUSIONS: Women with governmental insurance had lower odds of undergoing microsurgical autologous breast reconstruction compared with commercial payers. Regardless of payer, greater reimbursement for microsurgical reconstruction increased the likelihood of microsurgical reconstruction. Current microsurgical autologous breast reconstruction reimbursements may not be commensurate with physician effort when compared to prosthetic techniques. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

Tbo-filgrastim versus filgrastim for stem cell mobilization and engraftment in autologous hematopoietic stem cell transplant patients: A retrospective review.

INTRODUCTION: Filgrastim, a granulocyte colony-stimulating factor, is commonly used in autologous hematopoietic stem cell transplants (HSCTs) to assist with peripheral blood progenitor cell (PBPC) collection and to support stem cell engraftment. In the United States, tbo-filgrastim is approved under its own Biologic License Application and is limited to a single indication excluding the HSCT population. METHODS: Approximately one year after a system-wide formulary change to tbo-filgrastim for all on- and off-label indications, our institution conducted an IRB-approved retrospective comparison of tbo-filgrastim to filgrastim in the autologous HSCT setting. The study included 71 patients who received an autologous HSCT from 1 January 2013 to 31 December 2016 with a documented administration of tbo-filgrastim or filgrastim. RESULTS: There were no statistically significant differences noted on CD34 + counts during stem cell mobilization, neutrophil engraftment, infection rates during the engraftment phase, nor duration of hospitalization during the engraftment phase. More patients in the tbo-filgrastim group received plerixafor per protocol resulting in more patients meeting their PBPC collection goal in one day with fewer collection days overall, a result potentially confounded by institutional protocol changes. Utilizing tbo-filgrastim offered an average cost savings per patient of $2664.26 ($1907.33 for PBPC mobilization and $756.93 for stem cell engraftment) when comparing dollars spent on granulocyte colony-stimulating factor products only. CONCLUSION: Tbo-filgrastim demonstrates comparable efficacy with a cost savings benefit compared to filgrastim for autologous PBPC mobilization and stem cell engraftment.

Cost-Effectiveness of the Use of Autologous Cell Harvesting Device Compared to Standard of Care for Treatment of Severe Burns in the United States.

INTRODUCTION: When introducing a new intervention into burn care, it is important to consider both clinical and economic impacts, as the financial burden of burns in the USA is significant. This study utilizes a health economic modeling approach to estimate cost-effectiveness and burn center budget-impact for the use of the RECELL® Autologous Cell Harvesting Device to prepare autologous skin cell suspension (ASCS) compared to standard of care (SOC) split-thickness skin graft (STSG) for the treatment of severe burn injuries requiring surgical intervention for definitive closure. METHODS: A hospital-perspective model using sequential decision trees depicts the acute burn care pathway (wound assessment, debridement/excision, temporary coverage, definitive closure) and predicts the relative differences between use of ASCS compared to SOC. Clinical inputs and ASCS impact on length of stay (LOS) were derived from clinical trials and real-world use data, American Burn Association National Burn Repository database analyses, and burn surgeon interviews. Hospital resource use and unit costs were derived from three US burn centers. A budget impact calculation leverages Monte Carlo simulation to estimate the overall impact to a burn center. RESULTS: ASCS treatment is cost-saving or cost-neutral (< 2% difference) and results in lower LOS compared to SOC across expected patient profiles and scenarios. In aggregate, ASCS treatment saves a burn center 14-17.3% annually. Results are sensitive to, but remain robust across, changing assumptions for relative impact of ASCS use on LOS, procedure time, and number of procedures. CONCLUSIONS: Use of ASCS compared to SOC reduces hospital costs and LOS of severe burns in the USA. FUNDING: AVITA Medical.

Autologous Chondrocyte Implantation with Chondrosphere for Treating Articular Cartilage Defects in the Knee: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

Chondrosphere (Spherox) is a form of autologous chondrocyte implantation (ACI). It is licensed for repair of symptomatic articular cartilage defects of the femoral condyle and the patella of the knee with defect sizes up to 10 cm2 in adults. In a single technology appraisal (STA) [TA508] undertaken by the National Institute of Health and Care Excellence (NICE), Warwick Evidence was the Evidence Review Group (ERG) invited to independently review the evidence submitted by the manufacturer, Co.Don. The clinical effectiveness data came from their COWISI randomised controlled trial (RCT), which compared Chondrosphere with microfracture (MF). The timing of this appraisal was unfortunate given that MF was no longer the most relevant comparator because NICE had contemporaneously published guidance approving ACI in place of MF. Moreover, the COWISI RCT enrolled mostly patients with small defect sizes. Evidence of clinical effectiveness for Chondrosphere used in people with larger defect size came from another RCT, which compared three doses of Chondrosphere and that by design could not provide evidence comparing Chondrosphere to any other forms of ACI. To estimate the relative clinical performance of Chondrosphere versus other ACI, Co.Don conducted an indirect treatment comparison by network meta-analyses (NMA). The NMA was flawed in that the distribution of population characteristics that are effect modifiers greatly differed across the treatment comparisons of the network. The ERG questioned both the appropriateness of the NMA and the validity of the resulting estimates. Co.Don estimated the cost-effectiveness of Chondrosphere using a lifetime Markov model with all patients receiving the first repair during the first cycle of the model then moving into one of three health states: success, no further repair (NFR), or a second repair, if necessary. Subsequent to the first cycle, those who were a success either remained a success or moved to second repair. All those in NFR remained in NFR. The cost-effectiveness of Chondrosphere compared to other ACI forms relied on the clinical effectiveness estimates of success and failure rates obtained from the company's indirect comparisons, the validity of which the ERG questioned. The company revised cost-effectiveness estimates for Chondrosphere versus MF and for Chondrosphere versus matrix-applied characterised autologous cultured chondrocyte implant (MACI) were £4360 and around £18,000 per quality-adjusted life year gained, respectively. NICE recommended ACI using Chondrosphere for treating symptomatic articular cartilage defects of the femoral condyle and patella of the knee in adults only if certain requirements were met.

Economic Analysis of Using Free Fat Graft or Acellular Dermis to Prevent Post-parotidectomy Frey Syndrome.

A decision tree was constructed to determine the incremental cost-effectiveness ratio (ICER) of grafting techniques used to prevent Frey Syndrome. The authors performed a sensitivity analysis to calculate what the probability of preventing Frey Syndrome would have to be and maximum costs associated with using grafting techniques to warrant their use as more "cost-effective" choice than using neither. Decision pathways utilized were uses of (1) free fat graft (FFG), (2) acellular dermis, and (3) no grafting. The probability of developing Frey syndrome and costs were extracted from previous studies to construct the decision tree. The primary effectiveness was the ICER of FFG or acellular dermis to prevent Frey syndrome. The initial outcomes included preventing Frey syndrome (effectiveness = 1) or developing Frey syndrome (effectiveness = 0). Compared with not using a graft, the ICER of using FFG and acellular dermis were $10,628 and $50,813, respectively. Frey syndrome was found in 2.6% of patients postoperatively in FFG group, 9.8% of patients in acellular dermis group, and 30.7% of patients who did not have a graft. The ICER shows absolute dominance of FFG with lower cost and high effectiveness over acellular dermis. This economic evaluation strongly supports the use of FFG over acellular dermis as cost-effective approach for prevention of postparotidectomy Frey syndrome.

Challenges in the Regulation of Autologous Stem Cell Interventions in the United States.

The direct-to-consumer marketing of stem cells for unproven therapeutic uses has grown rapidly in the United States in recent years. This development is surprising since the marketing and distribution of human cell-based medical products is stringently regulated in the US. This essay describes ambiguities, gaps, and inconsistencies in the current regulatory system that have enabled such businesses to thrive. In addition to directly challenging the authority of the Food and Drug Administration (FDA) over autologous cell-based products in the courts, stem cell marketing firms have also identified and exploited regulatory loopholes, such as the same surgical procedure exception, which exempts from FDA oversight human cell-based products that are harvested and reimplanted in a single procedure. Many businesses also advertise stem cell clinical studies on a pay-to-participate basis, which requires patients to pay large sums to enroll in clinical research. This business model not only shifts many of the cost and risks of medical experimentation from providers to patients but may also indemnify sellers from fraud litigation. Lastly, stem cell advertisers borrow heavily from the language and concepts of science-based medicine in their marketing. The inaccurate promotion of autologous stem cell injections as a form of "personalized" medicine lends a veneer of credibility and precision that may encourage patients to undergo procedures of uncertain effectiveness and to sympathize with stem cell businesses in their efforts to evade oversight.

Conditional Approvals for Autologous Stem Cell-Based Interventions: Conflicting norms and institutional legitimacy.

Demands from patients, health-care professionals, and industry to streamline the market approval process for promising new therapies has prompted the introduction of programs that can provide more rapid access to stem cell-based products before evidence of safety and efficacy has been demonstrated in clinical trials. These products may be approved for marketing under "conditional authorizations," while uncertainty around safety and efficacy is reduced through the collection of clinical data in observational trials or registries. The rationale for conditional approval programs assumes that patients with unmet medical needs will benefit with rapid access to novel stem cell therapies. It also assumes that data gathered in actual clinical contexts is inherently better at reducing uncertainty than conventional clinical trial methods of demonstrating safety and efficacy. These assumptions may be overly optimistic and do not account for the broader societal burdens of prematurely releasing high-cost therapies with uncertain safety risks and benefits on to health-care markets. This essay focuses on the introduction of conditional approval programs for autologous somatic stem cell therapies and argues that these programs may conflict with, and potentially undermine, the normative commitments of regulatory agencies charged with promoting population health and protecting vulnerable groups from harm and exploitation. It concludes with suggestions of how programs designed to accelerate access to potentially helpful but experimental interventions could be reconfigured to be more equitable.

Vulnerabilities and the Use of Autologous Stem Cells for Medical Conditions in Australia.

Australia has a booming market of unproven autologous stem cell- based interventions (SCBIs) for a wide range of medical conditions. Multiple SCBIs are provided in private practices outside of formal clinical trials. Some defend the provision of unproven SCBIs on grounds of patient choice. This essay interrogates this argument for patient choice and explores patients' vulnerabilities in clinical practice with autologous SCBIs. While all patients are inherently vulnerable, the regulatory framework for autologous stem cells in Australia exacerbates the problems associated with inherent vulnerabilities and generates situational and pathogenic vulnerabilities. A just state ought to implement regulatory measures that mitigate vulnerabilities and foster patients' autonomy.

Impact of the affordability of novel agents in patients with multiple myeloma: Real-world data of current clinical practice in Mexico.

BACKGROUND: The treatment of multiple myeloma (MM) has become costly and difficult to access for patients living in low-income to middle-income countries. METHODS: The current retrospective study included 148 patients in Mexico with newly diagnosed MM, and was performed to compare the outcomes of patients with and without access to novel agents. The records of 77 patients admitted to a public hospital (PubC) and 71 patients cared for within private health systems (PrivC) from November 2007 to July 2016 were reviewed. RESULTS: Compared with those treated in PrivC, patients receiving care at PubC were more likely to be diagnosed with advanced disease. A thalidomide-based regimen was the most common induction treatment used at PubC, whereas a bortezomib-based regimen was used most often in PrivC. The median follow-up was 41 months. Patients in PrivC demonstrated better response rates and survival; 65% of patients treated in PrivC versus 41% treated at PubC achieved a very good partial response or better (P = .005). The median progression-free survival and median overall survival were 23 months and 51 months, respectively, for patients treated at PubC and 41 months and 79 months, respectively, for those treated in PrivC (P<.001). More patients underwent autologous stem cell transplantation in PrivC. When adjustments were made for covariates, patients treated at PubC experienced a higher risk of death compared with patients receiving care in PrivC (hazard ratio, 2.0; 95% confidence interval, 1.0-4.3 [P = .04]). CONCLUSIONS: Stage at diagnosis, induction regimen, and autologous stem cell transplantation were found to be contributors to survival disparities between patients with MM treated at PubC compared with PrivC in Mexico. These findings underscore the need to improve access to novel agents and stem cell transplantation in public health systems. Cancer 2018;124:1946-53. © 2018 American Cancer Society.

Low CD34+ Cell Doses Are Associated with Increased Cost and Worse Outcome after Tandem Autologous Stem Cell Transplantation in Patients with Relapsed or Refractory Germ Cell Tumors.

Tandem autologous stem cell transplantation (ASCT) improves long-term survival of platinum-refractory germ cell tumors (GCT) patients. Studies, predominantly in lymphoma, showed that CD34+ cell doses > 5.0 × 106/kg/single transplant led to decreased resource utilization. Because most GCT patients have received prior cisplatin-based treatment, collecting >10 × 106 CD34+ cells/kg is challenging. We analyzed the effect of CD34+ cell dose on resource utilization and outcome in 131 GCT patients, median age 29.5 years (range, 16 to 58), undergoing tandem ASCT. Of 262 individual transplants performed, 120 were performed as inpatient and 142 as planned outpatient. Overall, median CD34+ dose per transplant was 3.1 × 106/kg (range, 0.8 to 16.0), with no significant difference between inpatient and outpatient transplants. Patients were divided into quartiles based on the CD34 cell dose infused: Q1, 0.8 to 1.9 × 106/kg; Q2, 2.0 to 2.9 × 106/kg; Q3, 3.0 to 4.1 × 106/kg; and Q4, 4.2 to 16.0 × 106/kg. For all patients higher CD34+ cell doses were associated with significantly shorter times to neutrophil (P <.001) and platelet recovery (P <.001). For inpatient transplants higher CD34+ doses were significantly associated with shorter length of hospital stay (P <.001), fewer days of filgrastim (P <.001), i.v. antibiotic (P = .012) and antifungal (P = .03) usage; and fewer RBC (P = .001) and platelet units transfused (P <.001), resulting in overall lower cost of care (P < .001). Of the 142 planned outpatient transplants, 100 admissions were required for a median length of hospital stay of 7.0 days (range, 1 to 18). Although there was no significant difference in the rates of hospitalization between patients in different CD34+ cell dose quartiles, a significant trend was observed for shorter hospitalization (P = .01) and fewer RBC (P = .002) and platelet (P = .005) transfusions with higher CD34+ cell dose quartile. Patients receiving CD34+ cell doses in the lowest dose quartile (Q1) had significantly worse progression-free survival and overall survival compared with patients receiving higher CD34+ cell doses. Overall, resource utilization, including cost of care, is significantly reduced when patients receive higher CD34+ cell doses, indicating greater efforts to improve peripheral blood stem cell collection in this population are needed.