Fixed-dose administration and pharmacokinetically guided adjustment of busulfan dose for patients undergoing hematopoietic stem cell transplantation: a meta-analysis and cost-effectiveness analysis.

This study aims to evaluate the efficacy, safety, and long-term cost-effectiveness of fixed-dose busulfan (Bu) administration and pharmacokinetically (PK) guided adjustment of Bu dose for patients who underwent hematopoietic stem cell transplantation. The efficacy and safety of both dosing strategies were compared using a systematic review and meta-analysis. A Markov model was used in estimating relevant cost and health outcomes from the perspective of the health system. The primary outcomes of interest were lifetime cost, quality adjusted life-years (QALYs) gained, and incremental cost-effectiveness ratio (ICER) in dollar per QALY gained. Results showed that progression-free survival and overall survival in the PK-guided group were higher than that in the fixed-dose group, and the PK-guided group was associated with low non-relapse mortality and relapse rate. In contrast to safety, the incidence of acute graft-versus-host disease (GVHD) was the same in the two groups (P > 0.05). Cost-effectiveness analysis showed that the QALY of the PK-guided group (12.8135 QALYs and $582,475.07) increased by 2.0609 relative to that in the fixed-dose group (10.7526 QALYs and $562,833.20), and the ICER was $9530.72/QALY. One-way and probability sensitivity analyses confirmed the reliability of the results. In conclusion, the PK-guided approach has higher efficacy and is safer.

Extracorporeal photopheresis vs standard therapies for steroid-refractory chronic graft-vs-host disease: Pharmacoeconomic assessment of hospital resource use in Spain.

BACKGROUND: This study assessed pharmacoeconomic costs associated with extracorporeal photopheresis (ECP) compared with other available second-line therapies for chronic graft-vs-host disease (cGvHD) in a tertiary Spanish institution. METHODS: Patients (≥18 years) diagnosed with steroid-refractory cGvHD were eligible. Data were collected retrospectively from index date until 1 year or relapse. Patients were distributed in two cohorts (ECP vs non-ECP), matched by age (≤ or > 40), hematopoietic stem cell transplant (HLA-identical sibling donor or other) and number of previous immunosuppressive lines (1, 2, or ≥ 3). Costs were assigned using the 2016 diagnosis-related group (DRG) system: DRG 579 (€22 383) overnight stay due to major complication (ie, sepsis, pneumonia, parenteral nutrition, or respiratory failure), and DRG 875 (€5154) if no major complication. The primary endpoint was healthcare resource utilization per patient. RESULTS: Forty patients (n = 20 per cohort) were included. Median age was 49, and 37.5% were female. Mean total cost per patient was €25 319 (95% CI: €17 049-€33 590) across the two cohorts, with a slightly lower mean cost per ECP-treated patient (€23 120) compared with the non-ECP cohort (€27 519; P = .597). Twenty-seven inpatient hospitalizations occurred among ECP-treated patients, vs 33 in the non-ECP cohort. Day hospital and external consultations were more frequent in the ECP cohort. However, fewer inpatient admissions included DRG 579 compared with the non-ECP cohort (44% vs 58%). Inpatient length of stay was slightly shorter in the ECP cohort (30 vs 49 days; P = .298). CONCLUSIONS: ECP treatment may yield economic savings in Spain through resource savings and moving costs toward outpatient care.

Continuation of systemic treatments and outcomes for patients with chronic graft-versus-host disease in the USA.

Aim: To compare secondary systemic treatment (SST) continuation and associated resource use and costs in chronic graft-versus-host disease (cGvHD) patients in the USA. Materials & methods: This was a retrospective study using Truven Health MarketScan database (2009-2016). cGvHD patients were classified as continuers or discontinuers if treated with SST for ≥180 days without or with a treatment gap (≥45 days), respectively. Results: Among 464 cGvHD patients with SST, mTOR inhibitors, extracorporeal photopheresis and imatinib were most frequently used. A total of 172 patients were SST continuers and 292 were discontinuers. Extracorporeal photopheresis treated patients were the highest continuers, followed by imatinib and mTOR inhibitors. SST continuers had lower monthly hospitalization costs versus discontinuers. Conclusion: This real-world analysis demonstrates high SST continuation rates in cGvHD patients are associated with lower resource utilization and cost.

Healthcare resource utilization and costs associated with acute graft-versus-host disease following allogeneic hematopoietic cell transplantation.

PURPOSE: The contribution of acute graft-versus-host disease (GVHD) to healthcare resource utilization (HCRU) and costs following allogeneic hematopoietic cell transplantation (HCT) has not been extensively investigated. The objective of this study was to estimate both inpatient and outpatient HCRU and costs associated with acute GVHD during the 100-day and 1-year periods after allogeneic HCT in the USA. METHODS: A retrospective analysis of administrative claims from the Optum® Research Database of patients aged ≥ 12 years who received HCT between 2010 and 2016 was conducted. Costs and HCRU among patients with acute GVHD and no GVHD were compared during the 100-day (acute GVHD, n = 723; no GVHD, n = 385) and 360-day (acute GVHD, n = 445; no GVHD, n = 227) periods after HCT. RESULTS: Patients with acute GVHD had significantly more (P < 0.001) mean office visits (47 vs 32), hospital outpatient visits (71 vs 35), and inpatient stays (2.8 vs 1.1) than patients with no GVHD during 360 days post-HCT; similar findings were observed over the 100-day period. Mean total all-cause costs were significantly higher (P < 0.001) for patients with acute GVHD versus no GVHD during both post-HCT periods (100-day, $316,458 vs $215,229; 360-day, $466,720 vs $263,568). Additional factors associated with increased 360-day costs included young age (12-17 years; P < 0.001) and peripheral blood as graft source (P = 0.03). CONCLUSION: Acute GVHD was associated with significant HCRU and costs in the first 100 days of transplant, increasing over the first year post-HCT. Inpatient care was the primary driver, but outpatient care and related costs were also increased.

Employment, Insurance, and Financial Experiences of Patients with Chronic Graft-versus-Host Disease in North America.

Understanding the socioeconomic impact of chronic graft-versus-host disease (GVHD) on affected patients is essential to help improve their overall well-being. Using data from the Chronic GVHD Consortium, we describe the insurance, employment, and financial challenges faced by these patients and the factors associated with the ability to work/attend school and associated financial burdens. A 15-item cross-sectional questionnaire designed to measure financial concerns, income, employment, and insurance was completed by 190 patients (response rate, 68%; 10 centers) enrolled on a multicenter Chronic GVHD Consortium Response Measures Validation Study. Multivariable logistic regression models examined the factors associated with financial burden and ability to work/attend school. The median age of respondents was 56years, and 87% of the patients were white. A higher proportion of nonrespondents had lower income before hematopoietic cell transplantation and less than a college degree. All but 1 patient had insurance, 34% had faced delayed/denied insurance coverage for chronic GVHD treatments, and 66% reported a financial burden. Patients with a financial burden had greater depression/anxiety and difficulty sleeping. Nonwhite race, lower mental functioning, and lower activity score were associated with a greater likelihood of financial burden. Younger age, early risk disease, and higher mental functioning were associated with a greater likelihood of being able to work/attend school. In this multicenter cohort of patients with chronic GVHD, significant negative effects on finances were observed even with health insurance coverage. Future research should investigate potential interventions to provide optimal and affordable care to at-risk patients and prevent long-term adverse financial outcomes in this vulnerable group.

Patient Perspectives Regarding Allogeneic Bone Marrow Transplantation in Myelofibrosis.

Hematopoietic stem cell transplantation (HCT) is a curative treatment for patients with myelofibrosis (MF); however, many HCT-eligible patients decline this potentially life-saving procedure. The reasons behind this decision are not clear. We sought to survey patients with MF to understand their perspective on HCT. A 63-question survey was posted on myeloproliferative neoplasm patient advocacy websites. A total of 129 patients with MF responded to the survey. Among these patients, 49 (41%) were referred for HCT, and 41(32%) attended the transplantation consult. Of the patients who attended the transplantation consult, 24 (59%) did not plan on going on to HCT, and 16 (41%) intended to proceed with HCT. Reasons for the decision to not undergo transplantation included the desire to not be ill, desire to not spend time in the hospital, and concerns about overall quality of life. Specifically, concerns related to financial impact and the risk of graft-versus-host disease (GVHD) were expressed. Patients who decided to proceed with HCT felt that this would extend their survival and allow them to be around family for longer. This is the first survey to investigate patient perceptions regarding HCT for MF. Less than one-half of the patients were referred for HCT, and of those, less than one-half planned on proceeding with the transplantation, suggesting that many patients do not receive this life-saving procedure. Further exploration of the basis of patients' reluctance to proceed with HCT is warranted.

Steroid Refractory Chronic Graft-Versus-Host Disease: Cost-Effectiveness Analysis.

Given the increasing incidence of chronic graft-versus-host disease (cGVHD) and its rapidly escalating costs due to many lines of drug treatments, we aimed to perform a meta-analysis to assess the comparative effectiveness of various treatment options. Using these results, we then conducted a cost-effectiveness analysis for the frequently utilized agents in steroid-refractory cGVHD. We searched for studies examining tacrolimus, sirolimus, rituximab, ruxolitinib, hydroxychloroquine, imatinib, bortezomib, ibrutinib, extracorporeal photopheresis, pomalidomide, and methotrexate. Studies with a median follow-up period shorter than 6 months and enrolling fewer than 5 patients were excluded. Meta-analysis for overall and organ system-specific GVHD response (overall response [ORR], complete response [CR], and partial response [PR]) was conducted for each intervention. Cost per CR and cost per CR + PR were calculated as the quotient of the 6-month direct treatment cost by CR and CR + PR. Forty-one studies involving 1047 patients were included. CR rates ranged from 7% to 30% with rituximab and methotrexate, respectively, and ORR ranged from 30% to 85% with tacrolimus and ruxolitinib, respectively. Cost per CR ranged from US$1,187,657 with ruxolitinib to US$680 with methotrexate. Cost per ORR ranged from US$453 for methotrexate to US$242,236 for ibrutinib. The most cost-effective strategy was methotrexate for all of the organ systems. Pomalidomide was found to be the least cost-effective treatment for eye, gastrointestinal, fascia/joint, skin, and oral GVHD, and imatinib was found to be the least cost-effective treatment for liver and extracorporeal photopheresis for lung GVHD. We observed huge cost-effectiveness differences among available agents. Attention to economic issues when treating cGVHD is important to recommend how treatments should be sequenced, knowing that many patients will cycle through available agents.

Economic and Practical Considerations in the Treatment of Oral Mucosal Chronic Graft-Versus-Host Disease.

Chronic graft-versus-host disease (cGVHD) frequently affects the oral mucosa and is generally responsive to topical immunomodulatory therapies. Clinicians may benefit from guidance in choosing the most appropriate therapy with respect to practicality and cost. To assess the economic considerations related to topical immunomodulatory treatments for management of oral mucosal cGVHD and their practical implications. Topical treatments used for management of oral cGVHD were obtained from the National Institutes of Health Consensus document for ancillary and supportive care. Cost data for a standard 1-month prescription was obtained from national databases for commercially available formulations and from compounding pharmacies for formulations requiring compounding. There are numerous topical preparations used for the management of oral cGVHD, many of which require compounding. The average wholesale price of the commercially available agents ranges from $5 to $277/month, and the cost of the compounded preparations ranges from $43 to $499/month. Costs can be influenced by drug-, patient-, and pharmacy-related factors. The costs associated with topical treatment of oral cGVHD are substantial, particularly because the disease is chronic and expenses accumulate over time. Rational prescribing according to a proposed algorithm, including de-escalation of therapy when indicated, can help to minimize associated costs. This has practical implications for patients, physicians, pharmacies, and insurance providers.

Costs of hematopoietic stem cell transplantation in a developing country.

Costs of HSCT in the United States have been widely reported, but complete information on costs in developing countries is lacking. We performed an analysis designed to assess the real, detailed costs of HSCT in Mexico. Using the database of the Current Accounts Department at our Institution, we performed a micro-costing based analysis of patients from 2010 through 2015 to obtain the overall cost of HSCT during the in-patient procedure and 2-month follow-up. One hundred five transplantations (57% autologous) were performed. The most frequent indications for transplantation were lymphomas (32%), followed by acute leukemias (22%). The most frequently used conditioning regimen was reduced BUCY 2 (38%), followed by BEAM (28%). Among post-transplant complications, acute graft-versus-host-disease was not associated with higher costs (p = 0.8). The median costs (in-patient and 2-month outpatient follow-up) for auto and allo-HSCT were 12,155 and 18,260 USD, respectively. Advances in HSCT technology have improved outcomes and increased the availability of this technique; however, this procedure can also significantly influence the socioeconomic wellbeing of patients, especially in developing countries. Our study highlights the feasibility of performing HSCT in Mexico at lower costs than developed countries, while preserving quality of care.

Extracorporeal Photopheresis for Second-Line Treatment of Chronic Graft-versus-Host Diseases: Results from a Health Technology Assessment in Italy.

OBJECTIVES: To develop a comparative, cost-effectiveness, and budget impact analysis of Therakos online extracorporeal photopheresis (ECP) compared with the main alternatives used for the treatment of steroid-refractory/resistant chronic graft-versus-host disease (cGvHD) in Italy. METHODS: The current therapeutic pathway was identified by searching medical databases and from the results of a survey of practice in Italian clinical reference centers. A systematic review was performed to evaluate the efficacy and safety of second-line alternatives. Budget impact and cost-effectiveness analyses were performed from the Italian National Health Service perspective over a 7-year time horizon through the adaption of a Markov model. The following health states were considered: complete and partial response, stable disease, and progression. A discount rate of 3% was applied to costs and outcomes. RESULTS: The most common alternatives used in Italy for the management of steroid-refractory/resistant cGvHD were ECP, mycophenolate, pentostatin, and imatinib. The literature review highlighted that complete and partial responses are higher with ECP than with the alternatives while serious adverse events are less common. The economic analysis showed that Therakos online ECP represents the dominating alternative, in that it delivers greater benefit at a lower cost. In fact, according to the alternatives considered, cost saving ranged from €3237.09 to €19,903.51 per patient with 0.04 to 0.21 quality-adjusted life-year gained. CONCLUSIONS: Therakos online ECP should be considered an effective, safe, and cost-effective alternative in steroid-refractory/resistant cGvHD. There is inequality in access, and a dedicated reimbursement tariff, however, should be introduced to overcome these barriers.

Prevalence and impact of financial hardship among New England pediatric stem cell transplantation families.

Poverty is correlated with negative health outcomes in pediatric primary care and subspecialties; its association with childhood hematopoietic stem cell transplantation (HSCT) patterns of care and clinical outcomes is not known. We describe family-reported financial hardship at a primary referral center in New England and explore the relationship between measures of poverty and patterns of care and clinical outcomes. Forty-five English-speaking parents of children after allogeneic HSCT in the prior 12 months completed a 1-time survey (response rate 88%). Low-income families, defined as ≤200% federal poverty level (FPL), were compared with all others. Eighteen (40%) families reported pre-HSCT incomes ≤200% FPL. Material hardship, including food, housing, or energy insecurity was reported by 17 (38%) families in the cohort. Low-income families reported disproportionate transplantation-related income losses, with 7 (39%) reporting annual income losses of >40% compared with 2 (18%) wealthier families (P = .02). In univariate analyses, 11 (61%) low-income children experienced graft-versus-host disease (GVHD) of any grade in the first 180 days after HSCT compared with 2 (7%) wealthier children (P = .004). We conclude that low income and, in particular, material hardship, are prevalent in a New England pediatric HSCT population and represent targets for improvement in quality of life. The role of poverty in mediating GVHD deserves further investigation in larger studies that can control for known risk factors and may provide a targetable source of transplantation-associated morbidity.

Lost in transition: the essential need for long-term follow-up clinic for blood and marrow transplantation survivors.

Because of expanding indications and improvements in supportive care, the utilization of blood and marrow cell transplantation (BMT) to treat various conditions is increasing exponentially, and currently more than 60,000 BMTs are performed annually worldwide. By the year 2030, it is projected that the number of BMT survivors will increase 5-fold, potentially resulting in one half of a million survivors in the United States alone. As the majority of survivors now live beyond the first 2 years after BMT, they are prone to a unique set of complications and late effects. Until recently, BMT experts assumed responsibility for almost all of the care for these survivors, but now oncologists/hematologists, pediatricians, and internists are involved frequently in offering specialized care and preventive services to these survivors. To integrate and translate into clinical practice the unique BMT survivorship issues with current preventive guidelines, a team effort is required. This can be facilitated by a dedicated "long-term-follow-up (LTFU)" clinic that provides lifelong care for BMT survivors. In this review, we first illustrate with clinical vignettes the need for LTFU and then focus upon the following: (1) types of LTFU clinic models, (2) challenges and possible solutions to the establishment of LTFU clinic, and (3) vulnerable transition periods.

Costs of allogeneic hematopoietic cell transplantation using reduced intensity conditioning regimens.

Reduced intensity conditioning (RIC) regimens have allowed older patients and those with comorbidities to receive hematopoietic cell transplantation (HCT). We analyzed medical costs from the beginning of conditioning to 100 days after HCT for 484 patients and up to 2 years for 311 patients who underwent a RIC HCT at two institutions from January 2008 to December 2010. Multiple linear regression was used to analyze the association between clinical variables, center effect, and costs. Patient and transplant characteristics were comparable between the sites, although differences were seen in pretransplant performance scores. Significant predictors for lower costs for the first 100 days included a diagnosis of lymphoma/myeloma and use of human leukocyte antigen-matched related donors. Grade II-IV acute graft-versus-host disease (GVHD) was associated with higher costs. The overall short-term costs between the two institutions were comparable when adjusted for clinical variables (p = .43). Late costs between 100 days and 2 years after HCT were available for one cohort (n = 311); median costs during this period were $39,000 and accounted for 39% of costs during the first 2 years. Late costs were not associated with any pretransplant variables, but were higher with extensive chronic GVHD and death. After adjustment for clinical characteristics, the overall costs of the RIC transplants were similar between the two institutions despite different management approaches (inpatient vs. outpatient conditioning) and accounting methodologies. Use of unrelated/alternative donors, transplant for diseases other than lymphoma or myeloma, and acute GVHD were predictors for higher early costs, and extensive chronic GVHD and death were associated with higher late costs.

High burden of BK virus-associated hemorrhagic cystitis in patients undergoing allogeneic hematopoietic stem cell transplantation.

BK virus (BKV) reactivation has been increasingly associated with the occurrence of late-onset hemorrhagic cystitis (HC) after allogeneic hematopoietic SCT (allo-HSCT) resulting in morbidity and sometimes mortality. We investigated the incidence, risk factors and outcome of BKV-HC in 323 consecutive adult patients undergoing allo-HSCT over a 5-year period. BK viremia values for HC staging were evaluated, as well as the medico-economic impact of the complication. Forty-three patients developed BKV-HC. In univariate analysis, young age (P=0.028), unrelated donor (P=0.0178), stem cell source (P=0.0001), HLA mismatching (P=0.0022) and BU in conditioning regimen (P=0.01) were associated with a higher risk of developing BKV-HC. In multivariate analysis, patients receiving cord blood units (CBUs) (P=0.0005) and peripheral blood stem cells (P=0.011) represented high-risk subgroups for developing BKV-HC. BK viremia was directly correlated to HC severity (P=0.011) with a 3 to 6-log peak being likely associated with grades 3 or 4 HC. No correlation was found between BKV-HC and acute graft versus host disease or mortality rate. Patients with BKV-HC required a significantly longer duration of hospitalization (P<0.0001), more RBC (P=0.0003) and platelet transfusions (P<0.0001). Over the 5-year study period, the financial cost of the complication was evaluated at \[euro]2 376 076 ($3 088 899). Strategies to prevent the occurrence of late-onset BKV-HC after allo-HSCT are urgently needed, especially in CBU and peripheral blood stem cell recipients. BK viremia correlates with the severity of the disease. Prospective studies are required to test prophylactic approaches.

Predictors and impact of thirty-day readmission on patient outcomes and health care costs after reduced-toxicity conditioning allogeneic hematopoietic cell transplantation.

Thirty-day readmission (30-DR) has become an important quality-of-care measure. Allogeneic hematopoietic cell transplantation (allo-HCT) presents a medical setting with higher readmission rates. We analyzed factors affecting 30-DR and its impact on patient outcomes and on health care costs in 91 patients who underwent reduced-toxicity conditioning (RTC) allo-HCT with fludarabine and busulfan. The patient cohort was divided into 2: the readmission group (R-gp) or the no-readmission group (NR-gp). Overall, 38% (n = 35) required readmission with a median time to readmission of 14 days. In multivariate analysis, only documented infection during the index admission predicted 30-DR, P = .01. With a median follow-up of 18 months (range, 1 to 69) for surviving patients, the 2-year overall survival was 49% and 58% in the R-gp and NR-gp respectively, P = .48. The 1-year nonrelapse mortality in R-gp and NR-gp was 18% and 13% respectively, P = .43. The median post-transplantation hospital charges in the R-gp and NR-gp were $85,115 (range, $32,015 to $242,519) and $45,083 (range, $10,715 to $485,456), P = .0002. In conclusion, only documented infections during the index hospitalization influenced 30-DR after RTC allo-HCT. Although 30-DR did not adversely affect mortality or survival, it was associated with significantly increased 100-day post-transplantation hospital charges, thus supporting its role as a quality-of-care measure in allo-HCT patients.

Costs of second allogeneic hematopoietic cell transplantation.

BACKGROUND: A second allogeneic transplantation after a prior allogeneic (allo-allo) or autologous (auto-allo) hematopoietic cell transplantation (HCT) is usually performed for graft failure, disease recurrence, secondary malignancy, and, as planned, auto-allo transplantation for some diseases. METHODS: We sought to describe the costs of second allogeneic HCT and evaluate their relationship with patient characteristics and posttransplantation complications. Clinical information and medical costs for the first 100 days after transplantation of 245 patients (allo-allo, 55; auto-allo, 190) who underwent a second HCT between 2004 and 2010 were collected. RESULTS: Median costs of the second allogeneic HCT were U.S. $151,000 (range, U.S. $62,000-405,000) for the allo-allo group and U.S. $109,000 (range, U.S. $26,000-490,000) for the auto-allo group. Median length of hospital stay was 23 days (range, 0-76) for the allo-allo group and 9 days (range, 0-96) for the auto-allo group. Only the year of transplantation and posttransplantation complications were significantly associated with costs in both groups when both pre- and posttransplantation variables were considered. The overall costs of the second HCT were higher than the first in the allo-allo group. For the auto-allo group, there was no difference between the costs whether preformed as a planned tandem or as salvage for relapse. CONCLUSIONS: Our results suggest that second allogeneic HCT is costly, particularly if it follows a prior allogeneic transplantation, and is driven by the costs of complications.

High readmission rates are associated with a significant economic burden and poor outcome in patients with grade III/IV acute GvHD.

Graft-versus-host disease (GvHD) is a common complication following haematopoietic stem cell transplant but little is published about the impact of this condition on hospital readmission rates. We report a retrospective analysis of readmission rates and associated costs in 187 consecutive allogeneic transplant patients to assess the impact of GvHD. The overall readmission rate was higher in patients with GvHD (86% (101/118) vs. 59% (41/69), p < 0.001). The readmission rate was higher both in the first 100 d from transplant (p = 0.02) and in the first year following transplant (p < 0.001). 151/455 (33%) of all readmission episodes occurred within 100 d of transplant. The mean number of inpatient days was significantly higher in patients with grade III/IV acute GvHD (101 d) compared with those with grade I/II GvHD (70 d; p = 0.003). The mean cost of readmission was higher in patients with GvHD (£28 860) than in non-GvHD patients (£13 405; p = 0.002) and in patients with grade III/IV GvHD (£40 012) compared with those patients with grade I/II GvHD (£24 560; p = 0.038). Survival was higher in those with grade I/II GvHD (55%) compared to grade III/IV GvHD (14%; p < 0.001). This study shows the high economic burden and poor overall survival associated with grade III/IV GvHD.

Hematopoietic cell transplantation for thalassemia: a global perspective BMT tandem meeting 2013.

Hematopoietic cell transplantation (HCT) remains the sole available curative option for patients with ß-thalassemia major. Expanded and improved supportive therapies for thalassemia now routinely extend the life span of affected individuals well into adulthood. Consequently, in regions of the world where this care is readily available, HCT has been pursued infrequently, in part owing to concerns about an expected lack of balance between risks and benefits. More recently, however, recognition of significant health problems in older patients with thalassemia, along with recognition of increased risks of graft-versus-host disease (GVHD), graft rejection, and impaired organ function leading to inferior HCT outcomes in this particular group, seem to be turning the wheels and tipping the balance again in the direction of consideration for earlier HCTs. In contrast, in countries where thalassemia is most prevalent (>100,000 new children born each year in Middle East and southeast Asia), lack of supportive care standards together with often insufficient access to dedicated health care facilities, results in the majority of these children not reaching adulthood, further supporting the need for expanded access to HCT for these patients. The cost of HCT is equivalent to that of a few years of noncurative supportive care, such that HCT in low-risk young children with a compatible sibling is justified not only medically and ethically but also financially. International cooperation can play a major role in increasing access to safe and affordable HCT in countries where there is a considerable shortage of transplantation centers. In this article, we review the current status of bone marrow transplantation for thalassemia major, with particular emphasis on a global prospective.

Development of a population-based cost-effectiveness model of chronic graft-versus-host disease in Spain.

BACKGROUND: Chronic graft-versus-host disease (cGvHD) is the leading cause of late nonrelapse mortality (transplant-related mortality) after hematopoietic stem cell transplant. Given that there are a wide range of treatment options for cGvHD, assessment of the associated costs and efficacy can help clinicians and health care providers allocate health care resources more efficiently. OBJECTIVE: The purpose of this study was to assess the cost-effectiveness of extracorporeal photopheresis (ECP) compared with rituximab (Rmb) and with imatinib (Imt) in patients with cGvHD at 5 years from the perspective of the Spanish National Health System. METHODS: The model assessed the incremental cost-effectiveness/utility ratio of ECP versus Rmb or Imt for 1000 hypothetical patients by using microsimulation cost-effectiveness techniques. Model probabilities were obtained from the literature. Treatment pathways and adverse events were evaluated taking clinical opinion and published reports into consideration. Local data on costs (2010 Euros) and health care resources utilization were validated by the clinical authors. Probabilistic sensitivity analyses were used to assess the robustness of the model. RESULTS: The greater efficacy of ECP resulted in a gain of 0.011 to 0.024 quality-adjusted life-year in the first year and 0.062 to 0.094 at year 5 compared with Rmb or Imt. The results showed that the higher acquisition cost of ECP versus Imt was compensated for at 9 months by greater efficacy; this higher cost was partially compensated for (€517) by year 5 versus Rmb. After 9 months, ECP was dominant (cheaper and more effective) compared with Imt. The incremental cost-effectiveness ratio of ECP versus Rmb was €29,646 per life-year gained and €24,442 per quality-adjusted life-year gained at year 2.5. Probabilistic sensitivity analysis confirmed the results. The main study limitation was that to assess relative treatment effects, only small studies were available for indirect comparison. CONCLUSION: ECP as a third-line therapy for cGvHD is a more cost-effective strategy than Rmb or Imt.

Challenges to preventing infectious complications, decreasing re-hospitalizations, and reducing cost burden in long-term survivors after allogeneic hematopoietic stem cell transplantation.

Even though the overall outcome after allogeneic transplant has improved significantly in the last decades, late infectious diseases are still the most important causes of late morbidity and mortality. Here, impaired immune reconstitution and therapy of chronic graft-versus-host disease (GVHD) represent the major risk factors. In this review, we give a comprehensive overview of late infectious complications and summarize possible diagnostic and therapeutic interventions to prevent these complications.