Real-World medical expenses of Hematopoietic Stem Cell Transplantation in Japan: A Nationwide Database Study

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To better understand the economic burden associated with hematopoietic stem cell transplantation (HSCT) and to support sustainable, equitable care, we analyzed medical expenses incurred during and after HSCT. A total of 19,500 patients who underwent HSCT between 2012 and 2017 were included, covering approximately 60–80% of all HSCT recipients during that period. The median 3-month and 1-year costs (USD) were: $ 15,660 / $ 24,195 for autologous HSCT; $ 20,565 / $ 33,904 for allogeneic bone marrow transplantation; $ 17,807 / $ 30,500 for peripheral blood stem cell transplantation; and $ 41,935 / $ 62,683 for cord blood transplantation. Costs were generally higher in older patients and showed a gradual increase over time. Transfusion accounted for the largest proportion of total costs, particularly in cord blood transplantation. Greater transplant center experience was associated with lower costs for allogeneic HSCT. Given the high costs, especially for cord blood transplantation, continuous efforts to reduce transplantation expenses, such as accelerating donor engraftment, are essential. Health sciences/Health care/Health services Health sciences/Health care/Therapeutics/Stem-cell therapies Medical expenses Hematopoietic stem cell transplantation auto-HSCT allo-HSCT Figures Figure 1 Figure 2 Figure 3 Introduction Japan has a unique healthcare system in which universal health coverage broadly covers the cost of healthcare for the entire population. This system has been under financial pressure due to escalating medical expenses, including those for hematopoietic stem cell transplantation (HSCT), which is one of the most expensive treatments requiring intensive care, multiple medications, and many transfusions. As in other areas of medicine, the expanded use of alternative donors, novel drugs, and recent therapeutic improvements for higher-risk and older patients have improved HSCT and its outcomes( 1 – 5 ), but at the cost of escalating costs. Previous reports comparing the costs/cost-effectiveness of different donor sources and settings have suggested that they may differ by age group, units of cord blood used, or intensity of conditioning regimens( 6 – 11 ). Trends in transplantation expenses and their influencing factors need to be reviewed considering their impact on our healthcare economy( 12 ). Hence, we comprehensively examined the medical costs of peri-HSCT from various perspectives, such as patient background, donor types, transplant center effects, and chronological changes, using data obtained from our National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB). The NDB encompasses nearly all data on Japan's inpatient and outpatient medical services, including drug use, medical devices, laboratory tests, surgeries, and rehabilitation covered by the National Health Insurance. It is likely one of the most comprehensive healthcare databases available for studying real-world utilization of healthcare services. The NDB has yet to be widely utilized due to the challenges of managing large and complex datasets. However, the Japanese government has continually improved its data provision system recently. This study marks the first use of the NDB for the expenses analysis of HSCT to find a way to provide stable and continuous financial support for patients who need HSCT as the only curative treatment. Methods Data of medical expenses Data of medical expenses used in patients meeting the inclusion criteria were obtained at the end of 2020 from the NDB, a database managed by the Ministry of Health, Labour and Welfare of Japan. The NDB collects health insurance claims data nationwide from all types of insurance schemes that reimburse medical services provided in all healthcare facilities and pharmacies(13). Since the health insurance system provides universal coverage, the NDB captures comprehensive data on medical expenses incurred during and after HSCT, excluding costs associated with donor coordination and stem cell harvesting from allogeneic donors. All data were accessed via the NDB onsite research center with permission from the Ministry. The 2-anonymized identifier hashing based on social insurance number and name was used for follow-up(14). Each cost was calculated in yen and then converted into dollars on the basis of the exchange rate of 151.1 yen to the dollar; original data with yen are attached as supplementary data, Supplementary Tables 5 - 13. Study design Patients of all ages who underwent autologous or allogeneic HSCT between 2012 and 2017 were included, with follow-up data collected until 2020. Patients were identified in the NDB using registered medical procedure and disease name codes. For autologous HSCT, data was identified based on either or both identifier numbers 150266310 (medical procedure) and 8842928 (disease name). For allo-HSCT, the identifiers used were: cord blood transplant (150349810 and 8842917), related/unrelated peripheral blood stem cell transplantation (150297810 and 8845448), and related/unrelated bone marrow transplantation (150225910 and 8842974). Identification of allo-HSCT recipients also required the registration of immunosuppressants specific to allo-HSCT, such as tacrolimus and cyclosporine, in the medication data. The date of transplantation was defined as the date when the transplant was registered as a medical procedure for auto-HSCT recipients and as one day after the initiation of continuous immunosuppressive treatment for allo-HSCT recipients. Statistical analysis Total expenses incurred and their breakdown (chemotherapy, immunosuppressants, antimicrobials such as antibacterial, antifungal, and antiviral drugs, transfusions, radiation, medical procedures such as ventilation dialysis) were calculated in both inpatient and outpatient settings in the period within 1 month, 3 months, 1 year or more than 1 year after the transplant date. Transplant centers were categorized into three groups by the number of transplantations per year (Low-volume center: <15, Middle-volume center: ≧15 & <30, High-volume center: ≧30). Overall survival was evaluated using the Kaplan-Meier method. The Kruskal–Wallis test was used to assess the differences in costs between the different donor sources. All statistical analyses were performed using commercial software (Stata version 14, Stata Corp.). Result Patient characteristics Patient characteristics are summarized in Table 1. A total of 19,500 patients who received auto-/allo-HSCT between 2012 and 2017 were included in this study, of which 9,155 patients received auto-HSCT, 4,765 received BMT, 2,045 received PBSCT, and 3,535 received CBT. More male patients were enrolled in each age group, and the number of patients aged 40 to 60 was the highest, regardless of donor source. The number of patients enrolled who received auto-HSCT, CBT, and PBSCT tended to increase, whereas the number who received BMT did not. The cumulative number of auto-HSCT, BMT, and PBSCT performed was most significant in the high-volume centers, but that of CBT was greatest in the low-volume centers. Overall survival probabilities at 300 days after transplantation were 76% for auto-HSCT, 68% for BMT, 61% for PBSCT, and 57% for CBT (p<0.001) (Figure 1) with higher survival probability in younger generations (p<0.001) (Figure 2). No apparent difference was seen in survival probabilities among different transplant center categories (auto-HSCT, p=0.891; allo-HSCT, p=0.387) (Figure 3). Medical expenses of auto-HSCT within 1, 3 months, and 1 year The median values or total expenses of auto-HSCT within 1, 3, and 12 months after transplant day were $9,946 (interquartile range [IQR]: 7,758-12,815), $15,660 (IQR: 12,577-20,304), and $24,195 (IQR: 16,660-39,276), respectively (Table 2). Breakdown and annual change The expenses of auto-HSCT during the early post-transplantation period showed minimal variation from 2012 to 2017, exhibiting a slight upward trend over time (p<0.001) (Supplemental Table 1). Table 3 summarizes a breakdown of the costs of auto-HSCT. Transfusion cost account for a large proportion of transfusion, especially within the first 3 months after transplantation; transfusion costs within 3 and 12 months were $2,045.5 (IQR: 1,136.8-3,328.7) and $2,114.6 (IQR: 1,169.4-3,878.1). Among antimicrobials, antifungals cost the most, followed by antibacterials in both periods; the cost of antifungals within 3 and 12 months was $519.1 (IQR: 153.1-1,149.0) and $653.0 (IQR: 178.8-1,498.7), and that of antibacterials was $426.9 (IQR: 216.9-768.3) and $530.5 (IQR: 274.5-946.6). Impact of patients’ age Patients in the youngest group (0-19 years old) cost most throughout the posttransplant periods: 1 month (median value, $12,830; IQR, 9,575-15,432), 3 months (median value, $26,170; IQR, 18,220-37,372) after transplant (p<0.001, Table 4). Among the adult categories, the more elderly patients tend to cost more. Medical expenses of allo-HSCT within 1, 3 months, and 1 year Impacts of donor sources The expenses of allo-HSCT, stratified by donor source (BMT, PBSCT, CBT), is summarized in Table 2. CBT was most costly regardless of the post-transplant period (within 1 month: median value, $22,669; IQR: 14,094-29,073; 3 months: median value, $41,935; IQR: 25,139-57,486; 1 year: median value, $62,683; IQR: 37,837-95,700), followed by BMT (1 month: median value, $12,066; IQR: 6,753-17,695; 3 months: median value, $20,565; IQR: 11,081-32,615; 1 year: median value, $33,904; IQR: 18,099-60,821) and PBSCT (1 month: median value, $10,774; IQR, 6,077-16,471; 3 months: median value, $17,807; IQR, 9,831-30,428; 1 year: median value, $30,500; IQR: 16,993-57,700) with p<0.001 for each period. This cost order among the three donor types was consistent throughout the study period. Breakdown and annual change Among the detailed categories, transfusion expenses were the largest, accounting for approximately 10-30% of the total cost for each donor and at a maximum in CBT. Median transfusion expenses in CBT were $7,809.1 (IQR: 3,907.9-11,330.3) for 1 month, $10,212.9 (IQR: 4,779.5-17,781.5) for 3 months, and $11,682.6 (IQR: 5,609.6-21,468.0) for 1 year, which were several times higher than in other donor types (Table 3). Antimicrobial expenses were also consistently the highest in CBT regardless of the types of antimicrobial agents and post-transplant period, which was 1.5 to 2 times higher than those used in BMT/PBSCT. The expenses of immunosuppressive agents such as graft-versus-host-disease (GVHD) prophylaxis were almost equivalent for the three donor types, with a trend towards lower costs for CBT over the longer period. For each donor source, the expense per patient tended to increase slightly over time (Supplemental Table 2). Looking at the breakdown of the trend in each category, transfusion cost did not change dramatically throughout the study period. Antimicrobial expenses in CBT showed a continuous tendency to increase (p=0.0031) in the early timing after transplantation, whereas GVHD prophylaxis costs showed a tendency to decrease only in PBSCT in12 months after transplant (Supplemental Table 3, 4). Impact of patients’ age The youngest age group (0–19 years) and the oldest age group (70–84 years) were associated with the highest costs. This tendency was more evident for the youngest in PBSCT and the oldest in CBT, regardless of the post-transplantation period (Table 5). Medical costs of HSCTs above 1 year after transplantation Expenses of CBT were the highest among auto and allogeneic donors when medical expenses in the 2nd and 3rd years after transplantation were examined: Auto-HSCT: median, $32,226 (IQR: 11,167-63,985); BMT: $32,446 (IQR: 12,790-56,262); PBSCT: $24,164 (IQR: 10,410-60,616); CBT: $36,453 (IQR: 15,175-67,980) (Table 2). Impact of center effects on overall HSCT expenses HSCT expenses consistently showed a tendency to be the lowest in the high-volume transplant centers for all donors (auto, BMT, PBSCT, and CBT), regardless of the post-transplantation period (Table 6). The differences in the median value of annual costs between the low- and the high-volume centers were the highest in CBT ($17,313), followed by BMT ($7,006). Discussion This is the largest and most comprehensive study that analyzed the medical expenses of auto- and allo-HSCT in Japan. Usage of the NDB enables us to include and analyze the expenses of almost all auto- and allo-HSCT transplants performed in Japan. Their detailed analysis clarified several important points that need to be evaluated to improve the economics of HSCT. First, and contrary to our expectations( 12 , 15 ), we found that the increase in the expense per patient over time was not dramatic. This could be explained in part by the fact that cost reductions from therapeutic improvements offset the cost escalation from increased drug costs. Surprisingly, transfusion expenses did not improve over time, which may be due to no efficient change in the engraftment period both in platelets and red blood cells. Second, CBT was the most expensive procedure in our analysis, almost twice as expensive as other donors, regardless of year of transplant, patient age, and type of transplant center. The most likely factor influencing this is the higher transfusion costs in CBT followed by antimicrobe agents, which consistently account for a certain proportion of total HSCT costs. This result was consistent with those reported in previous studies( 16 , 17 ). Lowering transfusion or antimicrobe costs by promoting earlier engraftment could lead to a reduction in total HSCT expenses, with the impact expected to be greatest in CBT( 18 ). It should be noted that our current data rarely include the costs of HSCT using haploidentical PB/BM donors, as the procedure will reach insurance coverage in 2021. Since the survival outcomes and risks of severe chronic GVHD of CBT are comparable to those of haplo-PBSCT/BMT even in long-term follow-up in Japan( 19 , 20 ), we should re-evaluate the differences in cost and cost-effectiveness between CBT and haplo-PBSCT/BMT using our own national data( 7 , 17 ). Since CBTs performed in Japan normally use single units, comparison with previous studies from other countries using double units is also suggestive( 21 ). Our data, together with our national transplant database (TRUMP)( 22 – 24 ), suggest that CBT continues and will continue to be performed in Japan; the expenses of CBT is an important issue and it should be applied to the appropriately selected patients from a cost point of view. Medical expenses in HSCT for pediatrics were generally higher than those for adult, except for the population over 60 years of age, which is consistent with previous studies( 25 ). This trend was more pronounced for auto-HSCT and allo-HSCT in the earlier period but not for CBT. This may reflect the different patient cohorts in terms of disease type, disease status between pediatrics and adults, and more intensive therapies in pediatrics, although this point could not be adequately assessed due to the lack of patient background in our cohort ( 26 , 27 ). Interestingly and unexpectedly, the more experienced centers provided more economical HSCT regardless of donor type. Because data from older patients or those with higher-risk diseases were more likely to be included in data from centers performing a higher number of HSCTs( 28 , 29 ), the accumulation of transplant experience could contribute to cost reduction through the appropriate use of medications or other therapeutic interventions. Investigating these differences in performance among different types of centers may provide a key to reducing transplantation costs. We have several limitations to this study. Firstly, it lacks information on cost-effectiveness, values reflecting patients’ quality of life such as Quality-adjusted life year, patients' diseases and their status, and transplantation strategies and outcomes other than survival such as posttransplant complications( 18 , 30 ), because it was an analysis of the budget database. It didn't include the expenses associated with allogeneic donors such as donor search( 31 ), donor coordination and stem cell harvesting either. Also, since this is the medical expense per patient in a specific timeframe, the patients' survival probability could affect the total expense in that period, making the result difficult to interpret simply. Another is that it is difficult to simply compare the expenses between ours and those reported from foreign countries, since the exchange rates have changed chronologically, and an economic situation such as inflation/deflation has influenced prices in all aspects of medical expenses. Conclusion The medical expenses of HSCT have not changed dramatically over time, including that of transfusion, which was the highest. CBT is the most expensive of all transplant procedures and should be re-evaluated so that it can continue to be used as an alternative donor. Declarations Conflict-of-interest disclosure The authors declare no competing financial interests. This work was supported in part by the Takeda Science Foundation (JK). Acknowledgements The authors would like to thank all the doctors, nurses and other medical staff involved in the transplantation procedures. We are also grateful to all those involved in the data management of the NDB systems and to those who maintain our insurance systems, which provided the backbones of this study. This work was supported by grants from AMED (Grant Number 24ek0510046h0001) and JSPS KAKENHI (Grant Number 24K11515). References Anasetti C. Use of alternative donors for allogeneic stem cell transplantation. Hematology / the Education Program of the American Society of Hematology American Society of Hematology Education Program. 2015;2015(1):220–4. Bachanova V, Burns LJ, Wang T, Carreras J, Gale RP, Wiernik PH, et al. 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Center effect on allogeneic hematopoietic stem cell transplantation outcomes for B-cell acute lymphoblastic leukemia. Cytotherapy. 2024 Oct;26(10):1185–92. Shimomura Y, Kitamura T, Murata M, Matsuo K, Ito Y, Ichinohe T, et al. Impact of Center Volume on Chronic Graft Versus Host Disease in Patients With Allogeneic Stem Cell Transplantation. Transplant Cell Ther. 2024 Mar;30(3):326.e1-326.e14. Lee SJ, Klar N, Weeks JC, Antin JH. Predicting Costs of Stem-Cell Transplantation. Journal of Clinical Oncology. 2000 Jan 1;18(1):64–64. Ottinger H, Grosse-Wilde M, Schmitz A, Grosse-Wilde H. Immunogenetic marrow donor search for 1012 patients: a retrospective analysis of strategies, outcome and costs. Bone Marrow Transplant [Internet]. 1994;14 Suppl 4:S34-8. Available from: http://www.ncbi.nlm.nih.gov/pubmed/7728122 Tables Tables 1 to 6 are available in the Supplementary Files section. Additional Declarations The authors have declared there is NO conflict of interest to disclose. Supplementary Files HSCTcostSupTable1.xlsx HSCTcostSupTable2.xlsx HSCTcostSupTable3.xlsx HSCTcostSupTable4.xlsx HSCTcostSupTable5.xlsx HSCTcostSupTable6.xlsx HSCTcostSupTable7.xlsx HSCTcostSupTable8.xlsx HSCTcostSupTable9.xlsx HSCTcostSupTable10.xlsx HSCTcostSupTable11.xlsx HSCTcostSupTable12.xlsx HSCTcostSupTable13.xlsx HSCTcostTable1.xlsx HSCTcostTable2.xlsx HSCTcostTable3.xlsx HSCTcostTable4.xlsx HSCTcostTable5.xlsx HSCTcostTable6.xlsx Cite Share Download PDF Status: Published Journal Publication published 15 Nov, 2025 Read the published version in Bone Marrow Transplantation → Version 1 posted Editorial decision: revise 28 Jul, 2025 Review # 1 received at journal 03 Jul, 2025 Reviewer # 1 agreed at journal 02 Jul, 2025 Reviewers invited by journal 02 Jul, 2025 Submission checks completed at journal 30 Jun, 2025 First submitted to journal 28 Jun, 2025 Editor assigned by journal 28 Jun, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Hospital","correspondingAuthor":false,"prefix":"","firstName":"Tomohide","middleName":"","lastName":"Iwao","suffix":""},{"id":479595639,"identity":"16876c5f-3fcf-481c-a6bc-bd8a03cdc390","order_by":5,"name":"Tomohiro Kuroda","email":"","orcid":"","institution":"Kyoto University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Tomohiro","middleName":"","lastName":"Kuroda","suffix":""},{"id":479595640,"identity":"86d25af4-3989-4c0a-a739-fa0fc222b557","order_by":6,"name":"Akifumi Takaori-Kondo","email":"","orcid":"https://orcid.org/0000-0001-7678-4284","institution":"Graduate School of Medicine, Kyoto University","correspondingAuthor":false,"prefix":"","firstName":"Akifumi","middleName":"","lastName":"Takaori-Kondo","suffix":""},{"id":479595641,"identity":"cf1c2ddd-23e5-485c-b3a1-b9ad02afd769","order_by":7,"name":"Genta Kato","email":"","orcid":"","institution":"Kyoto University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Genta","middleName":"","lastName":"Kato","suffix":""}],"badges":[],"createdAt":"2025-06-28 15:45:20","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6998815/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6998815/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41409-025-02753-5","type":"published","date":"2025-11-15T05:00:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":86129699,"identity":"bfe940b6-6cde-41dc-9c7e-7c1743213362","added_by":"auto","created_at":"2025-07-07 06:31:25","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":122342,"visible":true,"origin":"","legend":"\u003cp\u003eOverall survival after autologous stem cell transplantation (A) and that after allogeneic stem cell transplantation stratified by donor source: bone marrow, peripheral blood and cord blood unit (B).\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-6998815/v1/b1562513a8bcb9f95009818a.png"},{"id":86129706,"identity":"5a7bb0ad-92e9-4a1d-ac80-dbd97834f8de","added_by":"auto","created_at":"2025-07-07 06:31:26","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":195041,"visible":true,"origin":"","legend":"\u003cp\u003eOverall survival after autologous stem cell transplantation (A) and allogeneic stem cell transplantation (B), both stratified by patient age into 5 groups: 0-19 years, 20-39 years, 40-59 years, 60-69 years and 70-84 years.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-6998815/v1/7b1365280369a931d528478a.png"},{"id":86131220,"identity":"3e984442-557b-46ec-a592-b12eca6a9200","added_by":"auto","created_at":"2025-07-07 06:47:26","extension":"png","order_by":3,"title":"Figure 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This system has been under financial pressure due to escalating medical expenses, including those for hematopoietic stem cell transplantation (HSCT), which is one of the most expensive treatments requiring intensive care, multiple medications, and many transfusions.\u003c/p\u003e \u003cp\u003eAs in other areas of medicine, the expanded use of alternative donors, novel drugs, and recent therapeutic improvements for higher-risk and older patients have improved HSCT and its outcomes(\u003cspan additionalcitationids=\"CR2 CR3 CR4\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e), but at the cost of escalating costs. Previous reports comparing the costs/cost-effectiveness of different donor sources and settings have suggested that they may differ by age group, units of cord blood used, or intensity of conditioning regimens(\u003cspan additionalcitationids=\"CR7 CR8 CR9 CR10\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). Trends in transplantation expenses and their influencing factors need to be reviewed considering their impact on our healthcare economy(\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eHence, we comprehensively examined the medical costs of peri-HSCT from various perspectives, such as patient background, donor types, transplant center effects, and chronological changes, using data obtained from our National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB).\u003c/p\u003e \u003cp\u003eThe NDB encompasses nearly all data on Japan's inpatient and outpatient medical services, including drug use, medical devices, laboratory tests, surgeries, and rehabilitation covered by the National Health Insurance. It is likely one of the most comprehensive healthcare databases available for studying real-world utilization of healthcare services. The NDB has yet to be widely utilized due to the challenges of managing large and complex datasets. However, the Japanese government has continually improved its data provision system recently.\u003c/p\u003e \u003cp\u003eThis study marks the first use of the NDB for the expenses analysis of HSCT to find a way to provide stable and continuous financial support for patients who need HSCT as the only curative treatment.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003eData of medical expenses\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData of medical expenses used in patients meeting the inclusion criteria were obtained at the end of 2020 from the NDB, a database managed by the Ministry of Health, Labour and Welfare of Japan. The NDB collects health insurance claims data nationwide from all types of insurance schemes that reimburse medical services provided in all healthcare facilities and pharmacies(13). Since the health insurance system provides universal coverage, the NDB captures comprehensive data on medical expenses incurred during and after HSCT, excluding costs associated with donor coordination and stem cell harvesting from allogeneic donors. All data were accessed via the NDB onsite research center with permission from the Ministry. The 2-anonymized identifier hashing based on social insurance number and name was used for follow-up(14). Each cost was calculated in yen and then converted into dollars on the basis of the exchange rate of 151.1 yen to the dollar; original data with yen are attached as supplementary data, Supplementary Tables 5 - 13.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy design\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatients of all ages who underwent autologous or allogeneic HSCT between 2012 and 2017 were included, with follow-up data collected until 2020. Patients were identified in the NDB using registered medical procedure and disease name codes. For autologous HSCT, data was identified based on either or both identifier numbers 150266310 (medical procedure) and 8842928 (disease name). For allo-HSCT, the identifiers used were: cord blood transplant (150349810 and 8842917), related/unrelated peripheral blood stem cell transplantation (150297810 and 8845448), and related/unrelated bone marrow transplantation (150225910 and 8842974). Identification of allo-HSCT recipients also required the registration of immunosuppressants specific to allo-HSCT, such as tacrolimus and cyclosporine, in the medication data. The date of transplantation was defined as the date when the transplant was registered as a medical procedure for auto-HSCT recipients and as one day after the initiation of continuous immunosuppressive treatment for allo-HSCT recipients.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTotal expenses incurred and their breakdown (chemotherapy, immunosuppressants, antimicrobials such as antibacterial, antifungal, and antiviral drugs, transfusions, radiation, medical procedures such as ventilation dialysis) were calculated in both inpatient and outpatient settings in the period within 1 month, 3 months, 1 year or more than 1 year after the transplant date. Transplant centers were categorized into three groups by the number of transplantations per year (Low-volume center: \u0026lt;15, Middle-volume center:\u0026nbsp;≧15 \u0026amp; \u0026lt;30, High-volume center:\u0026nbsp;≧30).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOverall survival was evaluated using the Kaplan-Meier method. The Kruskal\u0026ndash;Wallis test was used to assess the differences in costs between the different donor sources. All statistical analyses were performed using commercial software (Stata version 14, Stata Corp.).\u003c/p\u003e"},{"header":"Result","content":"\u003cp\u003e\u003cstrong\u003ePatient characteristics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatient characteristics are summarized in Table 1. A total of 19,500 patients who received auto-/allo-HSCT between 2012 and 2017 were included in this study, of which 9,155 patients received auto-HSCT, 4,765 received BMT, 2,045 received PBSCT, and 3,535 received CBT. More male patients were enrolled in each age group, and the number of patients aged 40 to 60 was the highest, regardless of donor source. The number of patients enrolled who received auto-HSCT, CBT, and PBSCT tended to increase, whereas the number who received BMT did not. The cumulative number of auto-HSCT, BMT, and PBSCT performed was most significant in the high-volume centers, but that of CBT was greatest in the low-volume centers.\u003c/p\u003e\n\u003cp\u003eOverall survival probabilities at 300 days after transplantation were 76% for auto-HSCT, 68% for BMT, 61% for PBSCT, and 57% for CBT (p\u0026lt;0.001) (Figure 1) with higher survival probability in younger generations (p\u0026lt;0.001) (Figure 2). No apparent difference was seen in survival probabilities among different transplant center categories (auto-HSCT, p=0.891; allo-HSCT, p=0.387) (Figure 3).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMedical expenses of auto-HSCT within 1, 3 months, and 1 year \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe median values or total expenses of auto-HSCT within 1, 3, and 12 months after transplant day were $9,946 (interquartile range [IQR]: 7,758-12,815), $15,660 (IQR: 12,577-20,304), and $24,195 (IQR: 16,660-39,276), respectively (Table 2). \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eBreakdown and annual change\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe expenses of auto-HSCT during the early post-transplantation period showed minimal variation from 2012 to 2017, exhibiting a slight upward trend over time (p\u0026lt;0.001) (Supplemental Table 1). Table 3 summarizes a breakdown of the costs of auto-HSCT. Transfusion cost account for a large proportion of transfusion, especially within the first 3 months after transplantation; transfusion costs within 3 and 12 months were $2,045.5 (IQR: 1,136.8-3,328.7) and $2,114.6 (IQR: 1,169.4-3,878.1).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAmong antimicrobials, antifungals cost the most, followed by antibacterials in both periods; the cost of antifungals within 3 and 12 months was $519.1 (IQR: 153.1-1,149.0) and $653.0 (IQR: 178.8-1,498.7), and that of antibacterials was $426.9 (IQR: 216.9-768.3) and $530.5 (IQR: 274.5-946.6). \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eImpact of patients\u0026rsquo; age\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003ePatients in the youngest group (0-19 years old) cost most throughout the posttransplant periods: 1 month (median value, $12,830; IQR, 9,575-15,432), 3 months (median value, $26,170; IQR, 18,220-37,372) after transplant (p\u0026lt;0.001, Table 4). Among the adult categories, the more elderly patients tend to cost more.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMedical expenses of allo-HSCT within 1, 3 months, and 1 year\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eImpacts of donor sources\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe expenses of allo-HSCT, stratified by donor source (BMT, PBSCT, CBT), is summarized in Table 2. CBT was most costly regardless of the post-transplant period (within 1 month: median value, $22,669; IQR: 14,094-29,073; 3 months: median value, $41,935; IQR: 25,139-57,486; 1 year: median value, $62,683; IQR: 37,837-95,700), followed by BMT (1 month: median value, $12,066; IQR: 6,753-17,695; 3 months: median value, $20,565; IQR: 11,081-32,615; 1 year: median value, $33,904; IQR: 18,099-60,821) and PBSCT (1 month: median value, $10,774; IQR, 6,077-16,471; 3 months: median value, $17,807; IQR, 9,831-30,428; 1 year: median value, $30,500; IQR: 16,993-57,700) with p\u0026lt;0.001 for each period. This cost order among the three donor types was consistent throughout the study period. \u0026nbsp; \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eBreakdown and annual change\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eAmong the detailed categories, transfusion expenses were the largest, accounting for approximately 10-30% of the total cost for each donor and at a maximum in CBT. Median transfusion expenses in CBT were $7,809.1 (IQR: 3,907.9-11,330.3) for 1 month, $10,212.9 (IQR: 4,779.5-17,781.5) for 3 months, and $11,682.6 (IQR: 5,609.6-21,468.0) for 1 year, which were several times higher than in other donor types (Table 3). Antimicrobial expenses were also consistently the highest in CBT regardless of the types of antimicrobial agents and post-transplant period, which was 1.5 to 2 times higher than those used in BMT/PBSCT. The expenses of immunosuppressive agents such as graft-versus-host-disease (GVHD) prophylaxis were almost equivalent for the three donor types, with a trend towards lower costs for CBT over the longer period.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFor each donor source, the expense per patient tended to increase slightly over time (Supplemental Table 2). Looking at the breakdown of the trend in each category, transfusion cost did not change dramatically throughout the study period. Antimicrobial expenses in CBT showed a continuous tendency to increase (p=0.0031) in the early timing after transplantation, whereas GVHD prophylaxis costs showed a tendency to decrease only in PBSCT in12 months after transplant (Supplemental Table 3, 4). \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eImpact of patients\u0026rsquo; age\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe youngest age group (0\u0026ndash;19 years) and the oldest age group (70\u0026ndash;84 years) were associated with the highest costs. This tendency was more evident for the youngest in PBSCT and the oldest in CBT, regardless of the post-transplantation period (Table 5).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMedical costs of HSCTs above 1 year after transplantation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eExpenses of CBT were the highest among auto and allogeneic donors when medical expenses in the 2nd and 3rd years after transplantation were examined: Auto-HSCT: median, $32,226 (IQR: 11,167-63,985); BMT: $32,446 (IQR: 12,790-56,262); PBSCT: $24,164 (IQR: 10,410-60,616); CBT: $36,453 (IQR: 15,175-67,980) (Table 2).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eImpact of center effects on overall HSCT expenses\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHSCT expenses consistently showed a tendency to be the lowest in the high-volume transplant centers for all donors (auto, BMT, PBSCT, and CBT), regardless of the post-transplantation period (Table 6). The differences in the median value of annual costs between the low- and the high-volume centers were the highest in CBT ($17,313), followed by BMT ($7,006).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis is the largest and most comprehensive study that analyzed the medical expenses of auto- and allo-HSCT in Japan. Usage of the NDB enables us to include and analyze the expenses of almost all auto- and allo-HSCT transplants performed in Japan. Their detailed analysis clarified several important points that need to be evaluated to improve the economics of HSCT.\u003c/p\u003e \u003cp\u003eFirst, and contrary to our expectations(\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e), we found that the increase in the expense per patient over time was not dramatic. This could be explained in part by the fact that cost reductions from therapeutic improvements offset the cost escalation from increased drug costs. Surprisingly, transfusion expenses did not improve over time, which may be due to no efficient change in the engraftment period both in platelets and red blood cells.\u003c/p\u003e \u003cp\u003eSecond, CBT was the most expensive procedure in our analysis, almost twice as expensive as other donors, regardless of year of transplant, patient age, and type of transplant center. The most likely factor influencing this is the higher transfusion costs in CBT followed by antimicrobe agents, which consistently account for a certain proportion of total HSCT costs. This result was consistent with those reported in previous studies(\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). Lowering transfusion or antimicrobe costs by promoting earlier engraftment could lead to a reduction in total HSCT expenses, with the impact expected to be greatest in CBT(\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). It should be noted that our current data rarely include the costs of HSCT using haploidentical PB/BM donors, as the procedure will reach insurance coverage in 2021. Since the survival outcomes and risks of severe chronic GVHD of CBT are comparable to those of haplo-PBSCT/BMT even in long-term follow-up in Japan(\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e), we should re-evaluate the differences in cost and cost-effectiveness between CBT and haplo-PBSCT/BMT using our own national data(\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). Since CBTs performed in Japan normally use single units, comparison with previous studies from other countries using double units is also suggestive(\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). Our data, together with our national transplant database (TRUMP)(\u003cspan additionalcitationids=\"CR23\" citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e), suggest that CBT continues and will continue to be performed in Japan; the expenses of CBT is an important issue and it should be applied to the appropriately selected patients from a cost point of view.\u003c/p\u003e \u003cp\u003eMedical expenses in HSCT for pediatrics were generally higher than those for adult, except for the population over 60 years of age, which is consistent with previous studies(\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e). This trend was more pronounced for auto-HSCT and allo-HSCT in the earlier period but not for CBT. This may reflect the different patient cohorts in terms of disease type, disease status between pediatrics and adults, and more intensive therapies in pediatrics, although this point could not be adequately assessed due to the lack of patient background in our cohort (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eInterestingly and unexpectedly, the more experienced centers provided more economical HSCT regardless of donor type. Because data from older patients or those with higher-risk diseases were more likely to be included in data from centers performing a higher number of HSCTs(\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e), the accumulation of transplant experience could contribute to cost reduction through the appropriate use of medications or other therapeutic interventions. Investigating these differences in performance among different types of centers may provide a key to reducing transplantation costs.\u003c/p\u003e \u003cp\u003eWe have several limitations to this study. Firstly, it lacks information on cost-effectiveness, values reflecting patients\u0026rsquo; quality of life such as Quality-adjusted life year, patients' diseases and their status, and transplantation strategies and outcomes other than survival such as posttransplant complications(\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e), because it was an analysis of the budget database. It didn't include the expenses associated with allogeneic donors such as donor search(\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e), donor coordination and stem cell harvesting either. Also, since this is the medical expense per patient in a specific timeframe, the patients' survival probability could affect the total expense in that period, making the result difficult to interpret simply. Another is that it is difficult to simply compare the expenses between ours and those reported from foreign countries, since the exchange rates have changed chronologically, and an economic situation such as inflation/deflation has influenced prices in all aspects of medical expenses.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe medical expenses of HSCT have not changed dramatically over time, including that of transfusion, which was the highest. CBT is the most expensive of all transplant procedures and should be re-evaluated so that it can continue to be used as an alternative donor.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eConflict-of-interest disclosure\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing financial interests.\u003c/p\u003e\n\u003cp\u003eThis work was supported in part by the Takeda Science Foundation (JK).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors would like to thank all the doctors, nurses and other medical staff involved in the transplantation procedures. We are also grateful to all those involved in the data management of the NDB systems and to those who maintain our insurance systems, which provided the backbones of this study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis work was supported by grants from AMED (Grant Number 24ek0510046h0001) and JSPS KAKENHI (Grant Number 24K11515).\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eAnasetti C. Use of alternative donors for allogeneic stem cell transplantation. Hematology / the Education Program of the American Society of Hematology American Society of Hematology Education Program. 2015;2015(1):220\u0026ndash;4. \u003c/li\u003e\n\u003cli\u003eBachanova V, Burns LJ, Wang T, Carreras J, Gale RP, Wiernik PH, et al. Alternative donors extend transplantation for patients with lymphoma who lack an HLA matched donor. Bone Marrow Transplant [Internet]. 2015 Feb 17;50(2):197\u0026ndash;203. Available from: http://www.nature.com/articles/bmt2014259\u003c/li\u003e\n\u003cli\u003eTran DT, Jin R, Zhu H, Schmidt G, Spellman SR, Ballen KK. Evidence into practice: Changes in haploidentical versus double umbilical cord blood graft utilization for hematopoietic cell transplantation in the U.S. in relation to a pivotal randomized clinical trial. Journal of Clinical Oncology. 2024 Jun 1;42(16_suppl):e23306\u0026ndash;e23306. \u003c/li\u003e\n\u003cli\u003eKawamura K, Tsukada N, Kanda Y, Ikeda T, Yoshida A, Ueda Y, et al. The Role of Allogeneic Transplantation for Multiple Myeloma in the Era of Novel Agents: A Study from the Japanese Society of Myeloma. Biology of Blood and Marrow Transplantation [Internet]. 2018;24(7):1392\u0026ndash;8. Available from: https://doi.org/10.1016/j.bbmt.2018.03.012\u003c/li\u003e\n\u003cli\u003eGhosh N, Ahmed S, Ahn KW, Khanal M, Litovich C, Aljurf M, et al. Association of Reduced-Intensity Conditioning Regimens With Overall Survival Among Patients With Non-Hodgkin Lymphoma Undergoing Allogeneic Transplant. JAMA Oncol [Internet]. 2020 Jul 1;6(7):1011. Available from: https://jamanetwork.com/journals/jamaoncology/fullarticle/2766566\u003c/li\u003e\n\u003cli\u003eLabopin M, Ruggeri A, Gorin NC, Gluckman E, Blaise D, Mannone L, et al. Cost-effectiveness and clinical outcomes of double versus single cord blood transplantation in adults with acute leukemia in France. Haematologica. 2014 Mar;99(3):535\u0026ndash;40. \u003c/li\u003e\n\u003cli\u003eSiani MD gonthier C, Faucher C, Touzani R, Lemari\u0026eacute;-basset C, Chabannon C, Furst S, et al. Cost-effectiveness analysis of haploidentical vs matched unrelated allogeneic hematopoietic stem cells transplantation in patients older than 55 years. Bone Marrow Transplant [Internet]. 2018;1096\u0026ndash;104. Available from: http://dx.doi.org/10.1038/s41409-018-0133-5\u003c/li\u003e\n\u003cli\u003eRamsey SD, Bansal A, Li L, O\u0026rsquo;Donnell P V., Fuchs EJ, Brunstein CG, et al. Cost-Effectiveness of Unrelated Umbilical Cord Blood Transplantation versus HLA-Haploidentical Related Bone Marrow Transplantation: Evidence from BMT CTN 1101. Transplant Cell Ther. 2023 Jul 1;29(7):464.e1-464.e8. \u003c/li\u003e\n\u003cli\u003eBart T. Cost effectiveness of cord blood versus bone marrow and peripheral blood stem cells. Clinicoecon Outcomes Res. 2010;2:141\u0026ndash;7. \u003c/li\u003e\n\u003cli\u003eSaito AM, Cutler C, Zahrieh D, Soiffer RJ, Ho VT, Alyea EP, et al. Costs of allogeneic hematopoietic cell transplantation with high-dose regimens. \u003c/li\u003e\n\u003cli\u003eSaito AM, Zahrieh D, Cutler C, Ho VT, Antin JH, Soiffer RJ, et al. Lower costs associated with hematopoietic cell transplantation using reduced intensity vs high-dose regimens for hematological malignancy. Bone Marrow Transplant. 2007 Aug;40(3):209\u0026ndash;17. \u003c/li\u003e\n\u003cli\u003ePreussler JM, Denzen EM, Majhail NS. Costs and Cost-Effectiveness of Hematopoietic Cell Transplantation. Vol. 18, Biology of Blood and Marrow Transplantation. 2012. p. 1620\u0026ndash;8. \u003c/li\u003e\n\u003cli\u003eLiterature Review of Studies Using the National Database of the Health Insurance Claims of Japan (NDB): Limitations and Strategies in Using the NDB for Research. JMA J. 2024;7(1):10\u0026ndash;20. \u003c/li\u003e\n\u003cli\u003eShinichiro K, Tatsuya N, Tomoya M, Yuichi N, Tsuneyuki H, Hiroki M, et al. National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB): Outline and Patient-Matching Technique. 2018. \u003c/li\u003e\n\u003cli\u003eStranges E, Russo CA, Friedman B. Procedures with the Most Rapidly Increasing Hospital Costs, 2004\u0026ndash;2007. 2006. \u003c/li\u003e\n\u003cli\u003eMajhail NS, Mothukuri JM, Brunstein CG, Weisdorf DJ. Costs of Hematopoietic Cell Transplantation: Comparison of Umbilical Cord Blood and Matched Related Donor Transplantation and the Impact of Posttransplant Complications. Biology of Blood and Marrow Transplantation. 2009 May;15(5):564\u0026ndash;73. \u003c/li\u003e\n\u003cli\u003eRamsey SD, Bansal A, Li L, O\u0026rsquo;Donnell P V., Fuchs EJ, Brunstein CG, et al. Cost-Effectiveness of Unrelated Umbilical Cord Blood Transplantation versus HLA-Haploidentical Related Bone Marrow Transplantation: Evidence from BMT CTN 1101. Transplant Cell Ther. 2023 Jul 1;29(7):464.e1-464.e8. \u003c/li\u003e\n\u003cli\u003eMajhail NS, Mothukuri JM, Brunstein CG, Weisdorf DJ. Costs of Hematopoietic Cell Transplantation: Comparison of Umbilical Cord Blood and Matched Related Donor Transplantation and the Impact of Posttransplant Complications. Biology of Blood and Marrow Transplantation. 2009 May;15(5):564\u0026ndash;73. \u003c/li\u003e\n\u003cli\u003eNarimatsu H, Miyakoshi S, Yamaguchi T, Kami M, Matsumura T, Yuji K, et al. Chronic graft-versus-host disease following umbilical cord blood transplantation: retrospective survey involving 1072 patients in Japan. Blood. 2008;112(6):2579\u0026ndash;82. \u003c/li\u003e\n\u003cli\u003eKuwatsuka Y, Atsuta Y, Horowitz MM, Inagaki J, Kanda J, Kato K, et al. Graft-Versus-Host Disease and Survival after Cord Blood Transplantation for Acute Leukemia: A Comparison of Japanese versus White Populations. Biology of Blood and Marrow Transplantation. 2014;20(5):662\u0026ndash;7. \u003c/li\u003e\n\u003cli\u003eLabopin M, Ruggeri A, Gorin NC, Gluckman E, Blaise D, Mannone L, et al. Cost-effectiveness and clinical outcomes of double versus single cord blood transplantation in adults with acute leukemia in France. Haematologica. 2014 Mar 1;99(3):535\u0026ndash;40. \u003c/li\u003e\n\u003cli\u003eKonuma T, Mizuno S, Kondo T, Arai Y, Uchida N, Takahashi S, et al. Improved trends in survival and engraftment after single cord blood transplantation for adult acute myeloid leukemia. Blood Cancer J. 2022 May 25;12(5):81. \u003c/li\u003e\n\u003cli\u003eKonuma T, Mizuno S, Harada K, Uchida N, Takahashi S, Eto T, et al. Reducing Mortality of Single-Unit Unrelated Cord Blood Transplantation for Relapsed Acute Myeloid Leukemia after a Previous Allogeneic Transplantation: A Real-World Retrospective Study Over the Past 19 Years in Japan. Transplant Cell Ther. 2022 Nov;28(11):777.e1-777.e11. \u003c/li\u003e\n\u003cli\u003eKonuma T, Kanda J, Inamoto Y, Hayashi H, Kobayashi S, Uchida N, et al. Improvement of early mortality in single‐unit cord blood transplantation for Japanese adults from 1998 to 2017. Am J Hematol [Internet]. 2020 Apr 2;95(4):343\u0026ndash;53. Available from: https://onlinelibrary.wiley.com/doi/10.1002/ajh.25705\u003c/li\u003e\n\u003cli\u003eThe Cost of Hematopoietic Stem-Cell Transplantation in the United States [Internet]. 2017. Available from: www.AHDBonline.com\u003c/li\u003e\n\u003cli\u003eMajhail NS, Mothukuri JM, MacMillan ML, Verneris MR, Orchard PJ, Wagner JE, et al. Costs of pediatric allogeneic hematopoietic-cell transplantation. Pediatr Blood Cancer. 2010 Jan;54(1):138\u0026ndash;43. \u003c/li\u003e\n\u003cli\u003eLin YF, Lairson DR, Chan W, Du XL, Leung KS, Kennedy-Nasser AA, et al. The costs and cost-effectiveness of allogeneic peripheral blood stem cell transplantation versus bone marrow transplantation in pediatric patients with acute leukemia. Biology of Blood and Marrow Transplantation. 2010 Sep 1;16(9):1272\u0026ndash;81. \u003c/li\u003e\n\u003cli\u003eKurosawa S, Fukuda T, Ichinohe T, Hashii Y, Kanda J, Goto H, et al. Center effect on allogeneic hematopoietic stem cell transplantation outcomes for B-cell acute lymphoblastic leukemia. Cytotherapy. 2024 Oct;26(10):1185\u0026ndash;92. \u003c/li\u003e\n\u003cli\u003eShimomura Y, Kitamura T, Murata M, Matsuo K, Ito Y, Ichinohe T, et al. Impact of Center Volume on Chronic Graft Versus Host Disease in Patients With Allogeneic Stem Cell Transplantation. Transplant Cell Ther. 2024 Mar;30(3):326.e1-326.e14. \u003c/li\u003e\n\u003cli\u003eLee SJ, Klar N, Weeks JC, Antin JH. Predicting Costs of Stem-Cell Transplantation. Journal of Clinical Oncology. 2000 Jan 1;18(1):64\u0026ndash;64. \u003c/li\u003e\n\u003cli\u003eOttinger H, Grosse-Wilde M, Schmitz A, Grosse-Wilde H. Immunogenetic marrow donor search for 1012 patients: a retrospective analysis of strategies, outcome and costs. Bone Marrow Transplant [Internet]. 1994;14 Suppl 4:S34-8. Available from: http://www.ncbi.nlm.nih.gov/pubmed/7728122\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables 1 to 6 are available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bone-marrow-transplantation","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"bmt","sideBox":"Learn more about [Bone Marrow Transplantation](http://www.nature.com/bmt/)","snPcode":"41409","submissionUrl":"https://mts-bmt.nature.com/cgi-bin/main.plex","title":"Bone Marrow Transplantation","twitterHandle":"@bmtjournal","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Medical expenses, Hematopoietic stem cell transplantation, auto-HSCT, allo-HSCT","lastPublishedDoi":"10.21203/rs.3.rs-6998815/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6998815/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eIn Japan, medical expenses are primarily covered by a universal health insurance system, with data recorded in the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB), enabling a comprehensive analysis of nearly all inpatient and outpatient costs. To better understand the economic burden associated with hematopoietic stem cell transplantation (HSCT) and to support sustainable, equitable care, we analyzed medical expenses incurred during and after HSCT. A total of 19,500 patients who underwent HSCT between 2012 and 2017 were included, covering approximately 60\u0026ndash;80% of all HSCT recipients during that period. The median 3-month and 1-year costs (USD) were: \u003cspan\u003e$\u003c/span\u003e15,660 / \u003cspan\u003e$\u003c/span\u003e24,195 for autologous HSCT; \u003cspan\u003e$\u003c/span\u003e20,565 / \u003cspan\u003e$\u003c/span\u003e33,904 for allogeneic bone marrow transplantation; \u003cspan\u003e$\u003c/span\u003e17,807 / \u003cspan\u003e$\u003c/span\u003e30,500 for peripheral blood stem cell transplantation; and \u003cspan\u003e$\u003c/span\u003e41,935 / \u003cspan\u003e$\u003c/span\u003e62,683 for cord blood transplantation. Costs were generally higher in older patients and showed a gradual increase over time. Transfusion accounted for the largest proportion of total costs, particularly in cord blood transplantation. Greater transplant center experience was associated with lower costs for allogeneic HSCT. Given the high costs, especially for cord blood transplantation, continuous efforts to reduce transplantation expenses, such as accelerating donor engraftment, are essential.\u003c/p\u003e","manuscriptTitle":"Real-World medical expenses of Hematopoietic Stem Cell Transplantation in Japan: A Nationwide Database Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-07 06:31:21","doi":"10.21203/rs.3.rs-6998815/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"revise","date":"2025-07-28T10:54:10+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"This content is not available.","date":"2025-07-04T00:53:58+00:00","index":1,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2025-07-02T12:31:04+00:00","index":1,"fulltext":"This content is not available."},{"type":"reviewersInvited","content":"","date":"2025-07-02T11:45:40+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-06-30T10:59:40+00:00","index":"","fulltext":""},{"type":"submitted","content":"Bone Marrow Transplantation","date":"2025-06-28T15:45:03+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-06-28T15:45:03+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bone-marrow-transplantation","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"bmt","sideBox":"Learn more about [Bone Marrow Transplantation](http://www.nature.com/bmt/)","snPcode":"41409","submissionUrl":"https://mts-bmt.nature.com/cgi-bin/main.plex","title":"Bone Marrow Transplantation","twitterHandle":"@bmtjournal","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"71e52a61-4700-4da6-bc72-1b126a4f9b22","owner":[],"postedDate":"July 7th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":50927076,"name":"Health sciences/Health care/Health services"},{"id":50927077,"name":"Health sciences/Health care/Therapeutics/Stem-cell therapies"}],"tags":[],"updatedAt":"2025-11-16T08:05:26+00:00","versionOfRecord":{"articleIdentity":"rs-6998815","link":"https://doi.org/10.1038/s41409-025-02753-5","journal":{"identity":"bone-marrow-transplantation","isVorOnly":false,"title":"Bone Marrow Transplantation"},"publishedOn":"2025-11-15 05:00:00","publishedOnDateReadable":"November 15th, 2025"},"versionCreatedAt":"2025-07-07 06:31:21","video":"","vorDoi":"10.1038/s41409-025-02753-5","vorDoiUrl":"https://doi.org/10.1038/s41409-025-02753-5","workflowStages":[]},"version":"v1","identity":"rs-6998815","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6998815","identity":"rs-6998815","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}