Ruxolitinib treatment outcomes in acute graft-versus-host disease (aGvHD) in a real-world setting in Finland

Ruxolitinib treatment outcomes in acute graft-versus-host disease (aGvHD) in a real-world setting in Finland | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Ruxolitinib treatment outcomes in acute graft-versus-host disease (aGvHD) in a real-world setting in Finland Eeva Martelin, Arttu Kuikka, Hanna Rajala, Tuomas Ruohonen, Hannu Mönkkönen, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6228702/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 06 Jun, 2025 Read the published version in Annals of Hematology → Version 1 posted 7 You are reading this latest preprint version Abstract In Europe, ruxolitinib is the first approved treatment for corticosteroid-refractory acute or chronic graft-versus-host disease (aGvHD/cGvHD). This retrospective, non-interventional study evaluated the real-world efficacy and safety of ruxolitinib in 56 adult aGvHD patients treated with ruxolitinib from January 2019 through August 2021 in Finland. The primary endpoint was best overall response rate (ORR) at any time. The main secondary endpoints were the time to response and loss of response, overall survival (OS), and corticosteroid discontinuation. The follow-up lasted until death/August 2022. The ORR was 91.0% (95% CI: 83.5–98.5; complete response, 69.6%; partial response, 21.4%). The median time to best response was 28.0 days (95% CI: 21.0–38.0). The median time to loss of response due to aGvHD progression, cGvHD, or a relapse-related death was 8.8 months (95% CI: 3.3–not reached). The most common cause of discontinuation was the achievement of response (64.3%). Two-thirds of the corticosteroid-treated patients discontinued corticosteroids before the end of follow-up; one-third were on a low dose at the end of follow-up. The three-year OS was 64.1% (95% CI: 48.2–76.3). Ruxolitinib appears effective and safe in real-world practice. The presented data is in line with the results of clinical trials. Acute graft-versus-host disease best overall response rate corticosteroid tapering response duration real-world evidence ruxolitinib Figures Figure 1 Figure 2 Figure 3 INTRODUCTION Graft versus host disease (GvHD) is a life-threatening multisystemic disorder, which remains one of the main complications of allogeneic hematopoietic stem cell transplantations (allo-HSCT) [1, 2]. GvHD in its acute form (aGvHD), as well as in its chronic form (cGvHD), is associated with high morbidity and mortality [3–5]. Clinical features dictate whether GvHD is acute or chronic, or a subtype showing both acute and chronic disease characteristics [6, 7]. The incidence of aGvHD is 30–50%, with 10–15% of the patients developing severe or very severe, grade 3 to 4 aGvHD [8, 9]. Corticosteroids (CSs) are the first-line treatment for grade 2 to 4, but approximately half of the patients are steroid-refractory (SR-GvHD) and have a dismal prognosis [10–14]. Patients with SR-GvHD may benefit from ruxolitinib, the first approved treatment for patients aged 12 years and older with SR-aGvHD [15, 16]. Real-world evidence on the therapeutic management of GvHD with ruxolitinib is increasing [17–20]. Before the approval of ruxolitinib by the European Medicines Agency in 2022, no drug was licensed for the second-line treatment of GvHD in Europe. Accordingly, before 2022, there have been no guidelines for choosing a second-line treatment, and thus the choice has been made based on the clinical evaluation of each patient [10–12, 21–23]. The aim of this retrospective, non-interventional cohort study was to evaluate the real-world efficacy and safety of ruxolitinib in the treatment of aGvHD in Finland, based on a pre-approval data. The primary endpoint was best overall response rate (ORR). The secondary endpoints were time to response and loss of response as well as overall survival (OS) and CS discontinuation. MATERIALS AND METHODS Study design and permissions This observational cohort study was conducted in accordance with the Declaration of Helsinki and the Act on Secondary Use of Health and Social Data 552/2019. The study protocol and data requests were approved by the Finnish Social and Health Data Permit Authority, Findata (THL/3757/14.02.00/2021). Due to the anonymity requirement of the data authority, results with low subject numbers were masked and it was ensured that the masked numbers cannot be deduced based on other available numbers. Study population, data extraction, and study period The study cohort was screened from medical records of Turku and Helsinki University Hospitals. The final cohort included all adult patients with aGvHD treated with ruxolitinib from Jan 2019 through Aug 2021. Ruxolitinib therapy was indicated for patients with either SR- or steroid-dependent (SD) aGvHD. However, some patients received ruxolitinib as part of the first-line therapy based on the clinician's discretion. For patients who received ruxolitinib treatment more than once, only the first exposure was considered in the analysis. All patients were followed until death or end of study (EOS), 31 August 2022, for OS and long-term utilization of CSs. Demographic and clinical data was reviewed from the local medical records and linked with the national data on healthcare contacts and diagnoses (the Register of Primary Health Care Visits and the Care Register for Health Care, Finnish Institute for Health and Welfare, THL) and causes of deaths (Statistics Finland). Findata linked the data sets using personal identification numbers and provided pseudonymized data in a secure data environment where all the analyses were carried out. Statistical analyses Continuous demographic and clinical variables were reported with medians and interquartile ranges (IQR), categorical variables with number and proportion of patients per level. Grade and stage of aGvHD were determined according to the MAGIC criteria [24]. SR/SD status were evaluated according to consensus definitions developed by the EBMT-NIH-CIBMTR task force [25]. The best ORR was defined as the number of patients who obtained a complete (CR) or partial response (PR) at any time for the first exposure. Timely events were estimated with Kaplan-Meier/competing risk models with 95% confidence intervals (CIs). Treatment duration was defined as the time from the onset of treatment to the end of treatment or death (event), or EOS (censoring event). Time to best overall response and time to CR were defined as the time from the onset of treatment to the best overall response or CR (event), respectively, with ruxolitinib discontinuation, death, or EOS considered as censoring events. Loss of response was defined as the time from the best overall response to aGvHD progression (event), cGvHD or death due to a relapse of the underlying hematologic disease (competing events), or other non-GvHD deaths or EOS (censoring events). OS was defined as the time from the onset of treatment to death (event) or EOS (censoring). The association of characteristic and treatment response with OS was assessed with a Cox proportional hazards model with age as a continuous covariate, sex and Charlson comorbidity index [26] as categorical covariates, and the type of response (CR, PR, or no response) as a time varying covariate. Public all-cause healthcare resource utilization (HCRU) was estimated using national register data on healthcare contacts. The corresponding costs were determined based on the unit costs of the healthcare in Finland 2017, scaled to 2022 prices using price index of public healthcare expenditure [27, 28]. The unit costs include the average cost of procedures, operations, laboratory examinations, inpatient medications, and overheads of contacts for each specialty field and contact type. The costs of ruxolitinib were also separately assessed using the dosing data and the retail prices as of May 2023 with value-added tax included. The HCRU and corresponding costs were assessed as per patient year estimates by diving the number of contacts/costs by the total number of patient years. 95% CIs were estimated using bootstrapping over the patients (10 000 samples). Statistical analyses were performed using R, A Language and Environment for Statistical Computing, in R server environment, version 4.0.3 [29]. Significance level was 0.05. RESULTS Patient characteristics A total of 56 adult aGvHD patients treated with ruxolitinib from January 2019 through August 2021 were reviewed and characterized ( Table 1 ). The median follow-up time from the first ruxolitinib exposure was 21.8 months (IQR: 11.8–32.5). The patients were transplanted either at Turku or Helsinki University Hospitals, the two centers performing all allo-HSCTs for adults in Finland. Between 2019 and 2021, approximately 380 adult patients received an allo-HSCT in Finland, and 15% of them were treated with ruxolitinib for aGvHD. Of the 56 ruxolitinib-treated aGvHD patients, 77% were transplanted for acute myeloid/monocytic (n = 17) or lymphoblastic leukemia (n = 7), or high-risk myelodysplastic syndrome (n = 19). Nearly all patients received peripheral blood stem cell transplant, either from haploidentical relative or unrelated matched donor ( Table 1 ). Myeloablative conditioning and reduced-intensity conditioning were equally used, and 64% (n = 36) received post-transplant cyclophosphamide for GvHD prophylaxis ( Table 1 ). At the start of the ruxolitinib treatment, 42% of the patients manifested grade 2 aGvHD and 31% grade 3–4, while 27% of the patients had mild grade 1 aGvHD ( Table 1 ). Ruxolitinib was also used in the front line for patients with high-risk and severe aGvHD. The median time from aGvHD diagnosis to the first ruxolitinib exposure was 10.0 days (IQR: 3.0–20.5). Clinical outcomes of ruxolitinib-treated aGvHD patients The best ORR at any time for the first ruxolitinib exposure was 91.0% (95% CI: 83.5–98.5; n = 51/56; Figure 1a ). CR was achieved by 69.6% of patients (n = 39) and PR by 21.4% (n = 12). The median time to the best overall response was 28.0 days (95% CI: 21.0–38.0; Figure 1b ); the median time to CR was 30.0 days (95% CI: 22.0–45.0). Of 39 patients with CR, 21 lost the response, while among 12 patients with PR, 7 experienced a loss of response during the follow-up. Time to loss of response was estimated with a competing risk model of aGvHD progression probability, where cGvHD and death due to a relapse of the underlying hematologic disease were considered as competing events ( Figure 1c ). aGvHD progression rate was highest during the first three months reaching a plateau at approximately six months ( Figure 1c ). At this time point, 15.8% (95% CI: 8.4–29.8) of the patients were estimated to show aGvHD progression, 23.9% (95% CI: 14.6–39.2) had onset of cGvHD, and 2.0% (95% CI: 0.3–13.7) had died due to a relapse of the hematologic disease. Among those who obtained a response, the onset of cGvHD reached a plateau at approximately 12 months (32.5%; 95% CI: 21.7–48.7; Figure 1c ). Overall, the median time to loss of response due to aGvHD progression, cGvHD, or relapse-related death was 8.8 months (95% CI: 3.3–not reached; Figure 1c). The median time to loss of response was 12.9 months (95% CI: 6.2–not reached) in patients with CR and 2.9 months (95% CI: 1.7–not reached) in patients with PR. Of all ruxolitinib-treated aGvHD patients, 16% (n = 9/56) had a relapse of the underlying hematologic disease during the follow-up and 32% died (n = 18/56), with nine of GvHD (16%; n = 9/56). Out of the patients who died of GvHD, five (56%) had obtained CR or PR. The nine patients who died of other reasons had all obtained CR or PR. The estimated three-year OS for all ruxolitinib-treated aGvHD patients was 64.1% (95% CI: 48.2-76.3; the median OS was not reached; Figure 1d ). The Cox regression model, adjusted for age, sex, and comorbidity burden, showed that patients who did not get CR or PR, had a 6.5-fold risk of death compared with patients with CR (hazard ratio: 6.47; 95% CI: 2.38–17.55; p < 0.001). Characteristics of ruxolitinib and corticosteroid treatments Almost all patients received ruxolitinib as part of a combination therapy ( Table 2 ). The median ruxolitinib daily dose was 10.0 mg both at the onset of treatment (IQR: 10.0–10.0) and one month later (IQR: 10.0–20.0). The median duration of the ruxolitinib treatment was 3.7 months (95% CI: 2.7–4.6; Figure 2 ), and the most common cause of discontinuation was the achievement of good response (64%, n = 36; Table 2 ). Most patients (93%, n = 51) were treated with systemic CSs: 82% (n = 46) of the patients received CS as the first-line treatment of aGvHD. Two-thirds (63%; n = 35) were considered as SR/SD ( Table 2 ). Of the patients treated with systemic CSs, 67% (n=34/51) discontinued the treatment before the end of follow-up (EOF) and the remaining 33% (n = 17) were on low dose at the EOF ( Table 2 ). Ruxolitinib and extracorporeal photopheresis (ECP) Approximately 40% of the patients were treated with ECP ( Table 2 ). The median number of treatment times per patient was 21. The best ORR remained statistically the same regardless of ECP use of the ruxolitinib-treated patients ( Figure 3 ). Healthcare resource utilization (HCRU) in ruxolitinib-treated aGvHD patients The total direct healthcare costs from the initiation of ruxolitinib treatment, and including e.g., the average costs of the inpatient medications, were 43 100€ per patient year. Of these costs, 23 700€ (95% CI: 16 700€–32 300€) were attributable to hospitalizations, 17 300€ (95% CI: 14 300€–20 600€) to outpatient specialty care contacts, 1 600€ (95% CI: 800€–2 800€) to primary care, and 500€ (95% CI: 400€–700€) to emergency care. Ruxolitinib costs, separately computed based on dosing data and median retail prices (with tax), were 7 400€ (95% CI: 5 500– 9 600€) per patient year. DISCUSSION The present study provides real-world evidence on the use of ruxolitinib in the treatment of aGvHD. A total of 56 adult patients were characterized for their first ruxolitinib exposure. The proportion of ruxolitinib-treated aGvHD was approximately 15% among patients who underwent allo-HSCT in Finland 2019–2021. The ORR at any time was 91% and the best overall response was achieved within the median of one month. The median duration of ruxolitinib treatment was less than four months and the treatment was most often discontinued due to obtaining a good response. The response was however estimated to be lost (either due to aGvHD progression, cGvHD, or hematologic relapse-related death) within the median of nine months. Two-thirds of the patients were able to discontinue CSs, and two-thirds were estimated to be alive at three years from the initiation of ruxolitinib treatment. Therefore, our study adds to the previous positive evidence on the efficacy and safety of ruxolitinib in the treatment of aGvHD [16, 30]. In a phase 3 randomized trial (REACH2) [16], the best ORR by day 28 was 82% (95% CI: 75–88; CR, 44%) and the day 28 ORR was 62% (95% CI: 54–70). In a phase 2 non-randomized, single-arm trial (REACH 1), the best ORR by day 28 was 55% (95% CI: 61-83; CR, 56%) and at any time, 73% (95% CI: 61–83) [30]. In the present study, the best ORR of 91% was based on the CR/PR obtained at any time, thus also including late responses. The differences in the study setting and ORR definition may partly explain the higher probability of the loss of response observed in the real-world setting: 42% (95% CI: 26–54) of the patients lost the response at six months in the present study compared with 10% (95% CI: 4–17) in the REACH2 trial [16]. Thrombocytopenia, infection, and other adverse events as a reason of ruxolitinib discontinuation were recorded in only 14% of the patients, while the most common reason was obtaining a good response (64%). In the REACH 2 trial, the most common reason was a lack of efficacy (21%), while 11% of the discontinuations were due to adverse events [16, 31]. The long-term outcomes were also positive. Two-thirds of the patients were able to discontinue CSs before the EOF. In the REACH2 trial, use of CSs was assessed at day 56, where the discontinuation rate was 21% [16]. Moreover, the median OS was 11.1 months (95% CI: 0.60 –1.15) in the clinical trial setting [16], while not reached in the present real-world study with the median follow-up time of 22 months. This study benefited both from the structured data of the national registers and the high-quality local clinical data collected in the manual chart review. The management of GvHD is complex, and as this work was based on retrospective real-world data on a heterogenous patient population, causality between ruxolitinib treatment and long-term outcomes should be assessed with caution. The results of this non-interventional real-world study cannot be compared directly with those of the clinical trials due to differences in the outcome definitions and characteristics of the study population, which were not matched between the real-world and clinical trial settings [16, 30, 31]. Limitations also exist in the analysis of small patient subgroups. Moreover, the analysis of the HCRU did not contain a control group, and in the lack of specific diagnoses code for GvHD, included all-cause resource use. There is a pressing need for efficient and safe therapies for aGvHD that can alleviate both disease of an individual patient and the burden on healthcare. In 2022, the European Medicines Agency approved the expanded use of ruxolitinib to patients with aGvHD [15]. Our study suggests that ruxolitinib appears effective and safe in real-world practice, thus complementing the outcome data from the clinical trials. Declarations Acknowledgements This study benefited from the data from Hospital District of Helsinki and Uusimaa and Hospital District of Southwest Finland (currently, Wellbeing services county of Southwest Finland), Finnish Institute for Health and Welfare, and Statistics Finland. We thank Samuli Tuominen (Medaffcon Oy, Espoo) for valuable help with the data analysis. Author contributions All authors contributed to the conception and design of the study. HM, KUR, and JV drafted the study protocol and statistical analyses plan, which were edited and approved by all authors. KUR and JV contributed to data permission, acquisition, and processing. EM, HR, AK, and TR screened and validated patient population and reviewed medical records for relevant variables, supervised by MIR and US. JV performed the statistical analyses on single-level data and EM, HR, AK, TR, MIR, and US validated the results. All authors contributed to interpretation of the results. JV and KUR designed the figures and wrote the first draft of the manuscript. All authors reviewed and revised previous versions of the manuscript and approved the final version. FUNDING This study was funded by Novartis Finland Oy. Data Availability The single-level data cannot be shared. Only the original register holders or Finnish Social and Health Data Permit Authority can grant rights to third parties to use the data in accordance with the Act on Secondary Use of Health and Social Data. Human Ethics and Consent to Participate Not applicable. This study was approved by the Finnish Social and Health Data Permit Authority, Findata, in accordance with the Act on Secondary Use of Health and Social Data. Competing interests The study was funded by Novartis (Espoo, Finland). Arttu Kuikka, Eeva Martelin, Hanna Rajala, and Tuomas Ruohonen have nothing to declare. Hannu Mönkkönen is employed by Novartis. Johanna Vikkula and Kristiina Uusi-Rauva are employed by Medaffcon Oy (Espoo, Finland), which received payments from Novartis for conducting the study. Urpu Salmenniemi has been a member of advisory boards for Takeda, AstraZeneca, and Immedica, and provided consultancy to Viatris. Maija Itälä-Remes has been a member of an advisory board for Novartis and provided consultancy to Incyte. References Jacobsohn DA, Vogelsang GB (2007) Acute graft versus host disease. Orphanet J Rare Dis 2:35. https://doi.org/10.1186/1750-1172-2-35 Ferrara JL, Levine JE, Reddy P, Holler E (2009) Graft-versus-host disease. Lancet 373:1550–1561. https://doi.org/10.1016/S0140-6736(09)60237-3 Jagasia M, Arora M, Flowers MED et al (2012) Risk factors for acute GVHD and survival after hematopoietic cell transplantation. Blood 119:296–307. https://doi.org/10.1182/blood-2011-06-364265 DeFilipp Z, Alousi AM, Pidala JA et al (2021) Nonrelapse mortality among patients diagnosed with chronic GVHD: an updated analysis from the Chronic GVHD Consortium. Blood Adv 5:4278–4284. https://doi.org/10.1182/bloodadvances.2021004941 Westin JR, Saliba RM, De Lima M et al (2011) Steroid-Refractory Acute GVHD: Predictors and Outcomes. Adv Hematol 2011:1–8. https://doi.org/10.1155/2011/601953 Lee SJ (2017) Classification systems for chronic graft-versus-host disease. Blood 129:30–37. https://doi.org/10.1182/blood-2016-07-686642 Zeiser R, Blazar BR (2017) Acute Graft-versus-Host Disease — Biologic Process, Prevention, and Therapy. N Engl J Med 377:2167–2179. https://doi.org/10.1056/NEJMra1609337 Di Francesco A, Raiola AM, Dominietto A et al (2024) Acute graft versus host disease 1976–2020: reduced incidence and predictive factors. Front Med 10:1320692. https://doi.org/10.3389/fmed.2023.1320692 Greinix HT, Eikema D-J, Koster L et al (2021) Improved outcome of patients with graft-versus-host disease after allogeneic hematopoietic cell transplantation for hematologic malignancies over time: an EBMT mega-file study. Haematol 107:1054–1063. https://doi.org/10.3324/haematol.2020.265769 A working group of the European Group for Blood and Marrow Transplantation (EBMT) and the European LeukemiaNet (ELN), Ruutu T, Gratwohl A et al (2014) Prophylaxis and treatment of GVHD: EBMT–ELN working group recommendations for a standardized practice. Bone Marrow Transplant 49:168–173. https://doi.org/10.1038/bmt.2013.107 Magro L, Forcade E, Giraud C et al (2017) Prise en charge de la maladie du greffon contre l’hôte chronique: recommandations de la Société francophone de greffe de moelle et de thérapie cellulaire (SFGM-TC) [Management of the chronic graft versus host disease: Guidelines from the Francophone society of bone marrow transplantation and cellular therapies (SFGM-TC)]. Bull Cancer 104:S145–S168. https://doi.org/10.1016/j.bulcan.2017.10.023 Penack O, Marchetti M, Ruutu T et al (2020) Prophylaxis and management of graft versus host disease after stem-cell transplantation for haematological malignancies: updated consensus recommendations of the European Society for Blood and Marrow Transplantation. Lancet Haematol 7:e157–e167. https://doi.org/10.1016/S2352-3026(19)30256-X Malard F, Huang X-J, Sim JPY (2020) Treatment and unmet needs in steroid-refractory acute graft-versus-host disease. Leukemia 34:1229–1240. https://doi.org/10.1038/s41375-020-0804-2 Biavasco F, Ihorst G, Wäsch R et al (2022) Therapy response of glucocorticoid-refractory acute GVHD of the lower intestinal tract. Bone Marrow Transpl 57:1500–1506. https://doi.org/10.1038/s41409-022-01741-3 Novartis Europharm Limited (2025) JAKAVI® (ruxolitinib) tablets: EU Summary of Product Characteristics. https://www.ema.europa.eu/en/documents/product-information/jakavi-epar-product-information_en.pdf Zeiser R, von Bubnoff N, Butler J et al (2020) Ruxolitinib for Glucocorticoid-Refractory Acute Graft-versus-Host Disease. N Engl J Med 382:1800–1810. https://doi.org/10.1056/NEJMoa1917635 Murray A, Linn SM, Yu B et al (2024) Real-world experience with ruxolitinib therapy for steroid-refractory acute graft versus host disease. Bone Marrow Transpl 59:759–764. https://doi.org/10.1038/s41409-024-02249-8 Battista ML, Patriarca F, Isola M et al (2024) Comparison of efficacy and tolerability of ruxolitinib alone or ruxolitinib with extracorporeal photopheresis or extracorporeal photopheresis monotherapy for steroid refractory aGvHD: A GITMO retrospective study. The 50th Annual Meeting of the European Society for Blood and Marrow Transplantation. Physicians – Poster Session (P001-P755). Bone Marrow Transplant 59:140–665. https://doi.org/10.1038/s41409-024-02348-6 Lastovytska I, Klyuchnikov E, Heidenreich S et al (2024) Improved long-term outcome of ruxolitinib plus ECP vs ruxolitinib alone in steroid-refractory acute graft-versus-host disease (SR-aGVHD). The 50th Annual Meeting of the European Society for Blood and Marrow Transplantation. Physicians – Poster Session (P001-P755). Bone Marrow Transplant 59:140–665. https://doi.org/10.1038/s41409-024-02348-6 Galopoulos D, Irvine D, Parker A et al (2024) Use of ruxolitinib in steroid dependent/refractory acute and chronic graft versus host disease: A single centre experience. The 50th Annual Meeting of the European Society for Blood and Marrow Transplantation. Physicians – Poster Session (P001-P755). Bone Marrow Transplant 59:140–665. https://doi.org/10.1038/s41409-024-02348-6 Carpenter PA, Kitko CL, Elad S et al (2015) National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: V. The 2014 Ancillary Therapy and Supportive Care Working Group Report. Biol Blood Marrow Transpl 21:1167–1187. https://doi.org/10.1016/j.bbmt.2015.03.024 Martin PJ, Rizzo JD, Wingard JR et al (2012) First- and Second-Line Systemic Treatment of Acute Graft-versus-Host Disease: Recommendations of the American Society of Blood and Marrow Transplantation. Biol Blood Marrow Transpl 18:1150–1163. https://doi.org/10.1016/j.bbmt.2012.04.005 Penack O, Marchetti M, Aljurf M et al (2024) Prophylaxis and management of graft-versus-host disease after stem-cell transplantation for haematological malignancies: updated consensus recommendations of the European Society for Blood and Marrow Transplantation. Lancet Haematol 11:e147–e159. https://doi.org/10.1016/S2352-3026(23)00342-3 Harris AC, Young R, Devine S et al (2016) International, Multicenter Standardization of Acute Graft-versus-Host Disease Clinical Data Collection: A Report from the Mount Sinai Acute GVHD International Consortium. Biol Blood Marrow Transpl 22:4–10. https://doi.org/10.1016/j.bbmt.2015.09.001 Schoemans HM, Lee SJ, Ferrara JL et al (2018) EBMT – NIH – CIBMTR Task Force position statement on standardized terminology & guidance for graft-versus-host disease assessment. Bone Marrow Transpl 53:1401–1415. https://doi.org/10.1038/s41409-018-0204-7 Quan H, Li B, Couris CM et al (2011) Updating and Validating the Charlson Comorbidity Index and Score for Risk Adjustment in Hospital Discharge Abstracts Using Data From 6 Countries. Am J Epidemiol 173:676–682. https://doi.org/10.1093/aje/kwq433 Mäklin M, Kokko P (2020) Terveyden- ja sosiaalihuollon yksikkökustannukset Suomessa vuonna 2017. https://www.julkari.fi/bitstream/handle/10024/142882/URN_ISBN_978-952-343-493-6.pdf?sequence=1&isAllowed=y . Accessed 28 Jun 2022 Statistics Finland (2022) Official Statistics of Finland (OSF): Price index of public expenditure. http://www.stat.fi/til/jmhi/index_en.html . Accessed 28 Jun 2022 R Core Team (2020) R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. https://www.R-project.org/ . Accessed 28 Jun 2022 Jagasia M, Perales M-A, Schroeder MA et al (2020) Ruxolitinib for the treatment of steroid-refractory acute GVHD (REACH1): a multicenter, open-label phase 2 trial. Blood 135:1739–1749. https://doi.org/10.1182/blood.2020004823 Zeiser R, von Bubnoff N, Niederwieser D et al (2020) Ruxolitinib Versus Best Available Therapy in Patients with Steroid-Refractory Acute Graft-Versus-Host Disease (aGVHD): Overall Response Rate by Baseline Characteristics in the Randomized Phase 3 REACH 2 Trial (S255). The 25th Congress of the European Hematology Association. https://journals.lww.com/hemasphere/Documents/EHA25_Abstracts_2020.pdf . Accessed 12 Dec 2023 Tables Table 1 Patient characteristics Variable Overall (N=56) Age at treatment initiation (years), median (IQR) 56.5 (41.2–63.4) Length of follow-up (months), median (IQR) 21.8 (11.8–32.5) Sex, n (%) Female 28 (50.0) Male 28 (50.0) Type of donor, n (%) Haploidentical relative 23-26 b HLA-identical sibling <5 Unrelated matched donor 29 (51.8) Graft source, n (%) Bone marrow <5 b Peripheral blood 52-55 b Pretransplantation conditioning, n (%) MAC 28 (50.0) RIC 28 (50.0) GvHD prophylaxis, n (%) MTX-based 20 (35.7) PTCy-based 36 (64.3) First-line treatment, n (%) Corticosteroid 46 (82.1) Other 10 (17.9) Time from aGvHD diagnosis to ruxolitinib initiation (days), median (IQR) 10.0 (3.0–20.5) aGvHD grade at treatment initiation, n (%) a Grade 1 15 (27.3) Grade 2 23 (41.8) Grade 3-4 17 (30.9) Stage of skin at treatment initiation, n (%) a Stage 0 16 (29.1) Stage 1 12 (21.8) Stage 2 14 (25.5) Stage 3-4 13 (23.6) Stage of intestine at treatment initiation, n (%) a Stage 0 24 (44.4) Stage 1 13 (24.1) Stage 2 8 (14.8) Stage 3-4 9 (16.7) Stage of liver at treatment initiation, n (%) a Stage 0 55 (100.0) Stage 2–4 0 (0) a The proportion of patients for whom the respective data was available. A few patients had missing data on grade/stage (stage skin/liver, 1.8%; stage intestine, 3.6%) b Due to the anonymity requirement of the data authority, results with low subject numbers were masked and it was ensured that the masked numbers cannot be deduced based on other available numbers Abbreviations: aGvHD, acute graft-versus-host disease; HLA, human leukocyte antigen; IQR, interquartile range; MAC, myeloablative conditioning [high-dose cyclophosphamide (HDCy) + high-dose busulfan (HDBu), HDCy + total body irradiation 12Gy (TBI12Gy), treosulfan 14 g/m 2 /day + fludarabine (Flu), or other]; MTX-based, methotrexate-based [methotrexate + calcineurin inhibitor (CNI)/mammalian target of rapamycin (mTOR) ± anti-thymocyte globulins (ATG)/anti-T lymphocyte globulins (ATLG) ± corticosteroid (CS) ± mycophenolate mofetil (MMF)]; PTCy-based, post-transplant cyclophosphamide-based (HDCy + CNI/mTOR ± MMF); RIC, reduced-intensity conditioning [Flu + two-day busulfan ± thiotepa, FluCy ± TBI 2Gy, Flu + treosulfan 10 g/m 2 /day]; SR/SD, steroid-refractory or -dependent Table 2 Characteristics of ruxolitinib and systemic corticosteroid treatments Variable Overall (N=56) Type of ruxolitinib treatment, n (%) Any combination with ECP 21-24 (≈40) c Any combination without ECP 31 (55.4) Ruxolitinib monotherapy <5 c Number of ECPs, median (IQR) 20.5 (12.0–23.5) Ruxolitinib starting daily dose (mg), median (IQR) 10.0 (10.0–10.0) Ruxolitinib daily dose after one month (mg), median (IQR) a 10.0 (10.0–20.0) Duration of ruxolitinib treatment (months), median (95% CI) 3.7 (2.7–4.6) Discontinuation of ruxolitinib, n (%) AE 8 (14.3) Death <5 c Good response 36 (64.3) Lack of efficacy <5 c Other <5 c Relapse of underlying disease <5 c Treatment ongoing at the end of follow-up <5 c Received systemic CS during the follow-up, n (%) 51 (91.1) On systemic CS at ruxolitinib discontinuation, n (%) b Yes 21 (41.2) No 30 (58.8) Daily dose of systemic CS at ruxolitinib discontinuation (mg/kg), median (IQR) b 0.1 (0.1–0.3) Discontinued systemic CS during the follow-up, n (%) b Yes 34 (66.7) No 17 (33.3) Daily dose of systemic CS at the end of follow-up (mg/kg), median (IQR) b 0.2 (0.1–0.5) SR/SD, n (%) Yes 35 (62.5) No 8 (14.3) Unknown 13 (23.2) a Analyzed in patients who were on the treatment at one month b Analyzed in patients who received systemic CS during the follow-up (n=51) c Due to the anonymity requirement of the data authority, results with low subject numbers were masked and it was ensured that the masked numbers cannot be deduced based on other available numbers Abbreviations : AE, adverse event; aGvHD, acute graft-versus-host disease; CI, confidence interval; CS, corticosteroid; ECP, extracorporeal photopheresis; IQR, interquartile range; SR/SD, steroid-refractory or -dependent Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 06 Jun, 2025 Read the published version in Annals of Hematology → Version 1 posted Editorial decision: Revision requested 28 Apr, 2025 Reviews received at journal 17 Apr, 2025 Reviewers agreed at journal 27 Mar, 2025 Reviewers invited by journal 27 Mar, 2025 Editor assigned by journal 24 Mar, 2025 Submission checks completed at journal 24 Mar, 2025 First submitted to journal 14 Mar, 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. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6228702","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":434954651,"identity":"fe1ffe02-783a-4187-98f7-8bce1c1e7718","order_by":0,"name":"Eeva Martelin","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA4klEQVRIie2OsQrCMBRFEzJ0iXSNg/gLkS666K8YCk6CuAkKRgp26Q8Ior/QKXPkQV36AQ6CujgrLo6mOrkkjg4503twD/ci5PH8N0RqNNHmwGf9k0ARNkpZhQn/XUF4+VGsyTDIWjc87I56wWIB481RbCXB1pZ6VkYMq7iT0Z2ElbqKXBNkVfhh0DcK4ZQJCTUFIkehtiq90zV+YjXntHkxyhqqYY4WRgrTAqYFG0WCkK5hrIyLtlB7TkszjBYQ5eBQwnSXHO5qyoMU4EFn0NimCbnZlDf9r4848x6Px+Nx8QITHlAqs+6zGAAAAABJRU5ErkJggg==","orcid":"","institution":"Helsinki University Hospital","correspondingAuthor":true,"prefix":"","firstName":"Eeva","middleName":"","lastName":"Martelin","suffix":""},{"id":434954652,"identity":"0ae9b2be-7a7c-4922-822b-f796c55ca963","order_by":1,"name":"Arttu Kuikka","email":"","orcid":"","institution":"Turku University Hospital, Hospital District of Southwest Finland","correspondingAuthor":false,"prefix":"","firstName":"Arttu","middleName":"","lastName":"Kuikka","suffix":""},{"id":434954653,"identity":"8b76be36-b735-4273-ae5b-65ff565ea458","order_by":2,"name":"Hanna Rajala","email":"","orcid":"","institution":"Helsinki University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Hanna","middleName":"","lastName":"Rajala","suffix":""},{"id":434954654,"identity":"2bb28518-e55f-4af9-92a8-df10d50e9a5b","order_by":3,"name":"Tuomas Ruohonen","email":"","orcid":"","institution":"Turku University Hospital, Hospital District of Southwest Finland","correspondingAuthor":false,"prefix":"","firstName":"Tuomas","middleName":"","lastName":"Ruohonen","suffix":""},{"id":434954655,"identity":"e3d7c871-ec39-4138-9e16-001e71950aeb","order_by":4,"name":"Hannu Mönkkönen","email":"","orcid":"","institution":"Novartis Finland Oy","correspondingAuthor":false,"prefix":"","firstName":"Hannu","middleName":"","lastName":"Mönkkönen","suffix":""},{"id":434954656,"identity":"f8d67988-6477-4f2f-9759-6c6c29accb86","order_by":5,"name":"Johanna Vikkula","email":"","orcid":"","institution":"Medaffcon Oy","correspondingAuthor":false,"prefix":"","firstName":"Johanna","middleName":"","lastName":"Vikkula","suffix":""},{"id":434954657,"identity":"3a5923dd-6e18-48b1-b8c5-7f265ec90d02","order_by":6,"name":"Kristiina Uusi-Rauva","email":"","orcid":"","institution":"Medaffcon Oy","correspondingAuthor":false,"prefix":"","firstName":"Kristiina","middleName":"","lastName":"Uusi-Rauva","suffix":""},{"id":434954658,"identity":"3cb93e56-a3f6-49a0-913f-7952f92439f2","order_by":7,"name":"Urpu Salmenniemi","email":"","orcid":"","institution":"Helsinki University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Urpu","middleName":"","lastName":"Salmenniemi","suffix":""},{"id":434954659,"identity":"ebf261ba-797a-495b-913d-0ec33b176f73","order_by":8,"name":"Maija Itälä-Remes","email":"","orcid":"","institution":"Turku University Hospital, Hospital District of Southwest Finland","correspondingAuthor":false,"prefix":"","firstName":"Maija","middleName":"","lastName":"Itälä-Remes","suffix":""}],"badges":[],"createdAt":"2025-03-14 18:53:09","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6228702/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6228702/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00277-025-06439-2","type":"published","date":"2025-06-06T15:57:54+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":79830858,"identity":"b54fff8c-626d-4ede-951a-f01be14ab8c0","added_by":"auto","created_at":"2025-04-03 10:28:54","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":179185,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ea) \u003c/strong\u003eBest overall response rate (ORR; complete response, CR, or partial response, PR, obtained at any time for the first exposure); \u003cstrong\u003eb) \u003c/strong\u003etime to best overall response; \u003cstrong\u003ec) \u003c/strong\u003eaGvHD progression with the competing risks of cGvHD or death due to the relapse of the underlying hematologic disease; and\u003cstrong\u003e d) \u003c/strong\u003eoverall survival. 95% confidence intervals are included in the estimates\u003c/p\u003e","description":"","filename":"Picture1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6228702/v1/8c238e48f44ddb3921bbadef.jpg"},{"id":79831486,"identity":"75d937f2-f4a1-4751-a895-2a9494ff6189","added_by":"auto","created_at":"2025-04-03 10:36:54","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":46488,"visible":true,"origin":"","legend":"\u003cp\u003eDuration of ruxolitinib treatment with 95% confidence intervals\u003c/p\u003e","description":"","filename":"Picture2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6228702/v1/42563d196bbfabac9009628d.jpg"},{"id":79830854,"identity":"7da52d7f-afb1-4278-95d0-b2304ab5c42c","added_by":"auto","created_at":"2025-04-03 10:28:54","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":50163,"visible":true,"origin":"","legend":"\u003cp\u003eBest overall response rate (ORR) at any time of patients treated with ruxolitinib combinations with or without extracorporeal photopheresis (ECP). CI, 95% confidence intervals; CR, complete response; PR, partial response\u003c/p\u003e","description":"","filename":"Picture3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6228702/v1/1ad13185619a953c96279a9f.jpg"},{"id":84242667,"identity":"1a031c83-e8ba-46bb-9c27-500e5331387a","added_by":"auto","created_at":"2025-06-09 16:11:05","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1470644,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6228702/v1/6a171b27-7da2-4357-afb3-f03fd2383ea1.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Ruxolitinib treatment outcomes in acute graft-versus-host disease (aGvHD) in a real-world setting in Finland","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eGraft versus host disease (GvHD) is a life-threatening multisystemic disorder, which remains one of the main complications of allogeneic hematopoietic stem cell transplantations (allo-HSCT) [1, 2]. GvHD in its acute form (aGvHD), as well as in its chronic form (cGvHD), is associated with high morbidity and mortality [3\u0026ndash;5]. Clinical features dictate whether GvHD is acute or chronic, or a subtype showing both acute and chronic disease characteristics [6, 7]. The incidence of aGvHD is 30\u0026ndash;50%, with 10\u0026ndash;15% of the patients developing severe or very severe, grade 3 to 4 aGvHD [8, 9].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCorticosteroids (CSs) are the first-line treatment for grade 2 to 4, but approximately half of the patients are steroid-refractory (SR-GvHD) and have a dismal prognosis [10\u0026ndash;14]. Patients with SR-GvHD may benefit from ruxolitinib, the first approved treatment for patients aged 12 years and older with SR-aGvHD [15, 16]. Real-world evidence on the therapeutic management of GvHD with ruxolitinib is increasing [17\u0026ndash;20]. Before the approval of ruxolitinib by the European Medicines Agency in 2022, no drug was licensed for the second-line treatment of GvHD in Europe. Accordingly, before 2022, there have been no guidelines for choosing a second-line treatment, and thus the choice has been made based on the clinical evaluation of each patient [10\u0026ndash;12, 21\u0026ndash;23].\u003c/p\u003e\n\u003cp\u003eThe aim of this retrospective, non-interventional cohort study was to evaluate the real-world efficacy and safety of ruxolitinib in the treatment of aGvHD in Finland, based on a pre-approval data. The primary endpoint was best overall response rate (ORR). The secondary endpoints were time to response and loss of response as well as overall survival (OS) and CS discontinuation.\u003c/p\u003e"},{"header":" MATERIALS AND METHODS","content":"\u003cp\u003e\u003cstrong\u003eStudy design and permissions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis observational cohort study was conducted in accordance with the Declaration of Helsinki and the Act on Secondary Use of Health and Social Data 552/2019. The study protocol and data requests were approved by the Finnish Social and Health Data Permit Authority, Findata (THL/3757/14.02.00/2021).\u0026nbsp;Due to the anonymity requirement of the data authority, results with low subject numbers were masked and it was ensured that the masked numbers cannot be deduced based on other available numbers.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy population, data extraction, and study period\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study cohort was screened from medical records of Turku and Helsinki University Hospitals. The final cohort included all adult patients with aGvHD treated with ruxolitinib from Jan 2019 through Aug 2021. Ruxolitinib therapy was indicated for patients with either SR- or steroid-dependent (SD) aGvHD. However, some patients received ruxolitinib as part of the first-line therapy based on the clinician's discretion. For patients who received ruxolitinib treatment more than once, only the first exposure was considered in the analysis. All patients were followed until death or end of study (EOS), 31 August 2022, for OS and long-term utilization of CSs.\u003c/p\u003e\n\u003cp\u003eDemographic and clinical data was reviewed from the local medical records and linked with the national data on healthcare contacts and diagnoses (the Register of Primary Health Care Visits and the Care Register for Health Care, Finnish Institute for Health and Welfare, THL) and causes of deaths (Statistics Finland). Findata linked the data sets using personal identification numbers and provided pseudonymized data in a secure data environment where all the analyses were carried out.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analyses\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eContinuous demographic and clinical variables were reported with medians and interquartile ranges (IQR), categorical variables with number and proportion of patients per level. Grade and stage of aGvHD were determined according to the MAGIC criteria [24]. SR/SD status were evaluated according to consensus definitions developed by the EBMT-NIH-CIBMTR task force [25]. The best ORR was defined as the number of patients who obtained a complete (CR) or partial response (PR) at any time for the first exposure. Timely events were estimated with Kaplan-Meier/competing risk models with 95% confidence intervals (CIs). Treatment duration was defined as the time from the onset of treatment to the end of treatment or death (event), or EOS (censoring event). Time to best overall response and time to CR were defined as the time from the onset of treatment to the best overall response or CR (event), respectively, with ruxolitinib discontinuation, death, or EOS considered as censoring events. Loss of response was defined as the time from the best overall response to aGvHD progression (event), cGvHD or death due to a relapse of the underlying hematologic disease (competing events), or other non-GvHD deaths or EOS (censoring events). OS was defined as the time from the onset of treatment to death (event) or EOS (censoring). The association of characteristic and treatment response with OS was assessed with a Cox proportional hazards model with age as a continuous covariate, sex and Charlson comorbidity index [26] as categorical covariates, and the type of response (CR, PR, or no response) as a time varying covariate.\u003c/p\u003e\n\u003cp\u003ePublic all-cause healthcare resource utilization (HCRU) was estimated using national register data on healthcare contacts. The corresponding costs were determined based on the unit costs of the healthcare in Finland 2017, scaled to 2022 prices using price index of public healthcare expenditure [27, 28]. The unit costs include the average cost of procedures, operations, laboratory examinations, inpatient medications, and overheads of contacts for each specialty field and contact type. The costs of ruxolitinib were also separately assessed using the dosing data and the retail prices as of May 2023 with value-added tax included. The HCRU and corresponding costs were assessed as per patient year estimates by diving the number of contacts/costs by the total number of patient years. 95% CIs were estimated using bootstrapping over the patients (10 000 samples).\u003c/p\u003e\n\u003cp\u003eStatistical analyses were performed using R, A Language and Environment for Statistical Computing, in R server environment, version 4.0.3 [29]. Significance level was 0.05.\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cp\u003e\u003cstrong\u003ePatient characteristics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total of 56 adult aGvHD patients treated with ruxolitinib from January 2019 through August 2021 were reviewed and characterized (\u003cstrong\u003eTable 1\u003c/strong\u003e). The median follow-up time from the first ruxolitinib exposure was 21.8 months (IQR: 11.8\u0026ndash;32.5). The patients were transplanted either at Turku or Helsinki University Hospitals, the two centers performing all allo-HSCTs for adults in Finland. Between 2019 and 2021, approximately 380 adult patients received an allo-HSCT in Finland, and 15% of them were treated with ruxolitinib for aGvHD.\u003c/p\u003e\n\u003cp\u003eOf the 56 ruxolitinib-treated aGvHD patients, 77% were transplanted for acute myeloid/monocytic (n = 17) or lymphoblastic leukemia (n = 7), or high-risk myelodysplastic syndrome (n = 19). Nearly all patients received peripheral blood stem cell transplant, either from haploidentical relative or unrelated matched donor (\u003cstrong\u003eTable 1\u003c/strong\u003e). Myeloablative conditioning and reduced-intensity conditioning were equally used, and 64% (n = 36) received post-transplant cyclophosphamide for GvHD prophylaxis (\u003cstrong\u003eTable 1\u003c/strong\u003e).\u003c/p\u003e\n\u003cp\u003eAt the start of the ruxolitinib treatment, 42% of the patients manifested grade 2 aGvHD and 31% grade 3\u0026ndash;4, while 27% of the patients had mild grade 1 aGvHD (\u003cstrong\u003eTable 1\u003c/strong\u003e). Ruxolitinib was also used in the front line for patients with high-risk and severe aGvHD. The median time from aGvHD diagnosis to the first ruxolitinib exposure was 10.0 days (IQR: 3.0\u0026ndash;20.5).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical outcomes of ruxolitinib-treated aGvHD patients\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe best ORR at any time for the first ruxolitinib exposure was 91.0% (95% CI: 83.5\u0026ndash;98.5; n = 51/56; \u003cstrong\u003eFigure 1a\u003c/strong\u003e). CR was achieved by 69.6% of patients (n = 39) and PR by 21.4% (n = 12). The median time to the best overall response was 28.0 days (95% CI: 21.0\u0026ndash;38.0; \u003cstrong\u003eFigure 1b\u003c/strong\u003e); the median time to CR was 30.0 days (95% CI: 22.0\u0026ndash;45.0).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOf 39 patients with CR, 21 lost the response, while among 12 patients with PR, 7 experienced a loss of response during the follow-up. Time to loss of response was estimated with a competing risk model of aGvHD progression probability, where cGvHD and death due to a relapse of the underlying hematologic disease were considered as competing events (\u003cstrong\u003eFigure 1c\u003c/strong\u003e). aGvHD progression rate was highest during the first three months reaching a plateau at approximately six months (\u003cstrong\u003eFigure 1c\u003c/strong\u003e). At this time point, 15.8% (95% CI: 8.4\u0026ndash;29.8) of the patients were estimated to show aGvHD progression, 23.9% (95% CI: 14.6\u0026ndash;39.2) had onset of cGvHD, and 2.0% (95% CI: 0.3\u0026ndash;13.7) had died due to a relapse of the hematologic disease. Among those who obtained a response, the onset of cGvHD reached a plateau at approximately 12 months (32.5%; 95% CI: 21.7\u0026ndash;48.7; \u003cstrong\u003eFigure 1c\u003c/strong\u003e). Overall, the median time to loss of response due to aGvHD progression, cGvHD, or relapse-related death was 8.8 months (95% CI: 3.3\u0026ndash;not reached; \u003cstrong\u003eFigure 1c).\u003c/strong\u003e The median time to loss of response was 12.9 months (95% CI: 6.2\u0026ndash;not reached) in patients with CR and 2.9 months (95% CI: 1.7\u0026ndash;not reached) in patients with PR.\u003c/p\u003e\n\u003cp\u003eOf all ruxolitinib-treated aGvHD patients, 16% (n = 9/56) had a relapse of the underlying hematologic disease during the follow-up and 32% died (n = 18/56), with nine of GvHD (16%; n = 9/56). Out of the patients who died of GvHD, five (56%) had obtained CR or PR. The nine patients who died of other reasons had all obtained CR or PR. The estimated three-year OS for all ruxolitinib-treated aGvHD patients was 64.1% (95% CI: 48.2-76.3; the median OS was not reached; \u003cstrong\u003eFigure 1d\u003c/strong\u003e). The Cox regression model, adjusted for age, sex, and comorbidity burden, showed that patients who did not get CR or PR, had a 6.5-fold risk of death compared with patients with CR (hazard ratio: 6.47; 95% CI: 2.38\u0026ndash;17.55; p \u0026lt; 0.001).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCharacteristics of ruxolitinib and corticosteroid treatments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAlmost all patients received ruxolitinib as part of a combination therapy (\u003cstrong\u003eTable 2\u003c/strong\u003e). The median ruxolitinib daily dose was 10.0 mg both at the onset of treatment (IQR: 10.0\u0026ndash;10.0) and one month later (IQR: 10.0\u0026ndash;20.0). The median duration of the ruxolitinib treatment was 3.7 months (95% CI: 2.7\u0026ndash;4.6; \u003cstrong\u003eFigure 2\u003c/strong\u003e), and the most common cause of discontinuation was the achievement of good response (64%, n = 36; \u003cstrong\u003eTable 2\u003c/strong\u003e).\u003c/p\u003e\n\u003cp\u003eMost patients (93%, n = 51) were treated with systemic CSs: 82% (n = 46) of the patients received CS as the first-line treatment of aGvHD. Two-thirds (63%; n = 35) were considered as SR/SD (\u003cstrong\u003eTable 2\u003c/strong\u003e). Of the patients treated with systemic CSs, 67% (n=34/51) discontinued the treatment before the end of follow-up (EOF) and the remaining 33% (n = 17) were on low dose at the EOF (\u003cstrong\u003eTable 2\u003c/strong\u003e).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRuxolitinib and extracorporeal photopheresis (ECP)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eApproximately 40% of the patients were treated with ECP (\u003cstrong\u003eTable 2\u003c/strong\u003e). The median number of treatment times per patient was 21. The best ORR remained statistically the same regardless of ECP use of the ruxolitinib-treated patients (\u003cstrong\u003eFigure 3\u003c/strong\u003e).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHealthcare resource utilization (HCRU) in ruxolitinib-treated aGvHD patients\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe total direct healthcare costs from the initiation of ruxolitinib treatment, and including e.g., the average costs of the inpatient medications, were 43 100\u0026euro; per patient year. Of these costs, 23 700\u0026euro; (95% CI: 16 700\u0026euro;\u0026ndash;32 300\u0026euro;) were attributable to hospitalizations, 17 300\u0026euro; (95% CI: 14 300\u0026euro;\u0026ndash;20 600\u0026euro;) to outpatient specialty care contacts, 1 600\u0026euro; (95% CI: 800\u0026euro;\u0026ndash;2 800\u0026euro;) to primary care, and 500\u0026euro; (95% CI: 400\u0026euro;\u0026ndash;700\u0026euro;) to emergency care. Ruxolitinib costs, separately computed based on dosing data and median retail prices (with tax), were 7 400\u0026euro; (95% CI: 5 500\u0026ndash; 9 600\u0026euro;) per patient year.\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThe present study provides real-world evidence on the use of ruxolitinib in the treatment of aGvHD. A total of 56 adult patients were characterized for their first ruxolitinib exposure. The proportion of ruxolitinib-treated aGvHD was approximately 15% among patients who underwent allo-HSCT in Finland 2019–2021. The ORR at any time was 91% and the best overall response was achieved within the median of one month. The median duration of ruxolitinib treatment was less than four months and the treatment was most often discontinued due to obtaining a good response. The response was however estimated to be lost (either due to aGvHD progression, cGvHD, or hematologic relapse-related death) within the median of nine months. Two-thirds of the patients were able to discontinue CSs, and two-thirds were estimated to be alive at three years from the initiation of ruxolitinib treatment. Therefore, our study adds to the previous positive evidence on the efficacy and safety of ruxolitinib in the treatment of aGvHD [16, 30].\u003c/p\u003e\n\u003cp\u003eIn a phase 3 randomized trial (REACH2) [16], the best ORR by day 28 was 82% (95% CI: 75–88; CR, 44%) and the day 28 ORR was 62% (95% CI: 54–70). In a phase 2 non-randomized, single-arm trial (REACH 1), the best ORR by day 28 was 55% (95% CI: 61-83; CR, 56%) and at any time, 73% (95% CI: 61–83) [30]. In the present study, the best ORR of 91% was based on the CR/PR obtained at any time, thus also including late responses. The differences in the study setting and ORR definition may partly explain the higher probability of the loss of response observed in the real-world setting: 42% (95% CI: 26–54) of the patients lost the response at six months in the present study compared with 10% (95% CI: 4–17) in the REACH2 trial [16].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThrombocytopenia, infection, and other adverse events as a reason of ruxolitinib discontinuation were recorded in only 14% of the patients, while the most common reason was obtaining a good response (64%). In the REACH 2 trial, the most common reason was a lack of efficacy (21%), while 11% of the discontinuations were due to adverse events [16, 31].\u003c/p\u003e\n\u003cp\u003eThe long-term outcomes were also positive. Two-thirds of the patients were able to discontinue CSs before the EOF. In the REACH2 trial, use of CSs was assessed at day 56, where the discontinuation rate was 21% [16]. Moreover, the median OS was 11.1 months (95% CI: 0.60 –1.15) in the clinical trial setting [16], while not reached in the present real-world study with the median follow-up time of 22 months.\u003c/p\u003e\n\u003cp\u003eThis study benefited both from the structured data of the national registers and the high-quality local clinical data collected in the manual chart review. The management of GvHD is complex, and as this work was based on retrospective real-world data on a heterogenous patient population, causality between ruxolitinib treatment and long-term outcomes should be assessed with caution. The results of this non-interventional real-world study cannot be compared directly with those of the clinical trials due to differences in the outcome definitions and characteristics of the study population, which were not matched between the real-world and clinical trial settings [16, 30, 31]. Limitations also exist in the analysis of small patient subgroups. Moreover, the analysis of the HCRU did not contain a control group, and in the lack of specific diagnoses code for GvHD, included all-cause resource use.\u003c/p\u003e\n\u003cp\u003eThere is a pressing need for efficient and safe therapies for aGvHD that can alleviate both disease of an individual patient and the burden on healthcare. In 2022, the European Medicines Agency approved the expanded use of ruxolitinib to patients with aGvHD [15]. Our study suggests that ruxolitinib appears effective and safe in real-world practice, thus complementing the outcome data from the clinical trials.\u003cbr\u003e\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study benefited from the data from Hospital District of Helsinki and Uusimaa and Hospital District of Southwest Finland (currently, Wellbeing services county of Southwest Finland), Finnish Institute for Health and Welfare, and Statistics Finland. We thank Samuli Tuominen (Medaffcon Oy, Espoo) for valuable help with the data analysis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors contributed to the conception and design of the study. HM, KUR, and JV drafted the study protocol and statistical analyses plan, which were edited and approved by all authors. KUR and JV contributed to data permission, acquisition, and processing. EM, HR, AK, and TR screened and validated patient population and reviewed medical records for relevant variables, supervised by MIR and US. JV performed the statistical analyses on single-level data and EM, HR, AK, TR, MIR, and US validated the results. All authors contributed to interpretation of the results. JV and KUR designed the figures and wrote the first draft of the manuscript. All authors reviewed and revised previous versions of the manuscript and approved the final version.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFUNDING\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eThis study was funded by Novartis Finland Oy.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe single-level data cannot be shared. Only the original register holders or Finnish Social and Health Data Permit Authority can grant rights to third parties to use the data in accordance with the Act on Secondary Use of Health and Social Data.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHuman Ethics and Consent to Participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable. This study was approved by the Finnish Social and Health Data Permit Authority, Findata, in accordance with the Act on Secondary Use of Health and Social Data.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was funded by Novartis (Espoo, Finland). Arttu Kuikka, Eeva Martelin, Hanna Rajala, and Tuomas Ruohonen have nothing to declare. Hannu M\u0026ouml;nkk\u0026ouml;nen is employed by Novartis. Johanna Vikkula and Kristiina Uusi-Rauva are employed by Medaffcon Oy (Espoo, Finland), which received payments from Novartis for conducting the study. Urpu Salmenniemi has been a member of advisory boards for Takeda, AstraZeneca, and Immedica, and provided consultancy to Viatris. Maija It\u0026auml;l\u0026auml;-Remes has been a member of an advisory board for Novartis and provided consultancy to Incyte.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eJacobsohn DA, Vogelsang GB (2007) Acute graft versus host disease. Orphanet J Rare Dis 2:35. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1186/1750-1172-2-35\u003c/span\u003e\u003cspan address=\"10.1186/1750-1172-2-35\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFerrara JL, Levine JE, Reddy P, Holler E (2009) Graft-versus-host disease. Lancet 373:1550\u0026ndash;1561. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/S0140-6736(09)60237-3\u003c/span\u003e\u003cspan address=\"10.1016/S0140-6736(09)60237-3\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJagasia M, Arora M, Flowers MED et al (2012) Risk factors for acute GVHD and survival after hematopoietic cell transplantation. Blood 119:296\u0026ndash;307. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1182/blood-2011-06-364265\u003c/span\u003e\u003cspan address=\"10.1182/blood-2011-06-364265\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDeFilipp Z, Alousi AM, Pidala JA et al (2021) Nonrelapse mortality among patients diagnosed with chronic GVHD: an updated analysis from the Chronic GVHD Consortium. Blood Adv 5:4278\u0026ndash;4284. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1182/bloodadvances.2021004941\u003c/span\u003e\u003cspan address=\"10.1182/bloodadvances.2021004941\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWestin JR, Saliba RM, De Lima M et al (2011) Steroid-Refractory Acute GVHD: Predictors and Outcomes. Adv Hematol 2011:1\u0026ndash;8. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1155/2011/601953\u003c/span\u003e\u003cspan address=\"10.1155/2011/601953\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLee SJ (2017) Classification systems for chronic graft-versus-host disease. Blood 129:30\u0026ndash;37. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1182/blood-2016-07-686642\u003c/span\u003e\u003cspan address=\"10.1182/blood-2016-07-686642\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZeiser R, Blazar BR (2017) Acute Graft-versus-Host Disease \u0026mdash; Biologic Process, Prevention, and Therapy. N Engl J Med 377:2167\u0026ndash;2179. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1056/NEJMra1609337\u003c/span\u003e\u003cspan address=\"10.1056/NEJMra1609337\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDi Francesco A, Raiola AM, Dominietto A et al (2024) Acute graft versus host disease 1976\u0026ndash;2020: reduced incidence and predictive factors. Front Med 10:1320692. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3389/fmed.2023.1320692\u003c/span\u003e\u003cspan address=\"10.3389/fmed.2023.1320692\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGreinix HT, Eikema D-J, Koster L et al (2021) Improved outcome of patients with graft-versus-host disease after allogeneic hematopoietic cell transplantation for hematologic malignancies over time: an EBMT mega-file study. Haematol 107:1054\u0026ndash;1063. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3324/haematol.2020.265769\u003c/span\u003e\u003cspan address=\"10.3324/haematol.2020.265769\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eA working group of the European Group for Blood and Marrow Transplantation (EBMT) and the European LeukemiaNet (ELN), Ruutu T, Gratwohl A et al (2014) Prophylaxis and treatment of GVHD: EBMT\u0026ndash;ELN working group recommendations for a standardized practice. Bone Marrow Transplant 49:168\u0026ndash;173. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1038/bmt.2013.107\u003c/span\u003e\u003cspan address=\"10.1038/bmt.2013.107\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMagro L, Forcade E, Giraud C et al (2017) Prise en charge de la maladie du greffon contre l\u0026rsquo;h\u0026ocirc;te chronique: recommandations de la Soci\u0026eacute;t\u0026eacute; francophone de greffe de moelle et de th\u0026eacute;rapie cellulaire (SFGM-TC) [Management of the chronic graft versus host disease: Guidelines from the Francophone society of bone marrow transplantation and cellular therapies (SFGM-TC)]. Bull Cancer 104:S145\u0026ndash;S168. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.bulcan.2017.10.023\u003c/span\u003e\u003cspan address=\"10.1016/j.bulcan.2017.10.023\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePenack O, Marchetti M, Ruutu T et al (2020) Prophylaxis and management of graft versus host disease after stem-cell transplantation for haematological malignancies: updated consensus recommendations of the European Society for Blood and Marrow Transplantation. Lancet Haematol 7:e157\u0026ndash;e167. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/S2352-3026(19)30256-X\u003c/span\u003e\u003cspan address=\"10.1016/S2352-3026(19)30256-X\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMalard F, Huang X-J, Sim JPY (2020) Treatment and unmet needs in steroid-refractory acute graft-versus-host disease. Leukemia 34:1229\u0026ndash;1240. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1038/s41375-020-0804-2\u003c/span\u003e\u003cspan address=\"10.1038/s41375-020-0804-2\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBiavasco F, Ihorst G, W\u0026auml;sch R et al (2022) Therapy response of glucocorticoid-refractory acute GVHD of the lower intestinal tract. Bone Marrow Transpl 57:1500\u0026ndash;1506. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1038/s41409-022-01741-3\u003c/span\u003e\u003cspan address=\"10.1038/s41409-022-01741-3\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNovartis Europharm Limited (2025) JAKAVI\u0026reg; (ruxolitinib) tablets: EU Summary of Product Characteristics. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.ema.europa.eu/en/documents/product-information/jakavi-epar-product-information_en.pdf\u003c/span\u003e\u003cspan address=\"https://www.ema.europa.eu/en/documents/product-information/jakavi-epar-product-information_en.pdf\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZeiser R, von Bubnoff N, Butler J et al (2020) Ruxolitinib for Glucocorticoid-Refractory Acute Graft-versus-Host Disease. N Engl J Med 382:1800\u0026ndash;1810. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1056/NEJMoa1917635\u003c/span\u003e\u003cspan address=\"10.1056/NEJMoa1917635\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMurray A, Linn SM, Yu B et al (2024) Real-world experience with ruxolitinib therapy for steroid-refractory acute graft versus host disease. Bone Marrow Transpl 59:759\u0026ndash;764. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1038/s41409-024-02249-8\u003c/span\u003e\u003cspan address=\"10.1038/s41409-024-02249-8\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBattista ML, Patriarca F, Isola M et al (2024) Comparison of efficacy and tolerability of ruxolitinib alone or ruxolitinib with extracorporeal photopheresis or extracorporeal photopheresis monotherapy for steroid refractory aGvHD: A GITMO retrospective study. The 50th Annual Meeting of the European Society for Blood and Marrow Transplantation. Physicians \u0026ndash; Poster Session (P001-P755). Bone Marrow Transplant 59:140\u0026ndash;665. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1038/s41409-024-02348-6\u003c/span\u003e\u003cspan address=\"10.1038/s41409-024-02348-6\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLastovytska I, Klyuchnikov E, Heidenreich S et al (2024) Improved long-term outcome of ruxolitinib plus ECP vs ruxolitinib alone in steroid-refractory acute graft-versus-host disease (SR-aGVHD). The 50th Annual Meeting of the European Society for Blood and Marrow Transplantation. Physicians \u0026ndash; Poster Session (P001-P755). Bone Marrow Transplant 59:140\u0026ndash;665. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1038/s41409-024-02348-6\u003c/span\u003e\u003cspan address=\"10.1038/s41409-024-02348-6\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGalopoulos D, Irvine D, Parker A et al (2024) Use of ruxolitinib in steroid dependent/refractory acute and chronic graft versus host disease: A single centre experience. The 50th Annual Meeting of the European Society for Blood and Marrow Transplantation. Physicians \u0026ndash; Poster Session (P001-P755). Bone Marrow Transplant 59:140\u0026ndash;665. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1038/s41409-024-02348-6\u003c/span\u003e\u003cspan address=\"10.1038/s41409-024-02348-6\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCarpenter PA, Kitko CL, Elad S et al (2015) National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: V. The 2014 Ancillary Therapy and Supportive Care Working Group Report. Biol Blood Marrow Transpl 21:1167\u0026ndash;1187. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.bbmt.2015.03.024\u003c/span\u003e\u003cspan address=\"10.1016/j.bbmt.2015.03.024\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMartin PJ, Rizzo JD, Wingard JR et al (2012) First- and Second-Line Systemic Treatment of Acute Graft-versus-Host Disease: Recommendations of the American Society of Blood and Marrow Transplantation. Biol Blood Marrow Transpl 18:1150\u0026ndash;1163. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.bbmt.2012.04.005\u003c/span\u003e\u003cspan address=\"10.1016/j.bbmt.2012.04.005\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePenack O, Marchetti M, Aljurf M et al (2024) Prophylaxis and management of graft-versus-host disease after stem-cell transplantation for haematological malignancies: updated consensus recommendations of the European Society for Blood and Marrow Transplantation. Lancet Haematol 11:e147\u0026ndash;e159. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/S2352-3026(23)00342-3\u003c/span\u003e\u003cspan address=\"10.1016/S2352-3026(23)00342-3\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHarris AC, Young R, Devine S et al (2016) International, Multicenter Standardization of Acute Graft-versus-Host Disease Clinical Data Collection: A Report from the Mount Sinai Acute GVHD International Consortium. Biol Blood Marrow Transpl 22:4\u0026ndash;10. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.bbmt.2015.09.001\u003c/span\u003e\u003cspan address=\"10.1016/j.bbmt.2015.09.001\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSchoemans HM, Lee SJ, Ferrara JL et al (2018) EBMT\u0026thinsp;\u0026ndash;\u0026thinsp;NIH\u0026thinsp;\u0026ndash;\u0026thinsp;CIBMTR Task Force position statement on standardized terminology \u0026amp; guidance for graft-versus-host disease assessment. Bone Marrow Transpl 53:1401\u0026ndash;1415. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1038/s41409-018-0204-7\u003c/span\u003e\u003cspan address=\"10.1038/s41409-018-0204-7\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eQuan H, Li B, Couris CM et al (2011) Updating and Validating the Charlson Comorbidity Index and Score for Risk Adjustment in Hospital Discharge Abstracts Using Data From 6 Countries. Am J Epidemiol 173:676\u0026ndash;682. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1093/aje/kwq433\u003c/span\u003e\u003cspan address=\"10.1093/aje/kwq433\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eM\u0026auml;klin M, Kokko P (2020) Terveyden- ja sosiaalihuollon yksikk\u0026ouml;kustannukset Suomessa vuonna 2017. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.julkari.fi/bitstream/handle/10024/142882/URN_ISBN_978-952-343-493-6.pdf?sequence=1\u0026amp;isAllowed=y\u003c/span\u003e\u003cspan address=\"https://www.julkari.fi/bitstream/handle/10024/142882/URN_ISBN_978-952-343-493-6.pdf?sequence=1\u0026amp;isAllowed=y\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Accessed 28 Jun 2022\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eStatistics Finland (2022) Official Statistics of Finland (OSF): Price index of public expenditure. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://www.stat.fi/til/jmhi/index_en.html\u003c/span\u003e\u003cspan address=\"http://www.stat.fi/til/jmhi/index_en.html\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Accessed 28 Jun 2022\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eR Core Team (2020) R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.R-project.org/\u003c/span\u003e\u003cspan address=\"https://www.R-project.org/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Accessed 28 Jun 2022\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJagasia M, Perales M-A, Schroeder MA et al (2020) Ruxolitinib for the treatment of steroid-refractory acute GVHD (REACH1): a multicenter, open-label phase 2 trial. Blood 135:1739\u0026ndash;1749. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1182/blood.2020004823\u003c/span\u003e\u003cspan address=\"10.1182/blood.2020004823\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZeiser R, von Bubnoff N, Niederwieser D et al (2020) Ruxolitinib Versus Best Available Therapy in Patients with Steroid-Refractory Acute Graft-Versus-Host Disease (aGVHD): Overall Response Rate by Baseline Characteristics in the Randomized Phase 3 REACH 2 Trial (S255). The 25th Congress of the European Hematology Association. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://journals.lww.com/hemasphere/Documents/EHA25_Abstracts_2020.pdf\u003c/span\u003e\u003cspan address=\"https://journals.lww.com/hemasphere/Documents/EHA25_Abstracts_2020.pdf\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Accessed 12 Dec 2023\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1\u0026nbsp;\u003c/strong\u003ePatient characteristics\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 501px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariable\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 141px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOverall (N=56)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 501px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge at treatment initiation (years), median (IQR)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 141px;\"\u003e\n \u003cp\u003e56.5 (41.2\u0026ndash;63.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 501px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLength of follow-up (months), median (IQR)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 141px;\"\u003e\n \u003cp\u003e21.8 (11.8\u0026ndash;32.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 501px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSex, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 141px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 501px;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 141px;\"\u003e\n \u003cp\u003e28 (50.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 501px;\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 141px;\"\u003e\n \u003cp\u003e28 (50.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 501px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eType of donor, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 141px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 501px;\"\u003e\n \u003cp\u003eHaploidentical relative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 141px;\"\u003e\n \u003cp\u003e23-26\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 501px;\"\u003e\n \u003cp\u003eHLA-identical sibling\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 141px;\"\u003e\n \u003cp\u003e\u0026lt;5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 501px;\"\u003e\n \u003cp\u003eUnrelated matched donor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 141px;\"\u003e\n \u003cp\u003e29 (51.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 501px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGraft source, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 141px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 501px;\"\u003e\n \u003cp\u003eBone marrow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 141px;\"\u003e\n \u003cp\u003e\u0026lt;5\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 501px;\"\u003e\n \u003cp\u003ePeripheral blood\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 141px;\"\u003e\n \u003cp\u003e52-55\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 501px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePretransplantation conditioning, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 141px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 501px;\"\u003e\n \u003cp\u003eMAC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 141px;\"\u003e\n \u003cp\u003e28 (50.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 501px;\"\u003e\n \u003cp\u003eRIC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 141px;\"\u003e\n \u003cp\u003e28 (50.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 501px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGvHD prophylaxis, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 141px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 501px;\"\u003e\n \u003cp\u003eMTX-based\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 141px;\"\u003e\n \u003cp\u003e20 (35.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 501px;\"\u003e\n \u003cp\u003ePTCy-based\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 141px;\"\u003e\n \u003cp\u003e36 (64.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 501px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFirst-line treatment, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 141px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 501px;\"\u003e\n \u003cp\u003eCorticosteroid\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 141px;\"\u003e\n \u003cp\u003e46 (82.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 501px;\"\u003e\n \u003cp\u003eOther\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 141px;\"\u003e\n \u003cp\u003e10 (17.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 501px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTime from aGvHD diagnosis to ruxolitinib initiation (days), median (IQR)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 141px;\"\u003e\n \u003cp\u003e10.0 (3.0\u0026ndash;20.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 501px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eaGvHD grade at treatment initiation, n (%)\u003csup\u003ea\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 141px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 501px;\"\u003e\n \u003cp\u003eGrade 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 141px;\"\u003e\n \u003cp\u003e15 (27.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 501px;\"\u003e\n \u003cp\u003eGrade 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 141px;\"\u003e\n \u003cp\u003e23 (41.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 501px;\"\u003e\n \u003cp\u003eGrade 3-4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 141px;\"\u003e\n \u003cp\u003e17 (30.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 501px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eStage of skin at treatment initiation, n (%)\u003csup\u003ea\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 141px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 501px;\"\u003e\n \u003cp\u003eStage 0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 141px;\"\u003e\n \u003cp\u003e16 (29.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 501px;\"\u003e\n \u003cp\u003eStage 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 141px;\"\u003e\n \u003cp\u003e12 (21.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 501px;\"\u003e\n \u003cp\u003eStage 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 141px;\"\u003e\n \u003cp\u003e14 (25.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 501px;\"\u003e\n \u003cp\u003eStage 3-4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 141px;\"\u003e\n \u003cp\u003e13 (23.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 501px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eStage of intestine at treatment initiation, n (%)\u003csup\u003ea\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 141px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 501px;\"\u003e\n \u003cp\u003eStage 0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 141px;\"\u003e\n \u003cp\u003e24 (44.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 501px;\"\u003e\n \u003cp\u003eStage 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 141px;\"\u003e\n \u003cp\u003e13 (24.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 501px;\"\u003e\n \u003cp\u003eStage 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 141px;\"\u003e\n \u003cp\u003e8 (14.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 501px;\"\u003e\n \u003cp\u003eStage 3-4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 141px;\"\u003e\n \u003cp\u003e9 (16.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 501px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eStage of liver at treatment initiation, n (%)\u003csup\u003ea\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 141px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 501px;\"\u003e\n \u003cp\u003eStage 0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 141px;\"\u003e\n \u003cp\u003e55 (100.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 501px;\"\u003e\n \u003cp\u003eStage 2\u0026ndash;4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 141px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003csup\u003ea\u0026nbsp;\u003c/sup\u003eThe proportion of patients for whom the respective data was available. A few patients had missing data on grade/stage (stage skin/liver, 1.8%; stage intestine, 3.6%)\u003c/p\u003e\n\u003cp\u003e\u003csup\u003eb\u003c/sup\u003e Due to the anonymity requirement of the data authority, results with low subject numbers were masked and it was ensured that the masked numbers cannot be deduced based on other available numbers\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAbbreviations:\u003c/strong\u003e aGvHD, acute graft-versus-host disease; HLA, human leukocyte antigen; IQR, interquartile range; MAC, myeloablative conditioning [high-dose cyclophosphamide (HDCy) + high-dose busulfan (HDBu), HDCy + total body irradiation 12Gy (TBI12Gy), treosulfan 14 g/m\u003csup\u003e2\u003c/sup\u003e/day + fludarabine (Flu), or other]; MTX-based, methotrexate-based [methotrexate + calcineurin inhibitor (CNI)/mammalian target of rapamycin (mTOR) \u0026plusmn; anti-thymocyte globulins (ATG)/anti-T lymphocyte globulins (ATLG) \u0026plusmn; corticosteroid (CS) \u0026plusmn; mycophenolate mofetil (MMF)]; PTCy-based, post-transplant cyclophosphamide-based (HDCy + CNI/mTOR \u0026plusmn; MMF); RIC, reduced-intensity conditioning [Flu + two-day busulfan \u0026plusmn; thiotepa, FluCy \u0026plusmn; TBI 2Gy, Flu + treosulfan 10 g/m\u003csup\u003e2\u003c/sup\u003e/day]; SR/SD, steroid-refractory or -dependent\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e2\u0026nbsp;\u003c/strong\u003eCharacteristics of ruxolitinib and systemic corticosteroid treatments\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 510px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariable\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOverall (N=56)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 510px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eType of ruxolitinib treatment, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 510px;\"\u003e\n \u003cp\u003eAny combination with ECP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003e21-24 (\u0026asymp;40)\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 510px;\"\u003e\n \u003cp\u003eAny combination without ECP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003e31 (55.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 510px;\"\u003e\n \u003cp\u003eRuxolitinib monotherapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026lt;5\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 510px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNumber of ECPs, median (IQR)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003e20.5 (12.0\u0026ndash;23.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 510px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRuxolitinib starting daily dose (mg), median (IQR)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003e10.0 (10.0\u0026ndash;10.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 510px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRuxolitinib daily dose after one month (mg), median (IQR)\u003csup\u003ea\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003e10.0 (10.0\u0026ndash;20.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 510px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDuration of ruxolitinib treatment (months), median (95% CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026nbsp;3.7 (2.7\u0026ndash;4.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 510px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDiscontinuation of ruxolitinib, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 510px;\"\u003e\n \u003cp\u003eAE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003e8 (14.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 510px;\"\u003e\n \u003cp\u003eDeath\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026lt;5\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 510px;\"\u003e\n \u003cp\u003eGood response\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003e36 (64.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 510px;\"\u003e\n \u003cp\u003eLack of efficacy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026lt;5\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 510px;\"\u003e\n \u003cp\u003eOther\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026lt;5\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 510px;\"\u003e\n \u003cp\u003eRelapse of underlying disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026lt;5\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 510px;\"\u003e\n \u003cp\u003eTreatment ongoing at the end of follow-up\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026lt;5\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 510px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eReceived systemic CS during the follow-up, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003e51 (91.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 510px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOn systemic CS at ruxolitinib discontinuation, n (%)\u003csup\u003eb\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 510px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003e21 (41.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 510px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003e30 (58.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 510px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDaily dose of systemic CS at ruxolitinib discontinuation (mg/kg), median (IQR)\u003csup\u003eb\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003e0.1 (0.1\u0026ndash;0.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 510px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDiscontinued systemic CS during the follow-up, n (%)\u003csup\u003eb\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 510px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003e34 (66.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 510px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003e17 (33.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 510px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDaily dose of systemic CS at the end of follow-up (mg/kg), median (IQR)\u003csup\u003eb\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003e0.2 (0.1\u0026ndash;0.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 510px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSR/SD, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 510px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003e35 (62.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 510px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026nbsp;8 (14.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 510px;\"\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003e13 (23.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003csup\u003ea\u003c/sup\u003e Analyzed in patients who were on the treatment at one month\u003c/p\u003e\n\u003cp\u003e\u003csup\u003eb\u003c/sup\u003e Analyzed in patients who received systemic CS during the follow-up (n=51)\u003c/p\u003e\n\u003cp\u003e\u003csup\u003ec\u003c/sup\u003e Due to the anonymity requirement of the data authority, results with low subject numbers were masked and it was ensured that the masked numbers cannot be deduced based on other available numbers\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAbbreviations\u003c/strong\u003e: AE, adverse event; aGvHD, acute graft-versus-host disease; CI, confidence interval; CS, corticosteroid; ECP, extracorporeal photopheresis; IQR, interquartile range; SR/SD, steroid-refractory or -dependent\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":"annals-of-hematology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"aohe","sideBox":"Learn more about [Annals of Hematology](http://link.springer.com/journal/277)","snPcode":"277","submissionUrl":"https://submission.nature.com/new-submission/277/3","title":"Annals of Hematology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Acute graft-versus-host disease, best overall response rate, corticosteroid tapering, response duration, real-world evidence, ruxolitinib","lastPublishedDoi":"10.21203/rs.3.rs-6228702/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6228702/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e In Europe, ruxolitinib is the first approved treatment for corticosteroid-refractory acute or chronic graft-versus-host disease (aGvHD/cGvHD). This retrospective, non-interventional study evaluated the real-world efficacy and safety of ruxolitinib in 56 adult aGvHD patients treated with ruxolitinib from January 2019 through August 2021 in Finland. The primary endpoint was best overall response rate (ORR) at any time. The main secondary endpoints were the time to response and loss of response, overall survival (OS), and corticosteroid discontinuation. The follow-up lasted until death/August 2022.\u003c/p\u003e \u003cp\u003eThe ORR was 91.0% (95% CI: 83.5\u0026ndash;98.5; complete response, 69.6%; partial response, 21.4%). The median time to best response was 28.0 days (95% CI: 21.0\u0026ndash;38.0). The median time to loss of response due to aGvHD progression, cGvHD, or a relapse-related death was 8.8 months (95% CI: 3.3\u0026ndash;not reached). The most common cause of discontinuation was the achievement of response (64.3%). Two-thirds of the corticosteroid-treated patients discontinued corticosteroids before the end of follow-up; one-third were on a low dose at the end of follow-up. The three-year OS was 64.1% (95% CI: 48.2\u0026ndash;76.3).\u003c/p\u003e \u003cp\u003eRuxolitinib appears effective and safe in real-world practice. The presented data is in line with the results of clinical trials.\u003c/p\u003e","manuscriptTitle":"Ruxolitinib treatment outcomes in acute graft-versus-host disease (aGvHD) in a real-world setting in Finland","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-04-03 10:28:49","doi":"10.21203/rs.3.rs-6228702/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-04-28T20:18:49+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-04-18T01:58:12+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"232414805977024069095610146730274032067","date":"2025-03-27T16:36:25+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-03-27T08:13:21+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-03-24T12:46:15+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-03-24T12:43:51+00:00","index":"","fulltext":""},{"type":"submitted","content":"Annals of Hematology","date":"2025-03-14T18:40:19+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"annals-of-hematology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"aohe","sideBox":"Learn more about [Annals of Hematology](http://link.springer.com/journal/277)","snPcode":"277","submissionUrl":"https://submission.nature.com/new-submission/277/3","title":"Annals of Hematology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"8887953a-8350-4d3f-8a92-89de68caf9fc","owner":[],"postedDate":"April 3rd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-06-09T16:04:59+00:00","versionOfRecord":{"articleIdentity":"rs-6228702","link":"https://doi.org/10.1007/s00277-025-06439-2","journal":{"identity":"annals-of-hematology","isVorOnly":false,"title":"Annals of Hematology"},"publishedOn":"2025-06-06 15:57:54","publishedOnDateReadable":"June 6th, 2025"},"versionCreatedAt":"2025-04-03 10:28:49","video":"","vorDoi":"10.1007/s00277-025-06439-2","vorDoiUrl":"https://doi.org/10.1007/s00277-025-06439-2","workflowStages":[]},"version":"v1","identity":"rs-6228702","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6228702","identity":"rs-6228702","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}