The Evaluation of Inflammatory Biomarkers in Predicting the Severity and Steroid Responsiveness of Acute Graft versus Host Disease after Haplo- Identical Transplantation

The Evaluation of Inflammatory Biomarkers in Predicting the Severity and Steroid Responsiveness of Acute Graft versus Host Disease after Haplo- Identical Transplantation | 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 The Evaluation of Inflammatory Biomarkers in Predicting the Severity and Steroid Responsiveness of Acute Graft versus Host Disease after Haplo- Identical Transplantation Khaled Zakaria, Mohamed Hamed Khalaf, George Bahig Soryal, Noha Mohamed El-Husseiny This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7568201/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background; Haematopoietic stem cell transplant (HSCT) is the transplant of stem cells usually derived from bone marrow, Peripheral blood, Umbilical cord, Matched sibling donor (HLA 6/6) , Or Haplo-Identical donor (HLA Matching less than 6/6but not less than 3/6) Aim and objectives; to assess the role of the EASIX formula, IL-6, CRP and Ferritin in the Severe and Steroid Responsiveness cases of a GVHD in Haploidentical Transplants. Subjects and methods; This Cohort Follow up study was conducted during the period from January 2020 to March 2023 and included 49 patients with different hematological malignancies indicated for Haploidentical bone marrow transplant who received Standard PTCy (50mg/kg) at Day +3,D+5 . Patients were recruited from BMT Unit in Maadi Armed Forces Medical Compound. Result; the Easix score, and the studied biomarkers increased significantly from baseline to D 7 of BMT, p <0.05. Easix score and other biomarkers increased significantly at Onset of a GVHD , there was correlation between Easix Pre and Overall survival , the rate of good steroid responsiveness among the GVHD patients was (54.9%), and the refractory response was (45.2%). there was a significant difference between serial Easix score measurements among GVHD patients, p<0.001. there was significant difference between good and refractory steroid responders regarding the mortality rate or cause. there was no significant relationship between the gut GVHD and 100-day survival rate, p>0.05. there was no significant relationship between the skin GVHD and 100-day survival rate, p>0.05. Conclusion; the current study showed that EASIX score was a good predictor for Onset of a GVHD and Overall survival in GVHD patients but was poor predictor of severity of disease and response to steroids in BMT patients. Also, inflammatory markers (IL-6, CRP and Ferritin) were reliable to predict the onset of a GVHD but nothing to do with response to steroids and mortality in BMT patients. Inflammatory Biomarkers Steroid Responsiveness Acute Graft vs Host Disease Haplo-Identical Transplantation Figures Figure 1 Figure 2 Introduction Hematopoietic stem cell transplant (HSCT) is the transplant of stem cells usually derived from bone marrow, Peripheral blood, Umbilical cord, Matched sibling donor (HLA 6/6), Or Haplo-Identical donor (HLA Matching less than 6/6but not less than 3/6) [ 1 ] . It is often performed for patients with Some Hematological Malignancies, such as Acute Myeloid and Lymphoblastic leukemia. In these cases, the recipient’s immune system is usually destroyed with Total body irradiation or salvage Chemotherapy before the transplantation [ 2 ] . Many patients who need a Stem Cell transplant cannot find a donor who matches their tissue type. In the study done by Bacigalupo et al. (2017) , Half of patients find a stem cell match among family members [ 3 ] . When a no matched donor is available, half-matched related (Haploidentical) donors are now safely used in Stem Cell Transplantation. Patients up to age 65 are potential candidates for Haploidentical Transplants. Potential donor matching will come from first-degree relatives, including siblings, children or parents [ 3 ] Outcomes of Haploidentical Stem Cell Transplantation have improved over time especially after using Post Transplant Cyclophosphamide (PTCy) as Graft Versus Host Disease (GHVD) Prophylaxis [ 2 ] . Acute GVHD remains the most serious complication of HSCT, Especially in Haploidentical transplants [ 4 ] . Acute GVHD generally occurs after Allogenic (HSCT) (around Day + 14 to Day + 100). It is characterized by a reaction of donor T- cells against host tissues. It can involve single and multiorgan diseases. Clinically, aGVHD is suspected when a patient of HSCT has developed any of the following symptoms which include skin rash, crampy abdominal pain, diarrhea, nausea, vomiting, and elevated liver enzymes (transaminitis) [ 5 ] . Acute GVHD is usually treated with Corticosteroids; in Steroid Refractory GVHD, Morbidity and Mortality would be worse and more common [ 6 ] . Previous studies linked endothelial dysfunction and thrombotic microangiopathy with Steroid refractory aGVHD, using endothelial dysfuncion and stress index score, and other Biomarkers such as (CRP, IL-6, Ferritin,) in predicting severity and steroid responsiveness in Acute GVHD during Allo-Transplant. The results were in favor of this scoring system on day zero, day + 7, and the day of Acute GVHD onset [ 7 ] . Haplo-identical HSCT carries a higher incidence of Acute GVHD, And Previous Studies mentioned Allo-Transplant complications without focusing on Haploidentical Transplants, therefore we aim to evaluate Severity and Steroid Responsiveness of Acute GVHD in Haploidentical Patients with standard PTCy as GVHD Prophylaxis [ 8 ] . The aim of this work was to estimate the level and discriminant power of the Endothelial Activation and Stress Index (EASIX) formula, IL-6, CRP and Ferritin in detecting the severity and steroid responsiveness of acute GVHD in haplo-identical transplants. Patients and Methods This cohort follow up was carried out on 49 patients aged from 15 to 45 years old, both sexes, with different haematological malignancies indicated for haploidentical bone marrow transplant who received standard PTCy (50mg/kg) at Day + 3, D + 5. An informed written consent was obtained from the patient or relatives of the patients. The study was done after approval from the Ethical Committee Haplo Transplant in Hematology and Bone Marrow Transplant Department at Maadi Armed Forces Medical Compound From January 2020 to March 2023. Exclusion criteria were any haploidentical transplant for non-haematological malignancies. bone marrow failure syndromes. All patients were subjected to full medical history, clinical examination, laboratory data [LDH, Ferritin, IL-6 and CRP level as well as PLT count at different time points before and early after Infusion in recipients Haplo-HSCT (day 0, day + 7 and day of aGVHD onset)], and clinical data [Dates of admission, discharge, Stem Cell Infusion and onset of aGVHD]. The applied protocol for all the study participants was as follows: Receiving T-cell Replete Haploidentical Stem cell Transplant using Reduced Intensity Conditioning (RIC) which consists of(Flu-Bu4 Protocol (Fludarabine 160mg/m2 total dose for 5 days, Busulphan 16 mg/kg 4 days))and Standard PTCy at D + 3, D + 5 along with Cyclosporine (5mg/kg from D zero) and MMF(15mg/kg starting from D + 6) platform as GHVD Prophylaxis. Sampling: Venous sample of 28 from the positive group and 12 from the negative group achieve 80% power to detect a difference of 0.26 between the Area Under the ROC Curve (AUC) and the null hypothesis of 0.5 using a two-sided z-test at a significance level of 0.050. The data were continuous responses. The AUC was calculated between false positive rates of 0.00 and 1.00. The ratio between the standard deviation of the responses in the negative group and the standard deviation of the responses in the positive group was 1. After adding 20% for dropout, the minimum required sample would be 50 patients (35 with AGVHD) [ 9 ] . Diagnostic Intervention : At day 0 / day + 7 & Day of onset of our investigated complications, EASIX score is calculated using the formula LDH (U/L) x Creatinine (mg/dl) / platelet count (10 9/L), and assess the rates of Complete Response (CR) and Overall Response Rate (ORR) of the studied group during the period of the study Statistical analysis Statistical analysis was done by SPSS v27 (IBM©, Armonk, NY, USA). Shapiro-Wilks test and histograms were used to evaluate the normality of the distribution of data. Quantitative parametric data were presented as mean and standard deviation (SD) and were analysed by ANOVA (F) test with post hoc test (Tukey). Qualitative variables were presented as frequency and percentage (%) and were analysed utilizing the Chi-square test. A two tailed P value < 0.05 was considered statistically significant. Correlation analysis using sperman correlation. Survival analysis was performed by kaplen mayer Results Demographic data are shown in Table 1 Only 47 patients achieved engraftment, and 2 patients died before Engraftment. The rate of full donor chimerism was 79.6% at Chimerism 30, then 71.4% at Chimerism 60, and 55.1% at Chimerism 90. the rate of GVHD was 31 (63.3%), and the mean duration to GVHD onset was 25.4 ± 16.3 days. The hundred-day mortality rate among the GVHD patients was (38.7%). A significant difference was detected regarding Easix score, ferritin, CRP, and IL-6 between on day 0 and on day 7+. As shown in Table 2 which compare Easix and other biomarkers (CRP, IL-6 and Ferritin) at D 0 and D + 7. There were significant differences between CRP at day zero, CRP and IL-6 at day 7, IL-6 (pg/ml) on day 7 from BMT between both groups, p < 0.05, but no significant difference between both groups regarding Easix score at baseline, Easix score on day 7 from BMT, ferritin (ng/mL) at baseline, Ferritin (ng/mL) on day 7 from BMT, and IL-6 (pg/ml) at baseline. As shown in Table 3 which compared Easix and Other biomarkers at Dzero and D + 7 and its coreelation with occurrence of aGVHD Significant relationship between steroid response and score and biomarkers, and Easix score and biomarkers were observed regarding Easix score at onset only (P < 0.05), while no significant relationship between steroid responsiveness and mortality data, Easix score or other biomarkers in the liver GVHD patients, score and biomarkers of the gut, and score and biomarkers of the liver of the GVHD group as shown in Table 4 which compared Easix and other biomarkers in Onset of acute GVHD and its correlation with steroid response. There was no correlation between steroid responsiveness and Easix score or other biomarkers in the liver GVHD patients, p > 0.05. There was no correlation between 100-day survival rate and either Easix score or other biomarkers among the GVHD patients, skin GVHD group, and gut GVHD group. There was no significant difference between GVHD forms and steroid response, score and biomarkers, and survival characteristics (P > 0.05). Hundred-day survival among GVHD and No-GVHD groups showed non-significant difference (p > 0.05). The average 100-day survival within GVHD group was 48 days. Furthermore, Median 100-day survival within No-GVHD 27 days (P-Value = 0.3452) (Fig. 1 ). OS between high-risk group according to Easix score at day zero (Easix at day zero > 1.07) and low risk group (Easix at day zero < 1.07) and No-GVHD groups showing significant difference (P-Value = 0.0373). OS between ALL and AML patients showing non-significant difference ( Fig. 2 ). Discussion The aim of this study is to demonstrate the results of our Maadi Military Compound transplant center in early detection of acute GVHD in Haploidentical transplant using Easix Score and other biomarkers (CRP, IL-6 and Ferritin ) and also its correlation with response to steroids. HSCT is widely performed as a treatment for Hematological malignancies. When a no matched donor is available, half-matched related (Haploidentical) donors are now safely used in Stem Cell Transplantation [10]. GVHD is the most unfavorable complication of HSCT. Although the diagnostic process and management of GVHD are improving, GVHD remains a major clinical problem in transplantation medicine [10]. The current study showed that the mean age of the studied group was 35 ± 11.2. They included 36 males (73.5%), and 13 females (26.5%). AML was the most common diagnosis 24 (49%). Regarding EASIX score and inflammatory biomarkers, the current study showed that the EASIX score, and the studied biomarkers increased significantly from baseline to D 7 of BMT, p < 0.05. Lia et al. , [ 11 ] revealed that post- BMT endothelial dysfunction occurs as a result of chemotherapy, infections, and allogeneic reactivity. Despite major advances in transplant immunology and improvements in supportive care medicine, these complications represent a major obstacle for successful BMT. Luft et al., [ 12 ] included 311 haploidentical patients from which 239 used RIC to avoid thrombocytopenia at EASIX pre showed that EASIX score was significant predictor for mortality after allogeneic hematopoietic cell transplantation. Regarding the frequency and subtypes of GVHD among the studied group, the current study showed that the rate of GVHD was (63.3%), and the mean duration to GVHD onset was 25.4 ± 16.3 days. However, Solh et al. , [ 13 ] showed that the cumulative incidences for grade II-IV and grade III-IV acute GVHD at day 180 post HCT were at 39% and 14%, respectively. The cumulative incidence of moderate to severe chronic GVHD, were 22% and 19% respectively, but the difference in this study that this study included 394 patients from which 180 patients with fully matched donor that probably affect rate of aGVHD, in contrast to our study which included only Haploidentical Patients. In the current study the most common acute GVHD targets were Skin (53%) followed by Gut (51%) then Liver (22.4%). In agreement with the current study, Levine et al. , [ 14 ] revealed that the most common acute GVHD targets were skin (82%) followed by gut (54%) then liver (14%) and this was explained by authors of the study as skin GVHD was the main indication of the study, for which there was high contribution of skin GVHD biomarker elafin to the performance and was considered Limitation of the study. Regarding treatment characteristics, the percentage of good steroid responsiveness among the GVHD patients was (54.9%), and the refractory response was (45.2%). In agreement with the current study Peña et al. , [ 15 ] revealed that there was no significant association between EASIX-PRE and the probability of TAM or acute GVHD onset during the post transplantation phase. Results of the present study showed that EASIX score and other biomarkers increased significantly from baseline to the time of GVHD onset (p < 0.001 ) in concordance with the previous literature. Our study is in agreement with Sanchez-Escamilla et al. , [ 16 ] who evaluated 152 adult patients who received an unmodified RIC AlloHCT but was done for 63 MSD and remaining 89 was MUD and MMUD and was found significant increase in EASIX score at the onset of GVHD. Our study revealed that Easix score and other biomarkers (Ferritin, IL-6, CRP) increased significantly from Easix D0 and Easix D7 in GVHD ( p < 0.001). This comes in agreement with Fingrut W et al , [ 17 ] which included 229 patients for allograft (type of matching not mentioned) and measured ferritin level pre and post HSCT and revealed that high ferritin Post-HCT levels were significantly associated with decreased OS and increased Morbidity and NRM independent of ferritin Pré-HCT or GVHD. In the current study we found that Easix GVHD was significantly higher in the patients with refractory steroid response, than in the good responders (p = 0.034) but there was no significant relationship between steroid responsiveness and other biomarkers, p > 0.05. This comes in agreement with Sanchez-Escamilla et al. , [ 18 ] who found that EASIX score calculated at onset of GVHD can predict response to steroids but the difference in this study that included 152 patients from which only 14 haploidentical patients with low dose Mtx not PTCy as GVHD prophylaxis. Regarding the relationship between day-100 survival and score and biomarkers of the GVHD group, our study revealed that there was no significant relationship between day-100 survival rate and either EASIX score or other biomarkers among the GVHD patients, p > 0.05. Moreover, there was no significant relationship between the skin GVHD and gut GVHD with 100-day survival rate, p > 0.05 and this result may be changed or modified with larger number of patients or multicenter variant analysis. Our study about Easix Dzero and OS revealed significant difference P value 0.0378 with median OS in high-risk group was 31% and within low-risk group was 71%. In contrast with the current study Peña et al. , [ 15 ] revealed that there was no significant association between EASIX-PRE and the outcome although there was correlation between EASIX pre and ICU admission in that study which included 167 patients, There was some limitations like absence of validations in retrospective analysis and variation in ICU admission from center to another. C-reactive protein is a nonspecific inflammatory protein that is elevated in GVHD patients along with IL-6, the main cytokine that induces C-reactive protein release [ 19 ] . Our study revealed CRP, IL-6 and ferritin increased significantly between baseline and Day + 7 and also onset of a GVHD among GVHD group of patients (n = 31) but revealed no significance with 100-day mortality among GVHD group Wang et al. , [ 20 ] that included 185 consecutive patients who underwent haplo-HSCT showed that elevated CRP levels, is related to worse survival in patients following HSCT, using CRP/Albumin ratio (CAR) was independent prognostic indicator for outcome in Haplo-identical transplant Patients were separated into low and high CAR groups using a cutoff of 0.087, which independently predicted OS, Higher CAR was related to worse outcome in Haplo patients. The difference in results may be due to the difference in sample size and inclusion criteria. The current study showed that that there was no significant difference between GVHD forms and steroid response, p > 0.05. However, Choe & Ferrara , [ 21 ] stated that the gastrointestinal (GI) tract is a key GVHD target organ that usually determines a patient’s response to therapy. Also, the current study reported that there was no significant difference between GVHD forms and the EASIX score or other biomarkers, p > 0.05. The current study showed that there was no significant difference between GVHD forms and the survival rate or cause of death, p > 0.05. Farhadfar et al. , [ 22 ] showed that lower gastrointestinal involvement in aGVHD was associated with increased risk of readmission (30%) and twice as many inpatient days, doubling the likelihood of ICU admission and mortality over the first 100 days. Regarding the relationship between steroid response and score and biomarkers of different forms of GVHD, it was revealed that there was no significant relationship between steroid responsiveness and score or other biomarkers, p > 0.05, in all forms of GVHD, except for skin group, it was revealed that EASIX score at skin GVHD onset was significantly higher in the patients with refractory steroid response, than those with good response, p = 0.025. These primary results need to be confirmed with a larger number of patients. The current study showed that there was difference but non-significant between the skin GVHD severity and EASIX score or other biomarkers, p > 0.05may be related to small numbers of patients. The current study showed that 100-day mortality rate among the GVHD patients was 12 (38.7%). Lower than the current study Yu et al. , [ 23 ] that included 455 patients with aGVHD from which only 125 with SR-GVHD revealed that the 100-day mortality rate among the GVHD patients was (20.2%). This may be due to the higher severity of the current study and limited number of patients. So, our results established that EASIX score was a poor predictor of response to steroids and mortality in BMT patients. But these results need further larger studies to confirm. We recommended that is why studies on larger sample size and longer follow-up are needed to confirm our results and to identify risk factors of adverse events Our strength is that our center is a one of the respected centers that perform Haplo transplantation more than any other center in Egypt, and it is one of the first studies in Egypt that deal with aGVHD and EASIX score on Egyptian patients. Limitations: We need to extent our study to include other centers in order to check result, being a single center study, the lack for similar studies for comparison and relatively short follow up period. Further comparative studies with larger sample size and longer follow-up are needed to confirm our results and to identify risk factors of adverse events. Conclusions EASIX score was significant in predicting outcome in Haplo-identical HSCT and also in onset of a GVHD but was poor predictor of response to steroids and mortality in BMT patients although results showed that higher Easix score was detected in steroid refractory patients than good responders. Therefore, Easix Score could be used as predictive tool for GVHD onset and OS in GVHD patients, but also need larger number of patients may be needed to assess accuracy in Severity and steroid response in a GVHD. Other biomarkers (CRP, IL-6, Ferritin) might be used as predictive tool for GVHD onset as it showed significant difference among GVHD patients and increased significantly from baseline to GVHD onset but has nothing to do with Steroid response and disease severity and this must be correlated with larger number of patients and multicenter variant analysis. Declarations Roles of authors: Dr Khaled Zakaria Abd El Hakeem: did the data extraction, statistics and writing the paper Prof.Mohamed Khalaf : Founder of Research Idea, participating in revision of paper Prof George Bahig : Revising Data and Supervision of Research Prof.Noha El Husseiny : Revising Data and Supervision of Research and writing the paper Ethical approaval : all patients participated in the study gave their informed written consent. Ethical committee : The study was done after approval from the Ethical Committee of Haplo Transplant in Hematology and Bone Marrow Transplant Department at Maadi Armed Forces Medical Compound from January 2020 to March 2023. The study followed declaration of Helsinki. Funding : Self Funding Competing Interest : All Authors confirmed no conflict of interest . Data Availability : All data of the patients are available upon request from corresponding author. Author Contribution Dr Khaled Zakaria Abd El Hakeem: did the data extraction, statistics and writing the paperProf.Mohamed Khalaf : Founder of Research Idea, participating in revision of paperProf George Bahig : Revising Data and Supervision of ResearchProf.Noha El Husseiny : Revising Data and Supervision of Research and writing the paper This is not a clinical trial and all what is applied for clinical trial is not applicable References Zeiser R, Burchert A, Lengerke C, Verbeek M, Maas-Bauer K, Metzelder SK, et al. 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Tables Table 1: Demographic features, and chimerism characteristics, and frequency and subtypes of GVHD of the studied group (N=49), treatment, and survival characteristics of the patients with GVHD among the studied group (n=31). Patients (n = 49) Demographic features Age (years) 35.0 ± 11.2 Sex Male 36 (73.5%) Female 13 (26.5%) Diagnosis AML 24 (49 %) ALL 19 (38.8 %) CML 3 (6.1 %) MDS 2 (4.1 %) HL 1 (2 %) BMT indication High risk 30 (61.2 %) CR2 15 (30.6 %) CML-BP 3 (6.1 %) Early relapse post autograph 1 (2 %) ABO matched. 17 (34.7 %) Major mismatch 15 (30.6 %) Minor mismatch 17 (34.7 %) CD 34 +ve (cells per Kg) 4.2 ± 1.4 Day of engraftment (n=47) 23.0 ± 5.2 OS Alive 25 (51 %) Dead 23 (46.9 %) Lost follow up 1 (2.1 %) Cause of death (n=23) Acute GVHD 6 (26 %) CRS 2 (8.8 %) Sepsis 11 (47.8 %) Relapse 4 (17.4 %) Chimerism Characteristics Chimerism 30 Full donor Chimerism 39 (79.6 %) Graft rejection 1 (2 %) Died 9 (18.4 %) Chimerism 60 Full donor Chimerism 35 (71.4 %) Died 14 (28.6 %) Chimerism 90 Full donor Chimerism 27 (55.1 %) Died 22 (44.9 %) Frequency and subtypes of GVHD GVHD 31 (63.3 %) Skin GVHD 26 (53.1 %) Stage of skin GVHD (n=26) 1 11 (42.3 %) 2 12 (46.2 %) 3 3 (11.5 %) Gut GVHD 25 (51 %) Stage of gut GVHD (n=25) 1 15 (60 %) 2 8 (32 %) 3 2 (8 %) Liver GVHD 11 (22.4 %) Stage of liver GVHD (n=11) 1 7 (63.6 %) 2 3 (27.3 %) 3 1 (9.1 %) Day of GVHD (n=31) 25.4 ± 16.3 Steroid response (n=31) Good 17 (54.9 %) Refractory 14 (45.2 %) Other treatments (n=14) Infliximab 3 (21.4 %) Ruxolitinib 5mg BID 7 (50 %) Tocilizumab 8/kg 4 (28.6 %) Day-100 Mortality (n=31) Alive 19 (61.3 %) Dead 12 (38.7 %) OS (6 months) (n=31) On follow up 14 (39.4 %) Lost follow up 5 (21.9%) Dead 12 (38.7 %) Data are presented as mean ± SD and number (%). AML: Acute myeloid leukemia, ALL: Acute lymphoblastic leukemia, CML: Chronic myelogenous leukemia, MDS: Myelodysplastic syndromes, HL: Hodgkin lymphoma, BMT: Bone marrow transplant, OS: overall survival, GVHD: Graft-vs-host disease, BMT: Bone marrow transplant, ABO: Blood Group System, CRS: cytokine release syndrome, CR2: Complement receptor type 2, BID: Twice a day, *: significant as P value < 0.05. Table 2: Score and biomarkers of the studied group (N=49). On day 0 On day 7+ P value Easix score 2.0 ± 0.9 3.6 ± 1.8 <0.001* Ferritin (ng/mL) 477.6 ± 413.8 816.4 ± 814.3 <0.001* CRP (mg/dL) 26.8 ± 29.8 77.1 ± 68.5 <0.001* IL-6 (pg/ml) 31.8 ± 63.0 99.3 ± 161.5 0.005* Data are presented as mean ± SD. CRS: cytokine release syndrome, *: significant as P value < 0.05. Table 3: Relationship between initial biomarkers and the occurrence of GVHD (N=49). GVHD n=31 No GVHD n=18 P value Easix score at baseline 2.1 ± 1.0 1.9 ± 0.8 0.445 Easix score on day 7 from BMT 3.5 ± 1.5 3.8 ± 2.2 0.086 Ferritin (ng/mL) at baseline 441.2 ± 380.6 546.1 ± 474.8 0.202 Ferritin (ng/mL) on day 7 from BMT 700.5 ± 352.02 1034.8 ± 1292.9 0.087 CRP (mg/dL) at baseline 20.8 ± 18.8 37.9 ± 42.2 0.027* CRP (mg/dL) on day 7 from BMT 60.6 ± 45.9 108.1 ± 91.8 0.009* IL-6 (pg/ml) at baseline 26.1 ± 36.8 42.5 ± 95.3 0.195 IL-6 (pg/ml) on day 7 from BMT 137.5 ± 189.13 27.47 ± 22.1 0.0107* Data are presented as mean ± SD and number (%). GVHD: Graft-vs-host disease, BMT: Bone marrow transplant, CRS: cytokine release syndrome, *: significant as P value < 0.05. Table 4: Relationship between steroid response and score and biomarkers, mortality data, Easix score and biomarkers, score and biomarkers of the gut, and score and biomarkers of the liver of the GVHD group (n=31). Good response (n=17) Refractory (n=14) P value Easix score at onset 4.2 ± 0.9 5.3 ± 1.8 0.034* Easix score on day 7 3.1 ± 2.6 4.4 ± 2.6 0.178 Ferritin at onset 763.4 ± 490.7 1087.1 ± 621.6 0.122 CRP at onset 57.2 ± 37.2 61.1 ± 40.3 0.781 IL-6 at onset 53.9 ± 33.2 72.5 ± 34 0.136 (n=17) (n=14) Mortality rate D100 Alive 10 (58.8 %) 9 (64.3%) 0.756 Dead 7 (41.2 %) 5 (35.7 %) Cause of death Acute GVHD 0 4 (80 %) 0.179 Sepsis 4 (57.2 %) 0 Relapse 3 (42.9 %) 1 (20 %) Data are presented as mean ± SD and number (%). GVHD: Graft-vs-host disease, CRS: cytokine release syndrome, *: significant as P value < 0.05. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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1","display":"","copyAsset":false,"role":"figure","size":39392,"visible":true,"origin":"","legend":"\u003cp\u003edifference in overall survival among those with and without GVHD\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7568201/v1/01377e2532c63fdde073785c.jpg"},{"id":93244325,"identity":"4e7635d9-8bfd-45c4-bb77-a87400118a63","added_by":"auto","created_at":"2025-10-10 15:05:12","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":43389,"visible":true,"origin":"","legend":"\u003cp\u003eoverall survival based on ESAIX score\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7568201/v1/45cf2f8434fd2b4b4f0fa0d4.jpg"},{"id":94645655,"identity":"e4e9d5c2-cd9f-42aa-bb21-d6adbff746d0","added_by":"auto","created_at":"2025-10-29 08:39:15","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2008567,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7568201/v1/fd117461-9faf-48dd-a99d-91830793608b.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"The Evaluation of Inflammatory Biomarkers in Predicting the Severity and Steroid Responsiveness of Acute Graft versus Host Disease after Haplo- Identical Transplantation","fulltext":[{"header":"Introduction","content":"\u003cp\u003eHematopoietic stem cell transplant (HSCT) is the transplant of stem cells usually derived from bone marrow, Peripheral blood, Umbilical cord, Matched sibling donor (HLA 6/6), Or Haplo-Identical donor (HLA Matching less than 6/6but not less than 3/6) \u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eIt is often performed for patients with Some Hematological Malignancies, such as Acute Myeloid and Lymphoblastic leukemia. In these cases, the recipient\u0026rsquo;s immune system is usually destroyed with Total body irradiation or salvage Chemotherapy before the transplantation \u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eMany patients who need a Stem Cell transplant cannot find a donor who matches their tissue type. In the study done by \u003cb\u003eBacigalupo et al. (2017)\u003c/b\u003e, Half of patients find a stem cell match among family members \u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eWhen a no matched donor is available, half-matched related (Haploidentical) donors are now safely used in Stem Cell Transplantation. Patients up to age 65 are potential candidates for Haploidentical Transplants. Potential donor matching will come from first-degree relatives, including siblings, children or parents \u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eOutcomes of Haploidentical Stem Cell Transplantation have improved over time especially after using Post Transplant Cyclophosphamide (PTCy) as Graft Versus Host Disease (GHVD) Prophylaxis \u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eAcute GVHD remains the most serious complication of HSCT, Especially in Haploidentical transplants \u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eAcute GVHD generally occurs after Allogenic (HSCT) (around Day\u0026thinsp;+\u0026thinsp;14 to Day\u0026thinsp;+\u0026thinsp;100). It is characterized by a reaction of donor T- cells against host tissues. It can involve single and multiorgan diseases. Clinically, aGVHD is suspected when a patient of HSCT has developed any of the following symptoms which include skin rash, crampy abdominal pain, diarrhea, nausea, vomiting, and elevated liver enzymes (transaminitis) \u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eAcute GVHD is usually treated with Corticosteroids; in Steroid Refractory GVHD, Morbidity and Mortality would be worse and more common \u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003ePrevious studies linked endothelial dysfunction and thrombotic microangiopathy with Steroid refractory aGVHD, using endothelial dysfuncion and stress index score, and other Biomarkers such as (CRP, IL-6, Ferritin,) in predicting severity and steroid responsiveness in Acute GVHD during Allo-Transplant. The results were in favor of this scoring system on day zero, day\u0026thinsp;+\u0026thinsp;7, and the day of Acute GVHD onset \u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eHaplo-identical HSCT carries a higher incidence of Acute GVHD, And Previous Studies mentioned Allo-Transplant complications without focusing on Haploidentical Transplants, therefore we aim to evaluate Severity and Steroid Responsiveness of Acute GVHD in Haploidentical Patients with standard PTCy as GVHD Prophylaxis \u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eThe aim of this work was to estimate the level and discriminant power of the Endothelial Activation and Stress Index (EASIX) formula, IL-6, CRP and Ferritin in detecting the severity and steroid responsiveness of acute GVHD in haplo-identical transplants.\u003c/p\u003e"},{"header":"Patients and Methods","content":"\u003cp\u003eThis cohort follow up was carried out on 49 patients aged from 15 to 45 years old, both sexes, with different haematological malignancies indicated for haploidentical bone marrow transplant who received standard PTCy (50mg/kg) at Day\u0026thinsp;+\u0026thinsp;3, D\u0026thinsp;+\u0026thinsp;5.\u003c/p\u003e\u003cp\u003eAn informed written consent was obtained from the patient or relatives of the patients. The study was done after approval from the Ethical Committee Haplo Transplant in Hematology and Bone Marrow Transplant Department at Maadi Armed Forces Medical Compound\u003c/p\u003e\u003cp\u003eFrom January 2020 to March 2023.\u003c/p\u003e\u003cp\u003eExclusion criteria were any haploidentical transplant for non-haematological malignancies.\u003c/p\u003e\u003cp\u003ebone marrow failure syndromes.\u003c/p\u003e\u003cp\u003eAll patients were subjected to full medical history, clinical examination, laboratory data [LDH, Ferritin, IL-6 and CRP level as well as PLT count at different time points before and early after Infusion in recipients Haplo-HSCT (day 0, day\u0026thinsp;+\u0026thinsp;7 and day of aGVHD onset)], and clinical data [Dates of admission, discharge, Stem Cell Infusion and onset of aGVHD].\u003c/p\u003e\u003cp\u003eThe applied protocol for all the study participants was as follows: Receiving T-cell Replete Haploidentical Stem cell Transplant using Reduced Intensity Conditioning (RIC) which consists of(Flu-Bu4 Protocol (Fludarabine 160mg/m2 total dose for 5 days, Busulphan 16 mg/kg 4 days))and Standard PTCy at D\u0026thinsp;+\u0026thinsp;3, D\u0026thinsp;+\u0026thinsp;5 along with Cyclosporine (5mg/kg from D zero) and MMF(15mg/kg starting from D\u0026thinsp;+\u0026thinsp;6) platform as GHVD Prophylaxis.\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eSampling:\u003c/h2\u003e\u003cp\u003eVenous sample of 28 from the positive group and 12 from the negative group achieve 80% power to detect a difference of 0.26 between the Area Under the ROC Curve (AUC) and the null hypothesis of 0.5 using a two-sided z-test at a significance level of 0.050. The data were continuous responses. The AUC was calculated between false positive rates of 0.00 and 1.00. The ratio between the standard deviation of the responses in the negative group and the standard deviation of the responses in the positive group was 1. After adding 20% for dropout, the minimum required sample would be 50 patients (35 with AGVHD) \u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003e\u003cb\u003eDiagnostic Intervention\u003c/b\u003e: At day 0 / day\u0026thinsp;+\u0026thinsp;7 \u0026amp; Day of onset of our investigated complications, EASIX score is calculated using the formula LDH (U/L) x Creatinine (mg/dl) / platelet count (10 9/L), and assess the rates of Complete Response (CR) and Overall Response Rate (ORR) of the studied group during the period of the study\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\u003ch2\u003eStatistical analysis\u003c/h2\u003e\u003cp\u003eStatistical analysis was done by SPSS v27 (IBM\u0026copy;, Armonk, NY, USA). Shapiro-Wilks test and histograms were used to evaluate the normality of the distribution of data. Quantitative parametric data were presented as mean and standard deviation (SD) and were analysed by ANOVA (F) test with post hoc test (Tukey). Qualitative variables were presented as frequency and percentage (%) and were analysed utilizing the Chi-square test. A two tailed P value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant. Correlation analysis using sperman correlation. Survival analysis was performed by kaplen mayer\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cb\u003eDemographic data are shown in\u003c/b\u003e Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e Only 47 patients achieved engraftment, and 2 patients died before Engraftment. The rate of full donor chimerism was 79.6% at Chimerism 30, then 71.4% at Chimerism 60, and 55.1% at Chimerism 90. the rate of GVHD was 31 (63.3%), and the mean duration to GVHD onset was 25.4\u0026thinsp;\u0026plusmn;\u0026thinsp;16.3 days. The hundred-day mortality rate among the GVHD patients was (38.7%).\u003c/p\u003e\u003cp\u003eA significant difference was detected regarding Easix score, ferritin, CRP, and IL-6 between on day 0 and on day 7+. As shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e \u003cb\u003ewhich compare Easix and other biomarkers (CRP, IL-6 and Ferritin) at D 0 and D\u0026thinsp;+\u0026thinsp;7.\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThere were significant differences between CRP at day zero, CRP and IL-6 at day 7, IL-6 (pg/ml) on day 7 from BMT between both groups, p\u0026thinsp;\u0026lt;\u0026thinsp;0.05, but no significant difference between both groups regarding Easix score at baseline, Easix score on day 7 from BMT, ferritin (ng/mL) at baseline, Ferritin (ng/mL) on day 7 from BMT, and IL-6 (pg/ml) at baseline. As shown in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e \u003cb\u003ewhich compared Easix and Other biomarkers at Dzero and D\u0026thinsp;+\u0026thinsp;7 and its coreelation with occurrence of aGVHD\u003c/b\u003e\u003c/p\u003e\u003cp\u003eSignificant relationship between steroid response and score and biomarkers, and Easix score and biomarkers were observed regarding Easix score at onset only (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05), while no significant relationship between steroid responsiveness and mortality data, Easix score or other biomarkers in the liver GVHD patients, score and biomarkers of the gut, and score and biomarkers of the liver of the GVHD group as shown in Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e \u003cb\u003ewhich compared Easix and other biomarkers in Onset of acute GVHD and its correlation with steroid response.\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThere was no correlation between steroid responsiveness and Easix score or other biomarkers in the liver GVHD patients, p\u0026thinsp;\u0026gt;\u0026thinsp;0.05.\u003c/p\u003e\u003cp\u003eThere was no correlation between 100-day survival rate and either Easix score or other biomarkers among the GVHD patients, skin GVHD group, and gut GVHD group.\u003c/p\u003e\u003cp\u003eThere was no significant difference between GVHD forms and steroid response, score and biomarkers, and survival characteristics (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e\u003cp\u003eHundred-day survival among GVHD and No-GVHD groups showed non-significant difference (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). The average 100-day survival within GVHD group was 48 days. Furthermore, Median 100-day survival within No-GVHD 27 days (P-Value\u0026thinsp;=\u0026thinsp;0.3452) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003e). OS between high-risk group according to Easix score at day zero (Easix at day zero\u0026thinsp;\u0026gt;\u0026thinsp;1.07) and low risk group (Easix at day zero\u0026thinsp;\u0026lt;\u0026thinsp;1.07) and No-GVHD groups showing significant difference (P-Value\u0026thinsp;=\u0026thinsp;0.0373). OS between ALL and AML patients showing non-significant difference \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e2\u003c/span\u003e\u003cb\u003e).\u003c/b\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe aim of this study is to demonstrate the results of our Maadi Military Compound transplant center in early detection of acute GVHD in Haploidentical transplant using Easix Score and other biomarkers (CRP, IL-6 and Ferritin ) and also its correlation with response to steroids. HSCT is widely performed as a treatment for Hematological malignancies. When a no matched donor is available, half-matched related (Haploidentical) donors are now safely used in Stem Cell Transplantation [10]. GVHD is the most unfavorable complication of HSCT. Although the diagnostic process and management of GVHD are improving, GVHD remains a major clinical problem in transplantation medicine [10].\u003c/p\u003e\u003cp\u003eThe current study showed that the mean age of the studied group was 35\u0026thinsp;\u0026plusmn;\u0026thinsp;11.2. They included 36 males (73.5%), and 13 females (26.5%). AML was the most common diagnosis 24 (49%).\u003c/p\u003e\u003cp\u003eRegarding EASIX score and inflammatory biomarkers, the current study showed that the EASIX score, and the studied biomarkers increased significantly from baseline to D 7 of BMT, p\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e\u003cp\u003e\u003cb\u003eLia et al.\u003c/b\u003e, \u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e revealed that post- BMT endothelial dysfunction occurs as a result of chemotherapy, infections, and allogeneic reactivity. Despite major advances in transplant immunology and improvements in supportive care medicine, these complications represent a major obstacle for successful BMT.\u003c/p\u003e\u003cp\u003eLuft et al., \u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e included 311 haploidentical patients from which 239 used RIC to avoid thrombocytopenia at EASIX pre showed that EASIX score was significant predictor for mortality after allogeneic hematopoietic cell transplantation.\u003c/p\u003e\u003cp\u003eRegarding the frequency and subtypes of GVHD among the studied group, the current study showed that the rate of GVHD was (63.3%), and the mean duration to GVHD onset was 25.4\u0026thinsp;\u0026plusmn;\u0026thinsp;16.3 days.\u003c/p\u003e\u003cp\u003eHowever, \u003cb\u003eSolh et al.\u003c/b\u003e, \u003csup\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e showed that the cumulative incidences for grade II-IV and grade III-IV acute GVHD at day 180 post HCT were at 39% and 14%, respectively. The cumulative incidence of moderate to severe chronic GVHD, were 22% and 19% respectively, but the difference in this study that this study included 394 patients from which 180 patients with fully matched donor that probably affect rate of aGVHD, in contrast to our study which included only Haploidentical Patients.\u003c/p\u003e\u003cp\u003eIn the current study the most common acute GVHD targets were Skin (53%) followed by Gut (51%) then Liver (22.4%).\u003c/p\u003e\u003cp\u003eIn agreement with the current study, \u003cb\u003eLevine et al.\u003c/b\u003e, \u003csup\u003e[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e revealed that the most common acute GVHD targets were skin (82%) followed by gut (54%) then liver (14%) and this was explained by authors of the study as skin GVHD was the main indication of the study, for which there was high contribution of skin GVHD biomarker elafin to the performance and was considered Limitation of the study. Regarding treatment characteristics, the percentage of good steroid responsiveness among the GVHD patients was (54.9%), and the refractory response was (45.2%).\u003c/p\u003e\u003cp\u003eIn agreement with the current study \u003cb\u003ePe\u0026ntilde;a et al.\u003c/b\u003e, \u003csup\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e revealed that there was no significant association between EASIX-PRE and the probability of TAM or acute GVHD onset during the post transplantation phase.\u003c/p\u003e\u003cp\u003eResults of the present study showed that EASIX score and other biomarkers increased significantly from baseline to the time of GVHD onset (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001 ) in concordance with the previous literature.\u003c/p\u003e\u003cp\u003eOur study is in agreement with \u003cb\u003eSanchez-Escamilla et al.\u003c/b\u003e, \u003csup\u003e[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/sup\u003e who evaluated 152 adult patients who received an unmodified RIC AlloHCT but was done for 63 MSD and remaining 89 was MUD and MMUD and was found significant increase in EASIX score at the onset of GVHD.\u003c/p\u003e\u003cp\u003eOur study revealed that Easix score and other biomarkers (Ferritin, IL-6, CRP) increased significantly from Easix D0 and Easix D7 in GVHD ( p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\u003cp\u003eThis comes in agreement with \u003cb\u003eFingrut W et al\u003c/b\u003e, \u003csup\u003e[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/sup\u003e which included 229 patients for allograft (type of matching not mentioned) and measured ferritin level pre and post HSCT and revealed that high ferritin Post-HCT levels were significantly associated with decreased OS and increased Morbidity and NRM independent of ferritin Pr\u0026eacute;-HCT or GVHD.\u003c/p\u003e\u003cp\u003eIn the current study we found that Easix GVHD was significantly higher in the patients with refractory steroid response, than in the good responders (p\u0026thinsp;=\u0026thinsp;0.034) but there was no significant relationship between steroid responsiveness and other biomarkers, p\u0026thinsp;\u0026gt;\u0026thinsp;0.05.\u003c/p\u003e\u003cp\u003eThis comes in agreement with \u003cb\u003eSanchez-Escamilla et al.\u003c/b\u003e, \u003csup\u003e[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/sup\u003e who found that EASIX score calculated at onset of GVHD can predict response to steroids but the difference in this study that included 152 patients from which only 14 haploidentical patients with low dose Mtx not PTCy as GVHD prophylaxis.\u003c/p\u003e\u003cp\u003eRegarding the relationship between day-100 survival and score and biomarkers of the GVHD group, our study revealed that there was no significant relationship between day-100 survival rate and either EASIX score or other biomarkers among the GVHD patients, p\u0026thinsp;\u0026gt;\u0026thinsp;0.05. Moreover, there was no significant relationship between the skin GVHD and gut GVHD with 100-day survival rate, p\u0026thinsp;\u0026gt;\u0026thinsp;0.05 and this result may be changed or modified with larger number of patients or multicenter variant analysis.\u003c/p\u003e\u003cp\u003eOur study about Easix Dzero and OS revealed significant difference P value 0.0378 with median OS in high-risk group was 31% and within low-risk group was 71%.\u003c/p\u003e\u003cp\u003eIn contrast with the current study \u003cb\u003ePe\u0026ntilde;a et al.\u003c/b\u003e, \u003csup\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e revealed that there was no significant association between EASIX-PRE and the outcome although there was correlation between EASIX pre and ICU admission in that study which included 167 patients, There was some limitations like absence of validations in retrospective analysis and variation in ICU admission from center to another.\u003c/p\u003e\u003cp\u003eC-reactive protein is a nonspecific inflammatory protein that is elevated in GVHD patients along with IL-6, the main cytokine that induces C-reactive protein release \u003csup\u003e[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eOur study revealed CRP, IL-6 and ferritin increased significantly between baseline and Day\u0026thinsp;+\u0026thinsp;7 and also onset of a GVHD among GVHD group of patients (n\u0026thinsp;=\u0026thinsp;31) but revealed no significance with 100-day mortality among GVHD group\u003c/p\u003e\u003cp\u003e\u003cb\u003eWang et al.\u003c/b\u003e, \u003csup\u003e[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e that included 185 consecutive patients who underwent haplo-HSCT showed that elevated CRP levels, is related to worse survival in patients following HSCT, using CRP/Albumin ratio (CAR) was independent prognostic indicator for outcome in Haplo-identical transplant Patients were separated into low and high CAR groups using a cutoff of 0.087, which independently predicted OS, Higher CAR was related to worse outcome in Haplo patients.\u003c/p\u003e\u003cp\u003eThe difference in results may be due to the difference in sample size and inclusion criteria.\u003c/p\u003e\u003cp\u003eThe current study showed that that there was no significant difference between GVHD forms and steroid response, p\u0026thinsp;\u0026gt;\u0026thinsp;0.05.\u003c/p\u003e\u003cp\u003eHowever, \u003cb\u003eChoe \u0026amp; Ferrara\u003c/b\u003e, \u003csup\u003e[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/sup\u003e stated that the gastrointestinal (GI) tract is a key GVHD target organ that usually determines a patient\u0026rsquo;s response to therapy.\u003c/p\u003e\u003cp\u003eAlso, the current study reported that there was no significant difference between GVHD forms and the EASIX score or other biomarkers, p\u0026thinsp;\u0026gt;\u0026thinsp;0.05.\u003c/p\u003e\u003cp\u003eThe current study showed that there was no significant difference between GVHD forms and the survival rate or cause of death, p\u0026thinsp;\u0026gt;\u0026thinsp;0.05.\u003c/p\u003e\u003cp\u003e\u003cb\u003eFarhadfar et al.\u003c/b\u003e, \u003csup\u003e[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/sup\u003e showed that lower gastrointestinal involvement in aGVHD was associated with increased risk of readmission (30%) and twice as many inpatient days, doubling the likelihood of ICU admission and mortality over the first 100 days.\u003c/p\u003e\u003cp\u003eRegarding the relationship between steroid response and score and biomarkers of different forms of GVHD, it was revealed that there was no significant relationship between steroid responsiveness and score or other biomarkers, p\u0026thinsp;\u0026gt;\u0026thinsp;0.05, in all forms of GVHD, except for skin group, it was revealed that EASIX score at skin GVHD onset was significantly higher in the patients with refractory steroid response, than those with good response, p\u0026thinsp;=\u0026thinsp;0.025.\u003c/p\u003e\u003cp\u003eThese primary results need to be confirmed with a larger number of patients.\u003c/p\u003e\u003cp\u003eThe current study showed that there was difference but non-significant between the skin GVHD severity and EASIX score or other biomarkers, p\u0026thinsp;\u0026gt;\u0026thinsp;0.05may be related to small numbers of patients.\u003c/p\u003e\u003cp\u003eThe current study showed that 100-day mortality rate among the GVHD patients was 12 (38.7%).\u003c/p\u003e\u003cp\u003eLower than the current study \u003cb\u003eYu et al.\u003c/b\u003e, \u003csup\u003e[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/sup\u003e that included 455 patients with aGVHD from which only 125 with SR-GVHD revealed that the 100-day mortality rate among the GVHD patients was (20.2%). This may be due to the higher severity of the current study and limited number of patients.\u003c/p\u003e\u003cp\u003eSo, our results established that EASIX score was a poor predictor of response to steroids and mortality in BMT patients. But these results need further larger studies to confirm.\u003c/p\u003e\u003cp\u003eWe recommended that is why studies on larger sample size and longer follow-up are needed to confirm our results and to identify risk factors of adverse events\u003c/p\u003e\u003cp\u003eOur strength is that our center is a one of the respected centers that perform Haplo transplantation more than any other center in Egypt, and it is one of the first studies in Egypt that deal with aGVHD and EASIX score on Egyptian patients.\u003c/p\u003e\u003cp\u003eLimitations: We need to extent our study to include other centers in order to check result, being a single center study, the lack for similar studies for comparison and relatively short follow up period. Further comparative studies with larger sample size and longer follow-up are needed to confirm our results and to identify risk factors of adverse events.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eEASIX score was significant in predicting outcome in Haplo-identical HSCT and also in onset of a GVHD but was poor predictor of response to steroids and mortality in BMT patients although results showed that higher Easix score was detected in steroid refractory patients than good responders. Therefore, Easix Score could be used as predictive tool for GVHD onset and OS in GVHD patients, but also need larger number of patients may be needed to assess accuracy in Severity and steroid response in a GVHD. Other biomarkers (CRP, IL-6, Ferritin) might be used as predictive tool for GVHD onset as it showed significant difference among GVHD patients and increased significantly from baseline to GVHD onset but has nothing to do with Steroid response and disease severity and this must be correlated with larger number of patients and multicenter variant analysis.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eRoles of authors:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;Dr Khaled Zakaria Abd El Hakeem: did the data extraction, statistics and writing the paper\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eProf.Mohamed Khalaf : Founder of Research Idea, participating in revision of paper\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eProf George Bahig : Revising Data and Supervision of Research\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eProf.Noha El Husseiny : Revising Data and Supervision of Research and writing the paper\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical approaval : all patients participated in the study gave their informed written consent.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical committee : The study was done after approval from the Ethical Committee of Haplo Transplant in Hematology and Bone Marrow Transplant Department at Maadi Armed Forces Medical Compound from January 2020 to March 2023. The study followed declaration of Helsinki.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding : Self Funding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interest : All Authors confirmed no conflict of interest .\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability : All data of the patients are available upon request from corresponding author.\u003c/strong\u003e\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eDr Khaled Zakaria Abd El Hakeem: did the data extraction, statistics and writing the paperProf.Mohamed Khalaf : Founder of Research Idea, participating in revision of paperProf George Bahig : Revising Data and Supervision of ResearchProf.Noha El Husseiny : Revising Data and Supervision of Research and writing the paper\u003c/p\u003e\u003cp\u003eThis is not a clinical trial and all what is applied for clinical trial is not applicable\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eZeiser R, Burchert A, Lengerke C, Verbeek M, Maas-Bauer K, Metzelder SK, et al. Ruxolitinib in corticosteroid-refractory graft-versus-host disease after allogeneic stem cell transplantation: a multicenter survey. Leukemia. 2015;29:2062-8.\u003c/li\u003e\n\u003cli\u003eMcDonald GB, Tabellini L, Storer BE, Lawler RL, Martin PJ, Hansen JA. Plasma biomarkers of acute GVHD and nonrelapse mortality: predictive value of measurements before GVHD onset and treatment. Blood. 2015;126:113-20.\u003c/li\u003e\n\u003cli\u003eBacigalupo A, Milone G, Cupri A, Severino A, Fagioli F, Berger M, et al. Steroid treatment of acute graft-versus-host disease grade I: a randomized trial. Haematologica. 2017;102:2125-33.\u003c/li\u003e\n\u003cli\u003eHenden AS, Hill GR. Cytokines in Graft-versus-Host Disease. J Immunol. 2015;194:4604-12.\u003c/li\u003e\n\u003cli\u003eToubai T, Mathewson ND, Magenau J, Reddy P. Danger Signals and Graft-versus-host Disease: Current Understanding and Future Perspectives. Front Immunol. 2016;7:539-43.\u003c/li\u003e\n\u003cli\u003eRoddy JV, Haverkos BM, McBride A, Leininger KM, Jaglowski S, Penza S, et al. Tocilizumab for steroid refractory acute graft-versus-host disease. Leuk Lymphoma. 2016;57:81-5.\u003c/li\u003e\n\u003cli\u003eGreco R, Lorentino F, Morelli M, Giglio F, Mannina D, Assanelli A, et al. Posttransplantation cyclophosphamide and sirolimus for prevention of GVHD after HLA-matched PBSC transplantation. Blood. 2016;128:1528-31.\u003c/li\u003e\n\u003cli\u003eMussetti A, Greco R, Peccatori J, Corradini P. Post-transplant cyclophosphamide, a promising anti-graft versus host disease prophylaxis: where do we stand? Expert Rev Hematol. 2017;10:479-92.\u003c/li\u003e\n\u003cli\u003eSerdar CC, Cihan M, Y\u0026uuml;cel D, Serdar MA. Sample size, power and effect size revisited: simplified and practical approaches in pre-clinical, clinical and laboratory studies. Biochem Med (Zagreb). 2021;31:105-20.\u003c/li\u003e\n\u003cli\u003eCiurea SO, Kongtim P. Haploidentical Hematopoietic Cell Transplantation. Manual of Hematopoietic Cell Transplantation and Cellular Therapies-E-Book. 2022;4:83-9.\u003c/li\u003e\n\u003cli\u003eLia G, Giaccone L, Leone S, Bruno B. Biomarkers for Early Complications of Endothelial Origin After Allogeneic Hematopoietic Stem Cell Transplantation: Do They Have a Potential Clinical Role? Front Immunol. 2021;12:641427.\u003c/li\u003e\n\u003cli\u003eLuft T, Benner A, Jodele S, Dandoy CE, Storb R, Gooley T, et al. EASIX in patients with acute graft-versus-host disease: a retrospective cohort analysis. Lancet Haematol. 2017;4:414-23.\u003c/li\u003e\n\u003cli\u003eSolh MM, Baron J, Zhang X, Bashey A, Morris LE, Holland HK, et al. Differences in Graft-versus-Host Disease Characteristics between Haploidentical Transplantation Using Post-Transplantation Cyclophosphamide and Matched Unrelated Donor Transplantation Using Calcineurin Inhibitors. Biol Blood Marrow Transplant. 2020;26:2082-8.\u003c/li\u003e\n\u003cli\u003eLevine JE, Logan BR, Wu J, Alousi AM, Bola\u0026ntilde;os-Meade J, Ferrara JL, et al. Acute graft-versus-host disease biomarkers measured during therapy can predict treatment outcomes: a Blood and Marrow Transplant Clinical Trials Network study. Blood. 2012;119:3854-60.\u003c/li\u003e\n\u003cli\u003ePe\u0026ntilde;a M, Salas MQ, Mussetti A, Moreno-Gonzalez G, Bosch A, Pati\u0026ntilde;o B, et al. Pretransplantation EASIX predicts intensive care unit admission in allogeneic hematopoietic cell transplantation. Blood Adv. 2021;5:3418-26.\u003c/li\u003e\n\u003cli\u003eSanchez-Escamilla M, Hilden P, Maloy M, Fatmi SA, Ponce D, Sauter CS, et al. The prognostic calculator Easix predicts acute Gvhd, non-relapse mortality and overall survival in adult patients undergoing reduced intensity conditioning allogeneic HCT. Blood. 2018;12:221-8.\u003c/li\u003e\n\u003cli\u003eFingrut W, Law A, Lam W, Michelis FV, Viswabandya A, Lipton JH, et al. Post-transplant ferritin level predicts outcomes after allogeneic hematopoietic stem cell transplant, independent from pre-transplant ferritin level. Ann Hematol. 2021;100:789-98.\u003c/li\u003e\n\u003cli\u003eSanchez-Escamilla M, Flynn J, Devlin S, Maloy M, Fatmi SA, Tomas AA, et al. EASIX score predicts inferior survival after allogeneic hematopoietic cell transplantation. Bone Marrow Transplant. 2023;58:498-505.\u003c/li\u003e\n\u003cli\u003ePaczesny S. Discovery and validation of graft-versus-host disease biomarkers. Blood. 2013;121:585-94.\u003c/li\u003e\n\u003cli\u003eWang K, Jian X, Xu Z, Wang H. Pre-transplant CRP-albumin ratio as a biomarker in patients receiving haploidentical allogeneic hematopoietic transplantation: Developing a novel DRCI-based nomogram. Front Immunol. 2023;14:128-33.\u003c/li\u003e\n\u003cli\u003eChoe H, Ferrara JLM. New therapeutic targets and biomarkers for acute graft-versus-host disease (GVHD). Expert Opin Ther Targets. 2021;25:761-71.\u003c/li\u003e\n\u003cli\u003eFarhadfar N, Leather HL, Wang S, Burton N, IrizarryGatell V, Itzler R, et al. Severity of Acute Graft-versus-Host Disease and Associated Healthcare Resource Utilization, Cost, and Outcomes. Transplant Cell Ther. 2021;27:1007.e1-.e8.\u003c/li\u003e\n\u003cli\u003eYu J, Judy JT, Parasuraman S, Sinha M, Weisdorf D. Inpatient Healthcare Resource Utilization, Costs, and Mortality in Adult Patients with Acute Graft-versus-Host Disease, Including Steroid-Refractory or High-Risk Disease, following Allogeneic Hematopoietic Cell Transplantation. Biol Blood Marrow Transplant. 2020;26:600-5.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1: Demographic features, and chimerism characteristics, and frequency and subtypes of GVHD of the studied group (N=49), treatment, and survival characteristics of the patients with GVHD among the studied group (n=31).\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"601\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 438px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePatients (n = 49)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" style=\"width: 601px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDemographic features\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 438px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge (years)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e35.0 \u0026plusmn; 11.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSex\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMale\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e36 (73.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFemale\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e13 (26.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"5\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDiagnosis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAML\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e24 (49 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eALL\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e19 (38.8 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCML\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e3 (6.1 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMDS\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e2 (4.1 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHL\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e1 (2 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"7\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBMT indication\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHigh risk\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e30 (61.2 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCR2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e15 (30.6 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCML-BP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e3 (6.1 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eEarly relapse post autograph\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e1 (2 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eABO matched.\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e17 (34.7 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMajor mismatch\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e15 (30.6 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMinor mismatch\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e17 (34.7 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 438px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCD 34 +ve (cells per Kg)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e4.2 \u0026plusmn; 1.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 438px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDay of engraftment (n=47)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e23.0 \u0026plusmn; 5.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOS\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAlive\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e25 (51 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDead\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e23 (46.9 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLost follow up\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e1 (2.1 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"4\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCause of death (n=23)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAcute GVHD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e6 (26 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCRS\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e2 (8.8 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSepsis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e11 (47.8 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRelapse\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e4 (17.4 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" style=\"width: 601px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eChimerism Characteristics\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eChimerism 30\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFull donor Chimerism\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e39 (79.6 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGraft rejection\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e1 (2 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDied\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e9 (18.4 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eChimerism 60\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFull donor Chimerism\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e35 (71.4 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDied\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e14 (28.6 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eChimerism 90\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFull donor Chimerism\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e27 (55.1 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDied\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e22 (44.9 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" style=\"width: 601px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFrequency and subtypes of GVHD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 438px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGVHD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e31 (63.3 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 438px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSkin GVHD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e26 (53.1 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eStage of skin GVHD (n=26)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e11 (42.3 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e12 (46.2 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e3 (11.5 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 438px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGut GVHD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e25 (51 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eStage of gut GVHD (n=25)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e15 (60 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e8 (32 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e2 (8 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 438px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLiver GVHD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e11 (22.4 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eStage of liver GVHD (n=11)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e7 (63.6 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e3 (27.3 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e1 (9.1 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 438px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDay of GVHD (n=31)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e25.4 \u0026plusmn; 16.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSteroid response (n=31)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGood\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e17 (54.9 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRefractory\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e14 (45.2 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOther treatments (n=14)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eInfliximab\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e3 (21.4 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRuxolitinib 5mg BID\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e7 (50 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTocilizumab 8/kg\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e4 (28.6 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDay-100 Mortality (n=31)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAlive\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e19 (61.3 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDead\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e12 (38.7 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOS (6 months) (n=31)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOn follow up\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e14 (39.4 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLost follow up\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e5 (21.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDead\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e12 (38.7 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eData are presented as mean \u0026plusmn; SD and number (%). AML: Acute myeloid leukemia, ALL: Acute lymphoblastic leukemia, CML: Chronic myelogenous leukemia, MDS: Myelodysplastic syndromes, HL: Hodgkin lymphoma, BMT: Bone marrow transplant, OS: overall survival, GVHD: Graft-vs-host disease, BMT: Bone marrow transplant, ABO: Blood Group System, CRS: cytokine release syndrome, CR2: Complement receptor type 2, BID: Twice a day, *: significant as P value \u0026lt; 0.05.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2: Score and biomarkers of the studied group (N=49).\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"616\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 165px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 156px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOn day 0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 205px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOn day 7+\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 165px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eEasix score\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 156px;\"\u003e\n \u003cp\u003e2.0 \u0026plusmn; 0.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 205px;\"\u003e\n \u003cp\u003e3.6 \u0026plusmn; 1.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 165px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFerritin (ng/mL)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 156px;\"\u003e\n \u003cp\u003e477.6 \u0026plusmn; 413.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 205px;\"\u003e\n \u003cp\u003e816.4 \u0026plusmn; 814.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 165px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCRP (mg/dL)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 156px;\"\u003e\n \u003cp\u003e26.8 \u0026plusmn; 29.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 205px;\"\u003e\n \u003cp\u003e77.1 \u0026plusmn; 68.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 165px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIL-6 (pg/ml)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 156px;\"\u003e\n \u003cp\u003e31.8 \u0026plusmn; 63.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 205px;\"\u003e\n \u003cp\u003e99.3 \u0026plusmn; 161.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.005*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eData are presented as mean \u0026plusmn; SD. CRS: cytokine release syndrome, *: significant as P value \u0026lt; 0.05.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3: Relationship between initial biomarkers and the occurrence of GVHD (N=49).\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"601\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 279px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 115px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGVHD\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en=31\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 115px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo GVHD\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en=18\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 279px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eEasix score at baseline\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 115px;\"\u003e\n \u003cp\u003e2.1 \u0026plusmn; 1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 115px;\"\u003e\n \u003cp\u003e1.9 \u0026plusmn; 0.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 92px;\"\u003e\n \u003cp\u003e0.445\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 279px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eEasix score on day 7 from BMT\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 115px;\"\u003e\n \u003cp\u003e3.5 \u0026plusmn; 1.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 115px;\"\u003e\n \u003cp\u003e3.8 \u0026plusmn; 2.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 92px;\"\u003e\n \u003cp\u003e0.086\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 279px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFerritin (ng/mL) at baseline\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 115px;\"\u003e\n \u003cp\u003e441.2 \u0026plusmn; 380.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 115px;\"\u003e\n \u003cp\u003e546.1 \u0026plusmn; 474.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 92px;\"\u003e\n \u003cp\u003e0.202\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 279px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFerritin (ng/mL) on day 7 from BMT\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 115px;\"\u003e\n \u003cp\u003e700.5 \u0026plusmn; 352.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 115px;\"\u003e\n \u003cp\u003e1034.8 \u0026plusmn; 1292.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 92px;\"\u003e\n \u003cp\u003e0.087\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 279px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCRP (mg/dL) at baseline\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 115px;\"\u003e\n \u003cp\u003e20.8 \u0026plusmn; 18.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 115px;\"\u003e\n \u003cp\u003e37.9 \u0026plusmn; 42.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.027*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 279px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCRP (mg/dL) on day 7 from BMT\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 115px;\"\u003e\n \u003cp\u003e60.6 \u0026plusmn; 45.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 115px;\"\u003e\n \u003cp\u003e108.1 \u0026plusmn; 91.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.009*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 279px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIL-6 (pg/ml) at baseline\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 115px;\"\u003e\n \u003cp\u003e26.1 \u0026plusmn; 36.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 115px;\"\u003e\n \u003cp\u003e42.5 \u0026plusmn; 95.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 92px;\"\u003e\n \u003cp\u003e0.195\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 279px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIL-6 (pg/ml) on day 7 from BMT\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 115px;\"\u003e\n \u003cp\u003e137.5 \u0026plusmn; 189.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 115px;\"\u003e\n \u003cp\u003e27.47 \u0026plusmn; 22.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.0107*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eData are presented as mean \u0026plusmn; SD and number (%). GVHD: Graft-vs-host disease, BMT: Bone marrow transplant, CRS: cytokine release syndrome, *: significant as P value \u0026lt; 0.05.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4: Relationship between steroid response and score and biomarkers, mortality data, Easix score and biomarkers, score and biomarkers of the gut, and score and biomarkers of the liver of the GVHD group (n=31).\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"601\" class=\"fr-table-selection-hover\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 240px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 162px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGood response (n=17)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRefractory (n=14)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 240px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eEasix score at onset\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 162px;\"\u003e\n \u003cp\u003e4.2 \u0026plusmn; 0.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e5.3 \u0026plusmn; 1.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.034*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 240px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eEasix score on day 7\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 162px;\"\u003e\n \u003cp\u003e3.1 \u0026plusmn; 2.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e4.4 \u0026plusmn; 2.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003e0.178\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 240px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFerritin at onset\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 162px;\"\u003e\n \u003cp\u003e763.4 \u0026plusmn; 490.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e1087.1 \u0026plusmn; 621.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003e0.122\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 240px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCRP at onset\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 162px;\"\u003e\n \u003cp\u003e57.2 \u0026plusmn; 37.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e61.1 \u0026plusmn; 40.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003e0.781\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 240px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIL-6 at onset\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 162px;\"\u003e\n \u003cp\u003e53.9 \u0026plusmn; 33.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e72.5 \u0026plusmn; 34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003e0.136\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 162px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e(n=17)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e(n=14)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 119px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMortality rate D100\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAlive\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 162px;\"\u003e\n \u003cp\u003e10 (58.8 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e9 (64.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 67px;\"\u003e\n \u003cp\u003e0.756\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDead\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 162px;\"\u003e\n \u003cp\u003e7 (41.2 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e5 (35.7 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" style=\"width: 119px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCause of death\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAcute GVHD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 162px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e4 (80 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 67px;\"\u003e\n \u003cp\u003e0.179\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSepsis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 162px;\"\u003e\n \u003cp\u003e4 (57.2 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRelapse\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 162px;\"\u003e\n \u003cp\u003e3 (42.9 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e1 (20 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eData are presented as mean \u0026plusmn; SD and number (%). GVHD: Graft-vs-host disease, CRS: cytokine release syndrome, *: significant as P value \u0026lt; 0.05.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Inflammatory Biomarkers, Steroid Responsiveness, Acute Graft vs Host Disease, Haplo-Identical Transplantation","lastPublishedDoi":"10.21203/rs.3.rs-7568201/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7568201/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground;\u003c/strong\u003e Haematopoietic stem cell transplant (HSCT) is the transplant of stem cells usually derived from bone marrow, Peripheral blood, Umbilical cord, Matched sibling donor (HLA 6/6) , Or Haplo-Identical donor (HLA Matching less than 6/6but not less than 3/6)\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAim and objectives;\u003c/strong\u003e to assess the role of the EASIX formula, IL-6, CRP and Ferritin in the Severe and Steroid Responsiveness cases of a GVHD in Haploidentical Transplants.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSubjects and methods;\u003c/strong\u003e This Cohort Follow up study was conducted during the period from January 2020 to March 2023 and included 49 patients with different hematological malignancies indicated for Haploidentical bone marrow transplant who received Standard PTCy (50mg/kg) at Day +3,D+5 . Patients were recruited from BMT Unit in Maadi Armed Forces Medical Compound.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResult; \u003c/strong\u003ethe Easix score, and the studied biomarkers increased significantly from baseline to D 7 of BMT, p \u0026lt;0.05. Easix score and other biomarkers increased significantly at Onset of a GVHD , there was correlation between Easix Pre and Overall survival , the rate of good steroid responsiveness among the GVHD patients was (54.9%), and the refractory response was (45.2%). there was a significant difference between serial Easix score measurements among GVHD patients, p\u0026lt;0.001. there was significant difference between good and refractory steroid responders regarding the mortality rate or cause. there was no significant relationship between the gut GVHD and 100-day survival rate, p\u0026gt;0.05. there was no significant relationship between the skin GVHD and 100-day survival rate, p\u0026gt;0.05.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion;\u003c/strong\u003e the current study showed that EASIX score was a good predictor for Onset of a GVHD and Overall survival in GVHD patients but was poor predictor of severity of disease and response to steroids in BMT patients. Also, inflammatory markers (IL-6, CRP and Ferritin) were reliable to predict the onset of a GVHD but nothing to do with response to steroids and mortality in BMT patients.\u003c/p\u003e","manuscriptTitle":"The Evaluation of Inflammatory Biomarkers in Predicting the Severity and Steroid Responsiveness of Acute Graft versus Host Disease after Haplo- Identical Transplantation","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-10 14:57:08","doi":"10.21203/rs.3.rs-7568201/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"9a95240e-6479-466d-a0ed-284dc0bf8e5b","owner":[],"postedDate":"October 10th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-10-29T08:38:46+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-10 14:57:08","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7568201","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7568201","identity":"rs-7568201","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}