Academic literature on the topic '342.002 69'

Caring for an aging society is a problem facing many countries including Thailand. This cross-sectional study investigated caregiver burden and related predictive factors among 69 caregivers who had older family members with physical disabilities. Burden Scale, World Health Organization Quality of Life-Bref Thai (QOL), Patient Health Questionnaire-9 (PHQ), Barthel Activity of Daily Living Index (ADL), and Lawton-Brody Instrumental Activities of Daily Living Scale (IADL) assessments were used in addition to demographic data. Thirteen caregivers (18.8%) reported no caregiver burden, 30 (43.5%) reported low-moderate burden, 21 (30.4%) reported moderate-high burden and 5 (7.2%) reported high burden. Using Fisher’s Exact Test the factors found to be significantly associated to caregiver burden were: categorical age of the caregiver (p = .000), education level of the caregiver (p = .002), relationship to the care recipient (p = .009), categorical income level of the caregiver (p = .041), QOL of the caregiver (p = .001) and ADL status of the care recipient (p = .003). Forward stepwise linear regression model revealed three factors which were PHQ score (β = .543, p < .000), ADL score (β = -.341, p = .001) and hours of care/week (β = .227, p = .017). Future studies should focus on interventions that impact depression levels, independence with activities of living and hours of care per week.

Macular pigment (MP) is composed of lutein (L), zeaxanthin (Z) and meso-zeaxanthin (MZ). The present study reports on serum response to three different MP supplements in normal subjects (n 27) and in subjects with age-related macular degeneration (AMD) (n 27). Subjects were randomly assigned to: Group 1 (20 mg L and 2 mg Z), Group 2 (10 mg L, 2 mg Z and 10 mg MZ) or Group 3 (3 mg L, 2 mg Z and 17 mg MZ). Serum carotenoids were quantified at baseline, and at 4 and 8 weeks using HPLC. Response data for normal and AMD subjects were comparable and therefore combined for analysis. We report response as the average of the 4- and 8-week concentrations (saturation plateau). Serum L increased significantly in Group 1 (0·036 μmol/l per mg (269 %); P< 0·001) and Group 2 (0·079 μmol/l per mg (340 %); P< 0·001), with no significant change in Group 3 (0·006 μmol/l per mg (7 %); P= 0·466). Serum Z increased significantly in Group 1 (0·037 μmol/l per mg (69 %); P= 0·001) and Group 2 (0·015 μmol/l per mg (75 %); P< 0·001), with no significant change in Group 3 ( − 0·0002 μmol/l per mg ( − 6 %); P= 0·384). Serum MZ increased significantly in Group 1 (0·0094 μmol/l (absolute value); P= 0·015), Group 2 (0·005 μmol/l per mg; P< 0·001) and Group 3 (0·004 μmol/l per mg; P< 0·001). The formulation containing all three macular carotenoids (Group 2 supplement) was the most efficacious in terms of achieving the highest combined concentration of the three MP constituent carotenoids in serum, thereby potentially optimising the bioavailability of these compounds for capture by the target tissue (retina).

Abstract Abstract 3831 The discovery of mutations in components of the RNA splicing machinery has underlined the importance of this pathogenetic mechanism in MDS biology. We and others reported that mutations in SF3B1 are frequent in refractory anemia with ring sideroblasts (RARS) and RARS associated with thrombocytosis (RARS-T). We recently reported good survival outcomes in a large cohort of SF3B1 mutant patients similar to the findings of Papaemmanuil et al, NEJM< 2011. Here, we aimed to evaluate the correlation between SF3B1 mutations in association with other poor prognostic clinical and pathologic factors in MDS. We focused on a large cohort of patients with several myeloid malignancies (n=340). Patients were grouped in MDS (n=176), MDS/MPN (n=88) and secondary AML (sAML) from a previous MDS (n=76). Diseases were classified according to the 2008 WHO classification. Survival outcomes (overall survival [OS], progression free survival [PFS] and event free survival [EFS]) were defined according to MDS IWG criteria. We studied a total of 340 patients with myeloid malignancies. median age, 69 years old (range 19–92), sex (Male, n=222; females, n=118). We performed direct sequencing for SF3B1 (exon 13–16) on a large cohort of MDS, MDS/MPN and sAML patients and found 11.8% SF3B1 mutants. The outcomes of SF3B1 mutant vs WT patients were compared based on the presence of poor clinicopathologic factors associated with MDS like RBC transfusion dependence, presence of SNP-A lesions, presence of acquired somatic uniparental disomy (AS-UPD), Age ≥ 60 years, presence of reticulin fibrosis in the bone marrow. We also assessed the effects of therapies in the prognostic effect of SF3B1 mutations. We previously reported that the presence of new SNP-A lesions in myeloid malignancies including MDS and AML are associated with poor prognostic outcomes. However, the good prognostic effects of SF3B1 mutation is still apparent even in the patients with new SNP-A abnormalities (OS: 40 vs 16 mos, p=.003; PFS: 40 vs 10 mos, p=.003, 40 vs 10 mos, p=.0007. However, when analysis is limited to acquired somatic uniparental disomy defects which we recently reported as the worst lesion among SNP-A abnormalities, the good prognostic effect of SF3B1 is lost (OS: 19 vs 9 mos, p=.29, PFS: 18 vs 7 mos, p=.20, EFS: 19 vs 8 mos, p=.17). Age is an important predictor of outcomes in MDS with higher age associated with worse outcomes. SF3B1 remained predictive of good outcomes in patients ≥ 60 years of age (OS: 40 vs 16, p=.002; PFS: 40 vs 11 mos, p=.003; EFS: 40 vs 10 mos, p=.0005). Persistent RBC transfusions are also associated with inferior survival in MDS, yet SF3B1 mutant patients continued to have good outcomes (OS 34 vs 13, p=.002; PFS: 27 vs 8 mos, p=.004; EFS: 14 vs 9 mos, p=.001). Reticulin fibrosis in the bone marrow is a characteristic feature of myeloproliferative neoplasms but their presence in MDS is associated with unfavorable results, SF3B1 mutant retain their good outcomes even in the presence of reticulin fibrosis in the BM (OS: 40 vs 15 mos, p=.09; PFS: 47 vs 12 mos, p=.04; EFS: 75 vs 13 mos, p=.008). Patients screened for SF3B1 were also further stratified according to treatments received. No patients with SF3B1 mutations underwent allogeneic hematopoietic stem cell transplantation and high intensity chemotherapy specifically induction chemotherapy or high dose cytarabine. However based on treatment with LIC, SF3B1 mutant patients have better survival outcomes compared to WT patients (OS: 61 vs 17 mos, p=.004; PFS: not reached [NR] vs 7 mos; p=.009; EFS: 61 vs 10 mos, p=.001). These observed survival outcomes remain significant when patients were stratified according to disease subtypes. MDS and MDS/MPN patients treated with LIC have better outcomes if they have SF3B1 mutation (OS: 61 vs 23 mos, p=.005; PFS: NR vs 16 mos, p=.01; EFS: 61 vs 16 mos, p=.001). A high number of TET2/DNMT3A mutations are found in SF3B1 mutants. TET2/DNMT3A mutations have been previously association with improved response to hypomethylating agents which is one of the possible reasons why SF3B1 mutants treated with LIC did better than their WT counterpart. In conclusion, SF3B1 retains its favorable prognostic effect even in the face of poor prognostic factors such as RBC transfusion dependence, presence of SNP-A lesions, Age ≥ 60 years, presence of reticulin fibrosis in the bone marrow except in the presence of AS-UPD. SF3B1 mutants treated with LIC also have better outcomes. Disclosures: No relevant conflicts of interest to declare.

Abstract Abstract 3791 Molecular mutations of genes important in MDS pathogenesis have been identified using next generation sequencing technologies. These mutations have variable effects on prognosis: results from individual studies are conflicting, and the impact of combining mutations based on pathogenetic pathways has not been explored. Furthermore, most studies do not take into account the types of therapies received by patients (pts). We hypothesized that analyses of mutations incorporating pathways would yield more meaningful results, especially if studied in the context of therapies. We studied 340 pts with MDS (N=176), MDS/MPN (N=88) and sAML (N=76). Median age was 69 years (range, 19–92), 118 (35%) were female. Direct sequencing of 14 genes important in MDS pathogenesis originally identified using whole exome sequencing and involved in methylation (TET2/IDH1/2/DNMT3A), histone modification (ASXL1/EZH2/UTX), signaling (CBL/KRAS, NRAS, JAK2), transcription (RUNX1/TP53) and RNA splicing (SRSF2/U2AF1) was performed. Pts were classified by 2008 WHO criteria. Prognosis was assigned by IPSS (low=67, Int-1=85, Int-2=56, high=64). Karyotypes by metaphase cytogenetics (MC) and SNP-A were stratified by IPSS cytogenetic risk group (Low=82, intermediate=87, poor=106). Treatment received included high intensity (cytarabine+ anthracycline, high dose ARA-C,) (N=75), low intensity (N=124) (hypomethylating therapy, IMiDs, low dose ARA-C), and supportive therapy (N=141) (growth factors, hydroxyurea). Categorical variables were analyzed using X2 or Fischer-exact test. Overall survival (OS) and progression-free survival (PFS) were defined using IWG criteria and analyzed by Kaplan-Meier and log-rank statistics. P-values0.05 were considered statistically significant. Univariate and multivariate analyses were performed by Cox Proportional Hazards, covariates included were age, BM blasts, cytopenias, karyotype, jointly with molecular pathway data. A total of 258 mutations were detected in 158 pts. Mutations involving genes key to methylation (41 vs 37%, p=.01), and histone modification (52 vs 25%, p=.008) were more common in MDS/MPN compared to MDS pts. Mutations in methylation (37 vs 23%, p=.05), transcription (38 vs 14%, p=.01) and splicing (38 vs 17%, p=.007) were more common in MDS compared to sAML pts, and mutations of genes involved in methylation (41 vs 23%, p=.02), signaling (60 vs 7%, p=.005), histone modification (52 vs 23%, p=.004), transcription (49 vs 13%, p=.001) and splicing (45 vs 17%, p=.0005) were more frequent in MDS/MPN compared to sAML pts. Worse outcomes were noted in pts with mutations in histone modification (OS: 17 vs 21 mos, p=.04), transcription (PFS: 7 vs 13 mos, p=.02) and splicing (OS: 11 vs 23 mos, p=.01) genes. This was evident in pts with MDS who had transcription factor-related gene mutations (OS: 9 vs 30 mos, p=<.0001), splicing (PFS: 8 vs 21 mos, p=.008) and in MDS/MPN and MDS pts with histone pathway (27 vs 31 mos, p=.04) and splicing mutations (7 vs 21 mos, p=.0001). Of note, this was clearly mentioned in WHO lower-risk MDS pts with histone pathway (OS: 30 vs 39 mos, p=.01; PFS: 21 vs 32 mos, p=.05) and splicing mutations (PFS: 15 vs 28 mos, p=.003). Pts with good-risk karyotype defects had poor survival if they had histone mutations (OS: 17 vs 35 mos, p=.005; PFS: 11 vs 20 mos, p=.002) while those with intermediate-risk karyotype had worse outcomes if they had splicing mutations (OS: 10 vs 35 mos, p=.001; PFS: 7 vs 35 mos, p=.0001). The survival effects were retained even after accounting for presence of new SNP-A lesions. By IPSS, lower-risk pts had worse outcomes if they had mutations in methylation (OS: 36 vs 18 mos, p=.02), histone modification (28 vs 37 mos, p=0.02) or splicing (OS: 7 vs 17 mos, p=.04; PFS: 14 vs 28 mos, p=.04). Therapeutically, LIC treated pts had better OS if they had methylation mutations (23 vs 8 mos, p=.0009) but worse outcomes if they had transcription factor (7 vs 11 mos, p=.02) or splicing (8 vs 13 mos, p=.05) mutations. Mutations in transcription factors (OS: HR=2.9 CI: 1.58–5.13, p=.0007; PFS: HR=3.3 CI: 1.87–5.63, p=<.0001) and splicing (OS: HR=2.1, CI=1.22–3.76, p=.008; PFS: HR=2.1, CI=1.27–3.71, p=.005) remained independent predictors of poor outcomes in MDS by multivariate analysis. In conclusion, the presence of molecular pathway mutations can modify morphologic, cytogenetic and prognostic scoring schemes in MDS, MPN, AML and other hematological cancers. Disclosures: No relevant conflicts of interest to declare.

Abstract Background: Therapy-related myeloid neoplasms develop after cytotoxic chemotherapy or radiation therapy. The available data on the outcome of pts with t-de novo AML without antecedent history of myelodysplastic syndrome (MDS) is limited. Methods: We reviewed the records of pts with newly diagnosed AML who presented to our tertiary care center from 1/2000 to 1/2014. t-de novo AML was defined as having at least 20% blasts in bone marrow with a history of any previous cytotoxic chemotherapy or radiation therapy, and without an antecedent history of MDS. Leukemia-free survival (LFS) was defined as time from achieving complete response (CR) to relapse or death. The overall survival (OS) and LFS in pts with t-de novo AML were compared to those of with de novo AML with normal karyotype (NK) and complex karyotype (CK). Results: Among 1677 pts with newly diagnosed AML, 383 had de novo NK-AML, 218 had de novo CK-AML, and 187 had t-de novo AML. The median follow-up was 9.3 months (range; 0.2-161.0). Pt characteristics and outcomes are described in Table 1. Among the 187 pts, 69 had a history of lymphoma; 63 pts breast cancer (Ca); 10 pts colon Ca; 10 pts sarcoma; 8 pts prostate; 7 pts bladder Ca; 6 pts uterine Ca; 5 pts lung Ca; 5 pts head and neck Ca; 30 pts other type of Ca. Among the pts with t-de novo AML, 15 pts (8%) had a favorable-risk karyotype by WHO, 53 pts (28%) intermediate-risk karyotype, and 119 pts (64%) poor-risk karyotype. The median LFS duration in t-de novo AML, NK-AML, and CK-AML were 7 months (95% confidence interval [CI]; 5.1-8.7), 19 months (95% CI; 13.0-25.2), and 6 months (95% CI; 9.0-13.5) (p<.001), respectively. The median OS duration in t-de novo AML, NK-AML, and CK-AML were 7 months (95% CI; 5.9-8.9), 21 months (95% CI; 16.2-25.5), and 12 months (95%CI; 10.6-13.5) (p<.001), respectively. The results of univariate (UVA) and multivariate analysis (MVA) associated with OS were summarize in Table 1. MVA identified age over 60, white blood cell count (WBC) over 10 x103/µL, thrombocytopenia below 30 x103/µL, non-favorable cytogenetic abnormalities, positive RAS mutation, and the absence of CR or CR with incomplete platelet recovery (CRp) as poor prognostic features related to OS. Conclusion: LFS and OS were shorter in patients with t-de novo AML than in those with NK-AML but did not differ significantly from patients with CK-AML. Abstract 2273. Table 1. Patient Characteristics and Outcomes t-de novo AML [n= 187] de novo AML with NK [n= 383] de novo AML with CK [n= 218] P Age at diagnosis, median (years) 64 (21-89] 63 (17-90) 67 (18-87) Prior radiation therapy, No. (%) 101 (54) 0 0 Prior chemotherapy, No. (%) 186 (99) 0 0 White blood cell count at diagnosis, median (x103/µL) 3.2 (0.2-191) 4.3 (0.2-390.0) 2.9 (0.5-278.2) Hemoglobin at diagnosis, median (g/dL) 9.1 (4.5-12.9) 9.1 (4-14.6) 9.0 (2.5-14.2) Platelet count at diagnosis, median (x103/µL) 34 (4-454) 51 (3-469) 42 (2-319) LDH at diagnosis, median (IU/L) 1359 (210-22090) 1189 (200-42000) 1274 (231-20572) Peripheral blood blast percent at diagnosis, median (%) 8 (0-98) 9.5 (0-98) 10 (0-98) Bone marrow blast percent at diagnosis, median (%) 41 (0-96) 44 (0-96) 33 (0-97) Molecular genetic abnormalities at diagnosis, No. (%) FLT3-ITD 17 (9) 96 (25) 5 (2) FLT3-D835 6 (3) 23 (6) 1 (1) NPM1 7 (4) 104 (27) 4 (2) JAK2 3 (2) 6 (2) 8 (4) RAS 17 (9) 50 (13) 8 (4) RUNX1-RUNX1T1 4 (2) 0 0 CBFb-MYH 6 (3) 0 0 Response, No. (%) <0.001 Complete response 89 (48) 237 (62) 76 (35) Complete response without platelet recovery 15 (8) 1 (0) 15 (7) 1-year LFS, (%) 33 60 27 <0.001 2-year LFS, (%) 33 52 20 <0.001 1-year OS, (%) 34 68 30 <0.001 2-year OS, (%) 24 46 13 <0.001 UVA and MVA of OS in t-de novo AML UVA MVA Hazard ratio 95% CI Age at diagnosis Age =< 60 years - Age >60 years < .001 .001 2.238 1.417-3.534 White blood cell count (WBC) (x103/µL) WBC =< 10.0 - WBC > 10.0 .002 .037 1.617 1.030-2.540 Hemoglobin (Hgb) (g/dL) Hgb >= 8 - Hgb < 8 .749 Platelet count (Plt) (x103/µL) Plt >= 30 - Plt < 30 .008 .004 1.852 1.224-2.803 LDH (IU/L) LDH =<1000 - LDH > 1000 .640 Peripheral blood blast percent (PB blast)(%) PB blast =< 10% - PB blast >10% .178 Bone marrow blast percent (BM blast) (%) BM blast =<40% - BM blast >40% .393 Cytogenetic abnormality Favorable - Non-Favorable .002 .019 5.836 1.342-25.370 FLT3-ITD Negative - Positive .768 RAS Negative - Positive .047 .003 2.576 1.367-4.856 Response CR or CRp - Non-CR or CRp <.001 .009 .331 0.145-0.757 CR - Non-CR <.001 0.903 .950 0.418-2.160 Figure 1. LFS and OS Figure 1. LFS and OS Disclosures Kantarjian: ARIAD, Pfizer, Amgen: Research Funding.

AbstractVascular surgery patients are nutritionally vulnerable. Various malnutrition screening and assessment tools are available; however, none has been developed or validated in vascular patients. The present study aimed to: (1) investigate the validity of four commonly administered malnutrition screening tools (Malnutrition Screening Tool (MST), Malnutrition Universal Screening Tool (MUST), Nutrition Risk Screen-2002 (NRS-2002) and the Mini-Nutritional Assessment – Short Form (MNA-SF) and an assessment tool (the Patient-Generated Subjective Global Assessment (PG-SGA)) compared against a comprehensive dietitian’s assessment and (2) evaluate the ability of the instruments to predict outcomes. Vascular inpatients were screened using the four malnutrition screening tools and assessed using the PG-SGA. Each was assessed by a dietitian incorporating nutritional biochemistry, anthropometry and changes in dietary intake. Diagnostic accuracy, consistency and predictive ability were determined. A total of 322 (69·3 % male) patients participated, with 75 % having at least one parameter indicating nutritional deficits. No instrument achieved the a priori levels for sensitivity (14·9–52·5 %). Neither tool predicted EuroQoL 5-dimension 5-level score. All tools except the MNA-SF were associated with length of stay (LOS); however, the direction varied with increased risk of malnutrition on the MUST and NRS-2002 being associated with shorter LOS (P=0·029 and 0·045) and the reverse with the MST and PG-SGA (P=0·005 and <0·001). The NRS-2002 was associated with increased risk of complications (P=0·039). The MST, NRS-2002 and PG-SGA were predictive of discharge to an institution (P=0·004, 0·005 and 0·003). The tools studied were unable to identify the high prevalence of undernutrition; hence, vascular disease-specific screening and/or assessment tools are warranted.

Abstract Introduction: Most pediatric patients (pts) with ALL receive total body irradiation (TBI) for myeloablative conditioning of allogeneic hematopoietic stem cell transplantation (allo-HSCT). It is unproven whether TBI can be replaced by chemotherapy (CHT). Methods: To compare the outcomes of TBI- versus (vs.) CHT-based conditioning, we performed a retrospective EBMT-registry based study. Children between 2 and 18 years of age (y.) after myeloablative conditioning for first allo-HSCT of bone marrow (BM) or peripheral blood SC (PBSC) from matched sibling (MSD) or unrelated donors (UD) in first (CR1) or second remission (CR2) between 2000 and 2012 were included. Propensity score weighting was used to consider the covariate "distribution of TBI recipients" for pts who did not receive TBI. Results: In total 3071 pts (CR1: 1504 (49%), CR2: 1567 (51%)) were included. CR1: 1045 pts (69%) received BM and 459 pts (31%) PBSC from MSD (760 (51%)) or UD (744 (49%)). CR2: 1067 pts (68%) received BM and 500 pts (32%) PBSC from MSD (675 (43%)) or UD (892 (57%)). Overall, conditioning was TBI- in 2647 (86%) and CHT-based in 424 pts (14%). Busulfan/Cyclophosphamide (Bu/Cy) and Bu/Cy/Etoposide (Bu/Cy/Eto) were the two most frequently applied CHT combinations in CR1 (68 (32%), 66 (31%)) and CR2 (68 (32%), 52 (25%)). The remaining conditionings included 5 different combinations of chemotherapeutics (other chemo). 1504 pts in CR1 were conditioned with TBI (1291), Bu/Cy/Eto (66) or other chemo (147) with a median follow-up of 4.4, 3.4 and 2.4 y. In weighted univariate analysis no significant differences were detected for LFS (5-y.-LFS, range: 62.4 to 67.5%) and relapse incidence (5-y.-RI, range: 24.0 to 29.0%). In pairwise testing, OS after Bu/Cy/Eto was significantly better compared with TBI (5-y.-OS, 78.7 vs. 66.8%, P=.006). Non-relapse mortality was significantly higher after other chemo (5-y.-NRM, 12.7%, P &lt;.001) and TBI (12.5%, P &lt;.001) compared with Bu/Cy/Eto (3.5%). Other significant influencing factors on LFS were age (5-y.-LFS, 2-11 y. 65.8 vs. 12-18 y. 58.0%, P=.009), y. of HSCT (2008-2012 65.9 vs. 2000-2007 59.6%, P=.035) and donor type (MSD 64.9 vs. UD 59.5%, P=.007). RI was influenced by y. of HSCT (5-y.-RI, 2008-2012 21.7 vs. 2000-2007 26.8%. P=.026). OS was influenced by age (5-y.-OS, 2-11 y. 72.7 vs. 12-18 y. 61.7%, P &lt;.001) and donor type (MSD 70.1 vs. UD 65.0%, P=.002). NRM was influenced by age (5-y.-NRM, 2-11 y. 9.0 vs. 12-18 y. 18.0%, P &lt;.001), donor sex (male 10.9 vs. female 16.6%, P=.007) and donor type (MSD 8.5 vs. UD 17.8%, P &lt;.001). In weighted multivariable Cox model clustered on EBMT centers, TBI-based conditioning in CR1 was associated with lower RI (HR 0.70, P=.047), lower OS (HR 1.54, P=.017) and higher NRM (HR 3.97, P &lt;.001). 1567 pts in CR2 were conditioned with TBI (1356), Bu/Cy (68) or other chemo (143) with a median follow-up of 3.9, 3.2 and 3.1 y. In weighted univariate analysis highly significant differences of survival were detected. TBI-based conditioning resulted in highest 5-y.-LFS of 52.2% (Bu/Cy 41.0%, other chemo 18.4%, P &lt;.001), lowest 5-y.-RI of 33.2% (Bu/Cy 38.3%, other chemo 55.3%, P &lt;.001), highest 5-y.-OS of 56.1% (Bu/Cy 43.6%, other chemo 23.6%, P &lt;.001) and lowest 5-y.-NRM of 14.6% (Bu/Cy 20.8%, other chemo 26.2%, P &lt;.001). Other significant influencing factors on LFS were age (5-y.-LFS, 2-11 y. 53.5 vs. 12-18 y. 43.0%, P &lt;.001), y. of HSCT (2008-2012 53.3 vs. 2000-2007 47.3%, P=.009) and SC source (BM 53.3 vs. PBSC 42.5%, P &lt;.001). RI was influenced by SC source (5-y.-RI, BM 33.1 vs. PBSC 36.6%, P=.024). OS was influenced by age (5-y.-OS, 2-11 y. 59.3 vs. 12-18 y. 46.8%, P &lt;.001), y. of HSCT (2008-2012 58.6 vs. 2000-2007 52.0%, P=.005), donor type (MSD 58.5 vs. UD 52.6%, P &lt;.024) and SC source (BM 58.4 vs. PBSC 47.5%, P &lt;.001). NRM was influenced by age (5-y.-NRM, 2-11 y. 12.5 vs. 12-18 y. 22.3%, P &lt;.001), donor type (MSD 10.2 vs. UD 19.8%, P &lt;.001) and SC source (BM 13.6 vs. PBSC 20.8%, P &lt;.001). In weighted multivariable Cox model clustered on EBMT centers, TBI-based conditioning in CR2 was associated with higher LFS (HR 0.48, P &lt;.001), lower RI (HR 0.48, P &lt;.001) and higher OS (HR 0.51, P &lt;.001). Conclusion: Conditioning by TBI demonstrated clear superiority in comparison to CHT for children with ALL undergoing HSCT in CR2. For pts in CR1, TBI- and CHT-based conditioning showed similar results. This retrospective data is currently re-evaluated in a prospective, randomized, international trial (ALL SCTped 2012 FORUM). Disclosures Büchner: Novartis Pharmaceuticals Corporation: Consultancy; Pfizer: Consultancy. Veys: Bellicum: Research Funding; Servier: Research Funding. Bader: Novartis, Medac, Amgen, Riemser, Neovii: Consultancy, Honoraria, Research Funding.

Age and gender are 2 important factors in the treatment of end-stage chronic kidney disease with hemodialysis. Understanding the influence of these 2 factors can help optimize treatment for this population. This study evaluated gender and age differences in achievement of Kidney Disease Improving Global Outcomes (KDIGO) treatment targets. A cross-sectional study was conducted on 324 chronic hemodialysis patients at a tertiary referral hospital in Ho Chi Minh City, Vietnam. KDIGO treatment targets included treatment time, prescribed Qb, treated blood volume, urea reduction ratio, spKt/V, hemoglobin, albumin, phosphorus, calcium, and parathyroid hormone. Men had significantly higher treatment time (P = .003), prescribed Qb (P = .037) and hemoglobin (P = .031) than women. However, women had significantly higher treated blood volume (P < .001), spKt/V (P < .001) and URR (P < .001). No significant difference between men and women was found in albumin, calcium, phosphorus, and parathyroid hormone. Based on KDIGO treatment targets, women had a significantly higher rate of achievement of spKt/V > 1.2 (91.4% vs 80.7%, P = .005) and URR ≥ 70% (77.0% vs 54.7%, P < .001) than men. A significantly higher rate of treated volume of ≥ 1 L/kg/BW, and phosphorus 2.5 to 4.6 mg/dL was found in women (90.0% and 40.2%) compared to men (68.7% and 27.3%). In contrast, men had a significantly higher rate of prescribed Qb ≥ 300 mL/min (26.7% vs 12.6%, P = .001), albumin ≥ 40 g/L (36.7% vs 26.4%, P = .047), and Hb > 12 g/dL (22.0% vs 11.5%, P = .011) than women. There was no significant difference between men and women in the rate of calcium 8.4 to 10.4 mg/dL, and parathyroid hormone 150 to 600 pg/mL. These differences were not the same across 4 age categories (<60, 60–69, 70–79, and ≥ 80). Most of the differences above were among patients aged < 60 and 60 to 69 years. Although men had higher satisfactory treatment parameters than women, based on KDIGO treatment targets, women received hemodialysis more effectively than men. Treatment targets for patients on hemodialysis should consider gender and age differences.

We evaluated angiogenin as a prospective biomarker in peripheral artery disease (PAD) patients with and without claudication symptoms. A pilot study suggested an elevation of angiogenin in critical limb ischemia. However, in PAD patients, the predictive value of angiogenin has not yet been evaluated. For this purpose, 342 patients with PAD (age: 69 ± 10 years, 34.5% women) were followed-up for 7 years in a cross-sectional study. Angiogenin was measured by enzyme-linked immunosorbent assay. All-cause and cardiovascular mortality were analyzed by Cox regression. Angiogenin levels were higher in men ( P = .001) and were associated with patient waist-to-hip ratio ( P < .001), fasting triglycerides ( P = .011), and inversely with estimated glomerular filtration rate ( P = .009). However, angiogenin showed no association with age, characteristics of diabetes, markers of lipid metabolism, or C-reactive protein. Angiogenin did not correlate with markers of angiogenesis such as vascular endothelial growth factor, angiopoietin-2, or tie-2. Furthermore, angiogenin was not associated with PAD Fontaine stages or with patient ankle-brachial index in addition to all-cause mortality (hazard ratio [HR] = 1.09 [95% CI: 0.89-1.34]) or cardiovascular morality (HR = 1.05 [0.82-1.35]). These results suggest that angiogenin does not provide further information regarding outcome prediction in patients with PAD.

Background: The JAK2 46/1, also referred to as the GGCC, haplotype, is represented by 4 main SNPs spanning a region of 250kb in chr9 including the JAK2 gene, that are in complete linkage disequilibrium. The GGCC haplo was found to confer susceptibility to JAK2 mutated myeloproliferative neoplasms (MPN) (Jones AV, 2009; Olcaydu D, 2009; Kilpivaara O, 2009) while association with JAK2-wildtype MPN remains controversial (Pardanani A, 2010; Jones AV, 2010; Guglielmelli P, 2010; Trifa A, 2016). The GGCC haplo was also found enriched in MPN pts with splancnic vein thrombosis (SVT) (Smalberg JH, 2011), and to correlate with higher JAK2V617F variant allele frequency (VAF) (Alvarez-Larran, A, 2012). Nullizigosity for GGCC haplo was associated with reduced survival (OS) in pts with myelofibrosis (MF) (Tefferi A, 2019), but no information on the impact of GGCC haplo status with phenotype and outcome in PV is available. Aim: To assess the clinical correlates and the prognostic significance of GGCC haplo status in a large cohort of pts with PV. Pts and Methods: A total of 399 PV pts, all JAK2V617F mutated, diagnosis revised according to 2022 ICC criteria, were genotyped for 46/1 haplotype by PCR allele discrimination with rs12343867 (with the “C” allele standing for 46/1 haplotype). Results: A total of 301 pts (75.4%) had the C allele, of which 143 (47.5%) were CC homo and 158 (52.5%) CT hetero; 98 (24.6%) were nullizygous for GGCC (TT). Since preliminary analysis disclosed no significant difference between CT and TT haplotype for all variables considered, homozygous CC pts were compared to TT+CT. The CC haplotype was associated with higher leukocytes (median 11.3x10e9/L vs 9.6, p&lt;.001), higher hemoglobin (18.4 g/dL vs 17.5, p&lt;.001), lower platelets (441x10e9/L vs 514, p=.002) more aquagenic pruritus (51.8% vs 33.2%, p=.001), and higher JAK2VAF (60.8+-24.8% vs 36.8+-19.7%, p&lt;.001) at diagnosis. Pts with a VAF &gt;50% were 69% in CC versus 24.1% in TT+CT pts (p&lt;.001). ASXL1 mutations were enriched among CC pts (20.3% vs 9.4%, p=0.04), otherwise no difference regarding additional myeloid mutations was noted. All above differences remained significant when considering CC versus TT and CT separately. More pts with CC haplotype suffered from venous thrombosis (VT) during the FU (16.1% vs 4.3%, p&lt;.001), no difference was noted for arterial thrombosis nor for splancnic vein thrombosis. VT-FS by Kaplan Meyer was significantly shorter (p&lt;.001) in CC pts; the rate of VT at 5, 10, 15y after diagnosis, was 5.5%, 12%, 20.2% for CC versus 2.6%, 3.4%, 6.4% for TT+CT, respectively (all p&lt;.001). In multivariable analysis, including JAK2VAF &gt;50%, age &gt;60y, history of VT, WBC &gt;15x10e9/L, only CC haplo remained significant (HR 3.6, 95%CI 1.4-9.5, p=.009). Progression to post-PV MF occurred in 81 pts (20.3%), significantly more among CC (n=45, 31.5%) than TT+CT (n=36; 14.1%; p&lt;.001). Myelofibrosis-FS was significantly shorter in CC vs other genotypes (p=.02). However, in multivariable analysis, only BM fibrosis G1 remained significant (HR 3.2, 1.7-5.9; p&lt;.001). Evolution to blast-phase occurred in 13 pts (3.2%), 9 (6.3%) with CC haplo vs 4 TT+CT (1.6%; p=.01). During the follow-up, 102 pts (25.5%) died, 50 (35%) CC and 52 TT+CT (20.3%; p=.001). In multivariable analysis, including MIPSS-PV variables (Tefferi A 2020), the CC haplo remained significant (HR 1.8, 1.04-3.2, p=.03) together with age (HR 3.0, 1.6-5.7; p&lt;.001), WBC (HR 2.6, 1.3-4.8; p=.004), and thrombosis history (HR 1.9, 1.0-3.7; p=.03). Conclusions. Homozygosity for the 46/1 or CC haplotype contributes to the phenotype diversity of PV, in part possibly mediated by associated higher JAK2V67F VAF, and predicts for incident VT and shorter OS. Supported by AIRC, 21267; MIUR,2022F4WMR3; IHM, PNRR-MAD-2022-12376695