Int-1 Groups Research Articles

The effect of crude alcoholic extract of Withania somnifera leaves in experimentally induced arthritis in mice

The alcoholic extract 70% of the leaves of Withania Somnifera was dried and percentage of extract 8.3 were used .Incomplete freunds adjuvant was used to induce arthritis in mice 0.1ml of this adjuvant was injected in the right tarsal joint. The mice were divided into four groups, the first group were treated with alcoholic extract 500mg/kg body weight (T1), the second group was treated with diclofenac sodium 3mg/kg body weight (T2) and third group was treated with distilled water (T3), the fourth group used as a control group (T4) non induced non treated.Vernier calipers was used for measuring the diameter of the joint. The mice in T1group showed a significant decrease in the diameter of tarsal joint of right leg as compared with mice in T2, T3 and T4 groups. The hematological results of mice in T1 group showed significant increase as compared with T4 group. While inT2 and T3 groups showed a significant decrease as compared with T4 group .The histological results showed that the joint of mice in T1 group showed no inflammatory response in the membrane of joint. The joint of mice in T2 group showed inflammatory cell infiltration while the joint of mice in T3 group showed fibrous connective tissue proliferation with mononuclear cell infiltration in the membrane of the joint .

The difference in the survival rate of patients with metastatic renal cell carcinoma in the intermediate-risk group of the Memorial Sloan Kettering Cancer Center criteria.

ObjectivesTo investigate the necessity of stratifying patients in the intermediate-risk group of the Memorial Sloan Kettering Cancer Center (MSKCC) criteria in a real-world population of patients with metastatic renal cell carcinoma.Patients and MethodsWe retrospectively analyzed 234 consecutively treated patients who had received molecular targeted drugs. We examined the difference between progression-free survival and overall survival among patients in the intermediate-risk group of MSKCC criteria. We divided the intermediate group into two subgroups as follows: patients positive for only one risk factor (Int-1) and those positive for two risk factors (Int-2) including performance status, serum hemoglobin level, time from diagnosis to treatment, and corrected calcium and lactate dehydrogenase levels. Next, we evaluated the association between the number of metastatic organs, the presence of pancreatic metastasis, Int-1 or Int-2 grouping, and overall survival.ResultsThe median overall survival was 41.2 months. The median overall survival of the favorable-, intermediate-, and poor-risk groups of the MSKCC criteria were 91.0, 33.6, and 15.2 months, respectively. Patient characteristics were similar between the Int-1 and Int-2 groups. Increased positivity for risk factors of MSKCC classification between the two groups was for performance status and serum hemoglobin level. Progression-free survival and overall survival of the Int-1 group were significantly higher than those of the Int-2 group. In Cox proportional stepwise multivariate analysis, the Int-1 and Int-2 classification was an independent risk factor for overall survival.ConclusionPatients in the intermediate-risk group had different prognoses depending on the number of positive risk factors.

Axial displacement of external and internal implant-abutment connection evaluated by linear mixed model analysis.

To analyze the axial displacement of external and internal implant-abutment connection after cyclic loading. Three groups of external abutments (Ext group), an internal tapered one-piece-type abutment (Int-1 group), and an internal tapered two-piece-type abutment (Int-2 group) were prepared. Cyclic loading was applied to implant-abutment assemblies at 150 N with a frequency of 3 Hz. The amount of axial displacement, the Periotest values (PTVs), and the removal torque values(RTVs) were measured. Both a repeated measures analysis of variance and pattern analysis based on the linear mixed model were used for statistical analysis. Scanning electron microscopy (SEM) was used to evaluate the surface of the implant-abutment connection. The mean axial displacements after 1,000,000 cycles were 0.6 μm in the Ext group, 3.7 μm in the Int-1 group, and 9.0 μm in the Int-2 group. Pattern analysis revealed a breakpoint at 171 cycles. The Ext group showed no declining pattern, and the Int-1 group showed no declining pattern after the breakpoint (171 cycles). However, the Int-2 group experienced continuous axial displacement. After cyclic loading, the PTV decreased in the Int-2 group, and the RTV decreased in all groups. SEM imaging revealed surface wear in all groups. Axial displacement and surface wear occurred in all groups. The PTVs remained stable, but the RTVs decreased after cyclic loading. Based on linear mixed model analysis, the Ext and Int-1 groups' axial displacements plateaued after little cyclic loading. The Int-2 group's rate of axial displacement slowed after 100,000 cycles.

Comparison of Risk Models for Patients with Lower Risk Myelodysplastic Syndromes

Accurate prognostication is essential for patients with myelodysplastic syndromes (MDS) to facilitate optimal patient management. Several systems for predicting the outcome of patients with MDS are commonly used in clinics, including the International Prognostic Scoring System (IPSS), revised IPSS, and a low risk MDS model developed by The University of Texas MD Anderson Cancer Center (MDA). We designed this study to evaluate and compare these three models in lower risk MDS patients in order to accurately identify patients with a poor prognosis who may need early therapeutic intervention.A total of 733 adult patients, median age 69 years (range, 24-91), who were diagnosed as lower risk MDS (IPSS low or intermediate-1) with complete cytogenetic evaluations at MDA were included in this study. Both IPSS and revised IPSS systems stratified the study cohort into groups with significantly different overall survival (OS) (P<0.001 in both). The MDA model further stratified patients into significantly different OS groups (P<0.001), and further stratified the revised IPSS low group (N=248, P<0.001) by OS, but not the very low or intermediate (INT) groups.Because both IPSS models are heavily weighted toward cytogenetic features, but over half of MDS patients present with normal (diploid) cytogenetics, we compared the effectiveness of these models in risk stratification among diploid MDS patients. Without the effects of cytogenetics, all 3 models still stratified OS significantly (P<0.001 for all). Revised IPSS further stratified IPSS low (N=171, P<0.001) and INT-1 (N=184, P=0.005) into significant different OS groups. The MDA model further stratified IPSS low (P=0.041) and INT-1 (p<0.001) into significant different OS groups. Multivariate analyses showed that age, bone marrow blast count, and hemoglobin and platelet levels were independent factors for survival in all MDS patients and in diploid MDS patients, whereas absolute neutrophil count was not significant for either group.Molecular markers hold promise for further risk stratification in diploid MDS patients. We assessed the prognostic significance of common gene mutations, such as NPM1, FLT3, DNMT3A, NRAS and KIT. We also identified a signature of plasma microRNAs of which expression levels can predict survival of diploid MDS patients more accurately than all three models.In summary, the revised IPSS system has improved the stratification of patients in the IPSS low and INT-1 categories. The MDA model improves the OS stratification in IPSS low and INT-1 groups, as well as the revised IPSS low group. All three systems effectively predict survivals in diploid MDS patients. Development of novel molecular markers will enable further risk stratification of MDS patients, especially in the diploid MDS group. [Display omitted] [Display omitted] DisclosuresKantarjian:ARIAD, Pfizer, Amgen: Research Funding. Cooper:InCellerate: Equity Ownership; Sangamo: Patents & Royalties; Targazyme: Consultancy; GE Healthcare: Consultancy; Ferring Pharmaceuticals: Consultancy; Fate Therapeutics: Consultancy; Janssen Pharma: Consultancy; BMS: Consultancy; Miltenyi: Honoraria.

The effect of crude alcoholic extract of Withania somnifera leaves in experimentally induced arthritis in mice

The alcoholic extract 70% of the leaves of Withania Somnifera was dried and percentage of extract 8.3 were used.Incomplete freunds adjuvant was used to induce arthritis in mice 0.1ml of this adjuvant was injected in the right tarsal joint. The mice were divided into four groups, the first group were treated with alcoholic extract 500mg/kg body weight (T1), the second group was treated with diclofenac sodium 3mg/kg body weight (T2) and third group was treated with distilled water (T3), the fourth group used as a control group (T4) non induced non treated.Vernier calipers was used for measuring the diameter of the joint. The mice in T1group showed a significant decrease in the diameter of tarsal joint of right leg as compared with mice in T2, T3 and T4 groups. The hematological results of mice in T1 group showed significant increase as compared with T4 group. While inT2 and T3 groups showed a significant decrease as compared with T4 group .The histological results showed that the joint of mice in T1 group showed no inflammatory response in the membrane of joint. The joint of mice in T2 group showed inflammatory cell infiltration while the joint of mice in T3 group showed fibrous connective tissue proliferation with mononuclear cell infiltration in the membrane of the joint .

Effect of cyclic loading on axial displacement of abutment into implant with internal tapered connection: a pilot study

statistically significant. Results: The mean axial displacement after 10,000 cycles were 0.714 ± 0.488 ㎛ in Ext group, 5.286 ± 1.604 ㎛ in Int-1 group, and 11.429 ± 1.902 ㎛ in Int-2 group. In the pattern analysis, Int-1 and Int-2 group showed continuous axial displacement at 10,000 cycles. There was no declining pattern of axial displacement in the Ext group. Conclusion: The pattern of linear mixed model in Ext group showed no axial displacement. There were continuous axial displacements in abutment-implant assemblies in the Int-1 and Int-2 group at 10,000 cycles. More axial displacement was found in Int-2 group than in Int-1 group. (J Korean Acad Prosthodont 2013;51:315-22)

Identification of Poor Risk Patients in Low and Intermediate-1 (Int-1) IPSS MDS with the New Ipssr Index and Comparison with Other Prognostic Indexes. A Study by the Spanish Group of MDS (GESMD)

AbstractAbstract 702Despite that low and intermediate-1 (int-1) IPSS groups are commonly considered as low risk diseases with a median overall survival exceeding 60 months, some of these patients will evolve as higher risk myelodysplastic syndrome (MDS). Recently several new prognosis indexes (PI) have been proposed: The new IPSSr, WPSSr, MD Anderson for lower risk patients (MDA) Index, and the Spanish Group of MDS (GESMD) proposal that considers as high risk those patients with int-1 IPSS and at least one of the following: platelets <30×109/L, granulocytes <0.5×109/L, poor or very poor-risk karyotype or the presence of bone marrow (BM) fibrosis. The aim of the study was to compare the four PI and to analyze which of them was the best to identify patients with the poorest risk (defined as those with a median overall survival (OS) lower than 30 months) and to segregate different risk groups in a population of lower risk MDS patients. Indexes were compared using the Akaike analysis methodology.A total of 2410 patients from the Spanish registry of MDS with low or int-1 IPSS were included. Median age was 74 years (42.6% female). The IPSS value was of: 0, 0.5 and 1 in 1314, 761 and 335 patients, respectively. The four poor risk variables defined by the GESMD confirmed its adverse predictive value for OS: granulocytes <0.5×109/L (n=101, P<0.001), platelets <30×109/L (n=94, P<0.001), poor or very poor risk karyotype (n=35, P=0.007), and BM fibrosis (n=109 of 698 evaluable patients, P<0.001). The presence of at least one of these was associated with adverse prognosis in the int-1 group but not in the low IPSS risk group, thus only the former was considered as high risk.The distribution of patients across the four PI is detailed in the Table. These new PI identified between 16.9% and 46% of patients having a median OS of around 30 months within the int-1 patients (wide line in the table), but none of the PIs could identify such a poor prognosis patients in the low IPSS group. The PI that identified the highest number of patients with shorter OS was the new IPSSr, while MDA IP was the most discriminative in the Akaike analysis. In conclusion, IPSS is not discriminative enough in the int-1 group. In contrast, the application of the new PI can be employed to better identify poor prognosis patients within the int-1 group who could benefit from a high-risk approach.TableOverall survival and AML evolution according to the different prognostic index.PROGNOSIS INDEX (AIC for the whole population/and for the Int-1) populations)PROGNOSIS GROUPIPSS LOW (N=1314) OS: 87.78 m (95% CI:74.5-101.0) AML EVOLUTION (3 years): 9.1% (95% CI: 6.9-11.3%)IPSS INT-1 (N= 1096) OS: 44.2 m (95% CI:39.1-49.3) AML EVOLUTION (3 years): 26.9% (95% CI: 23-30.8%)N (%)Overall Survival Median (95% CI) monthsAML evolution (3 years) % (95% CI)N (%)Overall Survival Median (95% CI) monthsAML evolution (3 years) % (95% CI)GESMD (12566.6/6425.9)LOW1314 (100)860 (78.5)48.1 (40.9-55.3)*25.1 (20.7-29.5)**HIGH0 (0)236 (21.5)32.7 (39.1-49.3)*34.3 (24.5-44.1)**MD. Anderson (12381.4/6357.2)LOW508 (39.3)130.3 (104.6-157.0)*9% (5.4-12.6)!109 (9.9)115.2 (83.8-146.6)*15.7 (6.5-24.9)*INT781 (59.4)69.7 (62.4-77.1)*8.9% (6.9-11.9)!653 (59.6)51.3 (44.2-58.3)*23.3 (18.3-28.3)*HIGH25 (1.9)58.4* (25.4-91.5)*——–——–—334 (30.5)24.1 (19.3-28.9)*39.9 (31.3-48.5)*IPSS-R (12409.9/6369.6)VERY LOW690 (52.5)118.8 (105.7-131.7)*6.4% (4.2-8.6)***79 (7.2)113.7 (39.9-187.4)*17.8 (4.6-31)*LOW602 (45.8)65.9 (57.6-74.2)*11.6% (7.8-15.4)***505 (46.1)60.3 (53.3-67.2)*18.2 (13.4-23)*INT22 (1.7)58.9 (25.2-92.7)*26% (2-50)***416 (38)30.5 (26.1-34.8)*38.6 (30-47.2)*HIGH0 (0)95 (8.7)21.2 (16.5-25.9)*48.5 (32.5-64.5)*VERY HIGH0 (0)1 (0.1)WPSS-R (12477.4/6414.7)VERY LOW517 (39.3)115.2 (103.0-127.4)*6.5 (3.7-9.3)$76 (6.9)56.5 (38.2-74.9)*22.8 (10.6-35)*LOW524 (39.9)78.5 (66.7-90.3)*12.1 (7.7-15.5)$289 (26.4)61.3 (48.3-74.2)*19.2 (12.4-25.6)*INT61 (4.6)46.0 (30.8-61.1)*13.7 (3.1-24.3)$386 (5.2)42.5 (32.8-52.2)*27.8 (20.8-34.8)*HIGH3 (0.2)185 (16.9)24.11 (19.4-28.8)*49.3 (35.7-62.9)*VERY HIGH0 (0)4 (0.4)NOT EVAL209 (15.9)87.8 (74.6-101.3)*7.2 (3-11.4)$156 (14.2)48 (30.8-65.2)18.3 (9.1-27.5)*AIC: Akaike Information Criteria. Int: Intermediate, Not Eval: Not evaluable, CI: Confidence interval.*P<0.001;**P=0.02;***P=0.04;!P=0.7 $P=0.1 [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Investigation of colour, texture and organoleptic properties of retailed conventional and organic chicken breast in Hungary

The large price variation paid for chicken meat originated from organic and conventional systems require up-todate knowledge of physical and sensory properties of the mentioned products. Our aim was to find differences between intensively vs. organically reared chicken breasts as they are currently presented to consumers in Hungary. A total of 30 broiler breast fillets (n = 10 per group) were purchased from 2 retail stores and a processor. Experimental groups were intensively reared (INT1 and INT2) and organically reared (ORG ). In this case no attempt was made to collect information on genotype, feed or growing conditions of the birds. We measured meat colour (L*, a*, b*), shear force, texture and sensory traits of cooked samples. L* and b* values were lower in INT1 and INT2 groups (P &lt; 0.001), however no differences were found in redness (a*) among the 3 groups. Shear force was highest in ORG samples, which panelists also found drier and tougher. An overall preference was observed for juiciness, tenderness, initial smell and taste in INT1 group. However, panelists did not recognize significant differences between INT2 and ORG samples in most traits, except juiciness. Profile and Bi-plot diagrams were created to demonstrate sensory traits and coherences. Although, samples of organically reared birds were less popular among our panelists, its contribution to healthy, traditional dishes is undeniable.

Effects of monolaurin and lactic acid bacteria starter culture on growth of vegetative cells of Bacillus cereus in Iranian white fresh cheese

The harmful effects of many chemical food preservatives are well established, so this has triggered interest in natural methods of preservation. Monolaurin, a monoester of lauric acid, founds naturally in some foods and has various antiviral and antibacterial activities. Evaluation of the effects of monolaurin separately and in combination with lactic acid bacteria (LAB) starter culture on growth of vegetative cells of Bacillus cereus ATCC11778 in manufactured cheeses was the purpose of this research. In this study, the number of B. cereus in four groups of cheese (C1: without starter culture and monolaurin, T1: without starter culture; with monolaurin, C2: with starter culture; without monolaurin, T2: with starter culture and monolaurin) was counted on days 0, 1, 3, 5, and 7 of manufacture. In T1 group, monolaurinin concentrations of 800, 1200, 1600 and 2000 ppm decreased the number of B. cereus by 1.2, 2.1, 3 and 3.4 logs, respectively in comparison with C1 group. InT2 group with the same concentrations of monolaurin, the number of B. cereus in comparison with C2 group was not significantly affected (p>0.05). In C2 group, starter culture decreased the number of B. cereus by 2.9 logs in comparison with C1 group. In contrary, the combination of starter culture with monolaurin in T2 group increased the number of B. cereus by 0.6 logs in comparison with C2 group. Furthermore, in C2 and T2 groups by increasing the storage time, the number of B. cereus decreased. According to these results, it can be concluded that in cheese samples of T1 group, monolaurin separately showed the inhibitory effects on the growth of B. cereus cells while in cheese samples of T2 group, the combination of monolaurin with starter culture did not demonstrate the synergistic inhibitory effects on the growth of this bacterium. Therefore, simultaneous use of monolaurin with starter culture is not recommended for improving the microbial shelf-life of Iranian white fresh cheese.

Prognostic Performance of the Cytogenetic Risk Classification Defined by the German-Austrian Myelodysplastic Syndromes (MDS) Study Group and Its Contribution to the International Prognostic Scoring System (IPSS) and the World Health Organization-Based Prognostic Scoring System (WPSS)

AbstractAbstract 4005 Background and objective:the cytogenetic risk classification defined by the 1997 IPSS remains the most widely used to assess the prognostic impact of karyotype in the MDS. Recently, the German-Austrian MDS Study Group (Haase, Ann Hematol 2008; 87:515) has proposed a new, more comprehensive cytogenetic risk classification. Our aim was to assess the prognostic performance of the Haase's cytogenetic classification, as compared to that defined by the IPSS, and what would be its contribution to the IPSS and WPSS. Methods: MDS patients seen at our center after 1986 were eligible for inclusion if they had a cytogenetic study performed at diagnosis that could be scored according to both the IPSS and the Haase's criteria. The prognostic performance was assessed by the Harrell's concordance index and the R2 explained variation (the closer both statistics to 1 the better the prognostic performance). Results: 327 out of 494 patients seen after 1986 met the eligibility criteria. Median age was 73 (range: 16–97) years and 55% were women. The 2001 WHO categories were refractory anemia (RA, 6%), RA with ringed sideroblasts (RARS, 2%), refractory cytopenia with multilineage dysplasia (RCMD, 54%), RCMD with ringed sideroblasts (RCMD-RS, 11%), RA with excess of blasts (RAEB-1, 11%; RAEB-2, 14%), and del(5q) (2%). According to the IPSS cytogenetic classification, 232 (71%) patients were in the low risk group, 46 (14%) in the intermediate, and 49 (15%) in the high risk group. According to Haase's criteria, 239 (73%) patients were in the good prognosis group, 26 (8%) in the int-1, 25 (8%) in the int-2, and 37 (11%) in the poor prognosis group. Agreement between both karyotype-based risk classifications was high (Kendall's tau=0.92; Kruskal's gamma=0.99). At the study closing date, median survival for the whole series was 4.1 years, 160 (49%) patients had died and 27 (8%) were lost to follow-up. Median survival (95% CI) in years according to the IPSS cytogenetic classification was 5.2 (4.2-6.4) for the low risk group, 3.8 (1.7-5.0) for the intermediate, and 0.9 (0.7-1.1) for the high risk group. Median survival (95% CI) in years according to Haase's criteria was 5.2 (4.1-6.4) for the good prognosis group, 3.9 (1.6-not reached) for the int-1, 3.1 (0.9-3.8) for the int-2, and 0.8 (0.6-1.9) for the poor prognosis group. There was no statistically significant difference in survival between the int-1 and Int-2 groups. Grouping the Int-1 and Int-2 into a single intermediate risk category yielded a median survival of 3.5 (1.7-4.4) years, which was significantly different from that of good and poor risk groups (p=0.014 and p=0.0001, respectively). The figure shows the concordance and R2 statistics for both cytogenetic classifications as well as those of the IPSS and the WPSS had they been based on the Haase's score, as compared to the standard ones. For this latter analysis, the Haase's int-1 and int-2 categories were grouped together. Conclusion: The new cytogenetic risk classification was comparable to that defined by the IPSS with regard to prognostic performance and did not improve the discriminatory power of the IPSS or the WPSS. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

IPSS-Independent Cytogenetic Risk Categorization in Primary Myelofibrosis.

Abstract 2909Poster Board II-885 Background:Previous studies have identified sole abnormalities of del(20q) and del(13q) as prognostically favorable cytogenetic markers in primary myelofibrosis (PMF) (Tefferi et al. BJH 2001;113:763). A more recent study (Tam et al. Blood 2009;113:4171) confirmed these findings and suggested additional cytogenetic markers of prognosis. In the current study with larger numbers of informative patients studied at time of diagnosis, we wanted to validate these observations and examine the prognostic interaction between cytogenetic risk categorization and the International Prognostic Scoring System (IPSS). Methods:Patients with cytogenetic information at diagnosis were selected from the Mayo Clinic database of WHO-defined PMF. Specific cytogenetic categories were considered only in the presence of at least 5 informative patients; otherwise, they were included in the category of “other cytogenetic abnormalities”. Follow-up information was updated in July, 2009. Survival curves were prepared by the Kaplan-Meier method and compared by the log-rank test. Cox regression model was used for multivariable analysis. Results:200 patients were studied (median age, 62 years; 63% males). The IPSS risk distributions were low in 66 patients, intermediate (int)-1 in 64, int-2 in 44 and high in 26. Cytogenetic findings at diagnosis were abnormal in 83 (42%) patients and included sole del(20q) in 21, complex (i.e. 3 or more abnormalities) in 13, sole del(13q) in 8, sole +8 in 7, sole +9 in 6, and other abnormalities in 28 patients. Median survivals in low, int-1, int-2 and high IPSS risk groups were 188, 71, 47 and 26 months, respectively (p < 0.0001). Median survival in patients with sole +9 was not reached and in those with sole del(13q), sole del(20q), normal karyotype, complex abnormalities and sole +8 was 112, 108, 80, 37 and 27 months, respectively, while it was 46 months for patients with other cytogenetic abnormalities (p = 0.01). Accordingly, sole abnormalities of +9, del(20q) and del(13q) were categorized as being favorable (n = 35) and complex abnormalities and sole +8 as unfavorable (n = 20); the respective median survivals were 112 and 34 months (p=0.002; Figure). Multivariable analysis confirmed the IPSS-independent prognostic value of cytogenetic risk categorization and the intra-IPSS risk prognostic distinction was most apparent in the int-1 group: median survival was 35 and 81 months in the presence of unfavorable or favorable cytogenetic markers, respectively (p=0.0009; Figure). Conclusion:The current study identifies sole +9, along with del(13q) and del(20q), as favorable and sole +8, along with complex abnormalities, as unfavorable cytogenetic markers of prognosis in PMF. Cytogenetic risk categorization in PMF has an IPSS-independent prognostic value that is important in patient selection for specific therapy. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

P126 Treatment of progression of myeloproliferative neoplasm (MPN) to MDS/AML by azacytidine (AZA): a report on 44 patients (pts)

Aberrant expression of the adhesion molecule CD44 correlates with poor prognosis in various neoplasms. To evaluate the prognostic impact of CD44 in myelodysplastic syndromes (MDS) serum levels of soluble CD44 (sCD44) were measured in 130 MDS patients using an enzymelinked immunosorbent assay (ELISA). sCD44 levels were significantly elevated in MDS patients compared to healthy donors (p< 0.05), and were found to correlate with distinct FAB subtypes. The highest levels of sCD44 were found in patients with CMML and in patients with MDS transformed into acute myeloid leukemia (AML). In univariate analysis elevated levels of sCD44 s were significantly correlated with shorter overall survival in MDS-patients (9 versus 37 months; p< 000). In multivariate analysis sCD44 s displayed prognostic significance for survival independent from the International Prognosis Scoring System (IPSS). To test for refined prognostication, each IPSS risk group was split into two separate categories based on sCD44 s levels. Using this approach, MDS patients with a shorter survival were identified both in the IPSS low-risk (p = 0.014) and in the IPSS Int-1 group (p = 0.031). The CD44 s-adjusted IPSS defines a cohort of MDS patients with unfavorable prognosis within the low and intermediate-1 IPSS groups, which might be helpful in risk stratification and in therapeutic algorithms.

Erythropoetin (EPO) and Granulocyte Colony Stimulating Factor (GCS-F) Based Therapy in Patients with Low Risk MDS: A Single Centre Experience from India.

MDS is a group of clonal disorders characterized by ineffective erythropoiesis and peripheral cytopenias. We report our single centre experience of treatment of low risk MDS. A total of 68 patients (M:F 49:19) were treated with either EPO or EPO with G-CSF combination and followed up for a period of 6 years. MDS diagnosis was based on the WHO criteria and patients with MDS-RAEB were excluded. The mean age was 48 years(range:24–72yrs). This treatment was offered as an upfront therapy in view of non feasibility of other modalities of treatment(e.g., non- availability of HLA matched donors, poor clinical status and co-morbid conditions). Patients were randomly divided into 2 Arms. Arm ‘A' (n = 55) received EPO(10,000 units) once a week and G-CSF(150μg) alternate day for 12 weeks. 13 Patients in Arm ‘B' received EPO alone in same dose for 12 weeks. If a patient did not show an erythroid response in Arm ‘B', he / she was shifted to the combination arm. Once adequate erythroid response was achieved, patients were put on lowest effective EPO dose. Patients who interrupted their treatment in between for whatever reasons were excluded (n =10) from study.14 Patients who showed a decline in response were given an escalated dose of EPO (20,000 units per week).The overall erythroid response rate was 58%. It was partial (100% reduction in red cell transfusion requirement) in 30% of patients and complete (maintaining hemoglobin at >11.5 G/dL without red cell transfusion) in 28%. The median response duration was 28 months (range:6–72 months). Erythroid response was better in the first Arm (65%) vis-à-vis Arm B (33%). Patients, who started therapy before they became transfusion dependent, achieved an earlier response within 8 weeks(range:4–24 weeks). The complete responders also showed a longer duration of response than the partial responders.35% of patients progressed to AML after a median duration of 28 months(range:3–60 months). Eleven patients who stopped therapy (5:AML progression, 6:unrelated causes) were excluded from the analysis. Patients with IPSS Low group showed durable response than the patients with Int-1 group. Though there was no definite survival benefit, the responders became transfusion free or less dependent on transfusion without any adverse effect on the outcome, thereby improving the quality of life.The erythroid response in our patients was better than in most reported series in the west. However, the progression to AML was 35% in our patients during the 60 months follow-up duration, which is marginally higher than the western series and it is important to be further studied. In conclusion, patients with IPSS low / Int-1 score should be offered EPO+ G-CSF combination therapy to achieve a durable response in contrast to the patients with high risk IPSS patients, in developing countries.