IDA Group Research Articles

Comparison of iron status markers in iron deficiency anemia and anemia of chronic kidney diseases

Comparison of iron status markers in iron deficiency anemia and anemia of chronic kidney diseases - IJCBR- Print ISSN No: - 2394-6369 Online ISSN No:- 2394-6377 Article DOI No:- 10.18231/j.ijcbr.2019.055, International Journal of Clinical Biochemistry and Research-Int J Clin Biochem Res

Intra-corporeal delta-shaped anastomosis in laparoscopic right hemicolectomy for right colon cancer: a safe and effective technique.

Background and objectiveIntra-corporeal delta-shaped anastomosis (IDA) is an important development in laparoscopic digestive-tract reconstruction. We applied it in laparoscopic right hemicolectomy for right colon cancer and compared the short-term outcomes between the patients treated with IDA and conventional extracorporeal anastomosis (EA).MethodsBetween 1 January 2016 and 1 October 2017, 36 and 50 patients who underwent IDA and EA, respectively, were included. Data on clinicopathological characteristics, surgical outcomes, post-operative recovery and complications were collected and compared between the two groups.ResultsSurgical outcomes and clinicopathological characteristics were similar between the two groups except the length of incision, which was significantly shorter in the IDA group than in the EA group (4.6 ± 0.6 vs 5.6 ± 0.7 cm, P < 0.001). The time to ground activities, fluid diet intake and post-operative hospitalization did not differ between the groups; however, the time to first flatus was significantly shorter in the IDA group than in the EA group (2.8 ± 0.5 vs 3.2 ± 0.8 days, P = 0.004). The post-operative visual analogue scale for pain was lower in the IDA group than in the EA group on post-operative Day 1 (4.0 ± 0.7 vs 4.5 ± 1.0, P = 0.002) and post-operative Day 3 (2.7 ± 0.6 vs 3.4 ± 0.6, P < 0.001). The surgical complication rates were 8.3 and 16.0% in the IDA and EA groups (P = 0.470), respectively. No complications such as anastomotic bleeding, stenosis and leakage occurred in any patient.ConclusionsIDA is safe and feasible and shows more satisfactory short-term outcomes than EA.

Effects of Iron Supplementation on Hemoglobin Concentration in 12-18 Month Old Iron-Deficient Anemic Infants

A randomized double blind clinical trial was conducted to study the effects of iron supplementation on hemoglobin values of 97 iron-deficient anemic (DA) and iron-sufficient (IS) infants, 12 to 18 months of age. IDA (n=SO) infants were assigned randomly to either receive dietary ferrous sulfate or placebo for 4 months. Similar treatment randomization was done among IS (n=4 7) infants. Before intervention, the mean hemoglobin value of the IDA infants was significantly (p&lt;0.01) lower than that of the IS group. After intervention, there was an increase in the hemoglobin values of the IDA infants who had received iron, and was significantly (p&lt;0.01) higher than those of the placebo treated IDA group, lS group, as well as placebo treated IS group. Hemoglobin values of the IDA infants who had received iron, increased up to the normal level as refer to the WHO's criteria used for normal hemoglobin values.

The Choice of Induction Regimen Affects Post Remission Survival of Acute Myelogenous Leukemia (AML) Patients with Intermediate or Poor Risk Disease

The fludarabine, high dose cytarabine and G_CSF with or without idarubicin combination regimen, referred to as FLAG+/-Ida, is commonly used as a salvage regimen for relapsed/refractory AML but its use as initial induction therapy has been more limited. The MRC trial 15 compared 2 induction courses of FLAG-Ida regimen to 3+7 (anthracycline plus cytarabine) regimens with etoposide (ADE) and found a higher relapse free survival among patients receiving FLAG-Ida. The findings of the MRC AML 15 trial are not widely applied in the United States as many experts use one course of induction followed by consolidation if patients achieve remission. The impact of choice of induction regimen on post remission survival in non-favorable risk AML patients remains unclear. To address this question, we assessed outcomes of 306 consecutive AML patients between aged 18 to75 years, with non-favorable NCCN risk who were received initial treatment at our center between January of 2009 and July of 2017 with either 3+7 (n=88) or FLAG+/-Ida (n=218). Our center's algorithm is to offer allogeneic HSCT as a consolidative therapy to all AML patients with non-favorable risk in CR1 who are considered transplant candidates. Patient characteristics were as follows: Median age 58(19, 75), male 55%, FLT-3 ITD positive 12%, NCCN risk ( intermediate 49%, poor 51%) and normal cytogenetics 45%. Baseline characteristics were similar between the two treatment groups with FLAG+/-Ida being younger at time of diagnosis (59 vs 66 years, P<0.001). A total of 240 (78%) patients achieved CR 1 after 3+7 (n=67, 76%) or FLAG+/-Ida (n=167, 79%) with no difference in the rate of achieving remission between the two groups. Patients in the FLAG-Ida group were more likely to achieve remission after one course of induction (74% vs 62%, p<0.001) and had a faster time to get into CR (30 days vs 37.5, p<0.001) compared to 3+7. CR was achieved in 84% and 73% of patients with intermediate and poor NCCN risk disease respectively. HSCT was performed in 172 patients accounting for 72% of the 240 patients who achieved CR post induction without any significant difference in transplant rates between FLAG+/-Ida and 3+7. The time from diagnosis to transplant was significantly shorter among CR patients after FLAG+/-Ida compared to 3+7 (FLAG+/- Ida 115 days vs 144 days for 3+7, p<0.001). After a median follow up of 41 months for patients achieving CR, the 3 year post remission OS and DFS was significantly better for patients receiving FLAG-Ida at 54% and 49% compared to 39% and 32% for patients receiving 3+7 respectively( P= 0.01 for both endpoints). In multivariate analysis, we analyzed factors associated with OS and DFS since achieving CR1 including age at CR1 (≤49, 50-64, ≥65), gender, race, NCCN risk, induction regimen, number of cycles to CR1, HSCT (yes, no) and year of CR1. HSCT was modelled as a time dependent covariate. A forward stepwise algorithm was implemented and variables were selected if p value was less than 0.05. Factors associated with r post remission survival included age at CR1 (≤49 vs50-64, HR 0.59, p=.02; ≤49 vs ≥65 HR 0.46, p=0.001), NCCN risk (intermediate vs poor HR 0.54, p<0.001), induction regimen (FlAG+/-Ida vs 3+7 HR 0.62, p=0.01) and receiving HSCT (yes vs no HR 0.68, p=0.02). Factors affecting DFS from time of CR also included age, NCCN risk, induction regimen (FlAG+/-Ida vs 3+7 HR 0.68, p=0.028) and receiving HSCT. This single center analysis shows that among patients with non-favorable risk AML, achieving CR after FLAG+/-Ida has better post remission survival than 3+7. This may be partially explained by the faster time to achieve CR and faster time to HSCT in the FLAG+/- Ida group. DisclosuresSolh:Amgen: Speakers Bureau; Celgene: Speakers Bureau; ADC Therapeutics: Research Funding.

Expression of Blimp-1 mRNA in Bone Marrow Mononuclear Cells in Multiple Myeloma Patients and Its Clinical Significance

To investigate the expression level of B lymphocyte-induced maturation protein-1(Blimp-1) mRNA in bone marrow mononuclear cells(BMMNC) of multiple myeloma(MM) patients and its clinical significance. Fluorescent quantitative real-time PCR(qRT-PCR) was used to measure Blimp-1 mRNA expression in BMMNC and flow cytometry(FCM) was performed to detect the number of malignant plasma cells in bone marrow of MM group (39 newly-diagnosed and untreated patients) and IDA group (5 IDA patients). The clinical data of all the patients' were collected, and the 39 patients in MM group were divided into 2 subgroups: in BD group 20 cases were treated with bortezomib-based regimen and in VOD group 19 patients were treated with VAD regimen. The age, sex, clinseal stage and type between the 2 subgroups were not statistically different. Blimp-1 mRNA expression level in BMMNC of MM patients was detected by qRT-PCR after 3 treatment cycles. The expression levels of Blimp-1 mRNA in BMMNC of IDA patients and MM patients divided into 3 groups according to ISS were (0.00047±0.00027), ISS I(0.09543±0.02800), Ⅱ(0.13606±0.04162),Ⅲ (0.21202±0.03940), separately. There was statistical difference among the 4 groups(F=56.929,P<0.05) and there was significant difference between any 2 groups of these 4 groups(P<0.05). Significant positive correlation was found between Blimp-1 mRNA expression level and the number of malignant plasma cells, serum monoclonal proteins (M protein), β2-microglobulin(β2-MG), lactic dehydrogenase(LDH), C-reactive protein(CRP)(P<0.05). There was significant negative correlation between Blimp-1 mRNA and hemoglobin (Hb) level (P<0.05). After 3 cycles of chemotherapy, Blimp-1 mRNA level of patients with a >50% reduction of M protein was significantly lower than that of patients whose M protein did not decrease significantly(P<0.05). After 3 treatment cycles, Blimp-1 mRNA expression in BMMNC in BD group was significantly lower than that in VAD group [(0.02388±0.00871) vs (0.04823±0.00219), P<0.05]. The Blimp-1 mRNA expression level in BMMNC may reflect the tumor burden in MM patients, which related with ISS, and positively correlated with the malignant plasma cell number, M protein, β2-MG, LDH, CRP level, and negatively correlated with Hb. The change of Blimp-1 mRNA expression level in BMMNC relates with the extent of M protein reduction, suggesting it may be used as a marker for response to therapy. Bortezomib may have effect on malignant plasma cells by suppressing Blimp-1 mRNA expression.

Augmented mitochondrial cytochrome c oxidase activity in children with iron deficiency: a tandem between iron and copper?

IntroductionDyshomeostasis of essential trace elements including iron and copper plays a key role in the pathogenesis of a myriad of serious conditions including iron deficiency (ID) anemia, in which impaired cellular energy metabolism is prominent. Although experimental studies documented decreased activity of cytochrome c oxidase (CytOx) in ID, there are not enough clinical data. The present study was conducted to determine serum copper levels and activity of mitochondrial CytOx in isolated lymphocytes of patients with iron deficiency.Material and methodsA total of 210 cases (2–17 years) were included in this prospective study. Serum iron and copper levels were measured. According to the serum iron levels, patients were allocated to iron deficient (ID, n = 70) and iron deficiency anemia (IDA, n = 70) groups, and iron-sufficient participants were allocated to the control group (n = 70). Activity of CytOx in the circulating lymphocytes was colorimetrically measured and compared with the controls.ResultsThe CytOx activity was significantly higher in the IDA (2.9 ±1.2 mOD/min, n = 62) group compared to the control group (2.4 ±1.3 mOD/min, n = 68, p < 0.001). Interestingly, serum copper levels were significantly higher in both the ID (106.9 ±55.5 μg/dl, n = 64, p = 0.0001) and IDA (115.1 ±50.2 μg/dl, n = 59, p = 0.0001) groups than the control group (72.1 ±46.7 μg/dl, n = 69).ConclusionsHigher serum copper levels in patients with IDA implicate co-operative interaction between these trace elements. The elevated CytOx activity in patients with IDA is probably secondary to the normal/elevated serum copper levels.

Metal complexes with N-(trifluoromethylbenzyl)iminodiacetate chelators (x-3F ligands). Part I. Copper(II) chelates of p-3F, m-3F, and o-3F with or without imidazole-like ligands

Eight Cu(II) complexes with N-(p-, m- or o-trifluoromethylbenzyl)iminodiacetate chelators (x-3F ligands) have been synthesized to promote C–F/H interligand interactions involving the F3C-group: {[Cu(μ2-p-3F)(H2O)]·3H2O]}n (1), [Cu(m-3F)(H2O)2] (2), [Cu(p-3F)(Him)(H2O)] (3), [Cu(m-3F)(Him)(H2O)] (4), [Cu(o-3F)(Him)(H2O)] (5), [Cu2(p-3F)2(H5Meim)2(H2O)2] (6), [Cu(m-3F)(H5Meim)(H2O)] (7), and [Cu(o-3F)(H5Meim)(H2O)] (8) [Him and H5Meim = imidazole and the “remote” tautomer 5-methylimidazole, respectively]. The compounds were studied by single-crystal X-ray diffraction, FT-IR, electronic spectra and coupled thermogravimetric + FT-IR methods. The conformation of the iminodiacetate chelating moiety (IDA group) is fac-NO + O(apical) in 1 and mer-NO2 in 2–8. The fac-IDA conformation observed in 1 is related to its polymeric structure and the coordination of a O’-carboxylate donor, from an adjacent complex unit, trans to the Cu–N(IDA) bond. The mer-IDA conformation in 2 is in agreement with similar compounds with an aqua ligand trans to the corresponding Cu–N(IDA) bond. As expected, the ternary complexes 3–8 feature a mer-IDA conformation. Some of the studied complexes exhibit disorder in the –CF3 group and C–H⋯F interligand interactions along with conventional N–H⋯O and O–H⋯O interactions. The thermal decomposition of all studied compounds under air flow produces variable amounts of trifluorotoluene.

Hematopoietic Cell Transplantation after TBI, Fludarabine, Idarubicine and Cytarabine Myeloablative Conditioning in Patients with Acute Myeloid Leukemia

▪IntroductionCombination of total body irradiation, fludarabine, cytarabine and idarubicine (TBI/Flu/AraC/Ida) is a disease-specific myeloablative conditioning regimen used in patients with acute myeloid leukemia. We report a single centre retrospective analysis of outcomes of allogeneic hematopoietic cell transplantation (allo-HCT) in patients with AML treated with TBI/Flu/AraC/Ida in comparison to TBI/Cy.MethodsPatients in the TBI/Flu/AraC/Ida arm received 12 Gy total body irradiation in 6 fractions on days -3 to -1, fludarabine 25mg/m2 on days -7 to -1, cytarabine 2000mg/m2 on days -7 to -3 and idarubicine 10mg/m2 on days -7,-5 and -3. Patients in TBI/Cy arm received 12Gy TBI in 6 fractions on days -3 to -1 and cyclophosphamide 60mg/kg on days -7 and -6.GvHD prophylaxis consisted of cyclosporine and methothrexate prior to year 2004. Since 2004, GvHD prophylaxis included cyclosporine with mycophenolate mofetil and ATG-Fressenius 20 – 40mg/kg was given to patients with unrelated donors.ResultsSixty four patients with AML received allo-HCT using TBI/Flu/Ida/AraC conditioning regimen between 2004 and 2012. Fifty three patients received TBI/Cy conditioning between 1987 and 1998 and between 2009 and 2014. Median age was 46 (range: 19-60) and 42 (range: 14-59) TBI/Flu/Ida/AraC and TBI/Cy, respectively.In the TBI/Flu/Ida/AraC group, 19 (30%) of patients received transplant from a HLA matched sibling donor, 16 (25%) from a HLA matched unrelated donor and 29 (45%) from HLA mismatched unrelated donor. In the TBI/Cy group, 24 (45%) of patients received transplant from a HLA matched sibling donor, 20 (38%) from a HLA matched unrelated donor and 9 (17%) from HLA mismatched unrelated donor (p = 0.0049). Other baseline patient and donor characteristics (patient/donor gender, CMV serology, AB0 matching, cytogenetic risk group, disease status and HCT-CI comorbidity score, ATG use) were not significantly different between the groups.Median time to neutrophil engraftment was 18 days (range 10 - 31) and 21 days (range 12 – 32) in TBI/Flu/AraC/Ida a TBI/Cy groups, respectively. Median time to platelet engraftment to more then 20G/l was 21 (range 12 – 103) and 22.5 (range 9 – 54) days, respectively. Among patients who survived more than 100 days, 2/45 patients did not engraft platelets in the TBI/Flu/AraC/Ida group and 3/35 in the TBI/Cy group.Overall survival (OS) at 2 years was 35% (95% CI: 25 – 49%) in TBI/Flu/Ida/AraC group and 47.5% (95% CI: 35 – 65%) in TBI/Cy group. Two years disease free survival (DFS) was 35% (95% CI: 25 - 49) in TBI/Flu/Ida/AraC group and 40% (95% CI: 27 - 58) in TBI/Cy group.Cumulative incidence of relapse at 2 years after transplant was 12.5% and 25% (p = 0,08), and the cumulative incidence of non-relapse mortality was 53% and 36% (p = 0.059) in the TBI/Flu/Ida/AraC and TBI/Cy groups, respectively.Survival curves and relapse incidence curves are presented in Figure 1.In multivariate analysis of the influence of baseline characteristics and conditioning regimen on OS and DFS, only HLA mismatch was significantly associated with increased risk of mortality with HR 2,22 (95% CI: 1,25 – 3,95). HR of death was 1.11 (95% CI: 0.62 – 1.98) and HR of death or relapse was 0.87 (95% CI: 0.50 - 1.52) in patients who recieved TBI/Flu/Ida/AraC.There was a trend towards increased incidence of acute graft versus host disease (aGVHD) grade II-IV in the TBI/Flu/AraC/Ida group (p = 0,09). The cumulative incidence of aGVHD was 46% and 34% in the TBI/Flu/AraC/Ida and TBI/Cy groups, respectively. Estimates of the cumulative incidence of aGVHD in the presence of competing risk of relapse or death are shown in Figure 2.ConclusionTBI/Flu/Ida/AraC regimen led to similar OS and DFS as TBI/Cy. There was a trend towards decreased rate of relapse, but increased non-relapse mortality with the TBI/Flu/Ida/AraC conditioning. In multivariate analysis, only HLA mismatch had significant effect on patient outcome.The retrospective nature of the study and inequalities in baseline transplant characteristics, mainly more frequent use of mismatched unrelated donors in the TBI/Flu/Ida/AraC group, are main limitations of the study. [Display omitted] DisclosuresOff Label Use: Fludarabine, Cytarabine and Idarubicine as part of conditioning regimen.

Similar Incidence of Typhlitis in Patients Receiving Various Doses of Daunorubicin or Idarubicin As Induction for Acute Myeloid Leukemia

Background: The current standard of care for the treatment of patients with newly diagnosed AML is an anthracycline plus cytarabine. Both anthracyclines and cytarabine have been associated with the development of typhlitis, a serious adverse event characterized by inflammation of the bowel wall in patients with profound neutropenia, diagnosed via abdominal CT imaging and clinical symptoms. Given the paucity of available data, the aim of our study was to determine the incidence of typhlitis among AML patients receiving induction with either idarubicin 12 mg/m2 (IDA), daunorubicin 60 mg/m2 (DNA60), or daunorubicin 90 mg/m2 (DNA90).Methods: Adult patients with AML or MDS receiving either daunorubicin or idarubicin along with cytarabine as part of their induction regimen between 1/1/2009 and 6/30/2013 were included. A definition of typhlitis required CT confirmation of inflammation of the cecum, according to CTCAE version 4.03 along with clinical symptoms. Two radiologists (OA, JC) blinded to the treatment and outcomes independently reviewed CT scans. Two additional definitions including inflammation of the ileocecal region only and enterocolitis were also evaluated. All statistical analyses were performed on SAS software version 9.3. P values were calculated using Fisher Exact and Wilcoxon tests. Inter-rater reliability was assessed with Cohen’s Kappa.Results: Baseline characteristics were similar among the 3 treatment groups with the exception of age. The median age was lower in the DNA90 arm (79 years, 74 years, and 49 years in the IDA group, DNA60 group, and DNA90 group, respectively). A pre-existing GI disorder was reported in 24.1% IDA, 25.7% DNA60, and 22.4% DNA90 patients.Of the 202 total patients, the two radiologists determined that 40 (20%) and 38 (19%) developed typhlitis, based on the predefined standard. Tables 1 and 2 illustrate the relationship between treatment arm and associated incidence of typhlitis. The incidence in each treatment group did not statistically differ (p=0.23 and p=0.29). When the definition was broadened to include ileocecal region and enterocolitis, the incidence increased (Tables 1 and 2). The inter-reliability ratings of the 2 radiologists’ evaluations for each definition indicated substantial agreement (0.803 cecum, 0.834 ileocecal region only, and 0.752 enterocolitis). Neither the anthracycline chosen, nor the dose had a statistically significant impact on the incidence of typhlitis. Of all patient and treatment specific risk factors assessed for association with development of typhlitis (pre-existing GI disorder, rheumatologic disorder or cancer, prior RT, stem cell transplant or anthracycline exposure, cytarabine regimen or AML risk group), none were found to be statistically significant. In patients that developed typhlitis, approximately 56% and 51% had a concurrent documented infection around the typhlitis episode (Tables 1-2).Conclusion: To our knowledge, this is the first study to compare the incidence of typhlitis in adult patients receiving idarubicin or daunorubicin for the treatment of AML. While the cumulative incidence of typhlitis was higher than in published literature, the incidence was similar irrespective of the anthracycline chosen or dose. Of the potential factors that may have contributed to the development of typhlitis, none were significantly associated with typhlitis. All patients were managed conservatively with broad-spectrum antibiotics. A more definitive definition of typhlitis may help clinicians identify affected patients sooner and choose appropriate targeted therapy.Abstract 3725. Table 1Association of treatment to Radiologist 1-rated typhlitisEnterocolitisIleocecal region onlyCecumNoYesPNoYesPNoYesPTreatment0.520.680.23DNA6058 (78%)16 (22%)58 (78%)16 (22%)61 (82%)13 (18%)DNA9034 (69%)15 (31%)35 (71%)14 (29%)35 (71%)14 (29%)IDA58 (73%)21 (27%)60 (76%)19 (24%)66 (84%)13 (16%)Concomitant infectionYes11 (26%)32 (74%)13 (30%)30 (70%)19 (44%)24 (56%)Abstract 3725. Table 2Association of treatment to Radiologist 2-rated typhlitisEnterocolitisIleocecal region onlyCecumNoYesPNoYesPNoYesPTreatment0.860.980.29DNA6057 (77%)17 (23%)57 (77%)17 (23%)62 (84%)12(16%)DNA9036 (73%)13 (27%)37 (76%)12 (24%)36 (73%)13 (27%)IDA58 (73%)21 (27%)61 (77%)18 (23%)66 (84%)13 (16%)Concomitant infectionYes11 (26%)32 (74%)13 (30%)30 (70%)21 (49%)22 (51%) DisclosuresNo relevant conflicts of interest to declare.

Low-dose Triptolide in combination with Idarubicin could induce apoptosis in leukemia stem and progenitor cells via affecting the intrinsic and extrinsic factors

BackgroundRelapse has been a major hurdle for the success of acute myeloid leukemia chemotherapy, whereas leukemia stem cells (LSCs) have been considered to be responsible for relapse recently. Thus new drug targeting LSCs is urgently needed. Triptolide (TPL), a diterpenoid triepoxide derived from Tripterygium wilfordii, has been used in Traditional Chinese Medicine (TCM) for centuries. Recently, it has been reported that TPL has the potential of depleting quiescent CD34+ primitive CML progenitor cells. Moreover, normal CD34+ hemopoietic stem cells are less sensitive than AML blasts to TPL, suggesting the seclectivity of TPL in targeting LSCs. AimsIn this study, the ability of triptolide to induce apoptosis in leukemia stem and progenitor cells was investigated with the underlying mechanism being explored. MethodsLeukemia stem and progenitor cells were sorted from KG1a cells using flow cytometry with cell cycle being analyzed and then were subjected to different treatments and thereafter MTT assay, flow cytometry and Western blot or RT-PCR, intracellular ROS measurement colony forming assay were used to determine IC50, apoptotic status and expression of Nrf2, HIF-1α and their target genes, ROS level and colony forming ability. ResultsTPL is highly cytotoxic to leukemia stem and progenitor cells with IC20 of 5.0±0.81nM and IC50 of 20.48±1.6nM after 72h exposure. Leukemia stem and progenitor cells were also exposed to series concentrations of IDA with or without TPL(IC20F5.0nM). TPL significantly enhanced cytotoxicity of IDA to LSCs (IC50-IDA: 285.20±13.7 nM vs. IC50-IDA+TPL: 27.01±0.73 nM, P<0.001) Combination index was also analyzed. Results of combination index showed that synergism effect was observed over a wide range of IC50-IC90 concentrations of IDA and TPL in combination. Moreover, apoptotic ratio of cells treated by IDA with TPL was significantly increased compared to cells treated by IDA alone (24.85±1.70% vs. 76.87±8.34%, P<0.001). What's more, TPL in combination with IDA significantly inhibited the clonogenicity of leukemia stem and progenitor cells (-VE: 2097.3±106.07/well; TPL: 1387.7±40.05/well; IDA: 1252±46.87/well; TPL+IDA: 211±93.18/well, P<0.001). Next, we explore the underlying mechanism of TPL-induced apoptosis in LSCs. The survival of LSCs are dependent of intrinsic factors (Nrf2 and ROS) and extrinsic factors(HIF-1α, VLA4). Induction of ROS while inhibition of protective factor Nrf2 could lead to the apoptosis of LSCs. ROS activation was concentration-dependent when IDA was combined with a constant concentration of TPL (IC20:5nM). The highest activity of intracellular ROS appeared in IDA 200nM+TPL5nM group. Down-regulation of Nrf2 as well as its target genes such as NQO1, GSR and HO-1 was also observed in our study. Moreover, extrinsic factors such as HIF-1α and its down-stream genes such as BNIP3, VEGF and CAIX were also down-regulated in TPL with IDA group. Important extrinsic factors affecting the adhesion of LSCs such as VLA4 and CXCR4 were also down-regulated in TPL with IDA group. ConclusionOur findings indicate that the cytotoxicity of triptolide and the enhancing effect of triptolide on the cytotoxicity of idarubicin in leukemia stem and progenitor cells may be caused by affecting the intrinsic and extrinsic factors. Disclosures:No relevant conflicts of interest to declare.

FLAG ± Idarubicin Compared with 7+3 As Initial Induction for Secondary Acute Myeloid Leukemia: A Single Institution Experience

AbstractAbstract 4330 Objective:Acute myeloid leukemia (AML) that arises from an antecedent hematologic disorder (most often myelodysplastic syndrome, MDS) or that is related to prior chemotherapy (therapy-related AML, t-AML) carries a poor prognosis. Secondary AML occurs in 16–50% of patients with MDS and in <5% of patients previously treated with alkylating agents or topoisomerase II inhibitors. Although 50–70% of patients with de novo AML achieve complete remission (CR) with conventional induction chemotherapy (i.e., cytarabine plus an antracycline, “7+3”), secondary AML is more resistant to such treatment (40–50% CR rate). This has led to the use in some centers of alternative induction regimens such as FLAG (fludarabine, cytarabine, filgrastim) ± idarubicin (Ida) in patients with secondary AML. FLAG ± Ida has been used in patients with relapsed, high-risk MDS and in relapsed/refractory AML, and has an overall CR rate of 33% when used first-line for secondary AML (Clavio M et al. Leuk Lymphoma 2001 Jan; 40(3–4):305-13). There is currently no published data directly comparing 7+3 to FLAG ± Ida in this setting. The present study was undertaken to compare the effectiveness and safety of FLAG ± Ida and 7+3 induction regimens in patients with secondary AML. Methods:A retrospective medical record review was conducted between January 1, 2007 and September 30, 2011 of all patients with AML aged ≥18 years seen at our institution who had either cytogenetic abnormalities commonly associated with MDS or had received prior alkylating agents or topoisomerase II inhibitors, and received either FLAG ± Ida or 7+3 for initial treatment of secondary AML. Patients with chronic myelogenous leukemia in blast crisis were excluded. The primary outcome was the CR rate after induction chemotherapy. Secondary outcomes were 30-day mortality, hospital and intensive care unit (ICU) length of stay (LOS), sources and types of infections, antibiotic usage, and time to neutrophil recovery. Fisher’s exact test was used to compare categorical outcomes (CR, documented infections) between groups. Kaplan-Meier curves and corresponding log-rank tests were used for time-to-event outcomes (hospital stay, ICU days, neutrophil recovery). Results:291 charts were reviewed. 48 patients were found to be eligible and were included in the final analysis. There were no significant differences in baseline demographic characteristics between the two treatment groups, with the exception of AML transformation from MDS being more prevalent in the FLAG ± Ida group (Table I). There were no significant differences in CR rates, 30-day mortality, or hospital LOS between the two groups (Table II). 7+3 was associated with a shorter ICU LOS (0.2 ± 0.7 days vs 2.3 ± 6.8 days, p=0.04) but a greater number of days of antibiotic therapy (56.7 ± 36.3 vs 33.6 ± 31.1, p=0.03), while FLAG ± Ida was associated with a shorter time to neutrophil recovery compared with 7+3 (20.6 ± 4.4 days vs 25.8 ± 7.9 days, p=0.01). Conclusion:In this retrospective study, we found no difference in efficacy between 7+3 and FLAG ± Ida when used as initial induction therapy for patients with secondary AML. Limitations of this study include its retrospective nature, the small sample size and lack of power to detect differences between the groups for both primary and secondary outcomes. A prospectively designed trial is warranted before one regimen can be recommended over the other. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Deterrence and Al-Qa'ida

A commonly held view is that nonstate actors cannot be deterred. A historical review of deterrence vis-à-vis nonstate actors, however, shows that deterrence can be applied successfully to terrorist groups for some purposes and at some times. An examination of the sensitivities, vulnerabilities, and other characteristics of the core al-Qa'ida group suggests a combination of denial and punitive deterrent measures could be used to discourage this nonstate actor from attempting a mass-casualty attack.

Erythrocyte and reticulocyte indices in the assessment of erythropoiesis activity and iron availability

Consequence of the imbalance between the erythroid marrow iron requirements and the actual supply is a reduction in red cell hemoglobin content, which causes hypochromic mature red cells and reticulocytes. Sysmex XE 5000 analyzer (Sysmex Corporation, Kobe, Japan) reports reticulocyte hemoglobin equivalent (Ret-He) and the percentages of erythrocyte subsets, including the hypochromic fraction (%Hypo-He). We study the value of these parameters of hemoglobinization in the evaluation of erythropoiesis and iron availability. Ninety healthy subjects, 85 patients with chronic kidney disease (CKD) and 65 patients on dialysis (HD) receiving therapy and 91 patients with iron deficiency (IDA) were analyzed. Pearson's correlation, t-test for independent, and receiver operating characteristic (ROC) curve analysis were utilized. The results in the IDA group reflected the state of iron depletion (low ferritin), low iron availability (low MCH and high percentage of hypochromic red cells (%Hypo-He)), and iron-restricted erythropoiesis (low Ret-He). In the HD and CKD, the reticulocyte percentage showed the increased erythropoiesis, maintained due to treatment (Ret-He over 30 pg) and good iron availability, MCH within reference range and %Hypo-He slightly increased. The results of ROC curves analysis for the diagnosis of iron deficiency (gold standard sTfR > 21 nm) were as follows: Ret-He area under curve (AUC) 0.935 cutoff 29.8 pg, sensitivity 90.7%, specificity 83.1%. % Hypo-He AUC 0.925 cutoff 3.5%, sensitivity 87.3%, specificity 88.0%. Percentage of hypochromic red cells and Ret-He provide information about individual cell characteristics, so the hypochromic cells are detected and quantitated improving the evaluation of erythropoiesis and iron status.

Survey of anaemia andHelicobacter pyloriinfection in adolescent girls in Suihua, China and enhancement of iron intervention effects byH. pylorieradication

In the present study, we investigated the prevalence of anaemia and Fe deficiency anaemia (IDA) and explored the relationship between Helicobacter pylori infection and IDA in adolescent girls. A total of 1037 adolescent girls from Suihua, China were enrolled. Hb, serum ferritin (SF), serum transferrin receptor (sTfR) and serum IgG antibodies to H. pylori were measured. Participants with IDA and co-existing H. pylori infection (n 80) who had an intake of >25 mg/d of Fe were assigned randomly to the intervention and control groups. Patients in the intervention group were administered a 12-week course of oral EDTA-Na-Fe (60 mg Fe/dose, three times a week) and a 2-week course of colloidal bismuth subcitrate, amoxicillin and metronidazole. Subjects in the control group were administered EDTA-Na-Fe alone. Hb, SF and sTfR were reassessed 3 months after the 12-week regimen ended. Prevalence of anaemia, Fe deficiency (defined as SF < 12·0 μg/l), IDA and H. pylori infection in the population of 1037 was 19.5, 40.4, 17.1 and 31.2 %, respectively. The prevalence of H. pylori infection in the IDA group was 46.9 %, while the non-anaemic group had 28.1 % prevalence. A significant increase in Hb and SF and a decrease in sTfR value were found in the intervention group and the H. pylori-negative group. Findings suggest that IDA is still one of the prominent problems in adolescent girls. There is an association between H. pylori infection and IDA. Treatment of H. pylori infection is associated with a more rapid response to oral Fe therapy.

Evaluation of serum transferrin receptor and sTfR ferritin indices in diagnosing and differentiating iron deficiency anemia from anemia of chronic disease

The present study was conducted to assess the utility of serum transferrin receptor (sTfR) and sTfR ferritin indices to differentiate ACD from IDA and also to diagnose coexisting IDA and ACD. The study group comprised of 30 IDA patients, 30 cases of ACD and 30 age and sex matched controls. Complete hemogram with peripheral smear examination, markers of ACD, iron profile including serum ferritin and serum transferrin receptor levels were done in all patients and controls. Serum TfR and ferritin indices were calculated. sTfR levels were significantly higher in the IDA group compared to ACD group (p<0.001). ACD group was further subdivided into two groups on the basis of sTfR levels (B1<3 microg/ml and B2 > or = microg/ml), suggesting coexisting IDA in group B2. sTfR/log ferritin index was > 1.5 in all cases of IDA and ACD with coexisting IDA while all pure ACD cases and control subjects had sTfR/log ferritin index < 1.5. All case in IDA group had log sTfR/serum ferritin index > 2.55 and all patients with ACD with or without associated iron deficiency had log sTfR/serum ferritin ratio < 2.55. The sTfR levels along with the above mentioned indices can be very useful in differentiating pure IDA, ACD and ACD with coexisting iron deficiency, thus providing a noninvasive alternative to bone marrow iron.

Red cell distribution width (RDW) in the diagnosis of iron deficiency with microcytic hypochromic anemia

To study the utility of red cell distribution width (RDW) in the diagnosis of iron deficiency among children with microcytic hypochromic anemia. 151 children (6 months-12 years) with microcytic (MCV<75 fl) anemia were classified into iron deficient (IDA) and non-iron deficient anemia (non-IDA) on the basis of serum ferritin and total iron binding capacity (TIBC). RDW values were obtained on an automated hematology analyzer. Receiver operator curves (ROC) were constructed and the utility of RDW in diagnosis of iron deficiency was studied. The mean RDW value was 18.37+/-2.22% in IDA group (97 children) compared to 16.55+/-1.51 % in the non-IDA group (54 children) (p<0.0001, unpaired t test). In IDA group, the mean RDW value was 16.60+/-1.78%, 17.95+/-1.91% and 20.55+/-1.32% among mild, moderate and severely anemic children (p<0.0001, ANOVA test). The corresponding values in non-IDA group were 16.03+/-1.25%, 16.76+/-1.20% and 16.77+/-2.68% respectively (p=0.269, ANOVA test). At a cut-off value of 17.4%, as obtained from the ROC curve, the sensitivity and specificity of RDW in diagnosis of IDA were 81.0% and 53.4% and a positive and negative predictive value of 63.0% and 72.2% respectively. RDW has a limited specificity for diagnosis of IDA among children with microcytic hypochromic anemia.

A Homoharringtonine-Based Protocol Is Superior to Daunorubicin and Idarubicin-Based Protocols in Elderly Patients with Newly-Diagnosed Acute Myeloid Leukemia with Comparable Effects and Low Toxicities: Experience in a Chinese Center.

Homoharringtonine (HHT) is a plant alkaloid which has been used in China for the treatment of acute myeloid leukemia (AML) and chronic myeloid leukemia for over 30 years. We present here a retrospective analysis designed to compare the efficacy and toxicity of HHT with daunorubicin (DNR) and idarubicin for the treatment of AML in elderly patients. Fifty-three patients over 60 years with newly diagnosed non-M3 AML between January 1998 and December 2007 were treated with cytarabine (Ara-c, 100mg/m2/day for 7 days) in combination with HHT (2mg/m2/day for 7 days; HA group; n=19), or DNR (40mg/m2/d for 3 days; DA group; n=16), or idarubicin (8mg/m2/d for 3 days; IDA group; n=18). In the HA group, 42.1% (8/19) of patients achieved complete remission (CR), 26.3% (5/19) of patients had partial remission (PR). In the DA group, the CR and PR rates were each 18.8% (3/16). In the IDA group, 55.5% (10/18) of patients achieved CR, 5.9% (1/18) patients had PR. The CR and OR rates were not significantly different between the three groups. However, whereas in the IDA and DA groups the early death rate within one month after chemotherapy was 33.3% (6/18) and 23.5% (4/16) respectively, there was no early death in the HA group. The estimated OS (overall survival) times were 23.2±7.9 months, 7.6 ±2.1 months, 14.0±3.4 months in HA, DA, and IDA groups (HA versus DA, P = 0.048; HA versus IDA, P = 0.678). The estimated mean disease-free survival (DFS) time of those patients who achieved CR in the HA group (44.3±17.3) were also significantly higher than those in the DA group (7.8±2.7; P = 0.047), and comparable with those in the IDA group (18.0±4.2; P = 0.598). In summary, the response to HA induction therapy was at least equal to that of DA and IDA induction, with relatively mild extramedullary toxicity and lower myocardial toxicity. So HHT is a particularly suitable candidate for the treatment of elderly AML patients.

Affinity of Cd and Ni on IDA Immobilized Magnetic Beads with Different Lengths of Spacer Arms

To develop the extraction media for Cd and Ni from aqueous solutions, magnetic beads containing IDA group with strong attraction to heavy metals were produced using the activating agents Epichlorhydrin (Ep) and 1,4-Butanedioldiglycidylether (Bu), respectively. Then the beads were agitated at a pH of 6 after being added to Cd and Ni aqueous solutions of various concentrations. It was confirmed that the heavy metals combined with the magnetic beads within a short time through the process. After the process, the magnetic beads were collected with a magnet, and then dissolved in acid for the analysis of heavy metal concentration. The analysis of heavy metals in the acid solution could be analyzed with an AAS (atomic absorption spectrometer). The results showed that the heavy metal extraction efficiency of Bu was relatively higher than that of the Ep. It supported the hypothesis that the relatively longer length of Bu’s spacer made more free positioning possible when the IDA group combined with the heavy metal.

The expression of TfR1mRNA and IRP1mRNA in the placenta from different maternal iron status

To investigate the mRNA expression of transferrin receptor 1 (TfR1) and iron regulatory protein 1 (IRP1) in the full-term placenta from different maternal iron status, and explore the mechanism of placental iron transport and regulation. The mRNA level of TfR1 and IRP1 in full-term placentae was detected by reverse transcription polymerase chain reaction (RT-PCR) in normal group (N), iron deficiency group (ID) and iron deficiency anemia group (IDA). (1) The expression of TfR1 mRNA in N group was 0.4813 +/- 0.1891, in ID group was 0. 6647 +/- 0.2788, and in IDA group was 0.9767 +/- 0.2858. There was significant difference between IDA group and N group or ID group (t = 0.002, P < 0.01 or t = 0.028, P < 0.05), and was no difference between ID group and N group (t = 0.117, P > 0.05). (2) The expression of IRP1 mRNA in N group was 0.2616 +/- 0.0785, in ID group was 0.3696 +/- 0.1801, and in IDA group was 0.3971 +/- 0.0902 and was no difference among the three groups (F = 1.845, P = 0.179). The expression of TfR1 mRNA is increased when maternal iron deficiency progressed while there is no change in the expression of IRP1 mRNA in the placentae of TfR1 mRNA indicated that IRP1 takes part in the regulation of placenta iron transport.

Preparation of Polylactic Acid Nonwoven Fabric-based Metal Adsorbent by Radiation-induced Graft Polymerization

Fibrous metal adsorbent was prepared by radiation-induced graft polymerization of glycidyl methacrylate onto a polylactic acid (PLA) nonwoven fabric and its subsequent modification based on ring opening of epoxides with disodium iminodiacetate (IDA-Na) . The degree of grafting of PLA fabric can be controlled in the range of up to 225% by optimizing the grafting conditions such as reaction time, preirradiation dose, monomer concentration and reaction temperature. The optimal IDA group density of the prepared adsorbent was 500 μmol/g-adsorbent, and its selectivity for metal ions was Cu2+>Pb2+>Ni2+>Zn2+>Cd2+>Co2+>Ca2+>Mg2+.