Anemia Grade Research Articles

Anemia Is Inversely Associated with Serum C-Peptide Concentrations in Patients with Type 2 Diabetes

Results: The aim of the study was to investigate the relationship between anemia and serum C-peptide concentrations in Korean patients with type 2 diabetes. A total of 1,300 subjects with type 2 diabetes were investigated in this cross-sectional study. Fasting C-peptide concentration, 2-hour postprandial C-peptide concentration, and δC-peptide (postprandial C-peptide minus fasting C-peptide) concentration were measured in all patients. Anemia was defined according to the World Health Organization. Fasting C-peptide level, postprandial C-peptide level, and δC-peptide level was lesser in subjects with anemia. According to the grade of anemia, the average C-peptide levels were significantly different after adjusting for other covariates (fasting C-peptide level: no anemia, 0.73 mmol/l; grade I anemia, 0.66 mmol/l; grade II anemia, 0.62 mmol/l; P for trend = 0.002; postprandial C-peptide level: no anemia, 1.54 mmol/l; grade I anemia, 1.36 mmol/l; grade II anemia, 1.32 mmol/l; P for trend < 0.001; δC-peptide level: no anemia, 0.75 mmol/l; grade I anemia, 0.64 mmol/l; grade II anemia, 0.60 mmol/l; P for trend = 0.001). In the multivariate model, the association between anemia and serum C-peptide concentrations remained significant, after adjustment for confounding factors including age, gender, familial diabetes, body mass index, duration of diabetes, glycated hemoglobin, free fatty acid, hypertension, and hyperlipidemia (fasting C-peptide level: β= -0.057, P =0.032; postprandial C-peptide level: β= -0.098, P <0.001; δC-peptide level: β= -0.095, P <0.001, respectively). Our results showed that anemia was inversely associated with serum C-peptide concentrations in subjects with type 2 diabetes. Disclosure J. Chung: None. S. Park: None. D. Cho: None. D. Chung: None. M. Chung: None.

Study of Anaemia in Children with Severe Acute Malnutrition

Introduction: Severe anaemia is a leading cause of paediatric morbidity, hospitalization, and mortality and it is very important co morbidity in children with severe acute malnutrition. Severe Acute Malnutrition (SAM) with anaemia has been shown to have 2.62 times higher mortality as compared to SAM with no anaemia. So this study was done to evaluate this co-morbidity further. The aim of present study was to determine the prevalence and type of anaemia and to evaluate the possible aetiologies of anaemia in severe acute malnourished (SAM) children.Material and Methods: In tertiary care hospital a cross sectional study was conducted over a period of 8 month with 100 cases of SAM children and 101 cases of normal children. In both cases disorders of primary haematological problem were excluded. Auto analysers were used to measure blood counts. Blood smear was analysed by pathology consultant of institute and recorded for all patients with anaemia. Grade of anaemia and morphologic type of anaemia was analysed. Data were entered in Excel spreadsheets and analysed using SPSS 20.0.Results: Patient with SAM 42% had moderate anaemia and 19% had severe anaemia in contrast 41.6% and 16.8% in NON SAM child respectively. Predominant morphologic type in SAM patient was macrocytic anaemia (33%), while in controls microcytic anaemia (40.6%) was more prevalent.Conclusion: There was a high prevalence of anaemia in SAM children. Major morphologic type in SAM children was macrocytic anaemia which may indirectly show vitamin B12 or folic acid deficiency in these children.

Risk of hematological toxicities in patients with advanced breast cancer treated with everolimus: A meta-analysis of phase 3 randomized controlled trials.

e13087 Background: Aberrant signaling through the phosphatidylinositol 3-kinase (PI3K)-Akt-mammalian target of rapamycin (mTOR) signaling pathway was shown to involve in endocrine and trastuzumab resistance in breast cancer. Everolimus (E) is an oral mTOR inhibitor and showed clinical benefit in these population with noteworthy safety concerns. We performed a systematic review and meta-analysis of randomized controlled trials (RCT) to determine the risk of hematological toxicities. Methods: MEDLINE, EMBASE databases and meeting abstracts from inception through January 2018 were queried. Phase 3 RCTs that mention hematological toxicities as adverse effects were incorporated in the analysis. Mantel-Haenszel method was used to calculate the estimated pooled risk ratio (RR) with 95% confidence interval (CI). Random effects model was applied. Results: Three phase 3 RCTs with a total of 1992 patients with advanced breast cancer were eligible for analysis. Studies compared E+ paclitaxel(P) + herceptin(H) vs P+H, E+ exemestane(Ex) vs Ex, E+ vinorelbine(V)+ H vs V+H. The RR of all-grade side effects were as follows: anemia, 2.07 (95% CI: 1.45-2.96, p < 0.001); neutropenia, 1.30 (95% CI: 0.97-1.73, p = 0.07); leukopenia, 1.27 (95% CI: 1.06-1.52, p = 0.009); thrombocytopenia, 6.19 (95% CI: 3.25-11.77, p < 0.001); and febrile neutropenia (FN), 4.27 (95% CI: 2.33-7.85, p < 0.001). The RR of high-grade side effects were as follows: anemia, 3.55 (95% CI: 2.33-5.42, p < 0.001); neutropenia, 1.36 (95% CI: 0.92-2.00, p = 0.11); leukopenia, 1.31 (95% CI: 1.04-1.63, p = 0.01); thrombocytopenia, 5.49 (95% CI: 1.82-16.54, p = 0.002); and FN, 4.33 (95% CI: 2.30-8.18, p < 0.001). Conclusions: Our meta-analysis demonstrated that patients on everolimus experienced a significant increase in all grades of anemia, leukopenia and thrombocytopenia. Everolimus-based regimens also contributed to a significant increase in all grades of FN with a relative risk of 4.33 for grade 3 and 4 FN. FN remains a major cause of morbidity, mortality and drug dosing inconsistencies among patients with cancer and proper supportive care is required.

Predictive factors in patients eligible for pegfilgrastim prophylaxis focusing on RDI using ordered logistic regression analysis.

Although pegfilgrastim prophylaxis is expected to maintain the relative dose intensity (RDI) of chemotherapy and improve safety, information is limited. However, the optimal selection of patients eligible for pegfilgrastim prophylaxis is an important issue from a medical economics viewpoint. Therefore, this retrospective study identified factors that could predict these eligible patients to maintain the RDI. The participants included 166 cancer patients undergoing pegfilgrastim prophylaxis combined with chemotherapy in our outpatient chemotherapy center between March 2015 and April 2017. Variables were extracted from clinical records for regression analysis of factors related to maintenance of the RDI. RDI was classified into four categories: 100% = 0, 85% or < 100% = 1, 60% or < 85% = 2, and < 60% = 3. Multivariate ordered logistic regression analysis was performed to identify predictive factors in patients eligible for pegfilgrastim prophylaxis to maintain the RDI. Threshold measures were examined using a receiver operating characteristic (ROC) analysis curve. Age [odds ratio (OR) 1.07, 95% confidence interval (CI) 1.04-1.11; P < 0.0001], anemia (grade) (OR 1.77, 95% CI 1.10-2.84; P = 0.0184), and administration 24-72h after chemotherapy (OR 0.44, 95% CI 0.22-0.89; P = 0.0224) were factors that significantly correlated with RDI maintenance. ROC curve analysis of the group that failed to maintain the RDI indicated that the threshold for age was 70years and above, with a sensitivity of 60.0% and specificity of 80.2% (area under the curve: 0.74). In conclusion, younger age, anemia (less), and administration of pegfilgrastim 24-72h after chemotherapy were significant factors for RDI maintenance.

Etoposide as a single agent in the treatment of mycosis fungoides: A retrospective analysis.

Several chemotherapy agents have shown efficacy in the treatment of mycosis fungoides (MF). In the literature, there is limited data on the use of single agent etoposide for MF. We aimed to retrospectively review our experience with single agent etoposide in the treatment of advanced-stage or refractory early-stage MF with focus on analyzing its efficacy and safety. We included 13 MF patients who were treated with single agent etoposide. Patients were identified through the Cutaneous T Cell Lymphoma Database of Indiana University that involves patients treated from 2006 to 2016. Overall nine patients (69%) responded to treatment. No complete response was identified. Median time to response was 12.5 weeks (range: 6-25.4). Median duration of response was 43 weeks (range: 5-60) and median time to treatment failure was 31.3 weeks (range: 12.4-230). Hematological toxicity was observed in eight patients including two patients with grade 4 neutropenia and/or lymphopenia leading to sepsis. Higher doses of etoposide were significantly correlated with higher grades of anemia, neutropenia or lymphopenia (p < .05). Our study demonstrates that etoposide is an effective treatment for MF and may be considered in selected patients with progressive MF who have failed other treatments.

Time trends in prevalence of anaemia in pregnancy.

Background & objectives:The prevalence of anaemia in pregnancy in India is among the highest in the world. In the last two decades, several national surveys have estimated haemoglobin levels in pregnant women. In this study, data from these surveys were analyzed to find out changes, if any, in prevalence of anaemia in pregnancy.Methods:National and State-level estimates on the prevalence of anaemia were tabulated from the reports of the National Family Health Survey (NFHS) 2, NFHS 3, Fact Sheets of NFHS 4 and District Level Household Survey (DLHS) 2. Unit level data from DLHS 4 and Annual Health Survey Clinical Anthropometric and Biochemical component (AHS CAB) were obtained and State level prevalence of different grades of anaemia was estimated. Time trends in the prevalence of anaemia and different grades of anaemia were assessed from these surveys.Results:NFHS 2, 3 and 4 reported relatively lower prevalence of anaemia as compared to DLHS and AHS CAB. There was not much change in the prevalence or severity of anaemia between NFHS 2, 3 and 4. There was substantial reduction in the prevalence and severity of anaemia in all States except Uttarakhand between DLHS 2 and 4 and DLHS 2 and AHS CAB.Interpretation & conclusions:There was a reduction in the prevalence and severity of anaemia in the last 15 years. The two-pronged strategy of increasing iron intake (dietary diversification and use of iron-fortified iodized salt) in all the population and testing, and detecting and treating pregnant women with anaemia will accelerate the pace of reduction in anaemia.

Lab Diagnosed Anemia among Women in Alyamamah Hospital in Riyadh, Saudi Arabia

Background: anemia in pregnancy is a common problem. Easy diagnosis and treatment enhance focus on anemia cases. AimandObjectives: to determine the common types and grades of anemia in a hospital lab in Riyadh and to compare types of anemia among age and pregnancy status. Method: cross-sectional study. Study area: a hematology-log in lab. Samples: convenience samples of 120 anemic ladies. Tool: questionnaires. Methods of data collection: CBC results. Results: This study-addressing anemia among women in a lab in Riyadh involves 120 ladies. When they were distributed as pregnant and non-pregnant women, 70% were pregnant. About 70% of the pregnant and 39% of non-pregnant had iron deficiency anemia, this difference statistically significance (P= 0.0013). Normocytic normochromic anemia was falling in 26% and 50% of the pregnant and non-pregnant ladies respectively; this difference was statistically significant (P= 0.0112). About 94.5% of iron deficiency anemias have low MCH. PCV was low in all cases of anemia. Conclusion: Anemia in women of child bearing age are more commonly observed in study. Most common type of anemia among cases was iron deficiency anemia. Iron deficiency anemia was the most common in pregnant, while normochromic normocytic anemia was the most common in non-pregnant. MCV & MCH were significant characteristics finding in iron deficiency anemia.

Veliparib with temozolomide or carboplatin/paclitaxel versus placebo with carboplatin/paclitaxel in patients with BRCA1/2 locally recurrent/metastatic breast cancer: randomized phase II study

Homologous recombination defects in BRCA1/2-mutated tumors result in sensitivity to poly(ADP-ribose) polymerase inhibitors, which interfere with DNA damage repair. Veliparib, a potent poly(ADP-ribose) polymerase inhibitor, enhanced the antitumor activity of platinum agents and temozolomide in early phase clinical trials. This phase II study examined the safety and efficacy of intermittent veliparib with carboplatin/paclitaxel (VCP) or temozolomide (VT) in patients with BRCA1/2-mutated breast cancer. Eligible patients ≥18 years with locally recurrent or metastatic breast cancer and a deleterious BRCA1/2 germline mutation were randomized 1:1:1 to VCP, VT, or placebo plus carboplatin/paclitaxel (PCP). Primary end point was progression-free survival (PFS); secondary end points included overall survival (OS) and overall response rate (ORR). Of 290 randomized patients, 284 were BRCA+, confirmed by central laboratory. For VCP versus PCP, median PFS was 14.1 and 12.3 months, respectively [hazard ratio (HR) 0.789; 95% CI 0.536-1.162; P = 0.227], interim median OS 28.3 and 25.9 months (HR 0.750; 95% CI 0.503-1.117; P = 0.156), and ORR 77.8% and 61.3% (P = 0.027). For VT (versus PCP), median PFS was 7.4 months (HR 1.858; 95% CI 1.278-2.702; P = 0.001), interim median OS 19.1 months (HR 1.483; 95% CI 1.032-2.131; P = 0.032), and ORR 28.6% (P < 0.001). Safety profile was comparable between carboplatin/paclitaxel arms. Adverse events (all grades) of neutropenia, anemia, alopecia, and neuropathy were less frequent with VT versus PCP. Numerical but not statistically significant increases in both PFS and OS were observed in patients with BRCA1/2-mutated recurrent/metastatic breast cancer receiving VCP compared with PCP. The addition of veliparib to carboplatin/paclitaxel significantly improved ORR. There was no clinically meaningful increase in toxicity with VCP versus PCP. VT was inferior to PCP. An ongoing phase III trial is evaluating VCP versus PCP, with optional continuation single-agent therapy with veliparib/placebo if chemotherapy is discontinued without progression, in this patient population. NCT01506609.

Anaemia in pregnancy in a setting of high HIV prevalence rates

Background: Although there is much literature on anaemia in pregnancy, there are limited data on anaemia specific to HIV in pregnancy. The aim of this study was to determine the prevalence of anaemia among HIV-infected antenatal attendees at their first visit.Methods: This was a secondary analysis of 2 000 antenatal attendees enrolled into a study on anaemia in pregnancy and was carried out at a regional hospital from 2012–2014. Demographic and clinical data including anaemia, perinatal and maternal outcomes of HIV infected women were analysed.Results: Of the 2 000 recruited, 854 (42.7%) were anaemic, 943 (47.2%) were infected with HIV, and 609 (64.6%) HIV-infected women had anaemia. There was a significant difference in the prevalence of anaemia in HIV-infected patients on antiretroviral (ARV) treatment compared to untreated patients (41.4% vs 92.1%; p 0.0001). Mild grades of anaemia were common in HIV-infected patients on ARVs, while moderate to severe grades were most common in patients who were not on ARVs. Besides birthweight and hypertensive disorders of pregnancy, there was no significant difference in neonatal and maternal outcomes irrespective of duration of ARV treatment.Conclusions: There was a high prevalence of anaemia among HIV-infected, untreated pregnant women. Assessment of anaemia at the first antenatal visit is, therefore, essential.

Low Impact of Genetic Modifiers on the Phenotype of Homozygous Beta Thalassemia in the Last Decennial Cohort of Thalassemia Newborns in Sardinia

Historically 15-20% of homozygous ß-thalassemia in Sardinia developed the phenotype of thalassemia intermedia not requiring transfusion for survival. However, this category of patients has broad and heterogeneous spectrum severity, embracing truly mild thalassemia patients and patients with severity similar to thalassemia major. Known genetic modifiers that ameliorate the severity of b-thalassemia are the mild genotypes of ß+-thalassemia, the coinheritance of α-thalassemia, of hereditary persistence of fetal hemoglobin (HPFH) and of polymorphic variants in the BCL11a, MYB and HBG1 genes. All together this modifiers allow the calculation of a genetic score of severity that predicts the possibility of remaining transfusion free at a given age, likely aiding in the clinical decision to start or delay the initiation of a stable transfusion program. In this study we planned to evaluate the ameliorating effects of these genetic modifiers on the thalassemia phenotype by prospectively evaluating 51 homozygous ß-thalassemia newborns followed at our Institution in the last ten years. All newborns were genotyped soon after birth for all known genetic modifiers and monitored clinically for the appearance of anemia or other complications with monthly check-ups from birth until they required transfusions, according to the TIF guidelines. In this decennial cohort, all but 2 patients younger than 20 months started a regular transfusion program before 36 months of age. Hence, the percentage of thalassemia intermedia in Sardinia has dropped in the last decade from 18 to 4% and might even reach 0% if the 2 patients non yet transfused will transfuse within the next year. This shift from thalassemia intermedia to major is mainly accounted for by the great improvement in mortality, morbility and quality of life for thalassemia major compared to thalassemia intermedia patients who frequently develop difficult to manage complications with advancing age. In the cohort, the reason for start of blood transfusions was anemia lower than 7gr/dl in 14 % of cases and the appearance of skeletal modifications or growth failure in the remaining 84% of patients. Thus, differently from the past, most patients were transfused despite an acceptable grade of anemia. As expected, the presence of a greater number of genetic modifiers significantly correlated with a delay in the time lag to the first transfusion. Even better positive correlation (p<0.0009) was found between the number of genetic modifiers and the levels of hemoglobin before beginning transfusion, confirming the positive influence of genetic modifiers on hemoglobin production. Since the start of transfusions, blood consumption did not positively correlated with the number of favorable genetic hits, but showed a trend toward significance, likely to achieve significance with increasing number of patients. Since the clinical decision to transfuse was taken mainly on the highly subjective parameter of appearance of skeletal modifications, it is possible that were transfused even the patients likely to have mild thalassemia intermedia and a good quality of life for most of their lifespan. We propose that at least the thalassemia patients with the best hemoglobin values (higher than 9 gr/dl) and a favorable background with at least 2 genetic modifiers (12% of our ߰-thalassemia newborns) should be more carefully evaluated for the possibility to evolve into a mild thalassemia intermedia phenotype with good quality of life for most of their lifespan. DisclosuresNo relevant conflicts of interest to declare.

Highly conformal combined radiotherapy with cisplatin and gemcitabine for treatment of loco-regionally advanced cervical cancer \u2013 a retrospective study

BackgroundCisplatin and gemcitabine combined with conventional radiation therapy in the treatment of cervical cancer patients results in a favorable outcome but with excess toxicity. The purpose of this study was to evaluate the toxicity profile of dual chemotherapy and highly conformal external beam radiotherapy with image guided adaptive brachytherapy.MethodsSeventeen patients with cervical carcinoma FIGO stage IB2–IIIB were treated with curative intent between 2011 and 2015. A total dose of 50.4 Gy was prescribed to the elective pelvic nodal volume. Patients with 18FDG-PET/CT positive lymph nodes (n = 15; 83.3%) received an additional boost to a total dose of 62 Gy. Chemotherapy prescription goals were: concomitant during 5 weeks of external beam radiotherapy (EBRT) 40 mg/m2 cisplatin and 125 mg/m2 gemcitabine, followed by adjuvant chemotherapy from week 10 (2 cycles 50 mg/m2 cisplatin and 1000 mg/m2 gemcitabine). EBRT was followed by 3–4 fractions (6 Gy per fraction) of intrauterine image guided adaptive brachytherapy. Toxicities were graded according to the common terminology criteria for adverse events (CTCAE v 4.0).ResultsOne (6%) patient developed acute grade 3 diarrhea. We did not record any other acute or late gastrointestinal or urogenital toxicity higher that grade 3. Most common acute hematological toxicity was anemia grade 2 recorded in 10 (59%) patients. There was only one case of grade 3 neutropenia (6%). The number of patients that received the complete chemotherapy regimen was gradually declining during the course of therapy. From week 2 to 5, gemcitabine was omitted in 4 (24%),7 (41%), 8 (47%), and 12 (71%) patients respectively, similarly, cisplatin was omitted in 2 (12%),3 (18%),1 (6%) and 7 (41%) patients respectively. Adjuvant chemotherapy was omitted in 8 patients (47%). During a median follow-up time of 20 months (5 to 63 months) 6 (35%) patients developed disease relapse with 5 (29%) of them in the form of systemic disease.ConclusionsIn contrast to previous findings cisplatin and gemcitabine in combination with highly conformal radiation therapy seems to have an acceptable toxicity profile. Further studies are needed to determine the optimal dosage of the proposed therapy concept.

MA 03.02 Timing of B12/Folate Supplementation in NSCLC Patients on Pemetrexed Based Chemotherapy: Final Results of the PEMVITASTART Randomized Trial

Vitamin B12 and folic acid supplementation (B12-FAS) reduces the incidence and severity of hematological toxicity [HTox] in pemetrexed-based chemotherapy. It is recommended to initiate B12-FAS 5-7 days before the first cycle. Observational and prospective single-arm studies have not shown any increase in HTox when pemetrexed was started earlier than the recommended duration of B12-FAS. An open-label, randomized trial (PEMVITASTART; NCT02679443) was conducted to evaluate differences in HTox between patients initiated on pemetrexed-platinum chemotherapy following 5-7 days of B12-FAS (Delayed Arm; DA) versus those receiving B12-FAS simultaneously(≤24 hours) with chemotherapy initiation (Immediate Arm; IA). Eligible patients had locally advanced/metastatic non-squamous NSCLC AND ECOG PS=0-2. Block randomization was 1:1 into DA and IA. All enrolled patients received 3-weekly pemetrexed-platinum doublet [500mg/m2 AND cisplatin (65mg/m2) OR carboplatin (AUC 5.0mg/mL/min) each on D1] for maximum of six cycles. Supplementation was 1000μgm FA PO daily and 3-weekly 1000μgm i/m vitamin B12. Primary outcome was any grade HTox while secondary outcomes were grade 3/4 HTox, relative dose intensity (RDI) delivered, inter-cycle delays (ICDs), supportive therapies usage (ESA/G-CSF/PRBC transfusions) and changes in serum levels of B12/FA/homocysteine. Of 161 patients recruited (81 IA, 80 DA), 150 patients (77 IA, 73 DA) received ≥1 cycle and were included in modified ITT analysis. Baseline parameters were matched except for gender (IA=10.4%, DA=23.3%, p=0.03) and baseline thrombocytopenia (IA=7.8%, DA=0%, p=0.03). Baseline anemia (Hb<12gm/dL) was present in 34.7% (IA=32.5%, DA=37.0%; p=0.56). Incidence of any grade anemia, leukopenia, neutropenia and thrombocytopenia was 87.0% vs. 87.7% (p=0.90), 37.7% vs. 28.8% (p=0.25), 20.8% vs. 15.1%(p=0.36) and 31.2% vs. 16.4%(p=0.04) in IA and DA respectively. Grade 3/4 anemia was 18.2% vs. 12.3% (p=0.32) in IA and DA respectively while other cytopenias were similar (<5% in each arm). Supportive therapies usage in IA vs. DA were 22.1% vs. 12.3% for PRBC transfusions (p=0.12), 3.9% vs. 6.8% for G-CSF (p=0.49) and 10.4% vs. 1.4% for ESAs (p=0.03). ICDs occurred in 14.3% of IA vs. 8.2% in DA (p=0.24). RDI delivered (median 93.5% for pemetrexed and 91.0% for platinum) was similar in both arms. Following continued B12-FAS, after C3 (compared to baseline), serum homocysteine was lower (median 10.0μmol/L vs. 17.6μmol/L;p<0.001) while FA (median 17.9ng/ml vs. 5.7ng/ml;p<0.001) and B12 levels (mean 1926.3pg/ml vs. 880.2pg/ml;p<0.001) were higher. In DA, serum FA and B12 on Day1 of C1(following 5-7days of B12-FAS) were significantly higher than baseline but homocysteine levels were similar. Simultaneous B12-FAS initiation with pemetrexed-based chemotherapy is feasible with acceptable HTox profile. Serum homocysteine levels are unaffected by 5-7 days of B12-FAS.

Anaemia in pregnancy in a setting of high HIV prevalence rates

AbstractBackground: Although there is much literature on anaemia in pregnancy, there are limited data on anaemia specific to HIV in pregnancy. The aim of this study was to determine the prevalence of anaemia among HIV-infected antenatal attendees at their first visit.Methods: This was a secondary analysis of 2 000 antenatal attendees enrolled into a study on anaemia in pregnancy and was carried out at a regional hospital from 2012–2014. Demographic and clinical data including anaemia, perinatal and maternal outcomes of HIV infected women were analysed.Results: Of the 2 000 recruited, 854 (42.7%) were anaemic, 943 (47.2%) were infected with HIV, and 609 (64.6%) HIV-infected women had anaemia.There was a significant difference in the prevalence of anaemia in HIV-infected patients on antiretroviral (ARV) treatment compared to untreated patients (41.4% vs 92.1%; p < 0.0001). Mild grades of anaemia were common in HIV-infected patients on ARVs, while moderate to severe grades were most common in patients who we...

Selinexor, a selective inhibitor of nuclear export (SINE), in patients with unresectable melanoma.

e21014 Background: Limited effective therapies exist for patients with melanoma after progression on immune- and targeted-therapies. Treatment with selinexor, a potent small molecule inhibitor of exportin-1 (CRM/XPO1), results in nuclear retention of major tumor suppressor proteins and cell cycle regulators, leads to growth arrest and apoptosis in vitro, in xenograft models (BRAF +/-), and Phase I solid tumor trial. (Yang et al PLOS One, 2014, Razak et al JCO, 2016). Methods: Objectives of this single institution trial were to determine: the safety in melanoma patients, the clinical benefit rate, and efficacy at the MTD as measured by PFS. Patients received prior immunotherapy and a BRAF inhibitor (mutation positive). Lead-in phase is completed. Median number of prior systemic therapies = 2 (2 – 4). Selinexor (50 mg/m2) was orally administered twice weekly, with 2-3 days off between doses. Toxicities were evaluated every 28-days. Tumor biopsies were collected for correlative analysis. Results: As of Jan 2017, 7 patients (0/7 BRAF mutant) were enrolled. Drug related AEs: neutropenia (grade 4) (1/7 patients), hyponatremia (grade 3) (1/7 patients), thrombocytopenia (Grade 3) (3/7 patients), anemia (Grade 3) (1/7 patients), and thromboembolic events (Grade 3) (1/7 patients). There were no DLT’s. Four patients experienced stable disease (SD); one patient had a minor response, for a disease control rate (DCR) of 71% (5/7). Mean duration of response was 207 days (70 – 335). One patient, removed from therapy due to a CNS met, continued with stable systemic disease off therapy for 177 days. Another patient, taken off therapy due to a non-drug related adverse event, remained SD for 127 days. Conclusions: These preliminary results demonstrate that selinexor is well tolerated with supportive care, is safe for melanoma patients dosed at the 50 mg/m2, and has the potential to control disease progression as a single agent in patients with prior BRAF inhibitor and immunotherapy. Patients are currently enrolling at a flat 60 mg dose. Correlative studies including evaluation of selinexor target engagement and exploratory markers of drug response are underway. Clinical trial information: NCT02120222. Clinical trial information: NCT02120222.

Hemoglobin level and prevalence of anemia in Soliga tribal children of Karnataka, India

Hemoglobin status of tribal children in Karnataka has not been investigated adequately and extensively. Hematological parameters help to understand the normal growth and nutritional status of the children. A cross-sectional purposive sampling study was undertaken to determine the prevalence of anemia among 152 Soliga tribal children belonging to 6+ to 10+ years of Mysore district, Karnataka, India. Hemoglobin level was determined by cyanmethaemoglobin method. As per the WHO cut-off points, the children were grouped under mild, moderate and severe anemia where the level of hemoglobin below 11.5 g/dL. BMI values were estimated based on the measurements of height and weight of the children. The overall prevalence of anemia was 91.4%; 7.2% mild, 74.3% moderate, and 9.9% severe anemia. Mean hemoglobin values between boys and girls of 7+ years age group were statistically significant. A higher proportion of girls were severely anemic in the age group of 9+ and 10+ years than boys. The prevalence of different grades of anemia was more or less equally distributed among boys and girls of Soliga children. Remarkably, about 94.3% normal BMI children were anemic. Comparison of mean values of anemia and BMI between boys and girls were found statistically significant. The level of hemoglobin among Soliga Children in Karnataka is a cause for concern. Appropriate measures should be taken by the respective authorities to decrease the prevalence of anemia and improve the condition of health among the children.South East Asia Journal of Public Health Vol.6(2) 2016: 37-41

Maternal and neonatal outcomes among women with HIV infection and their infants in Malawi.

To describe maternal and neonatal morbidity and mortality among women with HIV infection and their infants. A secondary analysis was undertaken of data obtained in the BAN Study, a trial of postnatal antiretrovirals among pregnant women with HIV infection enrolled in 2004-2010. Mothers and infants had 13 scheduled visits through 48weeks of follow-up. Serious maternal morbidity and mortality were examined at delivery (n=2791), from delivery to 6weeks later (n=2369) and from 7 to 48weeks (n=1980). Neonatal morbidity and mortality were examined (n=2685). Of 2791 deliveries, 169 (6.1%) were by cesarean (153 emergency). Compared with women with vaginal delivery, those with cesarean delivery had lower prenatal HIV viral loads (P=0.016) and increased odds of pre-eclampsia/eclampsia (odds ratio [OR] 10.8, 95% CI 4.4-26.8). Women with cesarean delivery also had increased odds of serious infection with 14days of delivery (OR 3.0, 95% CI 1.3-7.4) and severe anemia (grade 3 or 4) by 6weeks (OR 6.7, 95% CI 2.3-19.1). Infants born by cesarean had increased odds of a low 5-minute Apgar score (OR 8.1, 95% CI 3.5-18.6) and admission to an intensive care unit (OR 5.4, 95% CI 3.7-7.8). Odds of serious maternal and neonatal morbidity were higher after cesarean than vaginal delivery, despite lower maternal viral loads.

Abstract P4-22-21: NCI9782: A phase 1 study of talazoparib in combination with carboplatin and paclitaxel in patients with advanced solid tumors

Abstract Background: Poly(ADP-ribose) polymerase (PARP) enzymes are involved in DNA repair and activated by DNA strand breaks. DNA damage from carboplatin is associated with activation of PARP. Preclinical data indicate that PARP inhibition potentiates the anti-tumor effect of platinum chemotherapy. Talazoparib (T) is an oral, selective PARP inhibitor with a single agent maximum tolerated dose (MTD) of 1mg orally qd. Primary dose-limiting toxicity (DLT) was thrombocytopenia. This phase I study combines T with the commonly used chemotherapy regimen of carboplatin (C) and paclitaxel (P). Methods: Two dosing schedules are being investigated. In both schedules, C is administered on day 1 and P on days 1, 8, and 15 of a 21-day cycle. T (100-1000mcg) is dosed once daily for days 1-7 (schedule A) or days 1-3 (schedule B) starting on day 1. A 3+3 design is used for dose escalation. Key eligibility criteria include age 318 with a measurable or evaluable solid incurable malignancy. Patients (pts) must have tumor type that is expected to respond to C + P or have BRCA germline or somatic mutation. Stable, treated brain metastases are allowed. No prior C for metastatic disease is allowed. Pts must have platelets&amp;gt;150 and no need for anticoagulation. After 4-6 cycles of combination therapy, pts may continue the combination, change to C and intermittent T without P or change to T alone with continuous daily dosing. Each schedule will have a 6 subject dose expansion at the MTD. The starting dose level for schedule B will be the MTD from schedule A. Results: Schedule A cohort results are reported: 11 pts (median age 59 [range 39-68]; 8 female; 3 male) have been enrolled. Pts had breast (6), ovarian (2), pancreatic (1), and SCC of oropharynx (1) and concurrent ovarian and pancreatic (1). Five pts are BRCA2+ and 3 pts are BRCA1+. Dose level 3 on schedule A (T 350mcg with C AUC 6 and P 80mg/m2) exceeded the MTD with 2 of 3 pts experiencing hematologic dose limiting toxicities (DLTs) including 1 pt with grade (gr) 3 neutropenic fever and gr 4 thrombocytopenia and another pt with grade 3/4 neutropenia lasting &amp;gt; 7 days. Most common AEs include neutropenia (grade 3-4: 7), anemia (grade 3-4: 3), and thrombocytopenia (grade 3-4: 4). Results from expansion of dose level 2 (T 250mcg with C AUC 6 and T 80mg/m2) will be presented. The 11 pts were on study a median of 9 weeks (range 9-36+). Four pts have discontinued study therapy: 1 due to need for anticoagulation for PE, 1 for prolonged cytopenias, and 2 for disease progression. Of the 8 pts with measurable disease evaluated for response to date, 4 had SD, 1 had a cPR, 1 had radiographic CR, and 2 with PD. A pt with BRCA 1+ triple negative breast cancer has maintained a prolonged PR (36+ weeks) even after dose reductions to T 100mcg with C AUC 3. One pt with ovarian cancer (BRCA WT) has radiographic CR (CA 125 remains mildly elevated) after 15+ weeks of therapy. Conclusion: PARP inhibition with talazoparib days 1-7 in combination with carboplatin and paclitaxel leads to DLT of myelosuppression. However, clinical responses are seen even with lower dose combinations. Citation Format: Turk A, Chan N, Leal T, O'Regan R, Tevaarwerk A, Rice L, Campbell T, Barroilhet L, Mehnert J, Eickhoff J, Kolesar J, Liu G, Wisinski K. NCI9782: A phase 1 study of talazoparib in combination with carboplatin and paclitaxel in patients with advanced solid tumors [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-22-21.

Craniospinal irradiation using helical tomotherapy for central nervous system tumors.

The aim of this study was to describe early and late toxicity, survival and local control in 45 patients with primary brain tumors treated with helical tomotherapy craniospinal irradiation (HT-CSI). From 2006 to 2014, 45 patients with central nervous system malignancies were treated with HT-CSI. The most common tumors were medulloblastoma in 20 patients, ependymoma in 10 patients, intracranial germinoma (ICG) in 7 patients, and primitive neuroectodermal tumor in 4 patients. Hematological toxicity during treatment included leukopenia Grades 1–4 (6.7%, 33.3%, 37.8% and 17.8%, respectively), anemia Grades 1–4 (44.4%, 22.2%, 22.2% and 0%, respectively) and thrombocytopenia Grades 1–4 (51.1%, 15.6%, 15.6% and 6.7%, respectively). The most common acute toxicities were nausea, vomiting, fatigue, loss of appetite, alopecia and neurotoxicity. No Grade 3 or higher late toxicity occurred. The overall 3- and 5-year survival rates were 80% and 70%, respectively. Survival for the main tumor entities included 3- and 5-year survival rates of 80% and 70%, respectively, for patients with medulloblastoma, 70% for both in patients with ependymoma, and 100% for both in patients with ICG. Relapse occurred in 11 patients (24.4%): 10 with local and 1 with multifocal relapse. One patient experienced a secondary cancer. M-status and the results of the re-evaluation at the end of treatment were significantly related to survival. Survival after HT-CSI was in line with the existing literature, and acute treatment-induced toxicity resolved quickly. Compared with conventional radiotherapy, HT offers benefits such as avoiding gaps and junctions, sparing organs, and better and more homogeneous dose distribution and coverage of the target volume.

Impact of Anemia on Menstruation and Academic Performance of Adolescent Girls attending Secondary Schools of Rural Wardha District

ABSTRACT Introduction In this research, we hope to understand the effect of anemia on the various menstrual parameters and disorders and on the academic performance of adolescent girls attending secondary schools of rural Wardha. Materials and methods Questionnaires were prepared and distributed to the female students who came to attend the adolescent clinic in Acharya Vinoba Bhave Rural Hospital, Sawangi, India, for health checkup. Their hemoglobin was estimated and recorded in their respective questionnaires. Questionnaires were designed to understand in the best way possible the effects of anemia on the menstrual health and academic life of the adolescent girls. Results The results revealed a remarkable correlation between the grades of anemia and poor menstrual health; a similar result was seen in case of academic performance as well. It also threw light on the prevalence of anemia, which was recorded as 80% in this study, though most students had only mild grade anemia. Conclusion The results of the study revealed that there was a significant relation between anemia and the menstrual parameters and academic performance of the adolescent girls. This study could prove helpful for future researches which aim to provide better quality of life for adolescent girls in terms of general and menstrual health. How to cite this article Binoy R, Acharya N. Impact of Anemia on Menstruation and Academic Performance of Adolescent Girls attending Secondary Schools of Rural Wardha District. World J Anemia 2017;1(1):1-4.

P1.07-013 Treatment Related Side Effects of Oral Topotecan in Small Cell Lung Cancer

Lung cancer is the most common tumor in men and the second most common tumor in woman according to the latest data available from the Croatian National Cancer Registry. Approximately 20% of all lung cancers are categorized as small cell lung cancer (SCLC). Topotecan is recommended as second-line chemotherapy in treatment of SCLC. Topotecan can be administrated orally with the same effectiveness as parenteral. The aim of this study was to determine toxicity of oral topotecan in second line of chemotherapy and to establish the frequency of drug related admissions. A total of 177 courses of therapy were administered to the 64 patients, 17 woman and 47 men, with SCLC patients ranging from 42 to 77 years with the mean age of 59.3. All the patients were treated in University Hospital Centre Zagreb from January 2012 to October 2015. Included patients had ECOG performance status of 0 or 1. Topotecan was administrated every 21 day, at the dose of 2.3 mg/m2/day, during 5 days. Average number of courses received was 2.8. Of all included patients 17 of them (26.5%) were admitted to hospital because of adverse events related to topotecan administration. The majority of patient hospitalizations (11 patients, 16.9%) was due to febrile neutropenia. Other reasons for hospitalization were severe diarrhea in 4 patients (6.2%), pneumonia in 1 patient (1.5%) and severe electrolyte imbalance in 1 patient (1.5%). Of 17 admissions to hospital 10 (58.9%) of them were after application of first chemotherapy cycle, 3 (17.6%) after second cycle and 4 (23.5%) after third cycle. Quantitative hematologic toxicities were assessed using the National Cancer Institute Common Toxicity Criteria. Anemia grade 3 or 4 occurred in 13 patients (20.3%). Grade 3 or 4 thrombocytpenia occurred in 7 patients (10.9%). Grade 3 or 4 neutropenia occurred in 16 patients (25%). Of other, non-hematologic adverse effects the most serious was grade 3 or 4 diarrhea that occurred in 5 patients (7.8%). although admission of oral topotecan is well tolerated it is related with high rate of hospitalizations due to myelotoxicity and gastrointestinal toxicity during therapy.