Significant Changes In Hemoglobin Levels Research Articles

The The Effect of Administration of Sweet Leaf on Hemoglobin Levels in Pregnant Women with Anemia at Bara-Baraya Health Center, Makassar City

Anemia poses a significant health problem in developing countries, particularly among pregnant women who experience a high morbidity rate. Globally, anemia ranks third among pregnant women, with a prevalence rate of 74%. The primary causes of anemia cases are iron deficiency and acute bleeding, which interact with each other.This study employed an experimental research design known as quasi-experimental. The treatment or intervention was administered to the respondents who were divided into two groups: the control group, which did not receive the treatment, and the intervention group, which did. Prior to the intervention, both groups underwent an initial examination. Subsequently, the intervention group was given sweet potato leaf decoction, followed by a post-administration examination.The results obtained from the SPSS test demonstrated significant changes in hemoglobin levels among 15 respondents in the intervention and control groups. The test yielded a p-value of 0.000, with p < α (α < 0.005), indicating a significant alteration in hemoglobin levels before and after administering sweet potato leaves to pregnant women with anemia. Moreover, the independent test revealed a p-value of 0.005, with (α < 0.005), highlighting a significant difference between the intervention and control groups. This research endeavor aims to enhance knowledge and comprehension regarding the benefits of sweet potato leaves, particularly for healthcare professionals. Sweet potato leaves serve as a viable alternative in increasing hemoglobin levels among pregnant women with anemia.

#3896 SAFETY OUTCOMES OF ORAL ANTICOAGULANT THERAPY IN PATIENTS WITH ATRIAL FIBRILLATION AND CHRONIC KIDNEY DISEASE

Abstract Background and Aims The comorbid conditions of atrial fibrillation (AF) and chronic kidney disease (CKD) leads to an increased risk of thromboembolic complications, but on the other hand is a risk factor for various bleeding. Oral anticoagulant therapy is the standard for the prevention of thromboembolic complications in AF. But with the deterioration of kidney function, the risk of hemorrhagic complications increases dramatically. This problem makes it difficult to choose an effective and safe oral anticoagulant therapy. Clinical data on the use of new oral anticoagulants (NOACs) in patients with AF and advanced CKD are limited, which determines the relevance of conducting studies in comparison with vitamin K antagonists. The aim of study was evaluation of safety parameters for the using of rivaroxaban in patients with stage 4 CKD with AF. Method The study included 109 patients over the age of 18 with a diagnosis of stage 4 CKD (eGFR – 15–29 ml/min/1.72 m2) and non-valvular AF. They were randomized in a 2:1 ratio to either rivaroxaban 15 mg (n = 73) or warfarin (n = 36). The mean follow-up period was 18 months. In the warfarin group, time in therapeutic range (TTR) >70% was achieved in 34 (94%) patients. Exclusion criteria were a history of bleeding that required hospitalization; decrease in hemoglobin level below 80 g/l, platelet count below 100 × 109/l; indications for taking antiplatelet therapy; chronic use of drugs that increase the risk of bleeding. The analysis of the observed hemorrhagic events was carried out using the BARC and ISTH scales. Classification of anemia was carried out according to the recommendations of the World Health Organization. Results Patients taking warfarin were significantly more likely to develop minor bleeding according to the BARC scales and ISTH and all clinically significant bleeding on the ISTH scale. In patients with AF and CKD receiving warfarin therapy, minor bleeding (MB) according to the BARC scale was observed in 72.2% (n = 26), minor clinically significant bleeding (MCSB) in 8.33% (n = 3), major bleeding in 8.33% (n = 3) of cases; and in the group of patients treated with rivaroxaban, MB was observed in 42.4% (n = 31, p<0.01), MCSB in 2.74% (n = 2, p = 0.32), major bleeding in 2.74% (n = 2, p = 0.32) of cases. When assessing bleeding on the ISTH scale during therapy with VKA, MB – 61.1% (n = 22), MCSB – 19.4% (n = 7), major bleeding – 8.33% (n = 3); against the background of NOACs therapy, MB – 36.9% (n = 27, p = 0.01), MCSB in 8.2% (n = 6, p = 0.06), major bleeding in 2.74% (n = 2, p = 0.32). All clinically significant hemorrhagic events according to the BARC scale in the warfarin group occurred more than 16.6% (n = 6) compared with the rivaroxaban group 5.4% (n = 4, p = 0.06); when analyzed according to the ISTH scale, the number of patients receiving VKA anticoagulant therapy 27.7% (n = 10) significantly prevailed over patients on the background of NOACs 10.9% (n = 8, p = 0.03). Analysis of hemoglobin level did not reveal significant dynamics and significant differences between the groups: the median hemoglobin level at inclusion was 129 g/l in the rivaroxaban group and 123 g/l in the warfarin group (p = 0.3), after 18 months - 130 g/l and 121 g/l, respectively (p = 0.7). Conclusion Data suggesting a favorable safety profile for NOACs (rivaroxaban) compared with VKAs (warfarin) in patients with AF and advanced CKD was obtained in this study. Taking rivaroxaban was accompanied by a significantly lower number of hemorrhagic events, which may indicate a safe effect of the drug. No significant changes in hemoglobin levels were found in both groups. Confirmation of these data may be key in choosing an anticoagulant in patients with AF and advanced CKD.

The Efficacy of Lactobacillus-Containing Probiotic Supplementation in Hemodialysis Patients: A Randomized, Double-Blind, Placebo-Controlled Trial

This study was performed to determine the effects of probiotic supplementation on cholesterol-triglyceride ratio, an indirect marker of insulin resistance, protein-bound uremic toxins, biomarkers of inflammation, and microbial translocation in end-stage renal disease patients on hemodialysis. Fifty-six patients aged 39-75years were assigned into two groups to receive either probiotic sachets (n=28) or a placebo (n=28) in a randomized double-blinded placebo-controlled clinical trial. The patients in the probiotic group received twice daily sachets that contained a mixture of three viable and freeze-dried strains: Lactococcus lactis subsp. Lactis LL358, Lactobaccillus salivarius LS159, and Lactobaccillus pentosus LPE588 at high dose (100 billion; 1×1011cfu/day) for 6months. A total of 50 patients were available for final analysis. Probiotic supplementation did not have a significant influence on cholesterol-triglyceride ratio. Probiotic supplementation for 6months caused a significant decrease in serum levels of indoxyl sulfate. Compared with the placebo, probiotic supplementation did not result in significant changes in hemoglobin levels, blood urea nitrogen, blood glucose, serum p-cresyl sulfate, inflammatory, and microbial translocation markers. No clinically significant changes in body composition were observed between the two groups during the study period. The probiotic supplementation was well tolerated by all subjects with minimal adverse effects during the 6-month-long study. Our results suggest that high-dose multistrain lactobaccillus probiotic supplementation over 6months as a monotherapy did not significantly decrease markers of insulin resistance, cholesterol-triglyceride ratio, and most of the studied markers, with the exception of levels of indoxyl sulfate in patients on HD.

Antithrombotic Therapy in Hereditary Hemorrhagic Telangiectasia: Real-World Data from the Gemelli Hospital HHT Registry.

Although Hereditary Hemorrhagic Telangiectasia (HHT) is characterized by an overwhelming bleeding propensity, patients with this disease may also present medical conditions that require antithrombotic therapy (AT). However, precise information on indications, dosage, duration, effectiveness, and safety of AT in HHT patients is lacking. We performed a retrospective analysis of the HHT Registry of our University Hospital and found 26 patients who received AT for a total of 30 courses (19 courses of anticoagulant therapy and 11 courses of antiplatelet therapy). Indications to treatments included: atrial fibrillation, venous thrombosis and pulmonary embolism, heart valve replacement, retinal artery occlusion, secondary prevention after either stroke or myocardial infarction, and thromboprophylaxis for surgery. The total time of exposure to antiplatelet therapy was 385 months and to anticoagulant therapy 169 months. AT was generally well tolerated, with no fatal bleedings and no significant changes in hemoglobin levels. However, we found three major bleedings, with an incidence rate of 6.5 per 100 patients per year. When only patients treated with anticoagulants were considered, the incidence rate of major bleedings increased to 21.6 per 100 patients per year. Our study indicates that major bleeding may occur in HHT patients receiving AT, with a substantially increased rate in those treated with anticoagulants. Further studies are needed to fully estimate the tolerability of antithrombotic drugs in HHT.

EFFECT OF ANGIOTENSIN CONVERTING ENZYME INHIBITORS ON HEMOGLOBIN LEVELS AMONG PATIENTS WITH ADVANCED CHRONIC KIDNEY DISEASE: A RANDOMIZED CONTROL TRIAL

Background: Anemia commonly occurs among patients with advanced stage chronic kidney disease (CKD) and has been associated with poor clinical outcomes. The role of angiotensin converting enzyme (ACE) inhibitors in aggravating the anemia of patients with CKD is controversial. Objective: To evaluate the effect of ACE inhibitors on hemoglobin levels among patients with advanced CKD. Method: Twenty-two patients with CKD stages IV or V and presenting stable hemoglobin levels over 12 weeks were randomly assigned either to receive enalapril (N=10) or amlodipine (N=12) among those whose blood pressure was controlled with antihypertensives other than ACE inhibitors. Hemoglobin level was monitored at 8 and 16 weeks after treatment. Results: Clinical characteristics were similar at baseline between the enalapril and amlodipine-treated groups, and no difference was observed in blood pressure control during follow-up. Enalapril exhibited no significant change in hemoglobin levels from 11.1 (IQR 11.1 to 11.5) g/dL at baseline to 11.4 (IQR 10 to 12) g/dL at 8 weeks and 10.7 (IQR 9.9 to 11.8) g/dL at 16 weeks of treatment. Hemoglobin levels during the 16-week follow-up declined on average by -0.3 (IQR -0.9 to 0.4) g/dL per 16 weeks in the enalapril group and by -0.1 (IQR-0.7 to 0.4) per 16 weeks in the amlodipine group (P=0.868). Conclusion: Administration of ACE inhibitors on blood pressure control was not associated with declining hemoglobin levels among patients with advanced CKD. Additional studies are necessary to confirm this result.

Oral zinc supplementation reduces the erythropoietin responsiveness index in patients on hemodialysis.

Background: In hemodialysis (HD) patients, zinc depletion caused by inadequate intake, malabsorption, and removal by HD treatment leads to erythropoiesis-stimulating agent (ESA) hyporesponsiveness. This study investigated the effects of zinc supplementation in HD patients with zinc deficiency on changes in the erythropoietin responsiveness index (ERI). Methods: Patients on HD with low serum zinc levels (<65 μg/dL) were randomly assigned to two groups: The polaprezinc group (who received daily polaprezinc, containing 34 mg/day of zinc) (n = 35) and the control group (no supplementation) (n = 35) for 12 months. All the 70 patients had been taking epoetin alpha as treatment for renal anemia. ERI was measured with the following equation: Weekly ESA dose (units)/dry weight (kg)/hemoglobin (g/dL). Results: There were no significant changes in hemoglobin levels within groups or between the control and polaprezinc groups during the study period. Although reticulocyte counts were increased immediately after zinc supplementation, this change was transient. Serum zinc levels were significantly increased and serum copper levels were significantly decreased in the polaprezinc group after three months; this persisted throughout the study period. Although there was no significant change in the serum iron or transferrin saturation levels in the polaprezinc group during the study period, serum ferritin levels significantly decreased following polaprezinc treatment. Further, in the polaprezinc group, ESA dosage and ERI were significantly decreased at 10 months and nine months, respectively, as compared with the baseline value. Multiple stepwise regression analysis revealed that the change in the serum zinc level was an independent predictor of lowered ERI. Conclusions: Zinc supplementation reduces ERI in patients undergoing HD and may be a novel therapeutic strategy for patients with renal anemia and low serum zinc levels.

Effect of Intravenous Iron Therapy on Quality of Life in Non-Anemic Iron-Deficient Young Women with Fatigue

▪IntroductionIron deficiency is defined as the presence of insufficient iron to maintain normal physiological function of tissues. Even in the absence of anemia, studies have demonstrated the effect of iron deficiency on cognition, exercise performance and endurance capacity. Menstruating women are at increased risk for developing iron deficiency. Studies have shown benefit of oral iron therapy in adult females but orally administered iron can be poorly absorbed and is often accompanied by gastrointestinal side effects impacting patient compliance. Intravenous iron therapy has been shown to be well tolerated and useful in adult patients but has not been well studied in a homogenous group of patients in the pediatric setting. The main objective of this study is to demonstrate the effect of a standardized regimen of intravenous iron on the quality of life of a prospective cohort of young women with low serum ferritin and symptoms of fatigue as measured by a standardized quality of life fatigue scale.MethodsOur study design is a prospective observational study. We include young post-menarchal girls with serum ferritin < 20 ng/ml and symptoms of fatigue as documented by the standardized and validated Peds QLTM Multidimensional Fatigue Scale (Score < 70). Only patients who have failed oral iron therapy due to poor response, non-compliance or side effects are included on our study. Patients with hemoglobin < 10g/dl are excluded from the study. Patients receive four 15-20 minute infusions of 200 mg intravenous iron sucrose given over a 14-day period. Hemodynamic stability is carefully monitored. Laboratory values including hemoglobin, iron, TIBC, iron saturations, ferritin, reticulocyte count and reticulocyte hemoglobin concentration are obtained prior to treatment, at the time of the fourth infusion, 6 weeks and 3 months after treatment. The Peds QLTM Multidimensional Fatigue Scale, using child self-report and parent proxy-report is administered at these time points as well.ResultsNine patients have been included in this study and recruitment is ongoing. Six adolescent girls (ages 16-18 years) have completed all four infusions. All the patients tolerated the infusions well without any severe adverse effects. The mean pre-treatment ferritin level was 11.33 ng/ml (SD 6.713) and the mean post-treatment ferritin level was 273.33ng/ml (SD 154.23) (p = 0.002); [95% CI: -402.427 to -121.57]. There was a statistically significant improvement in the quality of life and fatigue scores as measured by the standardized Peds QLTM Multidimensional Fatigue Scale for both the patient and parent questionnaires. The mean score for the patients pre-treatment was 41.172 (SD 20.696) and post-treatment was 75.043 (SD 10.657) (p = 0.005); [95% CI: -55.268 to -12.476]. The mean score for the parents pre-treatment was 43.048 (SD 21.307) and post-treatment was 73.608 (SD 13.145) (p = 0.01); [95 % CI: -53.334 to -7.786]. The individual ferritin levels, hemoglobin levels and fatigue scores of the subjects that have completed all the infusions have been included in the Table. The patients who were not anemic before the iron infusions did not have a significant change in hemoglobin levels. The post-treatment hemoglobin levels for patient 5 and patient 6 were obtained at the fourth infusion. Abstract 4858. TableSubjectAge (years)Pre-Ferritin (ng/ml)Post-Ferritin (ng/ml)PedsQL Patient-PrePedsQL Patient-PostPedsQL Parent-PrePedsQL Parent-PostPre-treatment Hemoglobin (g/dl)Post-treatment Hemoglobin (g/dl)1181726626.3970.8336.1170.8312.912.7217313572.27583.361.1111.713.4317171891890.5537.584.7211.913.1417621036.1158.3334.7263.8813.513.85161857133.337520.8366.6711.911.761672696180.5545.8394.4410.510.5ConclusionAlthough our study population is small, our results demonstrate promise that intravenous iron objectively improves fatigue and quality of life in young women with iron deficiency and mild/no anemia. Intravenous iron appears to be well tolerated and effective in this adolescent age group and leads to a substantial increase in ferritin levels. In non-anemic patients, iron administration did not influence hemoglobin concentration. Therefore, the fatigue-reducing effects of iron therapy reflect the non-hematological functions of iron. DisclosuresNo relevant conflicts of interest to declare.

Randomized double-blind clinical trial of a new human epoetin versus a commercially available formula for anemia control in patients on hemodialysis

OBJECTIVES:Anemia is a common complication among chronic kidney disease patients on hemodialysis, occurring mostly due to erythropoietin deficiency. This randomized noninferiority trial sought to compare the efficacy and safety of a new epoetin formulation developed by Bio-Manguinhos, a biologics manufacturer affiliated with the Brazilian government, with those of a commercially available product currently used in Brazil (a biosimilar epoetin formulation).METHODS:The sample size needed to enable demonstration of noninferiority with a statistical power of 85% for a between-group difference in hemoglobin levels of no more than 1.5 g/dL was calculated. In total, 74 patients were randomly assigned to receive the epoetin formulation from Bio-Manguinhos (n = 36) or the biosimilar epoetin formulation (n = 38) in a double-blind fashion. The inclusion criteria were current epoetin therapy and stable hemoglobin levels for at least 3 months prior to the study. The primary and secondary outcomes were mean monthly hemoglobin levels and safety, respectively. The dose was calculated according to international criteria and adjusted monthly in both groups according to hemoglobin levels and at the assistant physicians' discretion. Iron storage was estimated at baseline and once monthly. Clinicaltrials.gov: NCT01184495.RESULTS:The study was conducted for 6 months after randomization. The mean baseline hemoglobin levels were 10.9±1.2 and 10.96±1.2 g/dL (p = 0.89) in the Bio-Manguinhos epoetin and biosimilar epoetin groups, respectively. During the study period, there was no significant change in hemoglobin levels in either group (p = 0.055, ANOVA). The epoetin from Bio-Manguinhos was slightly superior in the last 3 months of follow-up. The adverse event profiles of the two formulations were also similar.CONCLUSIONS:The epoetin formulations tested in this study are equivalent in efficacy and safety.

Oxaliplatin-induced acute-onset thrombocytopenia and hemorrhage: Case report and review of the literature

We report the case of a woman who developed acute thrombocytopenia with hemorrhagic diathesis during adjuvant treatment of colorectal adenocarcinoma with oxaliplatin, 5-fluorouracil and leucovorin. A 55-year-old woman started adjuvant chemotherapy with oxaliplatin, 5-fluorouracil and leucovorin (mFOLFOX6). Prior to starting the 12th course of chemotherapy, a complete blood cell count showed the following values: neutrophils 1800/mm(3), platelets 136,000/m(3) and hemoglobin 11.1 g/dl. A blood count revealed that the platelet levels had dropped to 35,000/mm(3), with no significant changes in hemoglobin levels following the course. The administration of corticosteroids was begun and the platelet number was recovered. Clinicians should be aware of the possibility of oxaliplatin-induced hematological emergencies during the treatment of colorectal cancer patients in order to optimize supportive treatment and avoid toxic mortality.

Antioxidant Vitamins C and E Supplementation Does Not Improve the Hemolytic Profile of Sickle Cell Anemia Patients: A Randomized, Double-Blind, Placebo-Controlled Trial

Abstract 1063▪▪This icon denotes a clinically relevant abstract Background:Erythrocytes of sickle cell anemia (SCA) patients continuously produce larger amounts of pro-oxidants than normal cells, and oxidative stress seems to play a significant role in the pathophysiology of this disease. In erythrocytes, oxidative stress primarily affects the membrane and results in hemolysis. The use of antioxidants in vitro reduces the generation of pro-oxidants, which could prevent adhesion and phagocytosis of oxidized erythrocytes. Aims:To evaluate the impact of antioxidant vitamins C (vitC) and E (vitE) supplementation in the hemolytic profile in SCA patients. Patients and methods:Homozygous SCA or S-β-thalassemia patients, over 18 years, were randomly assigned to receive VitC 1,400 mg + VitE 800 mg per day or placebo, administered orally for 180 days. Pregnant women and patients with iron overload out of chelation therapy were excluded. Patients were evaluated clinically and blood samples were collected at days 0 and 180 for complete blood count, automated reticulocyte count, indirect bilirubin, lactate dehydrogenase (LDH), haptoglobin, uric acid, and serum levels of VitC and VitE. Results:Overall, 83 patients were enrolled (44 vitamins, 39 placebo). The median (range) age was 27 (18–68) years, and 53 (64%) were female. There were no significant differences between the two groups as regards clinical complications of SCA or baseline laboratorial tests and serum vitC and vitE. Sixty percent of the patients were VitC deficient (30% with severe deficiency), 70% were VitE deficient (33% with severe deficiency) and 44% were deficient in both vitamins. Vitamin supplementation increased VitC from 27.2 to 62.6 μMol/L (p<0.0001) and VitE from 13.9 to 20.2 μMol/L (p<0.0001). No changes in vitC or vitE were observed in patients receiving placebo. No significant changes in hemoglobin levels, hematocrit, mean corpuscular volume were observed in either group. However, patients receiving vitamin supplementation presented a significant increase in the median reticulocyte count (from 152 to 195 ×106/μL, p=0.01), LDH (from 396 to 425 U/L, p=0.018), indirect bilirubin (from 1.45 to 1.73 mg/dL, p<0.0001), and uric acid (from 4.75 to 5.15 mg/dL, p=0.02), and a decrease in the haptoglobin levels (from 3.95 to 3.45 mg/dL, p=0.06). Conclusion:Supplementation with vitamins C and E did not improve anemia and, surprisingly, increased markers of hemolysis in patients with SCA and S-β-thalassemia. The exact mechanisms to explain our findings and their clinical significance remain to be determined. Disclosures:No relevant conflicts of interest to declare.

Improvement of Oxidative Stress Parameters in MDS Patients with Iron Overload Treated with Deferasirox

Introduction: Using flourescence markers, evidence for oxidative stress has been documented by flow cytometry in red cells (RBC) and other blood cells of patients with congenital and acquired hemolytic anemias (e.g. thalassemia, sickle cell anemia, hereditary spherocytosis and paroxysmal nocturnal hemoglobinuria) as well as in myelodysplatic syndrome (MDS) (Eur. J. Hematol. 79:463,2008). These data included increased generation of reactive oxygen species (ROS) concomittant with a decrease in the cellular content of the major antioxidant reduced gluthatione (GSH), and increased membrane lipid peroxidation. Oxidative stress in these anemias is thought to be mainly due to the accumulation of non-transferrin-bound iron (NTBI) which affects iron homeostasis and results in excess extra-cellular and intra-cellular labile pools: labile plasma iron (LPI) and cellular labile iron pool (LIP) (Cytometry 73:22,2008), respectively, catalyzing ROS generation. The presence of these free iron components is correlated with the severity of hemolysis and the subsequent repetitive blood transfusions, resulting in iron-overload. The purpose of the present study was to measure changes in parameters of iron-overload and oxidative stress in iron-overloaded patients with MDS following treatment with the oral iron-chelator Deferasirox.Patients and Methods: Fifteen patients–5 males and 10 females-(mean age 66 ± 13 years) with “low risk” MDS (IPSS < 1.0) received Deferasirox 20 mg/kg/day (12 patients) or 4–6 mg/kg/day (3 patients) due to side effects mainly gastrointestinal, increased creatinine and rash, for an average period of 95 days (63–163 days). All of them had evidence of iron-overload. Their mean number of transfusions was 65 ± 62, and mean ferritin levels before treatment was 3008 ± 1797 ng/ml. ROS, GSH, lipid peroxidation, LIP and LPI were measured every 3–4 weeks, in RBC, platelets and polymorphonuclear leukocytes (PMN). Blood cell counts, hemoglobin levels and serum ferritin were assayed simulteneously.Results: There was a statistically significant decrease in ROS (28%, p=0.006), lipid peroxidation (138%, p=0.008) and the LIP (23%, p=0.004) of RBC, concomittant with an increase in GSH (123%, p=0.001). GSH was also increased in platelets (48%, p=0.008) and PMN (72%, p=0.001), and LIP decreased in platelets (23%, p=0.004). In 8 patients the mean initial LPI levels of 0.39 units decreased to 0.12 units (p=0.028). There were no significant changes in hemoglobin levels or in any of the other types of blood cells. Mean serum ferritin levels increased in 8 patients by 964 ± 927 ng/ml and decreased in the rest by 1432 ± 1267 ng/ml.Discussion: The results clearly demonstrate that administration of Deferasirox to iron-overloaded MDS patients for a mean period of 3 months resulted in a significant decrease in parameters of oxidative stress mainly in RBC and platelets and in intra-(LIP) and extra-cellular (LPI) species of free iron. Serum ferritin, a major parameter in the assessment of the severity of iron-overload, was increased in 8 patients in the present study, similar to previously reported findings of increased ferritin levels at 12 months following iron chelation with Deferasirox (Am. J. Hematol. 83:611–3, 2008). However, unlike iron stored in ferritin, the major risk of iron-overload is the presence of excess extra and intracellular iron species (LPI and LIP) which are playing an important role in ROS generation and consequent membrane damage in blood cels and in other major organs.. These preliminary data suggest that treatment with Deferasirox, a once-a-day oral iron chelator, reduced the toxic iron species and several parameters of oxidative stress in iron overloaded MDS patients. Furthermore, the novel methodologies applied in this study may be useful for evaluating the severity of the iron-overload and for monitoring the efficacy of iron chelation therapy. Additional studies assessing the correlation of these changes to the long-term morbidity, mortality, and quality of life are definitely warranted in this patient population.

Phase I evaluation of 773U82 HCI, a member of a new class of DNA intercalators

The arylmethylaminopropanediols (AMAPs) are a new class of DNA intercalators. 773U82.HCl is the second of these compounds to enter clinical trial. Significant antitumor activity for 773U82.HCl was documented in a variety of murine and human tumor models. This phase I study examined a 1-, 2- and 6-hour infusion given every 28 days. Thirty-six patients received 58 courses of drug at doses ranging from 15 mg/m2 to 980 mg/m2. The dose-limiting toxicity of 773U82.HCl was hemolysis noted at 980 mg/m2. Change in color of the plasma and decreases in haptoglobin were correlated with drug concentrations of the infusate greater than or equal to 3 mg/ml. Clinically significant changes in hemoglobin levels requiring blood transfusions did not occur. Neurologic toxicity occurred at 720 mg/m2 with the most severe neurologic toxicity occurring in a patient with the highest peak plasma concentration (4.1 micrograms/ml). With an increase in duration of the infusion and amount of fluid administered, the neurologic toxicity resolved. Other toxicities included mild nausea and vomiting and a dose-related phlebitis. Pharmacokinetic studies were completed in 22 patients. The mean terminal t1/2 beta was 4.4 h with a mean apparent volume of distribution at steady state (Vdss) of 314 l/m2. The mean total body clearance was 72 l/h/m2. Peak plasma levels ranged from 0.04 to 4.14 micrograms/ml. Further studies with 773U82.HCl on this schedule at the doses studied are not recommended. Hematologic monitoring for evidence of intravascular hemolysis should be included in future studies with 773U82.HCl.