OBJECTIVETo explore the efficacy and safety of deferasirox in aplastic anemia (AA)patients with iron overload.

METHODSA single arm, multi- center, prospective, open- label study was conducted to evaluate absolute change in serum ferritin (SF)from baseline to 12 months of deferasirox administration, initially at a dose of 20 mg·kg(-1)·d(-1), and the safety in 64 AA patients with iron overload.

RESULTSAll patients started their deferasirox treatment with a daily dose of 20 mg · kg(-1) ·d(-1). The mean actual dose was (18.6±3.60) mg · kg(-1)·d(-1). The median SF decreased from 4 924 (2 718- 6 765)μg/L at baseline (n=64) to 3 036 (1 474- 5 551)μg/L at 12 months (n=23) with the percentage change from baseline as 38%. A median SF decrease of 651 (126-2 125)μg/L was observed at the end of study in 23 patients who completed 12 months' treatment, the median SF level decreased by 1 167(580-4 806)μg/L [5 271(3 420-8 278)μg/L at baseline; 3 036(1 474-5 551)μg/L after 12 months' treatment; the percentage change from baseline as 42% ] after 12 months of deferasirox treatment. The most common adverse events (AEs) were increased serum creatinine levels (40.98%), gastrointestinal discomfort (40.98%), elevated liver transaminase (ALT: 21.31%; AST: 13.11%)and proteinuria (24.59%). The increased serum creatinine levels were reversible and non-progressive. Of 38 patients with concomitant cyclosporine use, 12(31.8%)patients had two consecutive values >ULN, 10(26.3%)patients had two consecutive values >1.33 baseline values, but only 1(2.6%)patient's serum creatinine increased more than 1.33 baseline values and exceeded ULN. For both AST and ALT, no patients experienced two post- baseline values >5 ×ULN or >10 × ULN during the whole study. In AA patients with low baseline PLT count (less than 50 × 10(9)/L), there was no decrease for median PLT level during 12 months' treatment period.

CONCLUSIONSAA patients with iron overload could achieve satisfactory efficacy of iron chelation by deferasirox treatment. The drug was well tolerated with a clinically manageable safety profile and no major adverse events.

Anemia, Aplastic ; drug therapy ; Benzoates ; therapeutic use ; Blood Transfusion ; China ; Ferritins ; blood ; Humans ; Iron ; blood ; Iron Chelating Agents ; therapeutic use ; Iron Overload ; drug therapy ; Liver ; Prospective Studies ; Triazoles ; therapeutic use

A 39-year-old woman with end-stage renal disease, which was maintained on haemodialysis, developed secondary haemochromatosis after receiving blood transfusions and intravenous iron supplementation without sufficient serum ferritin concentration monitoring. The patient received intravenous deferoxamine three times a week, combined with high-dose recombinant human erythropoietin therapy and haemodialysis. After three months, improvements in biochemical indicators and iron overload were noted.
Adult ; Chelating Agents ; chemistry ; Erythropoietin ; therapeutic use ; Female ; Ferritins ; blood ; Hemochromatosis ; complications ; Hemoglobins ; analysis ; Humans ; Kidney Failure, Chronic ; complications ; therapy ; Recombinant Proteins ; therapeutic use ; Renal Dialysis ; adverse effects ; Sequence Analysis, DNA ; Tomography, X-Ray Computed ; Transferrin ; chemistry ; Transfusion Reaction ; Treatment Outcome

This study was aimed to evaluate the effectiveness of solution form of 17% ethylenediaminetetraacetic acid (EDTA) on removing smear layer of root canals at different exposure time periods and to provide scientific basis for EDTA as a choice of root canal irrigation in clinical practice. Twenty-five single-rooted teeth were randomly divided into 5 groups: control group (group A) was given 2.5% NaOCl, and 4 experimental groups were given 2.5% NaOCl and 17% EDTA, including groups B, C, D and E with exposure time of 1, 3, 5 and 7 min, respectively. After preparation of the root canals, the teeth were split along their longitudinal axis, and the root sections were examined under scanning electron microscope for evaluation of smear layer removal and erosion on the surface of the root canal walls. The specimens in group B showed presence of smear layer on the walls of the root canal with no statistical difference from that in group A (P>0.05). In groups C and D, partial removal of smear layer was obtained, and there was no significant difference between the two groups (P>0.05), but there was significant difference in removal of smear layer between group C and group B (P<0.05). Root canal walls in group E specimens showed almost complete removal of smear layer, and the removal of smear layer was significantly different from that in group D (P<0.01). There was no significant change in the structure of the surface of root canal for each sample. It was concluded that combined irrigation with 17% EDTA and 2.5% NaOCl could remove the smear layer with no significant alteration in dentinal structure when the chelating agent was applied for 7 min. At 3 and 5 min of application, partial removal of smear layer was observed and at 1 min negligible removal of smear layer was achieved.
Adolescent ; Bicuspid ; surgery ; ultrastructure ; Chelating Agents ; therapeutic use ; Edetic Acid ; therapeutic use ; Humans ; Microscopy, Electron, Scanning ; Root Canal Irrigants ; therapeutic use ; Root Canal Preparation ; methods ; Smear Layer ; Sodium Hypochlorite ; therapeutic use ; Solutions ; Time Factors ; Treatment Outcome ; Young Adult

OBJECTIVETo observe the status of iron deposition in patient with β thalassemia major, and to formulate appropriate treatment strategies.

METHODThe data of status of transfusion and chelation in 135 patients aged from 6 years and 4 months to 17 years and 11 months with β thalassemia major were collected and analyzed. Serum ferritin levels were determined and cardiac and hepatic iron deposition was determined using MRI T2(*) technology.

RESULTOf the 135 cases studied, 66 were male, and 69 were female, their average age was 12.1 years. Serum ferritin (SF) was determined for 111 cases, it varied from 1 086.8 µg/L to 15 011.5 µg/L. Among them, 16 cases had SF level <2 000 µg/L (14.5%) , in 41 cases SF were between 2 000 and 4 000 µg/L (36.0%) ;in 54 cases SF >4 000 µg/L (48.7%) . Liver MRI T2(*) results showed that in only 8 cases (5.9%) iron content in the liver was in normal range, 19 cases (14.9%) showed mild liver iron deposition;34 (25.2%) moderate and 74 (54.8%, the youngest one was only 6 years and 4 months of age) had severe iron deposition respectively. Cardiac MRI T2(*) showed that in 89 cases (65.9%) iron content in the heart was in normal range;19 cases (14.1%) had mild cardiac iron deposition and 27 (20.0%) presented severe iron deposition (the youngest one was only 9 years and 3 months of age) . SF level was obviously related to liver and cardiac iron deposition (MRI T2(*)) r and P value were -0.284, 0.003 and -0.374, 0.000 respectively. In 108 cases regular transfusion and chelation were delayed due to financial problem. The late and insufficient dosage administered and irregular chelation caused the higher SF level and the severe iron deposition.

CONCLUSIONThe survival status of β thalassemia major in China is worrisome. Majority of them had not received regular transfusion and chelation. Liver and cardiac iron deposition occur early and had a high incidence.

Adolescent ; Child ; Female ; Ferritins ; blood ; Humans ; Iron ; metabolism ; Iron Chelating Agents ; adverse effects ; therapeutic use ; Iron Overload ; epidemiology ; etiology ; Liver ; metabolism ; Magnetic Resonance Imaging ; Male ; Myocardium ; metabolism ; Radiography ; Retrospective Studies ; Transfusion Reaction ; beta-Thalassemia ; diagnostic imaging ; metabolism ; therapy

Recent advances in the treatment of aplastic anemia (AA) made most of patients to expect to achieve a long-term survival. Allogeneic stem cell transplantation (SCT) from HLA-matched sibling donor (MSD-SCT) is a preferred first-line treatment option for younger patients with severe or very severe AA, whereas immunosuppressive treatment (IST) is an alternative option for others. Horse anti-thymocyte globuline (ATG) with cyclosporin A (CsA) had been a standard IST regimen with acceptable response rate. Recently, horse ATG had been not available and replaced with rabbit ATG in most countries. Subsequently, recent comparative studies showed that the outcomes of patients who received rabbit ATG/CsA were similar or inferior compared to those who received horse ATG/CsA. Therefore, further studies to improve the outcomes of IST, including additional eltrombopag, are necessary. On the other hand, the upper age limit of patients who are able to receive MSD-SCT as first-line treatment is a current issue because of favorable outcomes of MSD-SCT of older patients using fludarabine-based conditioning. In addition, further studies to improve the outcomes of patients who receive allogeneic SCT from alternative donors are needed. In this review, current issues and the newly emerging trends that may improve their outcomes in near futures will be discussed focusing the management of patients with AA.
Anemia, Aplastic/blood/diagnosis/mortality/*therapy ; Humans ; Immunosuppressive Agents/adverse effects/*therapeutic use ; Iron Chelating Agents/adverse effects/*therapeutic use ; Risk Factors ; *Stem Cell Transplantation/adverse effects/mortality ; Survival Analysis ; Time Factors ; Treatment Outcome

Paraquat (PQ) has known negative human health effects, but continues to be commonly used worldwide as a herbicide. Our clinical data shows that the main prognostic factor is the time required to achieve a negative urine dithionite test. Patient survival is a 100% when the area affected by ground glass opacity is <20% of the total lung volume on high-resolution computed tomography imaging 7 days post-PQ ingestion. The incidence of acute kidney injury is approximately 50%. The average serum creatinine level reaches its peak around 5 days post-ingestion, and usually normalizes within 3 weeks. We obtain two connecting lines from the highest PQ level for the survivors and the lowest PQ level among the non-survivors at a given time. Patients with a PQ level between these two lines are considered treatable. The following treatment modalities are recommended to preserve kidney function: 1) extracorporeal elimination, 2) intravenous antioxidant administration, 3) diuresis with a fluid, and 4) cytotoxic drugs. In conclusion, this review provides a general overview on the diagnostic procedure and treatment modality of acute PQ intoxication, while focusing on our clinical experience.
Acute Kidney Injury/*diagnosis/pathology/therapy ; Antioxidants/therapeutic use ; Creatinine/blood ; Hemoperfusion ; Herbicides/*poisoning ; Humans ; Iron Chelating Agents/therapeutic use ; Lung Diseases/*diagnosis/pathology/therapy ; Paraquat/blood/*poisoning/urine ; Tomography, X-Ray Computed

INTRODUCTIONSevelamer hydrochloride (Renagel) is frequently used as a second-line phosphate binder in patients on renal replacement therapy. Many studies have shown that sevelamer can improve vascular calcification, serum uric acid and low-density lipoprotein (LDL) cholesterol levels. The main objectives of this study were to assess the efficacy of sevelamer against calcium-based phosphate binders, as well as its tolerability and side-effect profile.

METHODSThis was a retrospective study that included all patients on renal replacement therapy (between 2008 and 2011) who had previously received calcium-based binders for ≥ 6 months and were subsequently switched to sevelamer. Data collected from the patients' medical records included demographics, as well as renal parameters three months prior to sevelamer treatment, and at three and six months post treatment. The study excluded patients on multiple, concomitant phosphate binders or with functioning renal transplants, and those who were noncompliant or had inadequate follow-up blood investigations.

RESULTSA total of 39 patients were included in the study. No major side effects were reported by any of the patients. There were improvements in calcium, phosphate, uric acid and LDL cholesterol levels at three and six months post-sevelamer treatment.

CONCLUSIONWe found sevelamer to be superior to calcium-based phosphate binders in reducing serum calcium, phosphate, uric acid and LDL cholesterol levels in our patient population with advanced renal bone disease. Sevelamer also appears to be well tolerated with no significant side effects.

Adult ; Bone Diseases ; complications ; Chelating Agents ; therapeutic use ; Female ; Humans ; Hypercalcemia ; drug therapy ; Hyperphosphatemia ; drug therapy ; Kidney Failure, Chronic ; drug therapy ; Male ; Middle Aged ; Phosphates ; chemistry ; Polyamines ; therapeutic use ; Renal Replacement Therapy ; methods ; Retrospective Studies ; Sevelamer ; Treatment Outcome ; Uric Acid ; blood

Many Korean patients with transfusion-induced iron overload experience serious clinical sequelae, including organ damage, and require lifelong chelation therapy. However, due to a lack of compliance and/or unavailability of an appropriate chelator, most patients have not been treated effectively. Deferasirox (DFX), a once-daily oral iron chelator for both adult and pediatric patients with transfusion-induced iron overload, is now available in Korea. The effectiveness of deferasirox in reducing or maintaining body iron has been demonstrated in many studies of patients with a variety of transfusion-induced anemias such as myelodysplastic syndromes, aplastic anemia, and other chronic anemias. The recommended initial daily dose of DFX is 20 mg/kg body weight, taken on an empty stomach at least 30 min before food and serum ferritin levels should be maintained below 1000 ng/mL. To optimize the management of transfusion-induced iron overload, the Korean Society of Hematology Aplastic Anemia Working Party (KSHAAWP) reviewed the general consensus on iron overload and the Korean data on the clinical benefits of iron chelation therapy, and developed a Korean guideline for the treatment of iron overload.
Anemia, Aplastic/therapy ; Benzoates/therapeutic use ; Blood Transfusion/*adverse effects ; Chelation Therapy/*methods ; Humans ; Iron Chelating Agents/*therapeutic use ; Iron Overload/*therapy ; Myelodysplastic Syndromes/therapy ; Pyridones/therapeutic use ; Republic of Korea ; Triazoles/therapeutic use

The aim of this study was to assess the clinical efficacy and safety of chelation treatment with penicillamine (PCA) in cross combination with sodium 2, 3-dimercapto-1-propane sulfonate (DMPS) repeatedly in patients with Wilson's disease (WD). Thirty-five patients with WD were enrolled. They were administrated intravenous DMPS in cross combination with oral PCA alternately which was practiced repeatedly, all with Zinc in the meantime. During the treatment, clinical observations and 24-h urine copper excretion as well as adverse effects of medicines were recorded and analyzed. Although the incidence of adverse effects was not significantly different after either intravenous DMPS or oral PCA treatment, levels of 24-h urine copper tended to be higher after short-term intravenous DMPS than that of oral PCA. Adverse effects in the course of intravenous DMPS were mainly neutropenia, thrombocytopenia, allergic reaction and bleeding tendency. As compared with oral PCA alone or intravenous DMPS alone, such repeated cross combination treatment could as much as possible avoid continued drug adverse effects or poor curative effect and had less chance to stop treatment in WD patients. Improved or recovered liver function in 71% of the patients, alleviated neurologic symptoms in 50% of the patients, and disappeared hematuria in 70% of the patients could be observed during the follow-up period of 6 months to 5 years after such combined chelation regimen. Chelation treatment repeatedly with oral penicillamine in cross combination with intravenous DMPS alternately could be more beneficial for WD patients to relieve symptoms, avoid continued drug adverse effects and maintain lifelong therapy.
Administration, Oral ; Adolescent ; Chelating Agents ; administration & dosage ; adverse effects ; therapeutic use ; Chelation Therapy ; adverse effects ; methods ; Child ; Copper ; urine ; Drug Administration Schedule ; Drug Hypersensitivity ; etiology ; Drug Therapy, Combination ; Hepatolenticular Degeneration ; drug therapy ; Humans ; Injections, Intravenous ; Male ; Neutropenia ; chemically induced ; Partial Thromboplastin Time ; Penicillamine ; administration & dosage ; adverse effects ; therapeutic use ; Prothrombin Time ; Thrombocytopenia ; chemically induced ; Time Factors ; Treatment Outcome ; Unithiol ; administration & dosage ; adverse effects ; therapeutic use

Multiple RBC transfusions inevitably lead to a state of iron overload before and after high-dose chemotherapy and autologous stem cell transplantation (HDCT/autoSCT). Nonetheless, iron status during post-SCT follow-up remains unknown. Therefore, we investigated post-SCT ferritin levels, factors contributing to its sustained levels, and organ functions affected by iron overload in 49 children with high-risk neuroblastoma who underwent tandem HDCT/autoSCT. Although serum ferritin levels gradually decreased during post-SCT follow-up, 47.7% of the patients maintained ferritin levels above 1,000 ng/mL at 1 yr after the second HDCT/autoSCT. These patients had higher serum creatinine (0.62 vs 0.47 mg/mL, P = 0.007) than their counterparts (< 1,000 ng/mL). Post-SCT transfusion amount corresponded to increased ferritin levels at 1 yr after the second HDCT/autoSCT (P < 0.001). A lower CD34+ cell count was associated with a greater need of RBC transfusion, which in turn led to a higher serum ferritin level at 1 yr after HDCT/autoSCT. The number of CD34+ cells transplanted was an independent factor for ferritin levels at 1 yr after the second HDCT/autoSCT (P = 0.019). Consequently, CD34+ cells should be transplanted as many as possible to prevent the sustained iron overload after tandem HDCT/autoSCT and consequent adverse effects.
Antigens, CD34/metabolism ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Benzoic Acids/therapeutic use ; Blood Transfusion/*adverse effects ; Child ; Child, Preschool ; Creatinine/blood ; Ferritins/blood ; Follow-Up Studies ; Humans ; Infant ; Iron Chelating Agents/therapeutic use ; Iron Overload/*etiology ; Neuroblastoma/drug therapy/*therapy ; Retrospective Studies ; Risk Factors ; *Stem Cell Transplantation ; Transplantation, Autologous ; Triazoles/therapeutic use