OBJECTIVETo evaluate the effect of NaFeEDTA on hemoglobin level in iron deficient population.

METHODSComprehensive literature retrieval was performed via searching electronic databases, hand searching bibliographies of books and relevant journals, collecting grey literatures, looking into conference abstracts, contacting fields experts and reviewing references and citations. Criteria from Cochrane EPOC review group were used to assess the quality of included studies. Generic inverse variance method was used to undertake meta-analysis.

RESULTSThe pooled estimate for hemoglobin level (weighted mean difference) was 12.14 g/L (95% CI: 5.60-18.69; P < 0.001). Subgroup analysis indicated that lower baseline hemoglobin level and higher dose for intervention were associated to greater increase in hemoglobin level.

CONCLUSIONThis systematic review indicated that NaFeEDTA improved hemoglobin significantly in iron deficient population.

Anemia, Iron-Deficiency ; blood ; drug therapy ; metabolism ; Edetic Acid ; therapeutic use ; Ferric Compounds ; therapeutic use ; Hemoglobins ; metabolism ; Humans ; Iron Chelating Agents ; therapeutic use

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

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

A 16-yr-old male patient with hemochromatosis due to multiple packed red blood cell transfusions was referred to our emergency center for the treatment of severe aplastic anemia and dyspnea. He was diagnosed with aplastic anemia at 11-yr of age. He had received continuous transfusions because an HLA-matched marrow donor was unavailable. Following a continuous, approximately 5-yr transfusion, he was noted to develop hemochromatosis. He had a dilated cardiomyopathy and required diuretics and digitalis, multiple endocrine and liver dysfunction, generalized bleeding, and skin pigmentation. A total volume of red blood cell transfusion before deferoxamine therapy was about 96,000 mL. He received a regular iron chelation therapy (continuous intravenous infusion of deferoxamine, 50 mg/kg/day for 5 days q 3-4 weeks) for approximately seven years after the onset of multiple organ failures. His cytopenia and organ dysfunctions began to be gradually recovered since about 2002, following a 4-yr deferoxamine treatment. He showed completely normal ranges of peripheral blood cell counts, heart size, and liver function two years ago. He has not received any transfusions for the last four years. This finding suggests that a continuous deferoxamine infusion may play a role in the immune regulation in addition to iron chelation effect.
Adolescent ; Anemia, Aplastic/pathology/*therapy ; Chelation Therapy/*methods ; Deferoxamine/therapeutic use ; Erythrocyte Transfusion ; Hemochromatosis/*complications/therapy ; Humans ; Immune System ; Iron/*therapeutic use ; Iron Chelating Agents/therapeutic use ; Male ; Radiography, Thoracic/methods ; Time Factors ; Treatment Outcome

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

BACKGROUND/AIMS: The financial burden of caring for iron-related complications (IRCs) is an emerging medical problem in Korea, as in Western countries. We produced a preliminary estimate of the costs of treating patients for IRCs. METHODS: The medical records of patients who had received multiple transfusions were reviewed. Newly developed cardiomyopathy, heart failure, diabetes mellitus, liver cirrhosis, and liver cancer were defined as IRCs. The costs of laboratory studies, medication, oxygenation, intervention, and education were calculated using working criteria we defined. Costs that had a definite causal relationship with IRCs were included to produce as accurate an estimate as possible. RESULTS: Between 2002 and 2006, 650 patients with hematologic diseases, including 358 with acute leukemia, 102 with lymphoma, 58 with myelodysplastic syndrome or myeloproliferative disease, 46 with multiple myeloma, and 31 with chronic leukemia, received more than 10 units of red blood cells. Nine patients developed IRCs. The primary diagnoses of eight patients were aplastic anemia and that of one patient was chronic lymphocytic leukemia. Two patients who had diabetes were excluded because one was treated at another hospital and the other was diagnosed as oxymetholone-induced diabetes. Of the seven patients included, liver cirrhosis developed in two, heart failure in four, and diabetes mellitus in three. Some of them had two diagnoses. The total cost attributed to IRCs for the seven patients was 47,388,241 KRW (approximately 50,000 USD). CONCLUSIONS: The medical costs of IRCs are considerable, and more effective iron-chelating therapy is necessary to save medical resources and improve patient care. More in the way of comprehensive health and economic studies of IRCs are needed to allow both clinicians and health-policy makers to make better decisions.
Adult ; Costs and Cost Analysis/methods ; Erythrocyte Transfusion/adverse effects ; Female ; Health Care Costs/*statistics & numerical data ; Hematologic Diseases/therapy ; Humans ; Iron/blood ; Iron Chelating Agents/*economics/therapeutic use ; Iron Overload/*economics/etiology/*therapy ; Korea ; Male ; Middle Aged ; Retrospective Studies

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

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

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