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Medicine Dec 2022Poor graft function (PGF) occurs in 5% to 27% of allogeneic hematopoietic stem cell transplantation (allo-HSCT) and is associated with high life-threatening... (Review)
Review
RATIONALE
Poor graft function (PGF) occurs in 5% to 27% of allogeneic hematopoietic stem cell transplantation (allo-HSCT) and is associated with high life-threatening complications. The etiology of PGF is complex and multifactorial, and iron overload (IOL) is considered as a predictive factor.
PATIENT CONCERN
A 45-years-old woman who was diagnosed as low-risk myelodysplastic syndrome in 2012 has been transfusion dependent and developed severe IOL.
DIAGNOSES
Due to transfusion dependency and also ineffective erythropoiesis, this patient was diagnosed as IOL and developed PGF after allo-HSCT.
INTERVENTIONS
Deferasirox (20mg/kg/d) was administered regularly after allo-HSCT for 2 years.
OUTCOMES
Hematopoiesis was gradually recovered during iron chelation therapy treatment after allo-HSCT and PGF was reverted.
LESSONS
IOL, as a prognostic factor for PGF, is a common problem in Transfusion dependent myelodysplastic syndrome patients undergoing HSCT. IOL issues should be considered at the time of diagnosis and throughout the treatment course for patients who are potential candidates for HSCT.
Topics: Female; Humans; Middle Aged; Iron Overload; Hematopoietic Stem Cell Transplantation; Risk; Myelodysplastic Syndromes; Chelation Therapy; Graft vs Host Disease
PubMed: 36595778
DOI: 10.1097/MD.0000000000032012 -
Annals of Medicine and Surgery (2012) Dec 2022Turner syndrome and β-thalassemia very rarely occur together in an individual.
BACKGROUND
Turner syndrome and β-thalassemia very rarely occur together in an individual.
CASE PRESENTATION
An Indonesian adolescent, 18 years old, complained is fatigue a week ago. She has a medical history of β-thalassemia for age 6 months and Turner syndrome identification for age 16 years. Meanwhile, she regular consumes deferasirox 500 mg every day. Physical examination showed pale conjunctiva and pale face. Body view similar children aged 13 years old. Laboratories investigation values included Hb of 7.7 gr/dL, MCV of 79.5 fL, MCH of 25.9 pg, MCHC of 28.6%, WBC of 6780/mm, PLT of 242,000/mm, AST of 15 U/L, ALT of 20 U/L, Ferritin of 1692.32 ng/mL, growth hormone of 0.468 ng/mL, Estradiol of <11.80 pg/mL, luteinizing hormone of 53.50 mIU/mL, and follicle-stimulating hormone of 115.19 mIU/mL. Chromosomal analysis showed Turner syndrome. The patient received a packed red cell transfusion of up Hb of 10 gr/dL, deferasirox 500 mg daily, and a contraceptive tablet. Due to financial issue in Indonesia, patient with Turner syndrome does not get proper hormonal therapy such as growth hormone, vitamin D supplementation, and other hormone replacement therapy.
DISCUSSION
Turner syndrome and thalassemia in low-resource settings are challenges in themselves, so in their implementation, only thalassemia can be controlled, but for therapy, it does not show an improvement in prognosis.
CONCLUSION
Turner syndrome and thalassemia both worsen the patient's condition.
PubMed: 36582921
DOI: 10.1016/j.amsu.2022.104854 -
World Journal of Clinical Cases Dec 2022A perforated gastroduodenal ulcer is rarely observed in children. Certain medications have been reported to cause ulcerations. Deferasirox, an iron chelating agent, has...
BACKGROUND
A perforated gastroduodenal ulcer is rarely observed in children. Certain medications have been reported to cause ulcerations. Deferasirox, an iron chelating agent, has been previously reported to be associated with the development of gastroduodenal ulcers.
CASE SUMMARY
We report a case of a 3-year-old boy who was diagnosed with beta thalassemia major and treated with deferasirox. He presented to the emergency department with an acute abdomen. A perforated duodenal ulcer was suspected after X-ray imaging and laparoscopic exploration. It was successfully managed with laparoscopic washout and drainage.
CONCLUSION
Due to the rarity and severity of this case, it is a reminder that prevention and early recognition of gastrointestinal complications in patients receiving deferasirox are crucial. Minimally invasive laparoscopic surgery is both safe and feasible to treat perforated duodenal ulcers in selected patients.
PubMed: 36579108
DOI: 10.12998/wjcc.v10.i34.12775 -
The Journal of International Medical... Dec 2022To examine the efficacy of deferasirox (DFX) by comparison with deferoxamine (DFO) in managing iron overload in patients with sickle cell anaemia (SCA). (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To examine the efficacy of deferasirox (DFX) by comparison with deferoxamine (DFO) in managing iron overload in patients with sickle cell anaemia (SCA).
METHODS
Online databases were systematically searched for studies published from January 2007 to July 2022 that had investigated the efficacy of DFX compared with DFO in managing iron overload in patients with SCA.
RESULTS
Of the 316 articles identified, three randomized clinical trials met the inclusion criteria. Meta-analysis of liver tissue iron concentration (LIC) showed that iron overload was not significantly higher in the DFX group compared with DFO group (WMD, -1.61 mg Fe/g dw (95% CI -4.42 to 1.21). However, iron overload as measured by serum ferritin was significantly lower in DFO compared with DFX group (WMD, 278.13 µg/l (95% CI 36.69 to 519.57). Although meta-analysis was not performed on myocardial iron concentration due to incomplete data, the original report found no significant difference between DFX and DFO.
CONCLUSION
While limited by the number of studies included in this meta-analysis, overall, the results tend to show that DFX was as effective as DFO in managing iron overload in patients with SCA.
Topics: Humans; Deferasirox; Deferoxamine; Iron Chelating Agents; Benzoates; Triazoles; Iron Overload; Iron; Anemia, Sickle Cell
PubMed: 36562113
DOI: 10.1177/03000605221143290 -
Pharmaceutics Dec 2022Microneedles are minimally invasive systems that can deliver drugs intradermally without pain and bleeding and can advantageously replace the hypodermal needles and oral...
Microneedles are minimally invasive systems that can deliver drugs intradermally without pain and bleeding and can advantageously replace the hypodermal needles and oral routes of delivery. Deferasirox (DFS) is an iron chelator employed in several ailments where iron overload plays an important role in disease manifestation. In this study, DFS was formulated into a nanosuspension (NSs) through wet media milling employing PVA as a stabilizer and successfully loaded in polymeric dissolving microneedles (DMNs). The release studies for DFS-NS clearly showed a threefold increased dissolution rate compared to pure DFS. The mechanical characterization of DFS-NS-DMNs revealed that the system was sufficiently strong for efficacious skin penetration. Optical coherence tomography images confirmed an insertion of up to 378 µm into full-thickness porcine skin layers. The skin deposition studies showed 60% drug deposition from NS-DMN, which was much higher than from the DFS-NS transdermal patch (DFS-NS-TP) (without needles) or pure DFS-DMNs. Moreover, DFS-NS without DMNs did not deposit well inside the skin, indicating that DMNs played an important role in effectively delivering drugs inside the skin. Therefore, it is evident from the findings that loading DFS-NS into novel DMN devices can effectively deliver DFS transdermally.
PubMed: 36559310
DOI: 10.3390/pharmaceutics14122817 -
Advanced Biomedical Research 2022In patients with β-thalassemia major (TM), one of the long-term complications of regular blood transfusion is renal dysfunction. The purpose of the current study was to...
BACKGROUND
In patients with β-thalassemia major (TM), one of the long-term complications of regular blood transfusion is renal dysfunction. The purpose of the current study was to evaluate the renal function in TM patients receiving Exjade dispersible tablets and a new film-coated tablet formulation of deferasirox (Nanojade).
MATERIALS AND METHODS
In this descriptive cross-sectional study, a total of 80 TM patients aged 11-48-year-old entered the study. Patients received 20-30 mg/kg/d (single dose) Exjade® (Exjade group, = 40) and Nanojade® (Nanojade group, = 40) orally. To evaluated renal function, serum creatinine (S), estimated glomerular filtration rate (eGFR), blood urea nitrogen (BUN), 24-h urine protein (U), U/U, spot U/U ratio, and serum ferritin were calculated at baseline and every 3 months to 9 months.
RESULTS
There was no significant difference in S, BUN, eGFR, 24-h U, U/U ratio, U/U ratio, and serum ferritin between groups at baseline and end of study ( > 0.05, > 0.05). There was no significant difference in proteinuria between groups at baseline and end of study ( > 0.05, > 0.05).
CONCLUSIONS
The proportion of S, BUN, eGFR, 24-h U, U/U ratio, and U/U ratio was not significantly different in TM patients treated with Nanojade compared to patients' received Exjade. Nanojade had similar effects to Exjade, and therefore, the use of Nanojade is safe in TM patients and does not seem to be associated with increased renal failure, proteinuria, and hypercalciuria.
PubMed: 36518868
DOI: 10.4103/abr.abr_89_21 -
Frontiers in Bioengineering and... 2022Iron as an essential element, is involved in various cellular functions and maintaining cell viability, cancer cell is more dependent on iron than normal cell due to its...
Iron as an essential element, is involved in various cellular functions and maintaining cell viability, cancer cell is more dependent on iron than normal cell due to its chief characteristic of hyper-proliferation. Despite that some of the iron chelators exhibited potent and broad antitumor activity, severe systemic toxicities have limited their clinical application. Polyaminoacids, as both drug-delivery platform and therapeutic agents, have attracted great interests owing to their different medical applications and biocompatibility. Herein, we have developed a novel iron nanochelator PL-DFX, which composed of deferasirox and hyperbranched polylysine. PL-DFX has higher cytotoxicity than DFX and this effect can be partially reversed by Fe supplementation. PL-DFX also inhibited migration and invasion of cancer cells, interfere with iron metabolism, induce phase G1/S arrest and depolarize mitochondria membrane potential. Additionally, the anti-tumor potency of PL-DFX was also supported by organoids derived from clinical specimens. In this study, DFX-based iron nanochelator has provided a promising and prospective strategy for cancer therapy iron metabolism disruption.
PubMed: 36518196
DOI: 10.3389/fbioe.2022.1078137 -
Biomolecules Nov 2022The chelating thiol dimercaptosuccinate (DMSA) and the traditional agent D-penicillamine (PSH) are effective in enhancing the urinary excretion of copper (Cu) and lead... (Review)
Review
The chelating thiol dimercaptosuccinate (DMSA) and the traditional agent D-penicillamine (PSH) are effective in enhancing the urinary excretion of copper (Cu) and lead (Pb) in poisoned individuals. However, DMSA, PSH, EDTA (ethylenediamine tetraacetate), and deferoxamine (DFOA) are water-soluble agents with limited access to the central nervous system (CNS). Strategies for mobilization of metals such as manganese (Mn), iron (Fe), and Cu from brain deposits may require the combined use of two agents: one water-soluble agent to remove circulating metal into urine, in addition to an adjuvant shuttler to facilitate the brain-to-blood mobilization. The present review discusses the chemical basis of metal chelation and the ligand exchange of metal ions. To obtain increased excretion of Mn, Cu, and Fe, early experiences showed promising results for CaEDTA, PSH, and DFOA, respectively. Recent experiments have indicated that p-amino salicylate (PAS) plus CaEDTA may be a useful combination to remove Mn from binding sites in CNS, while the deferasirox-DFOA and the tetrathiomolybdate-DMSA combinations may be preferable to promote mobilization of Fe and Cu, respectively, from the CNS. Further research is requested to explore benefits of chelator combinations.
Topics: Humans; Manganese; Copper; Iron; Chelating Agents; Ions; Metals; Neurotoxicity Syndromes; Succimer; Water
PubMed: 36421727
DOI: 10.3390/biom12111713 -
Transplantation and Cellular Therapy Jan 2023During conditioning chemotherapy prior to allogeneic haematopoietic stem cell transplantation (HSCT), non-transferrin-bound iron and its chelatable form, labile plasma... (Observational Study)
Observational Study
During conditioning chemotherapy prior to allogeneic haematopoietic stem cell transplantation (HSCT), non-transferrin-bound iron and its chelatable form, labile plasma iron (LPI), regularly appear in the blood of patients at high levels of transferrin saturation (TfS). As these free iron species potentially favor infection and mediate transplantation-associated toxicities, chelation therapy could be an approach to improve outcome after transplantation. However, data addressing iron chelation in the immediate peritransplantation period are sparse. In this study, we investigated the influence of iron chelation with deferasirox during conditioning chemotherapy on the appearance of LPI, the incidence of infection and toxicities, and the tolerability of this treatment in the peritransplantation period. We conducted this single-center prospective observational study in 25 adults with iron overload (serum ferritin >1000 µg/L) undergoing allogeneic HSCT after myeloablative busulfan-based conditioning chemotherapy. Patients received iron chelation with deferasirox (14 mg/kg) from the start of conditioning until day 3 post-transplantation. Iron parameters, including LPI, were obtained at the chelator's trough level daily until day 0 and then on days 4, 7, and 14. Data on infection (bacteremia or invasive fungal disease) and toxicity, as well as the tolerability of deferasirox, were collected until the end of the follow-up period on day 28. Data were analyzed descriptively. TfS levels exceeded 70% in median on 6 days (range, 4 to 10 days) and in 63.6% (range, 36.4% to 90.9%) of the samples per patient, although in 19 of 25 patients (76%), no elevated LPI values were detected during the intake of deferasirox despite high TfS levels. Only 6 patients (24%) showed mildly increased LPI values (≤0.5 units) during the intake of deferasirox, 3 of whom had presented with elevated LPI values before the start of conditioning. Deferasirox was well tolerated, and no aggravation of toxicities was observed. Infection occurred in 5 patients (20%), including 3 of the 6 patients with elevated LPI values despite chelation therapy. In the present study, we demonstrate that iron chelation with deferasirox safely suppresses the appearance of LPI and might decrease the incidence of infection, whereas the impact on transplantation-associated toxicities remains to be elucidated.
Topics: Adult; Humans; Iron; Deferasirox; Ferritins; Iron Chelating Agents; Hematopoietic Stem Cell Transplantation
PubMed: 36241148
DOI: 10.1016/j.jtct.2022.10.002 -
JPMA. the Journal of the Pakistan... Jul 2022Duodenal ulcer disease is uncommon in paediatric age group. Its perforation is even rarer. However, it should be kept in mind when examining children with acute abdomen...
Duodenal ulcer disease is uncommon in paediatric age group. Its perforation is even rarer. However, it should be kept in mind when examining children with acute abdomen especially if there are signs of shock or possibility of upper gastrointestinal bleed. We report a case of a 6 years old female child, a known case of thalassemia major and taking oral Deferasirox since two years of age. She had atypical presentation as there was no previous history of peptic ulcer disease and she only suffered epigastric pain and vomiting for a week but due to lack of proper diagnosis at a local clinic developed duodenal ulcer perforation, which was ultimately diagnosed at a tertiary care hospital and managed with Graham Patch Closure.
Topics: Chelating Agents; Child; Deferasirox; Duodenal Ulcer; Female; Humans; Iron; Peptic Ulcer Perforation; beta-Thalassemia
PubMed: 36156578
DOI: 10.47391/JPMA.4345