2020 CiteScore: 2.6
Ardeshir Ghavamzadeh, MD.
Vol 9, No 4 (2015)
Background: Imatinib is known as the drug of choice for treatment of chronic myeloid leukemia (CML). For adults the recommended daily dosage of 400 mg requires simultaneous intake of up to four capsules or tablets each 100 mg. A new 400 mg film coated tablet developed due to the need to swallow multiple capsules or tablets per dose and that was a negative impact on treatment adherence.
Subjects and Methods: A group of 36 patients were randomly assigned to receive Imatinib as 4×100 mg capsules, 4×100 mg tablets, and 1×400 mg tablet. Blood sampling was performed for up to 48 h after first dosing. After that, subjects were monitored to assess drug related adverse events. Pharmacokinetic parameters were assessed using concentration-time curves for plasma Imatinib and its metabolite.
Results: Mean area under the curve (AUC (0–∞)) values were 27011, 25811 and 25699 ng/ml for 4×100 mg capsules, 4×100 mg tablets, and 1×400 mg tablets, respectively. Cmax values were 1548, 1605 and 1622 ng/ml, and t1/2 values were 15.7, 15.8 and 15.6 h. The Test/Reference ratios for AUC (0–∞), AUC (0–48), and Cmax were 0.99, 0.99 and 1.02 for 4×100 mg tablets versus 4×100 mg capsules and 0.96, 0.96 and 0.99 for 1×400 mg tablet versus 4×100 mg capsules. The 95% confidence intervals were fully contained within the accepted interval. The mild and moderate adverse events considered to be drug related were reported. These events showed no clustering by type of dosage form and were of little to no clinical significance.
Conclusion: Film coated (400 mg) tablet dosage formulations of Imatinib is bioequivalent to the commercial available 100 mg hard gelatin capsule, and is as safe and well tolerated.
Background: Despite recent advances in mobilization techniques, a considerable portion of patients fail to mobilize sufficient number of cells for successful autologous stem cell transplantation. There are several studies available that have demonstrated enhanced mobilization of endothelial progenitor cells with atorvastatin. Therefore, this prospective trial was conducted to evaluate the mobilizing effect of atorvastatin on hematopoietic progenitor cells.
Subjects and Methods: Forty-four autologous HSCT candidates were randomized in a double-blind controlled trial to receive atorvastatin 40 mg daily or placebo plus standard G-CSF regimen. Treatment was initiated at the time of hospitalization and continued until the day of cell harvest. Independent-samples T-Test, Repeated Measures ANOVA and Mann-Whitney U test were performed to compare means. Categorical variables were analyzed using Chi-square and Fisher’s exact test.
Results: Mean number of hematopoietic progenitor cells per microL of peripheral blood at the time of cell harvest did not differ significantly between the two groups. There was no statistically significant difference in secondary outcomes like time of platelet or PMN engraftment, occurrence of bleeding or infectious episode, duration of hospitalization and etc.
Conclusion: The results of this study did not support beneficial effects of atorvastatin on mobilization of hematopoietic progenitor cells from bone marrow.
Background: Breast cancer is the most common invasive cancer in females worldwide. It accounts for 16% of all female cancers and 22.9% of invasive cancers in women. 18.2% of all cancer deaths worldwide including both males and females are from breast cancer. In this study we compared few serum elements in patients with benign and malignant breast tumor to find any related prognostic and predictive value.
Subjects and Methods: A case-control study was carried out in a hospital (Tehran - Iran) in 2012. Target population was divided in 2 groups; subjects with benign and malignant breast tumors. We did preoperative hematological test. Five milliliter fasting blood vein was collected, centrifuged in 3000 g for 15 minutes to obtain serum. We measured serum Calcium (Ca), Phosphorus (P), Magnesium (Mg), Zinc (Zn), and high sensitive-CRP, analyzed statistically and compared recorded elements in 2 groups by software package SPSS version 16. The level of significant was considered P < 0.05.
Results: Of 87 women, 49 cases with benign breast disease (group A) and 38 cases with breast cancer (group B) entered our study. Serum concentration of Ca, mg, and P in group A were higher than group B, however these differences were not significant. We found no significant correlation between serum Zn and type of tumor in our patients. On the other hand, a significant elevation in hs-CRP in patient with breast cancer was seen (P Value=.000).
Conclusion: Our results have shown similar concentration of Ca, Mg, Zn, P and completely different hs-CRP concentration in patients with benign and malignant breast disease.
Background: Although catalytic properties of different genetic polymorphisms of VKORC1 and CYP2C9 products have been identified, there is limited study available regarding warfarin dose requirement in Iranian patient population. This study investigates the impact of these polymorphisms on 115 patients, referred to Payvand Clinical and Specialty Laboratory for determining the appropriate dose of warfarin. Results of the study may be applicable to individuals who are under warfarin therapy to avoid warfarin resistance or intolerance.
Subjects and Methods: PT-INR test was utilized as a screening method. Genotyping were performed for VKORC1 and CYP2C9 using PCR method. Statistical analyses including unpaired t-test or ANOVA and regression were done using SPSS.
Results: VKORC1 GA was the most common genotype of VKORC1 allele among the study samples, with a rate of 57.4%. In CYP2C9 variant, 20% and 14.8% of subjects carried CYP2C9*1/*2 and CYP2C9*1/*3 genotyping, respectively. By contrast, the WT *1/*1 genotype was more abundant and dominant. The high frequency of VKORC1 (_1639) GA genotype (57.4%), was significant versus for the rest of the cohort (42.6%). In addition, a significant relationship was found between CYP2C9*1 and drug dose (P>0.021).
Conclusion: In this study, samples were characterized by higher frequencies of CYP2C9*1 and VKORC1 G/A, determined as higher warfarin taking doses. The results showed a significant relationship of the VCORC1 and CYP2C9 polymorphisms with warfarin sensitivity and severe side effects. Estimating right doses of warfarin to prescribe can help to reduce the risk of over- or under-anticoagulation and subsequently, the risk of thromboembolism or bleeding.
Background: Langerhans' cell histiocytosis (LCH) is a reactive proliferative disease of unknown pathogenesis characterized by proliferation of Langerhans cells. Involvement of bone marrow (BM), liver and lung are related to high risk factors and poor survival. The aim of this report is to highlight the clinical and haematological findings of 5 cases of LCH with BM infiltration which may help to predict involvement of BM.
Case series: Five cases of Langerhan’s cell histiocytosis with bone marrow infiltration were retrieved from archives of Department of Hematology, PGIMER and Chandigarh for review and further analysis.Male to female ratio was 3:2 with mean age of 9.4 months. Two out of 5 patients had obvious skull swelling; however, radiography of the skull revealed lytic lesion of skull in 4 cases and 2 had skin rashes. Hepatomegaly was present in 4 cases and 2 of whom also had lymphadenopathy and splenomegaly. All patients had anaemia at the time of presentation. Bone marrow aspiration and trephine biopsy in all 5 cases revealed infiltration by large histiocytes with abundant cytoplasm and coffee bean shaped nucleus. Nodules of these Langerhans cells with admixture of eosinophils were seen on trephine biopsy. Immunohistochemistry showed positivity for CD1a stain.
Conclusion: BM evaluation is important in LCH patients to categorize disease which further determines the type of therapy to be given. Clinical details may help to predict the BM involvement; however, demonstration of CD1a positive cells in marrow is most important tool to diagnose marrow infiltration by LCH.
Background: Thalassemia syndromes are the most prevalent single gene disorders in Iran. This study aimed to evaluate the effect of different types of beta-globin gene mutations, co-inheritance of alpha-globin gene mutations and/or Xmn1 SNP on disease phenotype in a large cohort of Iranian patients.
Subjects and Methods: In total, 433 patients were clinically classified into β-thalassemia major (TM) or intermedia (TI). Multiplex PCR, ARMS-PCR, RFLP-PCR and DNA sequencing were performed to identify both α- and β-globin gene mutations and Xmn1 polymorphism as well. All data were compared and analyzed by SPSS software in TM and TI groups consequently.
Results: A total of 39 different β-globin mutations were identified. Among them, the most common were IVS IInt1 (40.33%) followed by IVS Int5 (9.56%), C30 (7.22%) and Fr8-9(7%). All patients were subjected to evaluate common α-globin gene deletions. The patients inherited concomitant mutations of α- and β-globin, showed no clinical modifications compared with those who had only β-globin mutation. The TI patients showed a significant increase in frequency of both heterozygous and homozygous form of the Xmn1 polymorphism. It was also found that β0/β0 genotype patients, inherited the Xmn1 polymorphism required lesser blood transfusion.
Conclusion: No significant differences were observed, on the severity of disease, between patient's inherited defective α- and β-globin genes and ones with just β-globin gene mutation. Taking the results of this research into account, Xmn1 polymorphism can be considered as an important genetic factor modulating the severity of disease.
Histone deacetylases (HDACs) are the enzymes causing deacetylation of histone and non-histone substrates. Histone deacetylase inhibitors (HDIs) are a family of drugs eliminating the effect of HDACs in malignant cells via inhibition of HDACs. Due to extensive effects upon gene expression through interference with fusion genes and transcription factors, HDACs cause proliferation and migration of malignant cells, inhibiting apoptosis in these cells via tumor suppressor genes. Overexpression evaluation of HDACs in leukemias may be a new approach for diagnosis of leukemia, which can present new targets for leukemia therapy. HDIs inhibit HDACs, increase acetylation in histones, cause up- or downregulation in some genes and result in differentiation, cell cycle arrest and apoptosis induction in malignant cells via cytotoxic effects. Progress in identification of new HDIs capable of tracking several targets in the cell can result in novel achievements in treatment and increase survival in patients. In this review, we examine the role of HDACs as therapeutic targets in various types of leukemia as well as the role of HDIs in inhibition of HDACs for treatment of these malignancies.
Treatment related acute myeloid leukemia (t-AML) is well documented phenomenon after chemotherapy. In this subgroup of patients acute promyelocytic leukemia (APML) due to delayed complication of using anthracycline is very rare occurrence. Very few cases are reported in world literature. We are reporting a rare case of occurrence of t-APML in cured breast cancer patient treated with doxorubicin. 43 year old female presented with triple negative early breast cancer treated initially with Right modified radical mastectomy. Pathological staging was pT2N0M0. She was treated with 6 cycle of adjuvant AC (Doxorubicin, Cyclophosphamide). After latent period of 23 months she developed symptoms of fever, weakness and generalized body ache. On further investigation she was found to have acute promyelocytic leukemia (APML). We had successfully treated t-APML with conventional 7+3 induction and subsequent consolidation with ATRA (All Trans Retinoic Acid) and arsenic trioxide. Patient was given maintenance treatment for 18 months after confirming negative PML RARA by RT PCR and declared cured. Patient is under regular surveillance in our centre.
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