Vol 12, No 3 (2018)

Original Article(s)

  • XML | PDF | downloads: 213 | views: 320 | pages: 184-190

    Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only treatment offered for acute leukemias with potential curative capability. One of the main reasons of treatment failure in patients after allo-HSCT is return of the primary disease. This study aimed to evaluate the role of different modalities available to treat the patients with relapsed acute leukemia after allo-HSCT, focusing mainly on donor leukocyte infusions (DLIs).
    Materials and Methods: This study included 277 patients who relapsed after myeloablative allo-HSCT between February 2003 and February 2015. Treatment option was offered to all patients, but it was not accepted by about one-third of the study participants. Treated patients were categorized based on receipt of DLI (DLI-based vs. non DLI-based). The effect of treatment in all patients and then the effect of DLI among the treated group was evaluated. Kaplan-Meier method was used for calculating survival rates. All patients were relapsed cases, thus only overall survival (OS) was calculated.
    Results: One hundred and forty-five ALL patients and 132 AML patients were included in the study. One year survival rate for treated patients was 25.13% and for patients who received best supportive care was 2.79% (P<0.001). The difference was significant in both AML and ALL groups. Using DLI-based treatments were accompanied by a noticeably superior outcome. Hazard ratio was 0.43 (0.29-0.63) for DLI-based treatments (P<0.001).
    Conclusion: Despite the poor prognosis of relapsed acute leukemia after HSCT, it seems that treatment interventions and, especially DLI-based treatments, can be of substantial benefit for patients.

  • XML | PDF | downloads: 172 | views: 774 | pages: 191-195

    Background: Treatment of choice for patients with refractory germ cell tumors (GCT) or recurrence after platinum containing chemotherapy regimens is not yet well recognized. This study is aimed to evaluate the role of high-dose chemotherapy (HDCT) followed by an autologous hematopoietic stem cell transplantation (ASCT) as the second-or third-line of salvage therapy in GCT patients.
    Materials and Methods: Since 1997 to 2013, 13 GCT patients failing at least one salvage chemotherapy protocol were included in the study. The patients underwent chemotherapy, and then after a primary response the ASCT was performed. Survival analysis was done using Kaplan-Meier method.
    Results: Eleven patients were male and 2 were female. All patients had gonadal tumors except one that had mediastinal GCT. Median follow-up time was 5.45±3.19 years. The estimated 5-year overall and disease-free survival rates were 84.00% and 69.23%, respectively. Five relapses after ASCT and 2 deaths occurred, and the cause of death was due to the relapse of primary disease in both cases. Transplant-related mortality (TRM) did not happen among the study participants.
    Conclusion: our results showed acceptable outcomes for ASCT in refractory or relapsed GCT in terms of survival and treatment-related mortality. Larger prospective studies will be required to elucidate different aspects of such an interpretation.

  • XML | PDF | downloads: 150 | views: 324 | pages: 196-202

    Background: Metastatic renal cell carcinoma is chemoresistant and radioresistant disease with poor survival historically, but outcome has improved in past decade after introduction of tyrosine kinase inhibitors like sunitinib and sorafenib. Sorafenib has not been tested in Indian patients with metastatic RCC till now.
    Material and Methods: This is a single arm, prospective, observational study done in unselected population of 60 patients with metastatic RCC treated with sorafenib as first- line therapy to assess efficacy and safety.
    Results: Twenty three out of 60 patients (38.33%) continued sorafenib by the end of the study. Overall response rates (ORR), stable disease (SD) and disease control rates (DCR) were 35%, 43.33% and 78.33%, respectively. Median progression- free survival (PFS) and overall survival (OS) were 6 and 8 months, respectively and associated with histopathology, Memorial Sloan Kettering Cancer Centre (MSKCC) risk groups, Heng risk groups and performance status. Best tolerated dose was 400 mg per day which was half of standard dose. Fatigue, diarrhea, rashes and hand foot syndrome were common side effects while hypertension was rare. 
    Conclusion: Sorafenib, as first-line therapy, is an effective and safe treatment in Indian patients with metastatic RCC with poor tolerance to dose more than 400 mg per day. Side effects are mostly manageable.

  • XML | PDF | downloads: 211 | views: 225 | pages: 203-211

    Background: The natural products and conventional chemotherapeutic drug combinations are believed to increase cure rates of anticancer treatment while reducing its toxicity. The current study investigates cytotoxic and apoptogenic effects of methanolic extract of Beryonia aspera, and also synergistic effects of this extract and Prednisolone on acute lymphoblastic leukemia cell lines.
    Materials and Methods: The under study populations were NALM-6 and REH cell lines. Cells were treated by Prednisolone and B. aspera extract alone and in combination. The effect of the drugs on survival and apoptosis were examined using MTT and flow cytometry, respectively. Moreover, the effects of the drugs on the mRNA expression levels of Bax and Bcl-2 were studied using RQ-PCR. Finally, both the transcriptional and enzymatic activity of caspase-3 were investigated by caspase-3 assay kit.
    Results: The B. aspera extract induced cell growth inhibition and triggered apoptosis in a dose- and time-dependent manner. Real-time PCR analysis of apoptotic target genes revealed that this agent shifted the ratio of the death promoter to death repressor genes via alteration of Bax and Bcl-2 expression levels. These changes resulted in caspase-3 activation, which led to DNA fragmentation and subsequent apoptosis. Our study has also demonstrated that the combined treatment of B. aspera extract with Prednisolone did not induce greater cytotoxic effect as compared to treatment series using either Prednisolone alone.
    Conclusion: Our study demonstrated that the B. aspera extract has anti-leukemic properties on BCP-ALL cell lines and could be regarded as a promising agent for the treatment of ALL.

  • XML | PDF | downloads: 179 | views: 260 | pages: 212-218

    Background: Over the past decades, interest in establishing a National Rare Donor Program has increased significantly worldwide. The experience of developing countries, however, is still limited. Rare blood is defined as a blood group found in a 1000- 5000 population and donor has an absence of a high-prevalence antigen, or the absence of multiple common antigens. Iranian national rare donor program was established in 2009. This paper reports the experiences and challenges of establishing a national rare donor program in Iran.
    Materials and Methods: This program provides services to all medical centers that need rare units. The main role of rare donor program is to maintain information of rare donors that are identified at the immunohematology reference laboratory located in Tehran. Good manufacturing practices and standard operating procedures are utilized to all activity. The IRL secures frozen blood to make them available when rare blood is required.
    Results: As many as 1000 different types of rare donors have been identified in Iran, including several individuals whose blood group had developed clinically significant allo-antibodies. In addition to routine donors' personally identifiable information such as addresses and telephone numbers, we also access to the contact information of their close relatives or friends for emergency situation. Contact data are kept up to date at least twice annually. IRL staff are ready to provide services to patients with rare blood types, 24 hours per day, 7 days per week.  To date, more than 80 donors with very rare blood group are listed on the IRL rare donor database in 31 centers. Current practice at IRL is to screen the first and second-degree relatives of any patient found to have a rare blood type for a matching blood donor. Iranian blood services need to establish special departments to provide rare blood RBCs and technical assistance for a quicker and more efficient responses to patients and request of their medical staff for blood transfusion. To achieve this aim, there were several challenges, including situation analysis and justification of the program, allocation of financial support by top managers, engineering and technical maintenance, facility and environmental services, employee awareness and communication between blood centers, technologist training in advanced immunohematology.
    Conclusion: The results of this survey are encouraging and indicate that the information and database for rare donors will provide services to patients with very difficult and complex serology test results requiring rare blood transfusion. The experience of IRL may be helpful for other transfusion centers in developing countries.


  • XML | PDF | downloads: 199 | views: 396 | pages: 219-228

    Background: Diabetes caused by insulin production disturbance is considered as the most common metabolic disorder all over the world. Diabetes may outbreak because of low insulin secretion by Islets of Langerhans β-cells, insulin resistance or both of them. In this way, using stem cells, which have the capability to differentiate into Pancreatic β-cells, is one of novel methods in this field. MSCs are the most important candidates for cellular therapy.
    Materials and Methods: Insulin level was examined using ELIZA method. In order to examine the morphology of differentiated cells, they were stained by Dithizone. Insulin-producer cells are cells which turn into red as a result of staining. Specific gene involving insulin-producing cells was evaluated by Real Time-PCR method.
    Results: The ELISA results showed that the treated cells secreted more insulin than the control group. Moreover, we found differentiation of MSCs toward insulin-secreting cells. In order to evaluate insulin production in clusters on day 21 of differentiation, we used dithizone (DTZ) staining. PDX-1 gene was confirmed by RT- PCR analysis.
    Conclusion: In this study, we differentiated MSCs into insulin-producing cells in vitro. It is concluded that MSCs may be considered as an excellent candidate in β-cell therapy in diabetes patients.

Review Article(s)

  • XML | PDF | downloads: 340 | views: 483 | pages: 229-233

    In recent years, mesenchymal stem cells have provoked much attentiveness in the field of regenerative medicine because of their differentiation potential and the capability to facilitate tissue repair via the emancipation of biologically active molecules. They have gained interest because of their distinctive curative properties. Mesenchymal stem cells are isolated from the Wharton’s jelly part of umbilical cord possessing higher proliferation capacity, immunomodulatory activity, plasticity, as well as self-renewal capacity than the mesenchymal stem cells from various origins, and it is considered to be the best resource for allogeneic transplantation. The isolated umbilical cord-derived mesenchymal stem cells are cultured in the Dulbecco’s Modified Eagle’s Medium, and thereby it begins to release soluble factors into the medium during the period of culture which is termed as conditioned medium. This conditioned media has both differentiation capacity and therapeutic functions. Thus, it can be able to differentiate the cells into different lineages and the paracrine effect of these cells helps in replacement of the damaged cells. This medium may accord to optimization of diagnostic and prognostic systems as well as the generation of novel and targeted therapeutic perspectives.

  • XML | PDF | downloads: 309 | views: 440 | pages: 234-247

    Thyroid cancer, one of the most widespread malignancies of the endocrine-related system that over the past three decades, has a vivid increasing rate. The diagnosis and management of it is dependent on the tumor type and stage. Thyroid cancer is divided into four main types, including PTC (papillary thyroid carcinoma), FTC (follicular thyroid carcinoma), MTC (medullarly thyroid carcinoma), and ATC (anaplastic thyroid carcinoma). The development of the noninvasive diagnostic tool for plasma genotyping, also known as “liquid biopsy”, brings a new insight for cancer diagnosis and prognosis. It is mainly containing circulating tumor DNA (ctDNA), circulating tumor cell (CTC), exosomes and extrachromosomal circular DNA (ecDNA). Liquid biopsy as a new plasma genotyping source brings a new prospective of tumor monitoring and therapy.  It beneficially reduces the need of tissue biopsy and made early recognition of relapse as well. This article summarizes its components characteristics and their benefit in diagnosis and treatment of thyroid cancer.

Case Report(s)

  • XML | PDF | downloads: 166 | views: 385 | pages: 165-167

    Chloroma (granulocytic sarcoma or myeloid sarcoma) is a rare malignant extra-medullary neoplasm of myeloid precursor cells. It is usually associated with myeloproliferative disorders but very rarely may precede the onset of leukaemia. Here we are presenting a rare case of chloroma in  a female patient without initial presentation of AML. 38 year old female patient, with performance score-1 had complaining of per vaginal bleeding for 1-2 days. Patient consulted gynaecologist and underwent biopsy from anterior fornix of vagina. Biopsy material was positive for LCA (leukocyte common antigen), MPO (myeloperoxidase), c-kit positive on IHC (immunohistocytochemistry) while negative for cytokeratin, synaptophysin, chromogranin, CD20 (cluster of differentiation. Whole body CT scan was non informative except mass lesion at vagina. Patient was given 3+7 induction chemotherapy which was tolerated well followed by high dose cytarabine as consolidation therapy.

  • XML | PDF | downloads: 155 | views: 378 | pages: 168-173

    The case report presented here describes the culturing and characterization of mesenchymal stem cells (MSCs) isolated from a primary indolent B-cell lymphoma, located in the CNS of an immunocompetent patient. The presence of such cells in the tumor mass can further elucidate the pathogenesis of the disease and reveal possible future approaches for its treatment.  We present a case report of a 61-year-old immunocompetent woman who had an episode of confusion with numbness in the right leg and the right arm, slurred and dysarthric speech and urine incontinence. The peripheral blood tests were normal. The neurological examination demonstrated a latent hemi-paresis of the right side, aphasia, discrete hypertension and bradypsychia. The ophthalmologic examination revealed left quadranopsia. Computed tomography and magnetic resonance imaging of the brain showed a 3.5 × 2.9 cm infiltrative neoplastic lesion involving the left temporal parenchyma. The morphological features and the immunophenotyping of the lymphoid cell composition were consistent with low-grade (indolent) B-lymphocyte non-Hodgkin’s lymphoma of CNS. Cells, isolated from the resected tumor mass, were cultured in vitro in medium containing 10% fetal bovine serum (FBS) and characterized by their morphology, growth, phenotype, clonogenicity and osteogenic differentiation. It was apparent that the cultured cells isolated from the indolent B- cell lymphoma located in the CNS have the basic characteristics of mesenchymal stem cells. The presence of MSCs is described for the very first time in such type of tumor. The well-known immunosuppressive properties of the MSCs may represent another mechanism favouring the tumor growth. 

  • XML | PDF | downloads: 216 | views: 666 | pages: 174-179

    We have described three uncommon cases of patients who presented with clinical thrombotic events (stroke, pulmonary embolism and deep venous thrombosis) during the course of a hypercalcemia-induced hypercoagulable state. After thorough investigation, the diagnosis of primary hyperparathyroidism - due to a parathyroid adenoma - was established in all cases. The association between hypercalcemia and venous or arterial thrombosis has been previously described; however, relevant data are still insufficient. The existing evidence in the field was reviewed and the interesting underlying pathophysiologic mechanisms were also discussed. Further studies are required to shed more light on the unusual, still intriguing relationship between calcium and thrombosis.

  • XML | PDF | downloads: 406 | views: 428 | pages: 180-183

    Rhnull phenotype is a rare blood group with a frequency of approximately 1 in 6 million individuals, transmitted via an autosomal recessive mode. It is characterized by the weak (Rh mod) or lack (Rh null) of expression of all Rh antigens on the red cells. The clinical significance of its assessment is that such patients with Rhnull syndrome are associated with chronic hemolytic anemia of varying degrees. Another clinical importance is that such subjects readily form alloantibodies when exposed to Rh antigens.
    We report herein a rare Rhnull phenotype in a sibling which was detected as a part of the difficult sample work-up for red cell antibody screening and identification.