Iranian Journal of Blood and Cancer
Volume:14 Issue: 4, Dec 2022

Although Imatinib has revolutionized the treatment of chronic myeloid leukemia (CML), not all patients reach complete remission and a considerable proportion of the patients develop resistance to Imatinib.

In an attempt to increase the tail on the survival curve, we conducted a Phase I/II study of PR1/BCR-ABL multipeptides vaccination trial in CML patients with at least 15 months of Imatinib treatment and 5 months of persistent molecular residual disease.

One month after the completion of the vaccinations, 4 patients nearly developed a 1-log fall in their BCR-ABL transcript level, with 4 patients achieving a major molecular response (MMR). Nine patients were followed for more than a period of 7 years. The vaccinations were associated with a MMR in five patients and a complete molecular response (CMR) in one patient. The removal of Imatinib in two patients who achieved MMR after the vaccinations led to a resurgence of the leukemia population and relapse.

Our study suggests that a combination of immunotherapy with Imatinib targeted therapy keeps the leukemia population under control, improving the long-lasting clinical and molecular response of CML patients, for at least 7 years.

 Acute myeloid leukemia (AML) is described by the clonal expansion of myeloid blasts with abnormal differentiation. Considering the role of Toll-like receptors (TLRs) in inflammation induction and the effect of chronic inflammation on cancer development, investigating the state of TLRs’ expression in human malignancies has attracted scientists’ attention.

 In this study, 36 newly-diagnosed AML patients and 36 control samples were examined. The mRNA expression levels of TLR1/2/4/7/8 were measured in both groups using real-time PCR. The student’s t-test was utilized to compare gene expression levels between the two populations and the one-way ANOVA test was used to compare data among multiple subtypes.

All TLR gene expression levels were significantly up-regulated in patients compared to the control group (p<0.05). Positive correlations between different TLRs were observed as well. AML patients under the age of 55 showed significantly higher TLR1/2/4 expression in comparison with healthy individuals of the same age; a similar comparison in people above 55 also showed an elevated expression of TLR1/2/4/8. Male patients overexpressed almost all genes compared to healthy subjects; the levels of TLR1/2/4 were also higher in female patients. No difference was observed comparing blast percentages and FAB subtypes.

 By considering the results of this experiment, it seems that TLRs up-regulation in AML patients may contribute to the pathogenesis and development of the disease; however, more investigations are required to elucidate the exact roles of these receptors in AML. 

Colorectal cancer (CRC) is the third leading cause of cancer-related death worldwide, and its occurrence can be ascribed to genetic susceptibility. Mitochondrial DNA 4977-bp (mtDNA 4977), as the most described mtDNA deletion, has been long proposed to be involved in various types of cancers. However, a few studies on mtDNA 4977-bp deletion in Iranian patients with CRC have been reported. The current study aimed to determine mtDNA 4977 frequency in CRC and its association with cancer susceptibility. We conducted a case-control study in which a total of 26 patients with CRC, 26 tumor tissues, adjacent normal tissues, peripheral blood samples, and peripheral blood samples from 50 healthy subjects were included. mtDNA 4977 was detected using multiplex PCR technique and direct DNA sequencing. Real-time PCR was also used to determine deletion levels. mtDNA 4977 was observed in six patients (23.07%), four (15.3%) in both tumor and matched surrounding normal tissues, and two (7.69%) in adjacent normal tissues, but not detected in both patients and control samples in peripheral samples. A significant difference was found between mtDNA 4977 deletion in tumoral and adjacent normal tissues (P=0.001). No relation was observed between mtDNA 4977 and categorical variables, including age and gender, and tumor stage. The analysis confirmed no association between the mtDNA 4977-bp deletion and susceptibility to colorectal cancer in Iranian patients. However, more extensive studies are required to confirm or reject these findings.

Infective endocarditis (IE) is a life-threatening systemic disease that mostly affects people with valvular heart disease, prosthetic valves, or intracardiac devices. Infective endocarditis is a dangerous cardiac involvement in thalassemia patients. Thus, a multidisciplinary approach is important to provide efficient and effective therapy.

A 31-year-old man came to our tertiary referral hospital complaining of right-side paralysis of the body and slurred speech. Vital signs were normal. There were grade III/VI systolic murmurs from chest examination in midclavicular line intercostal space V sinistra. Head CT scan without contrast showed an embolic event. Peripheral blood smear showed iron deficiency anemia. Further electrophoresis hemoglobin (Hb) examination showed HbE-pathy. Echocardiography showed vegetations on the anterior and posterior mitral leaflet, leading to severe mitral regurgitation (MR). Blood culture examinations showed no bacterial growth. The patient was then diagnosed with severe MR due to possible IE, acute stroke infarction, and HbE thalassemia. The patient was treated with optimal medical therapy because he refused surgery. After six months of follow up, patients were found dead at his house

Thalassemia is a risk factor for infective endocarditis. Both are a dangerous combination, and early recognition should be made carefully to prevent worse outcome.

Nearly 50 % of newly diagnosed colorectal cancer, affect people over 70 years of age. Inclusion of older patients in clinical trials has been extremely rare. As a result, there is debate on how to manage these patients because it is still unclear how to balance the therapeutic advantages and toxicities. For patients who do not have comorbid conditions, with performance status (P.S.) 0–1, treatment guidelines are comparable to those for younger ones. Chemotherapy is an option for older patients; however, a full geriatric evaluation is recommended. Bevacizumab, an anti-vascular epithelial growth factor (anti-VEGF), combined with chemotherapy has become a standard of care in older patients. Anti-epidermal growth factor receptor (anti-EGFR) treatment is proposed both as monotherapy in the third-line or with chemotherapy in first or second line. Clinical trials that compared chemotherapy alone versus doublet chemotherapy plus anti-EGFR in older patients found that age is not an absolute contraindication for using anti-EGFR in first or second line. In fit older patients, anti-EGFR monotherapy in the first second or third line has demonstrated feasibility and antitumor efficacy. The major side effect is cutaneous rash which is easily managed. However, treatment in older patients should be carried out and be based on co-morbidities.

The common reported adverse impacts of COVID-19 vaccination include the injection site’s local reaction followed by various non-specific flu-like symptoms. Nevertheless, uncommon cases of vaccine-induced immune thrombotic thrombocytopenia (VITT) and cerebral venous sinus thrombosis (CVST) following viral vector vaccines (ChAdOx1 nCoV-19 vaccine, Ad26.COV2 vaccine) have been reported. This literature review was performed using PubMed and Google Scholar databases using appropriate keywords and their combinations: SARS-CoV-2, adenovirus, spike protein, thrombosis, thrombocytopenia, vaccine-induced immune thrombotic thrombocytopenia (VITT), NF-kappaB, adenoviral vector, platelet factor 4 (PF4), COVID-19 Vaccine, AstraZeneca COVID vaccine, ChAdOx1 nCoV-19 COVID vaccine, AZD1222 COVID vaccine, coagulopathy. The abstracts and titles of each article were assessed by authors for screening and inclusion English reports about post-vaccine CVST and VITT in humans were also collected. Some SARS-CoV-2 vaccines based on viral vector, mRNA, or inactivated SARS-CoV-2 virus have been accepted and are being pragmatic global. Nevertheless, the recent augmented statistics of normally very infrequent types of thrombosis associated with thrombocytopenia have been stated, predominantly in the context of the adenoviral vector vaccine ChAdOx1 nCoV-19 from Astra Zeneca. The numerical prevalence of these side effects seems to associate with this particular vaccine type, i.e., adenoviral vector-based vaccines, but the meticulous molecular mechanisms are still not clear. The present review summarizes the latest data and hypotheses for molecular and cellular mechanisms into one integrated hypothesis demonstrating that coagulopathies, including thromboses, thrombocytopenia, and other associated side effects, are correlated to an interaction of the two components in the COVID-19 vaccine.

Radiotherapy (RT) is generally considered to be one of the most effective cancer treatments. The primary goal of RT is to accurately induce radiation damage to the tumor while limiting radiation toxicity to a level acceptable to normal tissue. This is accomplished by targeting the tumor with radiation. On the other hand, the status of RT procedures as they stand today is not substantial enough to eliminate advanced metastatic and radio-resistant hypoxic tumors. Radiologists and medical physicists all face the same fundamental challenge of improving treatment efficacy while minimizing damage to surrounding healthy tissue. Through a process called radio-sensitization, tumor cells become more sensitive to the damaging effects of radiation. Therefore, radiosensitizers are compounds that are either medicinal or inactive and boost the efficacy of radiation treatment. In the last few years, there has been a surge of interest in the use of formulations to enhance the effectiveness of radiotherapy, especially when employing metallic, primarily gold-based nanoparticles. The aim of combining NPs with radiation therapy is to enhance the differential effect of treatment between normal and malignant cells. Gold nanoparticles (AuNPs) have been the most widely investigated nanoplatforms for use in radiation therapy due to their high X-ray absorption rate and synthetic modifiability, which allows precise control over the physical properties of the particles. We only highlight the radio-sensitization characteristics of gold nanoparticles in cancer treatment in the current review article.

Biological resources, along with patient-related clinical data, are basically required for personalized medicine and translational research. In this regard, pediatric cancer biobanks have considerable significance due to their special challenges, which include the need for long-term sample collection (due to high diversity and rare tumors), the difficulty of working with children, as well as the limited volume of samples available in children.

After obtaining all necessary approvals (from the ethics committee, scientific board, and financial support), standard operating procedures (SOPs) were defined for all aspects of the biobank procedures, including equipping the lab, sample collection, processing, storage, as well as clinical data recording.

Until July 2022, approximately 8,000 samples from 720 patients have been collected in the biobank. In summary, the samples in the biobank are classified into three categories: leukemia (40.7%), solid tumors (39.44%), and central nervous system tumors (15.56%). The unique activities of the biobank include the collection of various biological samples from patients and their parents, inter-university cooperation, the use of a vacuum system to preserve tissue, the launching of an online database for recording patients' medical data, and the setting up of a bilingual website for announcements at the national and international levels.

 Iranian Childhood Cancer Biobank (ICCBB) is the first pediatric biobank center in Iran that collects various samples and associated clinical data from patients with a wide range of childhood cancers. The ICCBB aims to advance clinical research in the field of pediatric cancer by providing both the required quantity and quality of biological samples.