mohammad vaezi

 The activities and functions of natural killer (NK) cells are regulated by a limited repertoire of activating and inhibitory receptors. Thus, we provided a study of inhibition of the NKG2A using monoclonal antibodies (mAbs), and as a primary endpoint, we evaluated whether it can be translated to enhance adoptive NK cell immunotherapy, as the secondary endpoint, we investigated safety and feasibility.

 In this study, we investigated the safety of anti-NKG2A-pretreated NK cells in improving ADCC function to manage hepatocellular carcinoma (HCC). After a conditioning regimen, we initiated a pilot study of expanded donor haploidentical NK cell infusion. Patients received a fludarabine/cyclophosphamide conditioning followed by adoptive immunotherapy with IL2–activated haploidentical NK cells. Anti-NKG2A pretreated NK cells were infused on days 0,+5, and+10 post-conditioning regimens at a dose of 7×108 cells (n=3). The median follow-up was 4 months for all patients.

 Although all patients were alive at the last follow-up, two of them showed progressive disease and an increase in tumor size. In addition, all patients showed a relative decrease in alpha-fetoprotein (AFP) expression levels after one month.

 This study demonstrated the safety and feasibility of infusing high doses of ex vivo expanded NK cells after conditioning with transient side effects.

One of the constant problems that people with mental health conditions are faced with now is that they cannot establish a good relationship with their therapist, or the client's disease type is not in the therapist's specialty. These clients may not receive adequate treatment and stop the therapy before feeling well. Therefore, the classification of mental patients based on their disorder types and allocating a therapist with the same expertise to them could lead to better treatment and improve the quality of the therapy sessions. This paper will compare several machine learning (ML) algorithms to classify patients with mental conditions. Moreover, benefiting from the best ML algorithm, patients will be categorized into different classes based on their disorder types. Finally, a mathematical model will be developed to determine the allocation policy of therapists to each group of patients to maximize the summation of the utilization between therapists and patients. To explore the implementation of the proposed method, we have conducted a real-life case study to assess the validation of the model.

Context: 

Adoptive T-cell therapy with chimeric antigen receptor (CAR) has shown tremendous progress in hematological cancers. However, some obstacles, such as high price tag, cytokine release syndrome, inability to penetrate solid tumors, and manufacturing complexity limit the wide application of this therapy. Natural killer (NK) cells can kill target cells via mechanisms similar to those of CD8+ cytotoxic T cells; therefore, CAR-NK cell therapy is a promising strategy for cancer treatment.

Evidence Acquisition:

 In this manuscript, all articles published in English regarding CAR-NKs and their application for the treatment of different types of cancers were collected from several databases, including PubMed, Scopus, and Google Scholar, using related keywords such as "Cancer, CAR construction, NK cells, and CAR-NK cells".

Compared with CAR-T cells, CAR-NK cells have several advantages, including less toxicity, a high potential opportunity for universal off-the-shelf manufacturing, increased infiltration into solid tumors, overcoming resistant tumor microenvironment, and absence of graft-versus-host disease (GVHD).

In this review, we discuss NK cell biology, the source of CAR-NK cells, CAR structure, advances, challenges, and ways to overcome these challenges in CAR-NK cell therapy. Furthermore, we have summarized and highlighted some preclinical and clinical studies in this field.

Allogeneic hematopoietic stem cell transplantation (HSCT) is considered the only effective therapeutic option for eradicating acute myeloid leukemia (AML) after achieving remission. Evaluating treatment outcomes and addressing challenges at each center are essential for improving conditions and overcoming obstacles. Thus, this study aimed to evaluate the outcomes of HSCT in AML patients who had. undergone transplantation at our center over the past three decades.

This retrospective cohort study was conducted at the Oncology, Hematology, and Transplant Research Institute on adult AML patients who underwent allogeneic HSCT between January 1991 and January 2022. Data on demographic, clinical, and laboratory characteristics were collected from medical records. The primary objectives included evaluating overall 5-year overall survival (OS) and disease-free survival (DFS) across all patients, and comparing outcomes based on the timing of transplant and pre-transplant remission status. Secondary objectives included assessing non-relapse mortality (NRM) and relapse incidence (RI). Statistical analyses were conducted to compare outcomes between two groups: those who received transplants before 2010 (D1) and those who received transplants after 2010 (D2).

In total, 1,337 AML patients were analyzed, with 477 in group D1 and 860 in group D2. The median follow-up duration was 111 months for D1 and 62 months for D2. OS was similar between the two groups (56.64% for D1 vs. 57.86% for D2), but OS improvements were observed only in patients who underwent transplantation in later remissions (CR2 and CR≥3) after 2010. DFS were also generally similar between the two groups, but significant improvements were noted for CR2 and CR≥3 patients transplanted after 2010. The 5-year RI and NRM were comparable between the two periods, except for CR2 patients who transplanted after 2010 and have had lower RI and NRM. Notably, a higher percentage of transplants involved haploidentical and unrelated donors in D2, reflecting evolving transplantation strategies.

Our findings indicate that despite significant advances in transplant techniques, supportive care, and donor availability, OS and DFS have remained relatively stable between the two periods. This is likely due to higher rate of HSCT from alternative donor and in high-risk patient after 2010. The study highlights the need for personalized approaches in managing AML, focusing on optimizing donor selection and addressing transplant-related complications.

Despite the advances in treatment, breast cancer (BC) remains a major cause of death in women. Thisstudy aims to evaluate the prognostic significance of detecting circulating tumor cells (CTCs) and disseminated tumorcells (DTCs) in paired peripheral blood (PB) and bone marrow (BM) samples obtained both before and after adjuvantchemotherapy from patients with operable BC. In this experimental study, from 160 patients with primary BC, we collected 160 PB and BM samplesbefore and we could be able to collect PB and BM samples from 100 of them after adjuvant chemotherapy. The expressionlevel of cytokeratin 19 (CK19), carcinoembryonic antigen (CEA), mammaglobin 1 (MGB1), mucin 2 (MUC2) and trefoil factor1 (TFF1) mRNAs in the PB/BM samples were analyzed by quantitative real-time polymerase chain reaction (PCR). Multivariate Cox regression analyses indicated that the detection of CK19 mRNA-positive CTCs/DTCs eitherbefore or after adjuvant chemotherapy was an independent factor for prognosis associated with decreased diseasefreesurvival (DFS). Patients with tumor cells detected in both PB and BM and patients with persistent detection oftumor cells before and after chemotherapy had worse outcomes compared to those with tumor cells detected in one orneither of the compartments. This study suggests that the detection of CK19 mRNA-positive CTCs/DTCs either before or after adjuvantchemotherapy could be an independent predictor of DFS in operable BC patients.

 Invasive fungal infections (IFIs) are a significant cause of mortality and morbidity in patients with hematological malignancies. Given the considerable prevalence and consequences of IFIs, hence revealing the exact cause of fungal infections, their rate, associated risk factors, and complications could contribute to reducing both financial and life costs, choosing targeted antifungal treatment, and avoiding unnecessary toxic treatments in individuals who are not suffering from mycoses.

 This prospective cross-sectional study was conducted in the first semester of 2019. All patients with hematologic malignancies (HM) admitted to Dr. Shariati Hospital were studied. Only those with probable/proven IFIs defined according to the last update of EORTC/MSG criteria were included in the study. The demographic and clinical data were recorded from the hospital information registration system using a questionnaire. Statistical analysis was performed using SPSS software version 24.

Out of 1109 HM patients hospitalized during the study period, 67 (6.04%) IFIs were diagnosed. Of these, 57 (85.04%) were aspergillosis, 7 (10.4%) were mucormycosis, and 3 patients developed other fungal infections. Males constituted 67.2% of the entire IFI population. The mean±SD age of the samples was 43.16 ± 13.8 years. The most common type of malignancy was AML. Lung imaging showed lesions associated with fungal infections in 52 cases (77.6%), with multiple nodules as the most prevalent pattern being observed in 64.2% of cases. Sinus involvement was evidenced in the PNS CT scan of 46 (68.6%) patients. The attributable mortality rate for IFIs was 62.7%. Both the types of IFI and malignancies had no significant relationship with the outcome of patients. Central venous catheter, mucositis, and antibiotic use were the most frequent risk factors.

  IFI represents a frequent complication for HM patients with high mortality. Aspergillus species are the predominant etiology in these settings. Considering our results, in high-risk patients, manifestations of warning signs in the sinus and lungs, which would not be cleared despite receiving antibiotics, should raise the possibility of IFIs.

Arsenic three oxide (As2O3) is the treatment choice for acute promyelocytic leukemia (APL). Little is known about possible risk factors with predictive value for toxicity caused by As2O3. Biomethylation is considered to be a major pathway of detoxification for inorganic arsenics (iAs). Arsenic Methyltransferase (AS3MT) is one of the key enzymes involved in the transfer of a methyl group from S-adenosyl-L-methionine to trivalent arsenical and plays a critical role in arsenic detoxification. Polymorphisms in hAS3MT lead to a change in the catalytic activity of the enzyme and may increase the risk of arsenic-related toxicity. In this study, we investigated the association of the AS3MT polymorphisms (rs11191439, rs3740390, and rs3740393) genes with hepatotoxicity in APL patients treated with As2O3.

Genotyping was performed in 140 adult patients with APL treated with As2O3 using PCR-RFLP for rs11191439 and tetra-primer ARMS-PCR for rs3740390 and rs3740393. The results of PCR-RFLP and ARMS-PCR were confirmed by direct sequencing of 10 % of DNA samples. The results were analyzed using SNPStats, SPSS, and FinchTV. Hepatotoxicity was graded according to the National Cancer Institute's Common Toxicity Criteria (CTC).

Hepatotoxicity was seen in 52 of the 140 patients (37.1%), with grades I and II hepatotoxicity in 40 (28.6%) and grades III and IV hepatotoxicity in 12 (8.5%) patients.  The association between the three polymorphisms and hepatotoxicity was evaluated using five genetic models and none of the three studied polymorphisms were significantly associated with hepatotoxicity.

The results of our study showed that AS3MT rs11191439, rs3740390, and rs3740393 polymorphisms are not associated with hepatotoxicity in APL patients. Genetic polymorphisms in enzymes which are involved in arsenic metabolism have been shown to have ethnicity and race-related differences. To more precisely characterize the association between AS3MT gene polymorphism and hepatotoxicity, future large-scale studies in non-Asian populations and other ethnicities are needed.

Thrombotic thrombocytopenic purpura (TTP) is associated with microangiopathic hemolytic anemia, thrombocytopenia, and microvascular thrombosis. No comprehensive report exists on clinical characteristics and risk factors of relapse and mortality in Iranian TTP patients. In this study, we aimed to report clinical features of Iranian TTP patients, to evaluate disease relapse and mortality rate and their associated risk factors.

This study was a cohort study of patients diagnosed with microangiopathic hemolytic anemia admitted to the Shariati Hospital, Tehran, a referral center for TTP patients, from 2010 to 2017. Demographic, clinical, and laboratory data were recorded and patients were followed for 3 years regarding disease relapse and mortality.

  114 patients (80 female, 34 male) with a mean age of 39.3 ± 14.99 years were included.  Hematologic and neurologic symptoms were the most common manifestations. Abnormal laboratory findings at the presentation included thrombocytopenia, anemia, and elevated LDH. All patients were treated with plasma exchange, and 75.5% of them had a response to treatment, while the 3-year relapse and mortality rate was 23.6 and 26.3%.  Lower platelet count was a predictor of disease relapse. Age, hematological, or neurological initial presentation were associated with TTP mortality.

Based on the largest study of TTP patients ever in Iran, the demographic and clinical characteristics of Iranian TTP patients are similar to other existing reports. Knowledge of the risk factors for TTP relapse and mortality could be useful to alert hematologists for prompt therapeutic actions when necessary.

Cardiotoxicity, a common complication of chemotherapy, may have irreversible adverse effects on the heart. Anthracycline-based chemotherapy for breast cancer can lead to dilation-hypokinetic cardiomyopathy, eventuating in heart failure. As the primary diagnostic tool for cardiovascular toxicity, echocardiography may be essential in evaluating the heart function of such patients.

This study aimed to identify the most important echocardiography findings for proper and timely diagnosis of cardiotoxicity in patients with HER2-positive breast cancer undergoing anthracycline-based chemotherapy.

Our final analysis included 132 female patients who were HER2-positive and had breast cancer. All of these patients had one pre-chemotherapy echocardiography and at least one echocardiography after three episodes of anthracycline-based chemotherapy. The patients’ age, body mass index, and history of chemotherapy were recorded. Mean alterations from baseline echocardiography to echocardiography after three episodes of chemotherapy were calculated for all parameters evaluated. Data analysis was conducted using the Statistical Package for the Social Sciences v. 26.

Significant changes were seen in three-dimensional left ventricular ejection fraction (LVEF 3D), two-dimensional left ventricular ejection fraction (LVEF 2D), left ventricular global circumferential strain (LVGCS), left ventricular global longitudinal strain (LVGLS), left ventricular end-diastolic volume (LVEDV), stroke volume (SV), left ventricular end-systolic volume (LVESV), right ventricular end-systolic dimension (RVESD) in patients with breast cancer (P < 0.0001). RVESD, LVESV, LVEDV, and SV significantly increased after three chemotherapy episodes, but LVEF (3D and 2D), absolute LVGCS, and absolute LVGLS fell significantly.

LVEF (3D and 2D), LVGCS, LVGLS, LVEDV, LVESV, SV, and RVESD are important echocardiography parameters in diagnosing cardiotoxicity in patients with HER2-positive breast cancer.

 The high mortality rate of Gastric Cancer (GC) is a consequence of delayed diagnosis. The early diagnosis of GC could increase the five-year survival rate among patients. We aimed to find a panel of microRNAs (miRNA) for the detection of GC in the early stages.

 In this case-control study, we selected consistently upregulated miRNAs from the results of 12 high-throughput miRNA profiling studies in GC. In the profiling phase, the differential expressions of 13 candidate miRNAs were analyzed by quantitative reverse-transcription PCR (qRT-PCR) in two pooled RNA samples prepared from the plasma of eight GC patients and eight matched controls. In the validation phase, significantly upregulated miRNAs from the profiling phase were further evaluated in the plasma samples of 97 patients with stage I-IV gastric adenocarcinoma and 100 healthy controls.

 In the profiling phase, six miRNAs (miR-18a, 21, 25, 92a, 125b and 221) were significantly upregulated in the GC patients compared to the controls (p<0.05). However, in the validation phase, only significant up-regulation of miR-18a, 21 and 125b was confirmed (p<0.05). A panel of miR-18a/21/125b was able to detect GC patients with stage I-IV from the controls (p<0.001; AUC=0.92, sensitivity=86%; specificity=85%). In addition, the panel could distinguish the early-stage GC (I+II) from the control group with an AUC of 0.83, a sensitivity of 83%, and a specificity of 75%.

 A panel of circulating miR18a/21/125b could be suggested as a potential biomarker for the early detection of GC.

Melanoma is a malignant tumor that predominantly arises in the skin. In rare cases, however, it can manifest in the bone too. In this paper, a primary malignant melanoma of the lesser trochanter of the right femur is described.In this case, the subject was a 19-year-old woman presenting with pelvic floor pain that lasted for 3 weeks.Magnetic resonance imaging (MDR) showed that T2MRI has bone melanoma soft tissue edema that sustained to malignant melanoma.Immunohistochemistry report revealed that tumoral cells were positive for HMB45, S100, which is suggestive of melanoma diagnosis.The patient was admitted and underwent CNB. Since the result was negative, the patient received a wide local excision from the right lesser trochanter. The histopathological examination of biopsy revealed fibro sclerotic tissue affected by malignant melanoma.The patient was then referred to an oncologist for postoperative adjust chemotherapy and target therapy.

Wilms’ tumor gene 1 (WT1) gene mutation has been reported to be a prognostic factor in normalcytogenetic acute myeloid leukemia (AML) patients. Higher rates of mutation in the WT1 gene have been reported in several tumors including normal-cytogenetic AML patients. Data regarding WT1 mutations in acute promyelocytic leukemia (APL) is very scarce. In this study, we evaluated the incidence and impact of WT1 mutation on the outcome of APL patients.

A total of 92 patients diagnosed with APL were studied in three distinct groups: early mortality, relapsed, and persistent complete remission. Genomic DNA of bone marrow samples of patients was analyzed. For quantification of expression levels of the WT1 gene, real-time quantitative PCR (rqPCR) was performed by a real-time PCR system. WT1 mutation and its impact on prognosis were considered the primary endpoint of the study. Statistical analysis was performed with STATA.

WT1 mutation frequency was 6.25% in the early mortality group (1/16 patients), 13.16% in the relapse group (5/38 patients), and 7.89% in the persistent complete remission group (3/38 patients). 8 mutations were in exon 7 and one mutation in exon 9. WT1 mutation in the relapse group was associated with a trend toward worse disease-free survival (DFS) while overall survival (OS) was not affected by WT1 mutation in univariate analysis. Patients with no mutations in WT1 and FLT3/ITD had better overall survival and diseasefree survival compared to patients with mutations in the WT1 gene or FLT3/ITD in the relapse group.

The frequency of WT1 gene mutations does not differ significantly between patients with early mortality, relapse, and persistent complete remission. The presence of WT1 mutation is associated with higher relapse and lower survival rates in relapse group patients.

Current treatment options of acute lymphoblastic leukemia(ALL) include chemotherapy alone or hematopoietic stem cell transplantation (HSCT) following induction chemotherapy both along with CNS prophylaxis. The usual and standard induction regimens currently administered could have severe complications and mortality.

To lessen induction regimen complications in ALL patients who undergo HSCT, we used a cytoreduction induction regimen including dexamethasone (8 mg, IV, three times a day, for 28 days) and vincristine(1.4 mg/m2, IV, on days 1,8,15 and 22) for 49 newly diagnosed adult ALL patients followed by an early sibling donor HSCT within two months. The results were matched with outcomes of HSCT in 172 ALL patients inducted by standard induction regimen.

Median follow-up time was 5.41 years in the standard group and 5.27 years in the other. All patients of the case group (100%) achieved complete remission. Landmark analyses were performed to scrutinize the effect of treatments on different time intervals: first two years and 2nd to end years. Type of treatment had no significant effect on the hazard of death in the first landmark (HR=0.87, P=0.64). Cytoreduction regimen amplified the hazard of death 3.43 times more than the standard regimen in the second landmark (HR=3.43 P=0.035). Multivariate analysis showed that the cytoreduction regimen reduced the hazard of relapse about 22%, but not statistically significant (HR=0.78, P-value=0.24).

Overall, it seems despite achieving complete remission in induction therapy, depth of response is a critical predictor for long-term outcomes of HSCT in ALL patients, and the use of multiple agents may be necessary to decrease tumor cell burden and minimal residual disease(MRD).

Breast cancer, as the most common malignancy among females, is a great concern for global health. Early diagnosis and advanced chemotherapy regimens have improved patients’ survival, while increasing morbidities caused by chemotherapy in the long run. Chemotherapy regimens have caused a decrease in myocardial functional, which can be detected by echocardiography.

The present study aimed to assess the decline curve in the left ventricular function parameters following chemotherapy and to compare the results among patients based on their Human Epidermal Growth Factor Receptor-2 (HER2) status.

This study was conducted on 427 consecutive female patients with breast cancer referred to the Cardio-Oncology Department of Rajaie Cardiovascular, Medical, and Research Center for pre-chemotherapy assessment between January 2019 and December 2020. The patients were divided into two groups based on the HER2 status. All the patients had at least one baseline (pre-chemotherapy) transthoracic echocardiography and were scheduled for four follow-up sessions: early post-anthracycline therapy and 3, 6, and 12 months following chemotherapy. Each echocardiography examination included the assessment of 2D Left Ventricular Ejection Fraction (LVEF), 3D LVEF, Global Longitudinal Strain (GLS), and Global Circumferential Strain (GCS). Linear mixed-effects models were utilized and the results were compared within and between the study groups. The R Project for Statistical Computing was used for data analysis.

The results revealed significant changes in the means of 2D LVEF, 3D LVEF, GLS, and GCS during the 12 months of follow-up (t = -27.04, -37.15, -33.3, and -21.5, respectively; P < 0.001). Besides, the decline was more prominent in the HER2 positive patients (t = -19.86, -15.35, -10.8, and -9.6, respectively; P < 0.001).

The study results revealed a significant decline in the LV function parameters including 2D LVEF, 3D LVEF, GLS, and GCS following chemotherapy with anthracycline. This decline was more prominent in the HER2 positive patients who underwent Herceptin treatment. These results showed that the use of cardioprotective agents might lower the rate of decline in LV function parameters.

There are conflicting data regarding the association between plasma concentration of voriconazole (VCZ) and both efficacy and safety. This study investigates the association of VCZ trough plasma level with clinical efficacy and hepatotoxicity in the Iranian population suffering hematological malignancies. This cross-sectional study was performed on adult Iranian patients (age ≥ 18 years) with hematological malignancies undergoing treatment with oral or intravenous VCZ for proven or probable invasive aspergillosis. Plasma concentrations of VCZ were measured at two time points on day 4 and 14 during the study period. A total of 60 VCZ trough concentrations of 30 patients were drawn on days 4 and 14 after the initiation of treatment. There was no definite correlation between the mean plasma concentration of VCZ and VCZ dosage (p = 0.134, r = 0.280). In multivariable model, only plasma concentration of VCZ on day 14 was associated with the incidence of hepatotoxicity (p = 0.013; OR = 1.42, 95% CI = 1.07-3.24). Plasma trough concentration neither on day 4 nor on day 14 was related to the treatment response. No significant association was observed between the mean plasma concentration of VCZ and 3-month patients’ survival (p = 0.696). To conclude, VCZ trough concentration may not be a predictor of treatment response or 3-month patients’ survival. However, the wide inter- and intra-patient variability of VCZ plasma concentration coupled with the observed association between VCZ trough level and the incidence of hepatotoxicity would pose the question regarding the potential benefit of VCZ concentration monitoring.

Endothelial injury by toxins, drugs, immune complexes leads to activation of coagulation cascade and thrombosis, which result in platelet consumption and red blood cell injury. These thrombotic microangiopathies can potentially injure numerous organs and result in organ dysfunction. In this case, we present the fourth reported patient with thrombotic thrombocytopenic purpura associated with COVID-19.

Finding a suitable donor at the optimal time is one of the most challenging issues in many transplant centers. We evaluated the clinical outcomes of 248 patients with acute leukemia and without matched sibling donors (MSD) who underwent alternative transplantation, including haploidentical (n=118), 10/10 matched unrelated (MUD, n=91), 9/10 mismatched unrelated (MMUD, n=21), and 9/10 mismatched related (MMRD, n=18) between January 2010 and November 2019 in our center.

The myeloablative conditioning regimen was used in most of the patients. Both post-transplant cyclophosphamide (40mg/kg at +3, +4) and pre-transplant ATG were used in most of Haploidentical transplantations. Patients with unrelated donors received ATG as a part of the conditioning regimen.

The median follow-up was 31.83 months. No significant difference in probability of 3-year leukemia- free survival (LFS) and overall survival (OS) as well as 3-year relapse incidence (RI) were noted between donor sources.A significant difference was found in the 3-year cumulative incidence (CI) of non-relapse mortality (NRM) among the donor sources: 37.89%, 24.20%, 24.30%, and 11.48%, for Haplo, 9/10 MMUD, 10/10 MUD, and 9/10 MMRD (p=0.02). Using the multivariable Cox model, the advanced age of patients and Major-ABO mismatched, were two risk factors independently associated with lower OS and DFS as well as higher NRM, whereas male donor and AML disease compared to ALL were associated with a better OS and DFS.

Given that no significant differences were observed in the overall outcome of Haplo with other alternative transplantations, suggesting that Haploidentical transplantation is a suitable, accessible, and inexpensive option.

Voriconazole as a triazole antifungal agent is widely used for prophylaxis or treatment of fungal infections in allogeneic hematopoietic stem cell transplantation (HSCT). It can increase blood concentrations of other medications including cyclosporine A (CsA) which are substrates for cytochrome P450 3A4. The aim of this study was to evaluate comparatively the interaction between oral/intravenous (IV) voriconazole and oral CsA.

Twenty‑nine recipients of allogeneic HSCT who had been already on a steady dose of CsA and were started on oral or IV voriconazole were evaluated in a prospective cohort study. Blood concentration of CsA was determined before and 5–8 days after voriconazole initiation. Plasma concentration of voriconazole was measured in steady state. The changes in blood concentration of CsA after administration of voriconazole were evaluated.

The concentration/dose (C/D) ratio of CsA increased significantly (P < 0.001) after voriconazole initiation in both routes of administration (8.40%–174.10% increase in C/D ratio). The C/D ratio alteration of CsA did not differ significantly between oral and IV voriconazole group (P = 0.405). There was a significant correlation in all patients between plasma concentration of voriconazole and percentage of CsA C/D ratio increment (P = 0.046).

There was a significant intrapatient variability in the magnitude of CsA blood concentration increment after voriconazole initiation. We also demonstrated that magnitude of drug interaction did not differ in IV and oral voriconazole administration. Furthermore, we found that the magnitude of drug interaction was correlated with plasma concentration of voriconazole.

On March 11th 2020, the coronavirus outbreak was declared a pandemic by the WHO. One of the groups that is considered high risk in this pandemic are cancer patients as they are treated with a variety of immune system suppressor treatment modalities and this puts them in a great risk for infectious disease (including COVID-19). Therefore, cancer patients require higher level measures for preventing and treating infectious diseases. furthermore, cancer patients may bear additional risk due to the restriction of access to the routine diagnostic and therapeutic services during such epidemic. Since most of the attention of health systems is towards patients affected with COVID-19, the need for structured and unified approaches to COVID-19 prevention and care specific to cancer patients and cancer centers is felt more than ever. This article provides the recommendations and possible actions that should be considered by patients, their caregivers and families, physician, nurses, managers and staff of medical centers involved in cancer diagnosis and treatment. We pursued two major goals in our recommendations: first, limiting the exposure of cancer patients to medical environments and second, modifying the treatment modalities in a manner that reduces the probability of myelosuppression such as delaying elective diagnostic and therapeutic services, shortening the treatment course, or prolonging the interval between treatment courses.

The present study investigated the patients with Chronic Myeloid Leukemia in chronic phase (CP-CML) who had beenon the first- line Imatinib Mesylate (IM) therapy for a period of 84 months.

This retrospective study was conducted in 295 newly-diagnosed CP-CML patients(age >18 years)who were admitted to the Hematology, Oncology and Stem Cell Transplantation Research Center, Shariati Hospital, Tehran during 1 January 2009 to 30 December 2016. Response to treatment was evaluated by molecular response assessment. Rates of IM dose adjustment, switching to another drug therapy, Progression to Accelerate Phase (AP) and Blastic Crisis (BC) and long-term outcomes included Overall Survival (OS) and Progression Free Survival (PFS) were assesed.

Patients’ average age was 41.7 years, and 52.9% were male. 44.4% of patients at the month 18 achieved Major Molecular Response (MMR). Progression to AP/BC occurred in 26 patients during 84 months, and the estimated rate of OS and PFS were 71.83 and 74.48, respectively. Among the patients who didn’t achieve MMR at month 18 , 61 patients were treated with IM ( 400 mg /day), and then after month 18, 24(39.3%) of whom  achieved MMR. Dose adjustments occurred in 60 patients (20.33%). IM dose increases were observed in 53 patients who didn’t achive optimal response to imatinib or loss of optimal response. IM dose decreases were observed in 7 patients. 25 (8.47%)  patients were switched to a different Tyrosine Kinase Inhibitor (TKI). Most of TKI changes(n=21) happened in patients who didn’t achieve optimal response to IM and for the 4 patients TKI changes were owing to adverse events of IM. Among the patients undergoing change in treatment, 24(43.75%) patient achieved MMR.

Our data showed the high effectiveness of the change in the treatment of IM-resistant condition. Moreover, our finding suggests that imatinib be effective in Iranian patients after a long period of time compared to the referenced studies.

Hematopoetic stem cell transplantation is considered as a standard treatment for cancer patients to stay hopeful toward treatment outcome. However, these patients experience many complications which might affect different aspects of their life. The aim of this study was to investigate the lived experience of patients after hematopoetic stem cell transplantation and introduce supportive care strategies.

In this study, Van Manen’s Hermeneutic phenomenological approach was used. Eleven patients (7 males and 4 females) were chosen by targeted sampling from visitors of Shariati Hospital’s outpatient clinic. Semi-structured interviews were conducted and the final data were analyzed by MAXQDA 10 software.

Data analysis revealed that the main theme was resiliency with two sub-themes of “not surrendering to disease” and “feeling closer to God”.

Participants declared that transplantation was like a second chance for life and considered this opportunity as a gift from God to overcome their disease. According to our findings, spirituality aids can help patients control the disturbances following HSCT and health professionals can use constructive strategies to support patients with spiritual needs.

One of the most frequent complications of high-dose chemotherapy regimen before hematopoietic stem cell transplantation (HSCT) is oral mucositis (OM). Vitamin D (VD) has well-known immunoregulatory, anti-inflammatory, and antioxidant properties.

This study aimed to evaluate the association of baseline VD levels with OM as well as neutrophil and platelet engraftments in patients with multiple myeloma, Hodgkin’s and non-Hodgkin’s lymphoma after autologous HSCT.

A sample of 71 patients was included after obtaining informed consent. Serum samples were collected in the morning prior to the administration of conditioning regimen to measure the baseline 25-OH-D. OM was examined daily during hospital stay. The WHO scale was used for scoring the OM. Absolute neutrophil count and platelet count were determined daily from transplantation until engraftment.

Patients aged between 18 to 65 years. Mean length of hospital stay was 15.8±5.7 days. OM was detected in 44/71 (62.0%) of patients. Mean time to the engraftment of neutrophils and platelets were 11.8±4.0 and 17.2±7.3 days, respectively. Mean level of baseline 25-OH-D was 17.5±14.0 ng/ml. VD deficiency (<20 ng/ml) was diagnosed in 51/71 (71.8%) of patients. No association between baseline 25-OH-D levels and the incidence of OM (P=0.69) or OM grade 3-4 (P=0.46) was found. No significant correlations were detected between the baseline 25-OH-D and engraftment time of neutrophils (P=0.46) or platelets (P=0.17).

The prevalence of VD deficiency was high among adult HSCT patients at the time of transplantation. No association was found between low baseline VD with post-HSCT OM and engraftment time.

Palladium doped silica membranes were synthesized by the sol-gel method using two different procedures. The first palladium-doped silica membrane (M1) was synthesized with a coating of four layers of silica-palladium sol. The second membrane (M2) was synthesized with a coating of two silica layers followed by a coating of two silica-palladium layers. Scanning electron microscopy (SEM) proved the formation of uniform γ-alumina interlayers on the supports. SEM results for M1 showed that  synthesis of a membrane with this procedure leads to the formation of crack on the membrane selective layer. Single gas permeation measurements of H2 and N2 were carried out at room temperature, 100 °C and 550 °C. Gas permeation results revealed that Knudsen diffusion was dominant in permeation of these gases through membrane M1 while the dominant mechanism in permeation of gases through  membrane M2 was activated transport which has exhibited different behavior in comparison with M1. This result is due to the activated sublayers of membrane M2. In this case, H2 permeance increases and N2 permeance decreases with increasing temperature, leading to better separation perforamce of membrane M2 over M1 in separation of H2. Therefore, using the activated silica sublayer in the synthesis of M2 can be used as a high potential method to synthesize a selective palladium-doped silica membrane.

Adjuvant chemotherapy (ACT) for patients with Stage II colorectal cancer (CRC) is an area of controversy in oncology. International guidelines recommend the use of ACT in patients with specific high‑risk features. This study aimed to investigate the effectiveness of ACT in improving survival in patients with and without high‑risk features. A total of 225 patients with Stage II CRC who underwent primary tumor resection were included in this study. Patients with one or more high‑risk features including T4 tumor, poor differentiation, lymphovascular invasion, perineural invasion, bowel obstruction, local perforation, positive resection margins, or suboptimal lymph node sampling (fewer than 12 nodes) were classified as high risk. The survival analysis was performed between patients who only received curative surgery and those received single‑agent (5‑fluorouracil [5‑FU] and leucovorin [LV] or capecitabine) or multiagent ACT (oxaliplatin and 5‑FU + LV or oxaliplatin and capecitabine). The 5‑year overall survival (OS) rate was 88.4%, and the 5‑year disease‑free survival (DFS) rate was 80.4%. The 5‑year OS and DFS rates improved insignificantly with ACT (89.8% vs. 81.2%, P = 0.59 and 81.3% vs. 74.6%, P = 0.41, respectively); however, multiagent ACT results to inferior 5‑year OS and DFS compared to single‑agent ACT (82.1 vs. 92.8%, P = 0.14 and 70.1% vs. 86%, P = 0.07, respectively). ACT was associated with insignificant improved OS and DFS in both high‑risk and low‑risk groups, but high‑risk patients who received multiagent ACT had a significant inferior OS and DFS in comparison with those received single‑agent ACT. T4 tumor and obstruction were independent poor prognostic factors affecting OS and DFS. In our population, the improvement of OS and DFS with ACT was not statistically significant in high‑risk and low‑risk patients with Stage II CRC.