ardeshir ghavamzadeh

Natural killer (NK) cells are the most professional innate immune cells that initiate extracellular apoptosis via cytotoxic granules in malignant cells. Antitumoral properties of NK-derived exosomes (Exos) are attributed to their parent cells. Loading drugs into Exos as a carrier can enhance their effect and enable targeted delivery. In the present study, we aim to deliver Doxorubicin (DOX) to the breast cancer spheroids by NK-Exos.

Peripheral blood mononuclear cells (PBMC) were used to harvest NK cells, and NK-Exos were isolated from NK cell expansion medium using an Exo-spinTM kit. DOX was loaded via the ultrasonication method. AO/EtBr, Annexin/PI, DAPI, MTT, and spheroids of human breast cancer were used to track the cytotoxic effect of DOX-NK-Exos. The colony formation assay, scratch and transwell assays, Real-Time PCR for p53 and VEGF-A, and WB for protein expression were also performed.

When compared to free DOX, all viability tests validated the inhibitory effects of DOX-NK-Exos. The obtained results indicated that DOX-NK-Exos selectively reduced tumor cell viability and spared fibroblast and MCF-10A as noncancerous cells. Long after spheroid treatment, DOX-NK-Exos’ remarkable effect persisted.

Human breast carcinoma mass treated with DOX-NK-Exos underwent apoptosis and showed a strong inhibitory effect on proliferation. Thus, they can reduce the side effects of chemotherapeutics and can be used as drug carriers with selective toxicity. Additionally, the additive action of this combination formula results in a more severe loss in cell viability.

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.

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.

Using echocardiographic parameters, we sought to predict cardiotoxicity in patients with breast cancer before treatment.
 
The study recruited 53 left-sided breast cancer patients with no previous history of heart failure or cancer treatment. The patients underwent 2D and 3D echocardiography before and 6 months after the end of treatment. The main criterion for cardiotoxicity was a reduction in posttreatment LVEF exceeding 10% compared with pretreatment. Systolic and diastolic parameters were compared between 2 groups: complicated and noncomplicated. Binary logistic regression was used to predict cardiotoxicity.
 
The patients’ mean age was 49 ± 11.2 years. No statistical differences existed between the groups in demographics and cardiac risk factors at study commencement. Posttreatment, 4 echocardiographic parameters (E/A ratio, sPAP, LVEF, and LVGLS) were significantly changed compared with pretreatment echocardiography. The regression analysis showed that E/A ratio was effective in predicting cardiotoxicity (sensitivity = 68%, specificity = 76%, AUC =77%; and P <0.001).
 
Echocardiography, aside from its usefulness in diagnosing cardiotoxicity, can be valuable in predicting complications, especially in patients with breast cancer at higher risk of cardiotoxicity due to chemotherapy and radiotherapy in the chest wall area. (Iranian Heart Journal 2023; 24(3): 62-69)

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.

FAT atypical cadherin 1 (FAT1) is a member of the cadherin superfamily whose loss or gain is associated with the initiation and/or progression of different cancers. FAT1 overexpression has been reported in hematological malignancies. This research intended to investigate FAT1 gene expression in adult Iranian acute leukemia patients, compared to normal mobilized peripheral blood CD34+ cells.

The peripheral blast (peripheral blood mononuclear cells) cells of 22 acute myeloid leukemia (AML), 14 acute lymphoid leukemia (ALL) patients, and mobilized peripheral blood CD34+ cells of 12 healthy volunteer stem cell donors were collected. Then, quantitative real-time polymerase chain reaction (qPCR) was used to compare FAT1 gene expression.

Overall, there were no significant differences in FAT1 expression between AML and ALL patients (p>0.2). Nonetheless, the mean expression level of FAT1 was significantly higher in leukemic patients (AML and ALL) than in normal CD34+ cells (p=0.029). Additionally, the FAT1 expression levels were significantly higher in both CD34+ and CD34- leukemic patients than in normal CD34+ cells (p=0.028).

No significant differences were found between FAT1 expression in CD34+ and CD34- leukemic samples (p> 0.3). Thus, higher FAT1 expression was evident in ALL and AML leukemia cells but this appeared unrelated to CD34 expression. This suggests in a proportion of adult acute leukemia, FAT1 expression may prove to be a suitable target for therapeutic strategies.

Hairy cell leukemia (HCL) is a distinct lymphoproliferative disorder with unique circulating lymphocyte morphology. It is now regarded as an indolent disease yet treatable with purine analogs. We are going to present a complete long-term clinical and prognostic report of our HCL patients as a large cohort in Iran.

All patients diagnosed with HCL according to WHO criteria referred to our academic center in the period of 1995 to 2020 are enrolled. Treatment with daily cladribine regimen was initiated as indicated and patients were followed. Survival data and clinical outcome of patients were calculated.

A total 50 patients were studied (76% male). Median time to treatment was 4.8 months and complete remission was achieved in 92% of patients. Nine patients (18%) experienced relapse with median time to relapse of 47 months. After median follow-up of 51 months, the median OS was not reached and after 234 months, the overall survival rate was 86%. Survival was worse in patients with non-classic HCL (vHCL) compared to classic HCL.

Our long-term follow up data confirmed favorable outcome of Iranian HCL patients with cladribine and provide a useful viewpoint of the disease.

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).

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.

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.

This study aimed to determine the portion of Iranian patients who attain therapeutic serum concentrations of voriconazole (VRCZ) following administration of fixed doses. In addition, the effect of CYP2C19 polymorphism on serum levels of VRCZ was also investigated.

Forty‑eight adult patients of Iranian origin with hematologic malignancies, who received VRCZ for treatment of invasive aspergillosis, were recruited into the study. Blood samples were drawn at day 4 of treatment to measure trough drug concentrations and determine genotyping of CYP2C19 polymorphisms of each patient. High‑performance liquid chromatography method was used for measuring VRCZ serum level and CYP2C19 polymorphisms were conducted by Sanger sequencing. Demographic and clinical characteristics of patients alongside with CYP2C19 polymorphisms were assessed to determine the effective factor/s on VRCZ serum concentration.

Seventy‑three percent of patients achieved therapeutic serum concentrations of VRCZ with administration of usual fixed doses in clinical practice. There was no correlation between weight‑adjusted dose and serum concentrations of VRCZ. Mean serum levels were significantly different neither in genders nor in routes of administrations. Extensive and ultrarapid metabolizers (URMs) comprised 48.7% and 21.6% study population, respectively. CYP2C19 polymorphism dramatically influenced the trough levels of VRCZ, so that all patients with subtherapeutic levels expressed URM phenotype.

With respect to high incidence of URM phenotype in Iranian population, and observed association of this phenotype with sub‑therapeutic levels in our study, performing therapeutic drug monitoring is strongly recommended for all patients.

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.

At present, hematopoietic stem cell transplantation is the only curative treatment for β thalassemic patients. Conventional myeloablative stem cell transplantation is associated with significant morbidity and mortality, and non-myeloablative stem cell transplantation is associated with high graft failure rate. Some modification in this treatment approach can result in successful transplantation in thalassemic patients.
Two successful Fludarabine - based non-myeloablative stem cell transplantation in two Class III β thalassemic patients are reported here. The first patient was a 14-year old girl that developed rapid engraftment and full Chimerism after rapid tapering of cyclosporine as graft-versus-host disease (GVHD) prophylaxis drug according to our protocol. Another patient was a 24-year old female patient that developed cyclosporine toxicity, and early tapering of cyclosporine helped for rapid engraftment and successful transplantation.After these two successful experiments in non-myeloablative peripheral blood stem cell transplantation for our class III β thalassemic patients, we concluded that Fludarabine-based nonmyeloablative stem cell transplantation with adequate number of stem cells at the time of transplantation and rapid tapering of GVHD prophylaxis drugs after transplantation can potentially help for rapid engraftment and successful stem cell transplantation in high risk β-thalassemic patients.

Opportunistic infections like cytomegalovirus (CMV) are among the primary causes of morbidity and mortality in patients undergoing hematipoetic stem cell transplantation (HSCT). This infection is frequently seen in early postengraftment period. So we determined to find the risk factors associated with CMV reactivation.

We retrospectively evaluated the medical records of 126 consecutive patients who underwent allogenic‑HSCT from peripheral blood stem cells from August 2011 to February 2013 in Shariati Hospital. We included HSCT patients with 15 years of age or older, who survived at least 100 days after transplantation. CMV reactivation was detected based on the weekly PP65 assessment. Patients with 10 or more positive cells per 50,000 cells were defined as having high‑level antigenemia.

From 126 patients which included in this study, 76 were male (60%). CMV antigenemia was documented in 43 patients (34%). The median time to CMV infection was 40 days (range: 3–77) after transplantation. The incidence of high‑level antigenemia during the first 100 days following HSCT was 11%.

We found that the significant risk factor for CMV antigenemia in multivariate analysis was prior graft‑versus‑host disease (GVHD) experience and higher donor age. For high‑level antigenemia, GVHD or duration of its treatment was significant determinant.

Gastric cancer (GC) is considered as one of the most common types of cancer worldwide with poor prognosis and generally limited treatment options. Recent studies have indicated that HER2, MDM2, MYC, MET, and TP53 play an important role in the development of gastric cancer. Therefore, the aim of this study was to evaluate the incidence of amplification/deletion of these genes in patients with gastric cancer.

In this descriptive study, a total of 37 gastric cancer tissue samples from GC patients including 23 males (62.2%) and 14 females (37.8%) referred to the Hematology-Oncology and Stem Cell Research Center of Shariati Hospital, Tehran, from March 2015 to February 2016 were evaluated. The patient's age at diagnosis ranged from 33 to 85 years (median: 65 years). The amplification pattern of HER2, MDM2, MYC and MET genes and TP53 deletion were investigated by fluorescence in situ hybridization (FISH) technique performed on 3 to 5 micron section obtained from formalin-fixed and paraffin-embedded cancer tissues.

The tumors were preferably identified at the distal stomach (54.05%) in comparison to tumors arising from the gastric cardia. The tumor size varied between 2 and 5 cm (average, 3.5 cm). Seven of the cases (19%) had advanced tumors at the time of diagnosis. HER2, MDM2, MYC, MET and TP53 copy number alteration were successfully determined in all samples obtained from the GC patients. HER2, MDM2, and c-MYC genes were amplified in 2 (5.41%), 1 (2.7%) and 3 (8.11%) of 37 patient samples, however, MET gene amplification and TP53 deletion were not observed in the obtained GC tissue samples. Co-amplification of HER2, MDM2, and MYC genes, and co-amplification of HER2 and MYC genes were detected in one patient.

The results of this study indicate the low frequency of MDM2, HER2 and MYC genes in gastric cancer patient and their copy number alterations may provide diagnostic and prognostic marker for GC patients.

The analysis of the gene copy number alterations in tumor samples are increasingly used for diagnostic and prognostic purposes in patients with gastric cancer (GC). However, these procedures are not always applicable due to their invasive nature. In this study, we have analyzed the copy number alterations of five genes (HER2, MDM2, c-MYC, c-MET, and TP53) with a fixed relevance for GC in the circulating tumor cells (CTCs) of GC patients, and, accordingly, as a potential approach, evaluated their usage to complete primary tumor biopsy.

We analyzed the status of the copy number alterations of the selected genes in CTCs and matched biopsy tissues from 37 GC patients using fluorescence in situ hybridization.

HER2 amplification was observed in 2 (5.41%) samples. HER2 gene status in CTCs showed a strong agreement with its status in 36 out of 37 patients’ matched tissue samples (correlation: 97.29%; Kappa: 0.65; p < 0.001). MDM2 amplification was found only in 1 (2.70%) sample; however, the amplification of this gene was not detectable in the CTCs isolated from this patient. c-MYC amplification was observed in 3 (8.11%) samples, and the status of its amplification in the CTCs indicated a complete agreement with its status in the matched tissue samples (correlation: 100%; Kappa: 1.0).

Our work suggests that the amplification of HER2 and c-MYC is in concordance with the CTCs and achieved biopsies, and, consequently, CTC may act as a non-invasive alternative for recording the amplification of these genes among GC patients.

It is well-known that Aurora kinase A (AURKA) shows oncogenic properties in various tumor types including gastric cancer (GC). Moreover, previous studies have demonstrated that AURKA has a specific androgen receptor (AR) binding site in its promoter; thus, it could be regulated by AR. Since it has been shown that AR overexpresses in gastric cancer (GC) as a male-predominant tumor, the goal of this study was to evaluate the association between AR and AURKA and its prognostic value in GC patients.

We assessed the expression profile of AURKA in 60 fresh GC and adjacent non-tumor tissues and 50 normal gastric specimen by qRT-PCR, and investigated the association of AURKA expression with clinicopathological features. Furthermore, we evaluated possible correlation between AURKA and AR to elucidate a novel prognostic marker using Kaplan-Meier method and Cox regression model.

Among GC patients, 65% (39/60) overexpressed AURKA relative to normal gastric tissues. AURKA overexpression was significantly correlated with the AR overexpression in GC patients. Although AURKA expression alone was not remarkably associated with poor outcome, we provided some evidence that combined evaluation of AURKA and AR expression could independently predict survival of GC patients adjusted for other variables (HR=1.7, CI=1.314-3.833 p=0.042).

These results indicate that AR and AURKA may crosstalk to promote GC progression. Our findings have clinical importance because they suggest simultaneous assessment of AURKA and AR expression as a novel potential prognostic marker.

Gastric cancer is one of the most common malignancies worldwide with a high case mortality rate. In metastatic gastric cancer, a proper combination of chemotherapy could increase the survival rate. The goal of this study is to evaluate the efficacy and safety of the combination regimen of irinotecan, oxaliplatin, and Xeloda in metastatic gastric cancer. A total of 45 patients with metastatic gastric cancer and good performance status according to the Eastern Cooperative Oncology Group (score: 0-1) received the irinotecan, oxaliplatin, and Xeloda chemotherapy regimen. Demographic data, responses to treatment, and adverse effects were gathered for all cases. Overall survival and progression-free survival rates for patients were calculated using the Kaplan-Meier estimate. Patients’ mean age was 58.3 ± 11.3 years (range: 24-81). There were 73.4% male patients and 26.6% female patients. Anorexia and weight loss were the most common symptoms. Overall response rate was 50%. The majority of toxicities were anemia, nausea and vomiting (grades 1 and 2), diarrhea (grades 1 and 2), neutropenia, alopecia, and hand and foot syndrome. The one-year progression-free survival rate was 31.5 ± 7.5%, whereas the twoyear progression-free survival rate was zero. The one-year overall survival rate was 34.91 ± 8.5%. Patients had a two-year overall survival rate of 7.7 ± 6.6%. Diffuse type cancer was linked to an inferior outcome. Regardless of our limited number of patients, this combination could be a suitable regimen for metastatic gastric cancer in terms of low toxicity, acceptable response rate, and survival results.

Cancer-related fatigue (CRF) is a very prominent complaint and disabling symptom in cancer patients probably influenced by endogenous cytokines. But, the published data on this subject are limited. We explored the relationship of cytokines such as tumor necrosis factor (TNF-α) and interleukin-6 (IL-6) with fatigue in patients with AML. This study was performed on 45 patients (25 men, 20 women) with newly diagnosed AML. We examined fatigue in these patients with validated questionnaire. Simultaneously, blood samples were obtained for quantitative measurement of IL-6 and TNF-α. Our results showed a positive correlation between fatigue and circulating levels of IL-6 (P=0.004, R=0.416). Many patients with AML experienced severe fatigue before the onset of treatment, which is not related to their hemoglobin (Hb) levels. Cytokine levels may be beneficial markers in resistance to fatigue, but further studies are needed before considering targeted therapies as a treatment for CRF.

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).
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.
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 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.

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.
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.
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.
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.

BACKGROUNDColorectal cancer (CRC) is one of the most common cancers worldwide. Recently treatments of advanced CRC have been immensely improved. In this study we reported the current state of advanced CRC in Iran regarding treatment and outcomes from 2000 to 2016.
METHODS370 subjects with stage III or IV of the disease were included in this study. Pathological subtypes other than adenocarcinoma were excluded. Demographics and other relevant clinical data were collected.
RESULTSMean age at diagnosis was 55.4±12.6 years. Significant differences regarding the age, sex, primary tumor complication and location, lymph node involvement, and tumor size were not detected between patients with stage III and IV. Overall survival rate at 5 years was 69.5% (95% confidence interval: 60.8%-76.6%) and 21.73% (95% CI: 12.46%-32.70%) for patients with stage III and IV, respectively. Analysis of prognostic factors revealed that tumor grade was an independent factor predicting poorer outcome (poorly differentiated vs. well or moderately differentiated). Furthermore, in stage IV of the disease, IVb subgroup was found to be associated with a poorer outcome compared with stage IVa.
CONCLUSIONEven with the acceptable survival rates and more effective treatments, it seems that clinico-pathological characteristics have yet the most important prognostic effect in advanced CRC.

Allogeneic hematopoietic stem cell transplantation has been used widely to treat various types of malignant and non-malignant disorders. Graft-versus-host disease is one of the main complications of this procedure which is associated with considerable mortality and affects quality of life. Despite careful selection of HLA-matched donors and implementing immunosuppressive therapy, the incidence rate of graft-versus-host disease remains high. Macrolide antibiotics are well-known immunomodulatory agents and have been effective as prophylaxis for graft-versus-host disease in preclinical studies.
Ninety-six adult patients with acute leukemia were recruited into a double-blind, randomized, placebo-controlled trial. All patients were first-time transplant candidates for a full-matched related or unrelated donor. Patients were allocated to receive azithromycin 500 mg daily (n=48) or placebo (n=48) from day -6 to . All patients received high-dose chemotherapy, standard immunosuppressive regimen and supportive care according to institutional protocols.
The incidence of acute graft-versus-host disease grade III-IV and chronic graft-versus-host disease garde I-III was not significantly different between the two study arms. Oral mucositis grade 1-3 occurred in significantly lower number of patients in the azithromycin group compared with placebo.
Based on the results of this study, protective effect of azithromycin on graft-versus-host disease could not be demonstrated.