Background: 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.
Materials and Methods: 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 +12. All patients received high-dose chemotherapy, standard immunosuppressive regimen and supportive care according to institutional protocols.
Results: 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.
Conclusion: Based on the results of this study, protective effect of azithromycin on graft-versus-host disease could not be demonstrated.

Background: Chronic lymphocytic leukemia (CLL) is characterized by accumulation of B cells in blood, lymphoid tissues and bone marrow. Addition of rituximab to CLL chemotherapy regimens has been associated with improved survival. The aim of this study was to establish efficacy and safety of Zytux™ in comparison to MabThera^® in treatment of CLL.
Materials and Methods: Seventy CLL patients who met the criteria for entering the study were randomized into two groups (35 patients in each group). Both groups received Fludarabine and Cyclophosphamide plus Rituximab as part of the FCR regimen. Group A was treated with Zytux™, and group B was treated with MabThera^®. A non-inferiority margin of 20% for the primary outcome was defined to examine the similarity between Zytux™ and MabThera^®.
Results: Baseline demographic characteristics showed no statistically significant difference between the two groups.
The two treatment groups were comparable in terms of laboratory and clinical findings, cellular index changes and CD (5, 19, 20 and 23) counts during therapy cycles and at the end of the treatment period. Regarding safety results, Zytux™ demonstrated a similar profile of adverse reactions in comparison to MabThera^®. Moreover, the overall response rate was 88% and 89% for Zytux™ and MabThera^®, respectively (CI -0.17, 0.18).
Conclusion: Results showed non-inferiority of Zytux™ in terms of efficacy and adverse events as a biosimilar version of MabThera^®.

Background: Breast cancer is one of the most common cancers among women in the world, especially in Iran. There are large numbers of molecular and genomic factors causing breast cancer as well as many markers associated with tumor invasion.
Chemokines are small proteins that primarily regulate leukocyte trafficking in the homeostatic conditions and specific immune responses. Chemokine receptor 7 (CCR7) belongs a class A subtype 7-span transmembrane G-protein coupled receptor. CCR7 plays a role in the migration of tumor cells such as immune cells into lymphoid organs through binding to its only two ligands CCL19/CCL21.
High expression of this marker has been observed in breast cancer. However, there have been limited and contradictory data in studies conducted on the relationship between the increasing expression of this marker with various clinical and pathological factors.
Materials and Methods: This case-control practical study was carried out on total mastectomy samples from 70 patients with breast cancer and tumor-adjacent normal tissue using immunohistochemistry technique to assess the expression of CCR7 marker. The relationship among the marker expression with different clinical and pathological tumor factors such as age, tumor size, microscopic grade, neurovascular invasion, lymph node metastasis and tumor stage were evaluated in all patients. Since the both groups were matched for age, so McNemar test, Chi-square test and Fisher's exact test were used to compare the expression of CCR7 marker in the case and control groups. Conditional logistic regression was employed to compare the effects of other variables regarding the age harmonization.
Results: CCR7 expression was observed in 63 (91.4%) out of 70 studied patients and in tumor-adjacent normal tissue of 55 patients (78.6%), while the marker expression intensity in normal tissue was lower than tumoral tissue (P<0.032)
There was a significant relationship among the expression of CCR7 marker with disease stage (P<0.001), grade (P<0.035), lymph node metastasis (P<0.003), perineural invasion (P<0.037) and vascular invasion (P<0.01), but no significant relationship was found among CCR7 expression with other tumor clinicopathologic parameters such as age (P>0.19) and tumor size (P>0.105).
Conclusion: Increased expression of CCR7 has a significant relationship with disease stage, grade, lymph node metastasis and neurovascular invasion of breast cancer but has no relationship with age of patients and tumor size. Therefore, this biomarker can be utilized as a predictive factor for tumor metastasis and survival of patients.

Background: Cholelithiasis and its predisposing factors are less characterized in thalassemia syndromes. In the present study, we assessed the prevalence of gallstones and related-risk factors among thalassemia major (TM) patients in south-east of Iran.
Materials and Methods: The patients were recruited form a single center in Zabol city, south-east of Iran. Demographic and clinical information were retrieved from medical histories. Abdominal ultrasonography was performed to scrutinize gallstones and organ dimensions of liver, spleen, gallbladder and kidney.
Results: The study participants (n=127) consisted of 50 (39.4%) males and 77 (60.6%) females. The mean age of the patients was 15.2±7.9 years. Cholelithiasis was observed in 11 (8.7%) patients. Cholelithiasis was significantly associated with age (P=0.002) and splenectomy (P=0.001). The patients with cholelithiasis received a significantly higher blood volume than patients without cholelithiasis (546±108.7 ml and 425.1±134.7 ml, respectively, P=0.007). There were significant differences between cholelithiasis and non- cholelithiasis TM patients regarding the length of right and left liver lobes (P=0.001), as well as the length of gallbladder (P=0.006). Ferritin level was not associated with cholelithiasis in our patients. In multivariate analysis, age older than 15 (OR=10.4, 95% CI: 1.2-86.3, P=0.02) and 30 years old (OR=42.6, 95% CI: 2.9-613, P=0.006), and splenectomy (OR=8.7, 95% CI: 2.1-35.4, P=0.002) were significant risk factors for cholelithiasis.
Conclusion: Cholelithiasis is a relatively common complication among TM patients in our region. The most prominent risk factors of cholelithiasis were advanced age, splenectomy and large-volume blood transfusion.

Background: The prognosis of allogeneic hematopoietic stem cell transplantation (HSCT) for non-remission hematological malignant diseases is usually unfavorable. The most uncontrollable factor is residual disease or relapse. To overcome this problem, intensified conditioning regimens- sequential and/or additional chemotherapy to the standard regimen- could be effective. However, increasing the intensity of conditioning might also lead to more complications.
Materials and Methods: We retrospectively analyzed 81 patients with non-remission disease who received allogeneic HSCT in our institution between 2007 and 2011.
Results: 55.6% in 36 myeloablative conditioning patients and 46.7% in 45 reduced-intensity conditioning patients received intensified conditioning. The 5-year probability of overall survival was 35.0% and 17.1% in the standard and intensified group, respectively (p=0.027). Relapse mortality was 30% in the standard regimen group and 36.6% in the intensified regimen group (p=0.54). Transplant-related mortality (TRM) at 30 and 100 days was 5%, 17.1% (p=0.086) and 27.5%, 34.2% (p=0.52) in the standard and intensified group, respectively. There was no difference in TRM between the 2 groups at 30 days and 100 days.
Conclusion: The results of the study confirm the safety of the intensified conditioning regimen. Meanwhile, it could be considered as one of the few methods available to reduce the tumor burden before HSCT for refractory malignant diseases.

Background: T-cell prolymphocytic leukemia (T-PLL) is a rare lymphoid malignancy with dismal prognosis. Most patients have increased lymphocyte count (>1,00,000/dL) and widespread disease at presentation. Despite high response rate seen with alemtuzumab, the disease relapse is inevitable.
Materials and Methods: This was a retrospective observational study done at a tertiary cancer center in South India. All patients diagnosed with T-PLL from August 2010 to July 2015 were studied for the clinical characteristics, pathological findings and treatment outcomes.
Results: Seven patients were diagnosed as T-PLL over a period of 5 years. The median age at diagnosis was 51 years. In the present series, 6 patients (86%) had splenomegaly and 3 had hepatomegaly (43%). Generalized lymphadenopathy was seen in 4 (57%) patients at presentation. Skin lesions were seen in 5 (71%) patients, whereas pleural effusion was seen in only one patient (14%). All had elevated total leukocyte count, with more than 1, 00,000/dL in 4 patients. The median survival was 5 months with different chemotherapy (CT) regimens (5 patients treated with CT and 2 received best supportive care).
Conclusion:T-PLL is a rare disease with no definite treatment guidelines. At present, the best outcomes are achieved if treatment with alemtuzumab is followed by stem cell transplant, but the disease invariably relapses. Countries where affordability remains a big challenge, the best approach needs to be defined beyond the monoclonal antibodies and transplant.

Background: Head and neck squamous cell carcinoma (HNSCC) is one most prevalent cancers among worldwide. Aim of this study was to evaluate possible effect of bevacizumab, a vascular endothelial growth (VEGF) factor monoclonal antibody on HNSCC cells in vitro to evaluate angiogenic profile changes.
Materials and Methods: HNSCC cells were grown and after that different concentrations of bevacizumab were added in order to evaluate cytotoxic concentration using MTT assay. Then after, the cultured cells in presence of different concentration of bevacizumab were evaluated for gene expression of VEGF, matrix metalloprotease-2 (MMP-2) and MMP-9 using real time polymerase chain reaction (PCR). Moreover, the VEGF expression was evaluated by enzyme-linked immunosorbent assay (ELISA).
Results: The concentration at which half cells died (IC59) was calculated 1779 µg/mL and at this concentration, VEGF protein secretion was decreased by over one fold. RT-PCR results showed that MMP2, MMP9 and VEGF decreased by 1, 0.6 and 1.1 folds, respectively.
Conclusion: It seems that bevacizumab could be considered as a side therapy for patients with HNSCC due to its potential for inhibition of angiogenic related factors, but further complementary studies are necessary.

Background: Patients who receive hematopoietic stem cell transplantation (HSCT) experience several complications that oral mucositis (OM) is a frequent symptom. This study was designed to evaluate the incidence, risk factors, prophylaxis and treatment strategies for established OM.
Materials and Methods: We included 173 adult patients who received autologous or allogeneic hematopoietic stem cell transplantation in this study. The World Health Organization oral toxicity scale was used to assess the severity of OM. Patients received two prophylactic regimens: regimen 1 contained nystatin, chlorhexidine, povidone iodine and amphotericin B. Regimen 2 contained nystatin and povidone iodine. 70 patients (40.5%) received the first prophylaxis regimen, 89 patients (51.4%) received the second prophylaxis regimen and the remaining 14 patients (8.1%) were not adherence to the use of the mouthwashes and were excluded from the analysis.
Results: OM was detected in 60.7% of patients with mean (SD) age of 38.1±14.6 years. Multivariate analysis showed that only the female gender and the prophylactic regimen were the significant predictors of OM.
Conclusion: We found that addition of amphotericin B and chlorhexidine, to the nystatin and povidone iodine resulted in a significant beneficial effect in prevention OM.

Breast cancer (BC) has a high mortality rate and metastatic BC is almost incurable despite hormonal therapy and chemotherapy. The second and third lines of chemotherapies usually yield transient responses and the median survival is generally as low as 18-24 months. Autologous and allogeneic hematopoietic stem cell transplantation (HSCT) have been extensively investigated in this setting. The presence of immune mediated anti-tumor effects referred to as graft-versus-tumor (GvT) effects after allogeneic HSCT among patients with solid tumors have been clearly defined. The advantages of allogeneic HSCT over autologous HSCT for metastatic BC are i) cancer-free graft and ii) immune-mediated GvT effects mediated by human leukocyte antigen compatible donor T-cells. In conclusion, a GvT effect does exist against metastatic BC and play a key role in tumor response. This review aims to describe the background, rationale, and clinical results of allogeneic HSCT as a potential alternative treatment in metastatic BC.

Tafazzin (TAZ) protein has been upregulated in various types of human cancers, although the basis for elevation is uncertain, it has been made definite that the effect of mutation in the hippo pathway, particularly when it is switched off, considerably activates tafazzin transcriptionally and thus this results in tissue or tumor overgrowth. Recent perceptions into the activity of tafazzin, have ascribed to it, a role as stem cell factor in mouse mesenchymal and as well as in neural stem cells. Being a downstream molecule in Hippo signalling, phosphorylation or dephosphorylation of tafazzin gene regulates its transcriptional activity and the stemness of mesenchymal stem cells. Commonly, extracellular matrix controls the stem cell fate commitment and perhaps tafazzin controls stemness through altering the extra cellular matrix. Extracellular matrix is generally made up of prime proteoglycans and the fate stabilization of the resulting lineages is surveilled by engineering these glycans. Tafazzin degradation and addition of proteoglycans affect physical attributes of the extracellular matrix that drives cell differentiation into various lineages. Thus, tafazzin along with major glycans present in the extracellular matrix is involved in imparting stemness. However, there are incoherent molecular events, wherein both tafazzin and the extracellular matrix components, together either activate or inhibit differentiation of stem cells. This review discusses about the role of tafazzin oncoprotein as a stemness factor.

The co-occurrence of different types of hemo-lymphopoietic malignancies within a family provides clues about the pattern of inheritance and common environmental risk factors. A family presented with developing hemo-lymphopoietic cancers in three female first-degree relatives: a mother and her daughters.
Case 1 was diagnosed with Walden Strom's macroglobulinemia at age 57. Case 2 and 3 presented with chronic myelogenous leukemia at age 32 and diffuse large B-cell lymphoma at age 28, respectively. There were not any significant common environmental risk factors in this family, but all three cases suffered from skin dermatitis and one of them, who suffered from chronic myelogenous leukemia, was diagnosed with morphea. This family had a sedentary and stressful lifestyle.
Genetic is the foundation of some familial aggregation of cancers. Common lifestyle habits and environmental etiologies are important. Morphea as an autoimmune disease could have the essential role in developing hematolymphoid malignancies.

Hodgkin’s Lymphoma is one of the commonly encountered lymphomas in childhood. Most of the children present with lymphadenopathy. A rare subset of children do present with constellation of atypical symptoms as paraneoplastic syndromes. We hereby present an 11-year-old boy with classical Hodgkin’s Lymphoma associated with Alopecia areata and demyelination as paraneoplastic manifestations. Both these paraneoplastic manifestations improved after initiating chemotherapy (ABVD regimen). A high index of suspicion for underlying malignancy would help clinicians in clinching an early diagnosis and would avert the associated complications.