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BACKGROUND: There are still inconsistencies about the role of metformin on breast cancer. This study was designed to assess metformin's effect on the prognosis of female breast cancer patients with type II diabetes. METHODS: The present research was carried out as a retrospective cohort study between 2003 and 2014. Breast cancer patients with pre-existing type II diabetes mellitus were included. Overall survival (OS) and relapse-free survival (RFS) were measured as the main endpoints. Kaplan-Meier estimate was used to calculate survival rates. RESULTS: 217 patients were included with a mean age of 53.32±11.10 years. 148 (68.2%) patients were prescribed metformin and 69 (31.8%) took other antidiabetic drugs (non-metformin group). Five-year OS and RFS rates for all patients were 82.5% (95% CI: 76.0%-87.4%) and 71.1% (95% CI: 64.2%-77.0%) respectively. Log-rank test showed that the metformin group had a significant advantage over the non-metformin group in terms of both OS and RFS rates (p.

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BACKGROUND: 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. MATERIALS AND METHODS: 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). RESULTS: 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. CONCLUSION: 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.

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BACKGROUND Colorectal 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. METHODS 370 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. RESULTS Mean 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. CONCLUSION Even with the acceptable survival rates and more effective treatments, it seems that clinicopathological characteristics have yet the most important prognostic effect in advanced CRC.

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BACKGROUND: Multiple myeloma (MM) accounts for a substantial mortality rate among hematological cancers. The prognosis of the disease has been noticeably changed during the past 2 decades. This study reports a retrospective analysis of 345 MM cases from 2 cancer centers. METHODS: Medical records of 345 MM cases were analyzed in retrospect. Diagnosis of MM was defined in presence of at least 10% plasma cells in bone marrow biopsy and one of the CRAB findings (hypercalcemia, renal failure, anemia and myeloma bone lesions). Survival analysis was performed using Kaplan-Meier method, and the effects of prognostic variables were assessed by Cox proportional hazards model. RESULTS: The mean age of the patients was 61.98 ± 11.44 years. Comparing to Mayo Clinic series, our patients were relatively younger and suffered from more advanced disease. By a median follow up time of 45 months, 1- and 5-year overall survival (OS) rates were 78.0% and 35.6%, respectively. Regarding first progression free survival (PFS1), similar rates of 57.7% and 17.0% were observed respectively. In multivariate analysis, hypercalcemia (corrected serum calcium >11 mg/dL), pancytopenia and elevated serum creatinine (Cr) (>2 mg/dL) were found to be independent prognostic factors affecting OS. CONCLUSION: Presentation of MM in Iran which is a developing country, was significantly different from developed countries. This finding might be generalized to other developing countries as well. In addition, vincristine-adriamycin-dexamethasone (VAD) therapy was an inferior protocol compared to bortezomib as first and second lines. Furthermore, pancytopenia was observed in about 9% of the patients and was an independent prognosticator of the disease.

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Several chemotherapy regimens have been developed for the treatment of acute lymphoblastic leukemia (ALL), but relapse still presents the most common obstacles to attaining long-term survival. The hyper-CVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, and prednisolone)/HD MTX and Ara-C (high-dose methotrexate and cytarabine) chemotherapy regimen was first started in the MD Anderson Cancer Center as an intensive regimen for adult patients with ALL. The purpose of this study was to evaluate the effectiveness of a modified hyper-CVAD protocol. We used hyper-CVAD as consolidation/maintenance after remission induction with daunorubicin, vincristine, and prednisolone (and cyclophosphamide for T-cell ALL only) rather than standard hyper-CVAD in order to reduce treatment complications. This study was conducted as a retrospective review of medical records of ALL patients at 501 army hospital, Tehran, Iran, from 2005 to 2015. Three hundred and one patients underwent modified hyper-CVAD chemotherapy regimen. Complete remission and overall survival (OS) rates were measured as primary endpoints. Two hundred and forty-six (81.7%) reached complete remission (CR) during the first 6 months of treatment, and 55 patients (18.3%) did not reach CR. The 5-year OS rate was 51.8% (95% CI (confidence interval): 45.1-57.8%). Modified hyper-CVAD regimen is an efficient intensive chemotherapy regimen for consolidation/maintenance of adults with newly diagnosed ALL and has an acceptable 5-year overall that is comparable to standard hyper-CVAD regimen.

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

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

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BACKGROUND: P53; a tumor suppressor gene has known to have a role in a group of human cancers. Its role in breast cancer; one of the most prevalent malignancies worldwide, is still controversial. The current study is designed to evaluate the prognostic role of p53 mutation in breast cancer. METHODS: one hundred and eighty five breast cancer patients were studied in this retrospective study. P53 mutation was detected by accumulation of p53 protein in the patients' pathology samples. Immunohistochemistry (IHC) was used to detect the protein. The effect of p53 on the final outcome was assessed using Kaplan-Meier estimate of survival and compared by log-rank test. Prognostic effects analyzed by cox proportional hazard models. RESULTS: while the stage of the disease at presentation was not significantly different between p53 positive and negative patients, those with p53 mutation had a significantly poorer outcome in terms of overall and disease-free survival rates (OS and DFS). In a multivariate analysis hazard ratio of p53 mutation was about 5 and 3.8 for OS and DFS respectively. They also had a higher cumulative incidence of relapse. CONCLUSION: It seems that p53 mutation is an independent prognostic factor for breast cancer. Although larger prospective studies are needed to clarify the importance of such a conclusion.

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Paroxysmal nocturnal hemoglobinuria (PNH) is a rare clonal disease of hematopoietic stem cell characterized by complement mediated intravascular hemolysis. There are different treatment modalities available for PNH, such as supportive care, eculizumab, and hematopoietic stem cell transplantation (HSCT); only the last one has a potential curative role. This study reported the outcome of HSCT transplanted PNH patients. Thirteen PNH patients between 2002 and 2014 participated in this study. All had full-matched sibling donors, and the conditioning regimen was Bu/Cy (busulfan plus cyclophosphamide), and the source of stem cells was peripheral blood of the donors. Mean age at transplant was 27.46 years, and mean time to transplant was 41.30 months. Three were female and 10 were male. Three patients died at the end of follow-up time, and the cause of death was graft versus host disease (GVHD) for all 3 cases. Survival analysis showed a 5-year and a 13-year survival rate of 74.07% and a significant relationship between a positive history of thrombosis and a higher mortality rate. HSCT has curative role in management of PNH with an acceptable survival rate and therefore can be considered as an acceptable choice for selected cases.

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BACKGROUND AND OBJECTIVES: Fanconi anemia (FA) is a rare genetic disorder caused by an impaired DNA repair mechanism which leads to an increased tendency toward malignancies and progressive bone marrow failure. The only curative management available for hematologic abnormalities in FA patients is hematopoietic stem cell transplantation (HSCT). This study aimed to report the results of HSCT in adult or adolescent FA patients. PATIENTS AND METHODS: Twenty FA patients with ages of 16 or more who underwent HSCT between 2002 and 2015 enrolled in this study. The stem cell source was peripheral blood, and all patients had a full human leukocyte antigen (HLA) matched donor, 19 patients had a sibling donor, and one had full matched other related. Indications for HSCT were severe bone marrow failure or dependence on blood products transfusion and failure of medical treatment to sustain peripheral blood elements at an acceptable level. RESULTS: Eleven patients were female and 9 male (55% and 45%). Mean age was 24.05 years. Mortality rate was 50% (n=10), and the leading cause of death was graft versus host disease (GVHD) which occurred in 5 patients (4 cases from acute GVHD and one from chronic GVHD). Survival analysis showed an overall 5-year survival of 53.63% (95% confidence interval: 29.53%-72.74%) and 13 year survival of 45.96 % (95% confidence interval: 22.08%-67.03%) among patients. CONCLUSION: HSCT is the only curative management for bone marrow failure in FA patients. But the high rate of mortality and morbidity in adolescent and adult patients makes it a challenging issue.