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Introduction: Donor choosing remains to play a pivotal role in allogeneic hematopoietic stem cell transplantation (allo-HSCT). Numerous criteria beyond HLA compatibility impact the selection of a suitable donor., Methods: We evaluated the effect of donor parity on transplant outcomes in a large homogeneously treated population that received an HLA-matched allo-HSCT between 2010 and 2021 at our center. All patients were transplanted from a peripheral blood stem cell source following a myeloablative Busulfan-based conditioning and an identical protocol for graftversus-host disease (GVHD) prophylaxis regimen., Results: A total of 1103 allo-HSCT recipients were included. 188 (17%) had transplants from parous female donors, whereas 621 (56.30%) and 294 (26.70%) received transplants from male and nulliparous female donors, respectively. HSCTs from parous female donors compared to male and nulliparous females were associated with a significantly higher incidence of grade III-IV acute (a) GVHD (55.27% vs. 11.34 and 10.84%) and extensive chronic (c) GVHD (64.32% vs. 15.52 and 13.65%), as well as lower relapse incidence (RI)., Discussion: This study finds that while parous female donors are associated with higher incidences of grade III-IV aGVHD and extensive cGVHD post-allo-HSCT, the advantages, such as a lower RI, outweigh the risks. The results of our study provide valuable insights for donor selection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Azari, Barkhordar, Bahri, Rad, Kamranzadeh Fumani, Mousavi, Tavakoli Shiraji, Azari, Shafaroudi and Vaezi.)

Imatinib, a selective BCR-ABL tyrosine kinase inhibitor (TKI), was introduced after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for patients with chronic myeloid leukemia (CML). However, the long-term effects of allo-HSCT in chronic phase CML patients are mostly unknown. We retrospectively analyzed the outcomes of 204 patients with sibling donors who received peripheral stem cells and underwent allo-HSCT of chronic phase I (CP1) in the pre- and post-TKI era at Shariati Hospital in Tehran, Iran, from 1998 to 2017 and followed up till the end of 2021. The median follow-up time for all patients was 8.7 (SD = 0.54) years. Fifteen-year overall survival (OS), disease-free survival (DFS), graft-versus-host disease-free relapse-free survival (GRFS), relapse, and non-relapse mortality (NRM) incidence were 65.70%, 57.83%, 17.56%, 13.17%, and 28.98%, respectively. Using multivariable analyses, the only risk factor increasing the hazard of death was the time between diagnosis to allo-HSCT greater than 1 year compared to this time less than 1 year by 74% [hazard ratio (HR) = 1.74, P = 0.039]. Also, age is a significant risk factor for DFS (HR = 1.03, P = 0.031). Our findings suggested that allo-HSCT is still an important treatment option for CP1 patients, especially those resistant to TKI treatment. TKI consumption can have a desirable effect on NRM after allo-HSCT for CP1 CML.

In haploidentical peripheral blood stem cell transplantation (haplo-PBSCT), the combination of anti-thymocyte globulin and post-transplant cyclophosphamide (ATG/PTCy) has a synergistic impact in preventing graft-versus-host disease (GvHD). However, little is known about the long-term consequences of the new combination approach. Our goal is to evaluate the efficacy of ATG/PTCy versus a standard ATG regimen by focusing at long-term outcomes in a more homogeneous group of patients. We retrospectively included 118 adult patients up to 60 years with acute leukemia who underwent haplo-PBSCT at our single institution, following the same myeloablative conditioning regimen. From 2010 to 2020, 78 patients received a modified combination of ATG (2.5 mg/kg/day, on days -3, -2, and -1) and PTCy (40 mg/kg/day on days +3 and +4) compared to 40 patients who had a standard ATG-based regimen (2.5 mg/kg/day from days -4 to -1) from 2008 to 2015. The median follow-up time for all patients was 5.36 years, respectively. The cumulative incidence (CI) of neutrophil and platelet engraftment, as well as CMV reactivation, did not differ statistically between the two groups. The CI of the acute GvHD of grades II-IV and III-IV and extensive chronic GvHD were considerably lower in the ATG/PTCy (34.6%, 8.97%, and 13.63%) than in the ATG cohort (57.5%, 30%, and 38.23%) as validated by multivariable modeling. Additionally, compared to the ATG arm, the ATG/PTCy was a hazard factor associated with a higher risk of relapse (HR = 2.23, p = 0.039). The probability of 5-year overall survival, disease-free survival, and GvHD-free relapse-free survival in the ATG/PTCy group (53.34%, 49.77%, and 36.04%) was comparable with the ATG group (47.5%, 42.5%, and 22.5%), respectively. Our finding suggested that a modified ATG/PTCy combination resulted in a lower risk of acute and chronic GvHD and a higher risk of relapse than the standard ATG-based protocol but had no effect on long-term outcomes. However, certain adjustments in the immunosuppression protocol are warranted to improve the outcome., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Barkhordar, Kasaeian, Janbabai, Kamranzadeh Fumani, Tavakoli, Rashidi, Mousavi, Ghavamzadeh and Vaezi.)

Background: Breast cancer is the second leading cause of death due to cancer in women. Triple negative breast cancer (TNBC) is a subgroup with unique behavior. There is a controversy in organ involvement in metastasis. In this study, we planned to define the prognostic factors, survival, and recurrence incidence of patients., Materials and Method: Among the 583 patients with breast mass referred to hematology and oncology clinic in Shariati hospital, Tehran, Iran from March 2005 to March 2015, fifty four patients entered the survival analysis whom we followed for two years until March 2017. Overall survival (OS) and disease-free survival (DFS) and Cumulative recurrence incidences (RI) were estimated. Univariate and multivariate Cox proportional hazards regression was performed to assess risk factors in predicting OS and DFS., Results: Median follow up for the patients was 5.00 years. The five-year OS, DFS and RI were 86.13% (95% CI (71.42-93.59), 63.09% (95% CI (47.04-75.49) and 32.15% (95% CI (19.52-47.43) respectively. Among the factors studied OS, DFS and RI differed significantly only between patients with and without nodal involvement (P = 0.004, P = 0.003, and P = 0.02 respectively). On the other hand, based on the univariate modeling, patients with nodal involvement had a higher risk of breast cancer-specific death (HR: 17.99, P = 0.004). Furthermore, patients with nodal involvement had a higher risk of breast cancer-specific death or recurrence (HR = 5.64, P = 0.008). In Multivariate model, just the nodal involvement significantly changed the hazard for OS (HR = 23.91, P = 0.001). As the nodal involvement was the only significant risk factor at the 0.2 level of significance, we can consider the hazard ratio of lymph node positivity in DFS univariate models as adjusted hazard., Conclusion: The only factor with significant effect on OS, DFS and RI was nodal involvement in the pathology report., Competing Interests: The authors have declared that no competing interests exist.

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.

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.

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., Competing Interests: CONFLICT OF INTEREST The authors declare no conflict of interest related to this work.

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.

Background: The conventional chemotherapeutic regimens which applied for treatment of acute myeloid leukemia (AML) mostly target tumor bulk but not leukemic stem cells (LSCs). Aberrant expression or activation of mediators such as osteopontin (OPN) or PI3K/PTEN/Akt/mTOR pathway plays a key role in making prone to develop leukemia. Preventing or treating cancer by curcumin (CUR) has been suggested recently. CUR induces apoptosis and growth inhibition through various mechanisms in leukemic cells. In present study, we tried to measure the toxic response in vitro to CUR for evaluation ofchangesin cell viability, survival and molecular-mediated resistance in primary AML cells. Materials and Methods: Isolated primary CD34+/CD38- bone marrow derived AML cells were treated with CUR, Daunorubicin (DNR) and/or their combination by MTT assay, Annexin V/PI staining, and colony-formation. The mRNA expression of OPN/AKT/mTOR/PTEN/β-catenin genes was measured by Real-Time PCR. The siRNA against OPN was applied for CUR- treated cells. Results: Growth inhibition effect of DNR increased in combination with CUR on primary CD34+/CD38- AML cells. Suppression of OPN with siRNA increased the cytotoxic effects of CUR. Likewise, OPN gene expression increased in response to CUR treatment in AML cells. AKT, mTOR, β-catenin or PTEN gene expression increased by CUR, but OPN siRNA decreased the level of mRNA expression of mentioned molecular pathway. Conclusion : The chemo-resistance of AML cells against therapy might be relevant to increasing of OPN mRNA expression and activity of other mediators including AKT, mTOR, PTEN, and β-catenin. In this context, targeting of OPN might be more impact on CD34+ AML cells.