Efficacy and safety of bupropion in cancer-related fatigue, a randomized double blind placebo controlled clinical trial.

BACKGROUND AND OBJECTIVES: Cancer-related fatigue (CRF) is one of the most prevalent complications experienced by cancer patients during and after the process of treatment. Despite conducting a lot of studies, there is no approved therapy to help manage CRF. This study aims to investigate the efficacy of bupropion on CRF. MATERIALS AND METHODS: In this double-blind randomized placebo-controlled clinical trial, a total of 30 eligible cancer patients suffering from fatigue were randomly divided into two groups (15 patients in each group). Bupropion was administered 75 mg/day for the first three days and 150 mg/day (divided in two doses) till the end of the study at week 6. Fatigue as the primary outcome was measured by BFI (Brief Fatigue Inventory) and FACIT-Fatigue (Functional Assessment of Chronic Illness Therapy) scales. Secondary outcomes included HADS (Hospital Anxiety and Depression Scale) and performance status (PS) measured by Karnofsky and ECOG (Eastern Cooperative Oncology Group) scales. Assessments were done at baseline, end of the second and sixth week. RESULTS: There was no significant difference between placebo and bupropion at baseline and the end of second week. Significant difference was seen between two groups at the end of week six (P = 0.006 based on BFI) in favor of bupropion. In-group assessment showed improvement in fatigue levels in both groups during study time (P = 0.000 based on BFI for both bupropion and placebo). Secondary outcomes (e.g., HADS and PS) were not different at baseline and the end of second week. However, at the end of week six, the difference was significant in favor of bupropion. CONCLUSION: A six-week trial of bupropion reduces the CRF and improves the PS of cancer patients. TRIAL REGISTRATION: Current Controlled Trials IRCT20090613002027N12, registration date: 2018-06-01.

Randomized double-blind clinical trial of combined treatment with megestrol acetate plus celecoxib versus megestrol acetate alone in cachexia-anorexia syndrome induced by GI cancers.

PURPOSE: Previous studies reported promising efficacy for celecoxib in the treatment of cancer cachexia. We designed this study to test the hypothesis that combination therapy with megestrol acetate (MA) plus celecoxib is superior to MA alone. METHODS: Ninety eligible gastrointestinal cancer patients randomly received either MA 320 mg/day plus placebo (arm1) or MA 320 mg/day plus celecoxib 200 mg/day (arm2). Patients were evaluated at baseline, then 1 and 2 months after starting interventions. The primary outcome was body weight. Secondary outcomes were quality of life, grip strength, appetite score, performance status, plasma albumin, CRP, IL-6, and Glasgow Prognostic Score. RESULTS: Patients were comparable at baseline. Sixty patients were assessable for the first month and 33 patients for the second month. After 2 months, patients in arm1 (MA + placebo) and arm2 (MA + celecoxib) experienced 4.0 ± 3.4 and 2.2 ± 3.6Kg of weight gain respectively (P = 0.163). Changes relative to baseline were statistically significant in both arms of the study (P = 0.001). Regarding secondary outcomes, comparisons between groups did not show any statistically significant difference, but within-group changes were significant in both arms of the study. CONCLUSION: Since both MA alone and MA plus celecoxib are associated with improvement of cachexia in GI cancer patients, this study failed to show that adding celecoxib (200 mg/day) to megestrol (320 mg/day) could enhance anti-cachexic effects of megestrol.

Investigation of Trace Elements in the Hair and Nail of Patients with Stomach Cancer.

Trace metals are beneficial nutrient materials that act as essential cofactors in physiological processes. Recent evidence suggests that increase or decrease in certain trace metals may be related with risk and development of chronic diseases such as cancer. This study analyzed some trace elements level in hair and nail of patients with stomach cancer, and compared with their level in healthy controls. Trace elements (Cu, Fe, K, Li, Mg, Mn, Na, P, Se, Sr and Zn) are estimated in hair and nail of the 73 cancer patients and 83 controls by atomic absorption spectrophotometric method. The levels of Cu, K, Li, P and Se in hair and nail samples, were significantly higher in cases than controls. Levels of Mg and Sr were significantly lower in cases than controls. Fe level in hair samples was significantly higher in cases than controls. The mean concentrations of Fe, Se and P significantly increased with increasing cancer stage in the hair of patients. The average concentration of k also significantly increased with increasing cancer stage in the nail of patients. The results of our study show that there is an association between the increase in Cu, K, Li, P, Se and Fe, and stomach cancer development. Our results reveal that the increase in the trace elements could be a potential diagnostic marker to predict cancer progression and its etiology.

Cardioprotective Effects of Carvedilol in Inhibiting Doxorubicin-induced Cardiotoxicity.

PURPOSE: Anthracyclines (ANTs) are a class of active antineoplastic agents with topoisomerase-interacting activity that are considered the most active agents for the treatment of breast cancer. We investigated the efficacy of carvedilol in the inhibition of ANT-induced cardiotoxicity. METHODS: In this randomized, single-blind, placebo-controlled study, 91 women with recently diagnosed breast cancer undergoing ANT therapy were randomly assigned to groups treated with either carvedilol (n = 46) or placebo (n = 45). Echocardiography was performed before and at 6 months after randomization, and absolute changes in the mean left ventricular ejection fraction, left ventricular end diastolic volume, and left ventricular end systolic volume were determined. Furthermore, the percentage change in the left atrial (LA) diameter and other variables of left ventricular (LV) diastolic function, such as transmitral Doppler parameters, including early (E wave) and late (A wave) diastolic velocities, E/A ratio and E wave deceleration time, pulmonary venous Doppler signals, including forward systolic (S wave) and diastolic (D wave) velocities into LA, late diastolic atrial reversal velocity, and early diastolic tissue Doppler mitral annular velocity (e') were measured. In addition, tissue Doppler mitral annular systolic (s') velocity, as a marker of early stage of LV systolic dysfunction, E/e' ratio, as a determinant of LV filling pressure, and troponin I level, as a marker of myocardial necrosis were measured. RESULTS: At the end of follow-up period, left ventricular ejection fraction did not change in the carvedilol group. However, this parameter was significantly reduced in the control group (P < 0.001). Echocardiography showed that both left ventricular end systolic volume and LA diameter were significantly increased compared with the baseline measures in the control group. In pulse Doppler studies, pulmonary venous peak atrial reversal flow velocity was significantly increased in the control group. Moreover, a significant decrease in the mitral annuli early diastolic (e') and peak systolic (s') velocities and a significant increase in the E (the peak early diastolic velocity)/e' ratio in the control group were also observed. However, none of these variables were adversely changed at the end of follow-up in the carvedilol group. Furthermore, the TnI level was significantly higher in the control group than in the carvedilol group (P = 0.036) at 30 days after the initiation of chemotherapy. CONCLUSIONS: Prophylactic use of carvedilol may inhibit the development of anthracycline-induced cardiotoxicity, even at low doses.

Efficacy of Sucralfate Mouth Wash in Prevention of 5-fluorouracil Induced Oral Mucositis: A Prospective, Randomized, Double-Blind, Controlled Trial.

Sucralfate has been used for the prevention and treatment of radiotherapy- and chemotherapy-induced stomatitis and mucositis in a number of studies, but the results are contradictory. To answer such discrepancies, the present study was designed to evaluate the efficacy of sucralfate mouthwash in prevention of 5-fluorouracil (5-FU)-induced oral mucositis in patients with gastrointestinal malignancies. Patients with gastrointestinal cancers receiving 5-FU-based chemotherapy regimens were included in this randomized, blinded, controlled trial and were randomly allocated to either sucralfate mouthwash (every 6 h) or placebo. The patients were visited at fifth and tenth day of trial; the presence and severity of oral mucositis and the intensity of pain were assessed. The patients receiving sucralfate experienced lower frequency and severity of mucositis (76% vs. 38.5%, P = 0.005 and 84 vs. 38.5%, P < 0.001, respectively) and less intense pain (2.5 ± 2.2 vs. 5.08 ± 3.82, P = 0.004 and 1.33 ± 0.86 vs. 4.12 ± 3.5, P = 0.001, respectively) compared with the placebo group both at day 5 and day 10. Within the sucralfate group, a decrease in frequency and severity of mucositis was observed throughout the trial period, while in the placebo group no such effect was observed. Sucralfate mouthwash reduced the frequency and severity of 5-FU-induced oral mucositis in patients with gastrointestinal malignancies compared with placebo, indicating its efficacy in the prevention of chemotherapy-induced mucositis.

Hematopoietic Stem Cell Transplantation in Sickle Cell Disease: A Multidimentional Review.

While exagamglogene autotemcel (Casgevy) and lovotibeglogene autotemcel (Lyfgenia) have been approved by the US Food and Drug Administration (FDA) as the first cell-based gene therapies for the treatment of patients 12 years of age and older with sickle cell disease (SCD), this treatment is not universally accessible. Allogeneic hematopoietic stem cell transplant (HSCT) has the potential to eradicate the symptoms of patients with SCD, but a significant obstacle in HSCT for SCD is the availability of suitable donors, particularly human leukocyte antigen (HLA)-matched related donors. Furthermore, individuals with SCD face an elevated risk of complications during stem cell transplantation due to SCD-related tissue damage, endothelial activation, and inflammation. Therefore, it is imperative to consider optimal conditioning regimens and investigate HSCT from alternative donors. This review encompasses information on the use of HSCT in patients with SCD, including the indications for HSCT, conditioning regimens, alternative donors, and posttransplant outcomes.

Graft failure after allogeneic hematopoietic stem cell transplantation in pediatric patients with acute leukemia: autologous reconstitution or second transplant?

BACKGROUND: Graft failure (GF) is a rare but serious complication after allogeneic hematopoietic stem cell transplantation (HSCT). Prevention of graft failure remains the most advisable approach as there is no clear recommendation for the best strategies for reversing this complication. Administration of growth factor, additional hematopoietic progenitor boost, or a salvage HSCT are current modalities recommended for the treatment of GF. Autologous recovery without evidence of disease relapse occurs rarely in patients with GF, and in the absence of autologous recovery, further salvage transplantation following a second conditioning regimen is a potential treatment option that offers the best chances of long-term disease-free survival. The preconditioning regimens of second HSCT have a significant impact on engraftment and outcome, however, currently there is no consensus on optimal conditioning regimen for second HSCT in patients who have developed GF. Furthermore, a second transplant from a different donor or the same donor is still a matter of debate. OBSERVATIONS: We present our experience in managing pediatric patients with acute leukemia who encountered graft failure following stem cell transplantation. CONCLUSIONS AND RELEVANCE: Although a second transplantation is almost the only salvage method, we illustrate that some pediatric patients with acute leukemia who experience graft failure after an allogeneic stem cell transplant using Myeloablative conditioning (MAC) regimen may achieve long-term disease-free survival through autologous hematopoiesis recovery.

Evaluation of Safety and Immunogenicity of a Recombinant Receptor-Binding Domain (RBD)-Tetanus Toxoid (TT) Conjugated SARS-CoV-2 Vaccine (PastoCovac) in Recipients of Autologous Hematopoietic Stem Cell Transplantation Compared to the Healthy Controls; A Prospective, Open-Label Clinical Trial.

Background: The urgent need for prompt SARS-CoV-2 immunization of hematopoietic stem cell transplant (HSCT) recipients in an endemic area raises many challenges regarding selecting a vaccine platform appropriate for HSCT recipients being economical for widespread use in developing countries. Methods: The trial is a prospective, single-group, open-label study to investigate the safety and serologic response of two doses of the recombinant receptor-binding domain (RBD)-Tetanus Toxoid (TT) conjugated SARS-CoV-2 vaccine (PastoCovac) early after autologous (auto) HSCT. For this reason, a total of 38 patients who completed the two-dose SARS-CoV-2 RBD-based vaccine between three to nine months after auto-HSCT and had an available anti-spike serologic test at three predefined time points of baseline and after the first and second doses and 50 healthy control individuals were included in the analysis. The primary outcome was defined as an increase in IgG Immune status ratio (ISR) to the cut-off value for the positive result (≥1.1) in the semiquantitative test. Findings: The median time between auto-HSCT and vaccination was 127 days. No participant reported any significant adverse effects (Grade 3). Pain at the injection site was the most common adverse event. The ISR increased significantly (p < 0.001) during the three-time point sampling for both patients and healthy control groups. In patients, the mean ISR increased from 1.39 (95% CI: 1.13−1.65) at baseline to 2.48 (1.93−3.03) and 3.73 (3.13−4.38) following the first and second dosages, respectively. In multivariate analysis, the higher count of lymphocytes [OR: 8.57 (95% CI: 1.51−48.75); p = 0.02] and history of obtaining COVID-19 infection before transplantation [OR: 6.24 (95% CI: 1.17−33.15); p = 0.03] remained the predictors of the stronger immune response following two doses of the RBD-TT conjugated vaccine. Moreover, we found that the immunogenicity of the COVID-19 vaccine shortly after transplantation could be influenced by pre-transplant COVID-19 vaccination. Interpretation: The RBD-TT conjugated SARS-CoV-2 vaccine was safe, highly immunogenic, and affordable early after autologous transplants. Funding: This work was mainly financed by the Hematology-Oncology-Stem Cell Transplantation Research Center (HORCSCT) of Tehran University and the Pasteur Institute of Iran.

Relative Expression of BATF and CD112 in PBMC of Patients with Chronic Lymphocytic Leukemia.

OBJECTIVE: BATF, as a transcription factor, and CD112, as a receptor for TIGIT, are involved in T-cell exhaustion. We investigated BATF and CD112 gene expression in the peripheral blood mononuclear cells from CLL patients and healthy subjects. METHODS: In a case-control study, 33 patients with CLL and 20 sex- and age-matched healthy individual were enrolled. Diagnosis and classification of patients was done according to immunophenotyping via flow cytometry and RAI staging system, respectively. Relative mRNA expression of BATF and CD112 was measured using qRT-PCR. RESULT: Our results showed that the expression of BATF and CD112 in CLL samples were significantly decreased in comparison those of the healthy controls (P = 0.0236 and P = 0.0002, respectively). CONCLUSION: These findings suggest the role of BATF and CD112 not only as a role in T cell exhaustion, but in effector differentiation program in CLL, which warrants further studies in future.

Incidence of hemorrhagic cystitis following unmanipulated peripheral blood stem cell transplantation in acute Leukemia: A retrospective single-center risk factor analysis.

BACKGROUND: Hemorrhagic cystitis (HC) is an important adverse event experienced after hematopoietic stem cell transplantation (HSCT). Severe HC could lead to significant morbidity, prolonged hospitalization with increased health-care costs, and may cause considerable mortality. OBJECTIVES: In order to investigate the influence of different contributing factors other than BK viruria on HC occurrence in a homogenous population, we retrospectively analyzed the potential risk factors. STUDY DESIGN: We conducted a retrospective study among 200 patients (median age 12.4 years, IQR: 7.9-16.1) with acute leukemia who received peripheral blood allogenic HSCT after radiation-free myeloablative conditioning regimen, in pediatric cell therapy department of Research Institute for Oncology, Hematology and Cell Therapy (RIOHCT), Tehran, Iran, between December 2014 and December 2021. Associations between risk factors and outcomes were examined by univariable and multivariable logistic regression models. RESULTS: A total of 46 patients (23%) had developed HC during the study period. The median onset of HC was 29 (IQR: 24-37) days post-transplant, and it persisted for a median of 33 (7-270) days. The incidence of HC in our patients was estimated to be 3 in 1000 cases (95% CI: 2-4). The results of multivariable logistic model shows that the chance of HC in T-cell acute lymphoblastic leukemia (ALL) compared to B-cell All is nearly five times more (OR = 4.88; 95%CI: (1.51-15.78), P = 0.008). The incidence of HC in patients who underwent HSCT from haploidentical donors was significantly higher than full matched donors (P < 0.001). Undergoing transplant from a matched unrelated and haploidentical donor both augment the chance of HC in about six times more than matched related donors (OR = 6.36; 95%CI: (1.58-25.49), P = 0.009 and OR = 5.7; 95%CI: (1.83-17.75), P = 0.003, respectively). In patients who developed HC compared to non-HC group, overall survival was much worse (P < 0.001). DISCUSSION: Most studies have failed to demonstrate any relationship between late-onset HC and the dose of cyclophosphamide. In our study, although the dose of cyclophosphamide was similar in HSCT from MRD and MUD, the hazard of HC incidence was significantly higher in the latter group. This could be accredited to ATG, as in patients in the MRD group who had not received any ATG, the incidence of HC was much lower than the patients who had underwent HSCT from MUD or haploidentical donor group. CONCLUSIONS: Patients with T-cell ALL and those who under haploidentical HSCT had the highest incidence of HC.

Comparable Outcomes of Pre- Versus Post-Tyrosine Kinase Inhibitor Era Treatment in Chronic Myeloid Leukemia: A Retrospective Cohort Study With Long-term Follow-up.

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.

Bilateral breast swelling in a 23-year-old woman with Burkitt lymphoma.

Primary breast lymphoma (PBL) of the breast is a rare type of localized non-Hodgkin lymphoma, which is usually of the B-cell. The majority of breast lymphoma present as a unilateral painless breast masses in an older woman, average age at diagnosis 55-60. A less common but distinctive presentation is a young woman of childbearing age who presents during or immediately after pregnancy. We present a 23-year-old postpartum woman with bilateral breast swelling. After surgical drainage and debridement and pathologic examination, the diagnosis of breast Burkitt lymphoma (BL) was confirmed. Chemotherapy was immediately started for her and the patient showed a good response with complete remission.

Late consequences of chemotherapy on left ventricular function in women with breast cancer.

Background: Cardiovascular disease is the main cause of death among breast cancer survivors. Several chemotherapy drugs may cause cardiovascular toxicity. Our study aimed to assess the late effects of chemotherapy on left ventricular (LV) systolic and diastolic function in a group of female breast cancer survivors. Methods: Our study was a case-control study consisted of 60 breast cancer survivors who had undergone chemotherapy for more than 5 years and a control group of 49 women without breast cancer. All patients underwent echocardiography and left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), pulse-Doppler early transmitral peak flow velocity (E wave), early diastolic (e'), and left atrial (LA) diameter were calculated. Results: The mean LVEF and GLS were reduced in chemotherapy group (51.63±7.93% vs. 55.37±3.50%, P=0.002 and -17.99±3.27% vs. -19.25±2.27%, P=0.025). Also, the chemotherapy group had a larger left ventricular end-systolic internal diameter than the control group (1.74±0.44cm/m2 vs. 1.58±0.22cm/m2, P= 0.011). Logistic regression analysis showed among the different cardiovascular risk factors, chemotherapy had an association with decreasing LVEF. Conclusion: Breast cancer survivors might have an excess risk of having subclinical LV dysfunction over time. These findings present the potential benefits of echocardiographic assessment in breast cancer survivors.

Association between hair dye use and cancer in women: a systematic review and meta-analysis of case-control studies.

Background: The use of hair dye for cosmetic purposes appears to be increasing worldwide. As 50-80% of women use hair dye throughout their lifetimes, the possible association between hair dye use and cancer is a public health concern. Method: This systematic review was performed by retrieving studies from PubMed, Scopus, WOS, and ProQuest databases. The inclusion criteria were case-control studies evaluating the association between hair dye use and cancer in women. Women with cancer who have used any hair dye were the focus of our study. Results: The present study combined 28 studies, to assess the association between hair dye use and cancer. The pooled odds ratio (OR) of hematopoietic system cancers among those who have generally ever used any type of hair dyes was 1.10 (95% CI:1.01-1.20) in 17 studies. In 11 studies investigating hair dye made before and after 1980 as a risk factor for cancer, the pooled OR for cancer was 1.31(95% CI:1.08-1.59). Likewise, in the 13 studies that evaluated the association of light and dark hair dye with cancer, the risk among those using dark hair dye increased by 9%, compared to non-users (OR=1.09; 95% CI:0.95-1.25). Conclusion: The present study suggests that, although the use of hair dye may increase the risk of cancer among users, a more detailed evaluation is required to assess the type of hair dye use in terms of guidelines and metrics.

Modified combination of anti-thymocyte globulin (ATG) and post-transplant cyclophosphamide (PTCy) as compared with standard ATG protocol in haploidentical peripheral blood stem cell transplantation for acute leukemia.

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.

Outcomes of haploidentical peripheral stem cell transplantation with combination of post-transplant cyclophosphamide (PTCy) and anti-thymocyte globulin (ATG) compared to unrelated donor transplantation in acute myeloid leukemia: A retrospective 10-year experience.

In the evolution of haploidentical hematopoietic stem cell transplantation (haplo-HSCT), In vivo T-cell modulation with concomitant use of anti-thymocyte globulin (ATG) and high-dose post-transplant cyclophosphamide (PTCy) provides a novel promising method on transplant outcomes; however, the long-term effects of this therapy are mostly unknown. We retrospectively compared the long-term outcomes of adult acute myeloid leukemia (AML) patients undergoing a haplo-HSCT (n = 92) with a new modified combination of ATG and PTCy in the context of peripheral blood stem cell (PBSC) and myeloablative conditioning (MAC) with an otherwise similar group of AML patients who received an unrelated donor (URD) HSCT (n = 57) with ATG protocol from February 2010 to December 2020 at our single-center (HORCSCT). Median follow-up was 3.73 and 4.28 years for haploidentical and URD-HSCT, respectively. In haplo-HSCT, the cumulative incidence of grades II-IV and III-IV acute graft versus host disease (aGvHD) and extensive chronic GvHD (cGvHD) was much lower than in URD (27% versus 56% for grades II-IV, 8.7% versus 24.5% for grades III-IV, and 15.4% versus 34.7% for extensive cGvHD, respectively). Five-year overall survival (OS) was 54.03% for haplo and 54.48% for URD (p = 0.927); GvHD-free relapse-free survival (GRFS) was 44.1% and 29.86% (p = 0.149); relapse incidence was 15.79% and 26.95% (p = 0.72); and non-relapse mortality (NRM) was 29.48% and 26.32% (p = 0.73), respectively. Using multivariable analyses, when compared to Haplo, URD was a significant predictor of relapse (HR=1.80, p = 0.039); however, no difference in OS, GRFS, and NRM was noted between haplo and URD. Therefore, given the favorable results with haplo-HSCT and considering donor availability promptly with low cost, it conservatively suggested that haplo-HSCT with the introduced protocol could be viewed as the first alternative for patients with AML in the absence of matched sibling donors.

Combined Blockade Of PD-1 and TIGIT is not Sufficient to Improve the Function Of CD8+ T-Cells in Chronic Lymphocytic Leukemia.

BACKGROUND AND OBJECTIVE: Blockade of immune checkpoint receptors in the treatment of cancers has been mentioned in several studies. Here, we investigated the efficacy of combined blockade of two inhibitory receptors, PD-1 and TIGIT, in restoring functional features of CD8+ T-cells in CLL. METHODS: CD8+ T-cells were separated from the peripheral blood of 11 CLL patients and targeted with malignant B-cells isolated from the same patients. Cells were then stimulated with anti-CD3/CD28 and PMA/ionomycin to assess their proliferative response and cytotoxic activity using MTT and CD107a degranulation assays, respectively. Cytokine production of isolated CD8+ T-cells was also determined using ELISA. RESULTS: There were no significant differences in proliferation and cytotoxic activity of CD8+ T-cells co-blocked with anti-PD-1/TIGIT compared to those single blocked with anti-PD-1, anti-TIGIT, or the control antibody. There was no significant difference in cytokine production of mentioned groups, either. CONCLUSIONS: Collectively, combined blockade of PD-1 and TIGIT failed to restore the proliferation and function of CD8+ T-cells isolated from CLL patients.

Toxoplasmosis among cancer patients undergoing chemotherapy: a population study based on the serological, molecular and epidemiological aspects.

BACKGROUND: Toxoplasmosis is highly prevalent in northern Iran and immunocompromised individuals are more susceptible to this infection. The present study aimed to determine the seroprevalence, parasitism and genetic diversity of Toxoplasma gondii among patients with cancer undergoing chemotherapy in northern Iran. METHODS: A total of 350 serum samples obtained from cancer patients were collected from laboratory centers in northern Iran. Immunodiagnosis and DNA detection were accomplished by ELISA and PCR. Thereafter, multiplex-nested PCR-restriction fragment length polymorphism was used for the genotyping of T. gondii. RESULTS: In general, out of 350 patients, 264 (75.4%) and 9 (2.57%) cases were positive for anti-T. gondii IgG and IgM, respectively. Moreover, 19 (5.43%) samples contained T. gondii DNA. From 19 positive samples, 10 high-quality samples with sharp and non-smear bands were selected to determine the genotypes of T. gondii. Accordingly, the samples were classified as genotype #1 (type II clonal; n=4, 40%), genotype #2 (type III clonal; n=3, 30%), genotype #10 (type I clonal; n=2, 20%) and genotype #27 (type I variant; n=1, 10%). CONCLUSIONS: As evidenced by the results, due to the high prevalence of T. gondii, cancer patients in northern Iran are at serious risk of severe toxoplasmosis and its complications. Therefore, oncologists need to regard this critical health problem as a matter requiring urgent attention.

Effect of Rosuvastatin in Preventing Chemotherapy-Induced Cardiotoxicity in Women With Breast Cancer: A Randomized, Single-Blind, Placebo-Controlled Trial.

OBJECTIVE: Chemotherapy-induced cardiotoxicity is a major and leading cause of death in breast cancer survivors. It can present decades after chemotherapy and can manifest in different ways; some chemotherapeutic agents have a powerful dose-dependent relationship with cardiotoxicity. The aim of this study was to investigate the effect of rosuvastatin on preventing chemotherapy-induced cardiotoxicity in patients with breast cancer. METHODS: Our study was a randomized, single-blind, placebo-controlled trial that involved 89 women with newly diagnosed breast cancer who were scheduled to receive chemotherapy. Patients were randomly assigned to receive rosuvastatin or a placebo in a 1:1 ratio for 6 months. Echocardiography, using 2-dimensional (2D) Doppler, tissue Doppler, and speckle-tracking methods, was used to determine the absolute changes in the left ventricular systolic ejection fraction (LVEF), left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left atrial (LA) diameter, transmitral Doppler early diastolic velocity (E wave), tissue Doppler early diastolic (e') and peak systolic (s') mitral annular velocities, E/e' ratio, and global longitudinal systolic strain. RESULTS: The LVEF was significantly reduced in the placebo group at the end of the study when compared with the baseline value. However, there was no significant difference in the LVEF in the intervention group (intergroup P = .012). Furthermore, compared with the intervention group at the end of the study, there was a significant increase in the 4- and 2-chamber LVESV, LA diameter, and E/e' ratio in the placebo group (intergroup P = .019, P = .024, P < .001, and P = .021, respectively) and a significant decrease in the e' and s' velocities in the placebo group (intergroup P < .001 and P < .006, respectively). CONCLUSIONS: The present study showed that the prophylactic use of rosuvastatin may prevent the development of chemotherapy-induced cardiotoxicity.