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Hematology-Oncology and Stem Cell Research - Volume:11 Issue: 1, Jan 2017

International Journal of Hematology-Oncology and Stem Cell Research
Volume:11 Issue: 1, Jan 2017

  • تاریخ انتشار: 1395/11/06
  • تعداد عناوین: 12
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  • Mahdi Jalili, Ali Salehzadeh, Yazdi, Saeed Mohammadi, Marjan Yaghmaie, Ardeshir Ghavamzadeh, Kamran Alimoghaddam Pages 1-12
    Background
    Acute promyelocytic leukemia (APL) is a unique subtype of acute leukemia. APL is a curable disease; however, drug resistance, early mortality, disease relapse and treatment-related complications remain challenges in APL patient management. One issue underlying these challenges is that the molecular mechanisms of the disease are not sufficiently understood.
    Materials And Methods
    In this study, we performed a meta-analysis of gene expression profiles derived from microarray experiments and explored the background of disease by functional and pathway analysis.
    Results
    Our analysis revealed a gene signature with 406 genes that are up or down-regulated in APL. The pathway analysis determined that MAPK pathway and its involved elements such as JUN gene and AP-1 play important roles in APL pathogenesis along with insulin-like growth factor–binding protein-7.
    Conclusions
    The results of this meta-analysis could be useful for developing more effective therapy strategies and new targets for diagnosis and drugs.
    Keywords: Acute promyelocytic leukemia, Gene expression profile, Meta, Analysis, Functional analysis
  • Seyed Asadollah Mousavi, Vahid Moazed, Niayesh Mohebbi, Molouk Hadjibabaie, Kamran Alimoghaddam, Babak Bahar, Mohammad Jahani, Ardeshir Ghavamzadeh Pages 13-18
    Background
    Hemorrhagic cystitis (HC) is one of the most challenging complications in hematopoietic stem cell transplantation (HSCT). Estrogen is one of the suggested treatments for controlling this problem.
    Subjects and
    Methods
    We performed a randomized case-control study to evaluate the efficacy of oral conjugated estrogen on HC management in 56 HSCT patients. Patients were randomly assigned to the drug group (received 6.25 mg conjugated estrogen oral tablets in a daily single dose during hematuria period) or control group.
    Result
    The median time to complete response was 36 and 24 days in the drug and control group, respectively. The median time of down stage was 24 days in the drug group and 12 days in control group. Adjusted for HC grades, the relative risk of complete response for patients in control group was 1.613 times more than that of patients in drug group; nevertheless, not significant (p=0.122).
    Conclusion
    Our study did not show any benefit in use of oral conjugated estrogen in the management of HC.
    Keywords: Conjugated estrogen, Late, onset hemorrhagic cystitis, Hematopoietic stem cell transplantation
  • Fatemeh Farhid, Fatemeh Nadali, Bahram Chahardouli, Saeed Mohammadi, Shahrbano Rostami, Kamran Alimoghaddam, Ardeshir Ghavamzadeh Pages 19-23
    Background
    To determine the frequency of the single nucleotide polymorphism M287T in exon 9 of the AS3MT gene in Iranian population and to assess the difference in allele frequencies with other ethnicities.
    Subjects and
    Methods
    Genotyping analysis was performed on 150 healthy subjects using the PCR-RFLP assay. We used chi-square analysis to check the deviation from Hardy–Weinberg equilibrium and compare of the observed genotype frequencies in various ethnic. The level of statistical significance was considered as p
    Results
    The homozygous CC, homozygous TT and heterozygous CT genotypes were observed in 2%, 80% and 18% of participated individuals. The SNP rs11191439 passed the Hardy-Weinberg equilibrium chi-squared test with p-value>0.05 and had a minor allele frequency (MAF)>5%.
    Conclusion
    Iranians are genetically very similar to Caucasian and African individuals and they are considerably different from other East Asians including Koreans, Chinese and Japanese individuals. Due to genetic polymorphisms can contribute to the variability in AS3MT activity; they may contribute to interindividual as well as intra-ethnic differences in response to the detoxification of arsenic.
    Keywords: AS3MT gene, Polymorphism, Arsenic
  • Seyed Asadollah Mousavi, Mina Javadimoghadam, Ardeshir Ghavamzadeh, Kamran Alimoghaddam, Azadeh Sayarifard, Seyed, Hamidollah Ghaffari, Bahram Chahardouli, Ali Basi Pages 24-29
    Background
    The study attempts to assess the relationship between chimerism analysis using polymerase chain reaction of short tandem repeat (STR) and the incidence of chronic graft versus host disease (GvHD) as well as survival.
    Methods
    The retrospective cohort included all patients who received allo-HSCT between 2005 to 2013. Data collected by day 흍 were reviewed in terms of the incidence of chronic GvHD and survival. Chimerism was evaluated for whole blood, T-cell and PMN cells on days 15, 30 and 60, respectively using polymerase chain reaction of short tandem repeat (STR).
    Results
    Forty (69%) patients developed chronic GvHD, 11 (19%) relapsed and 22 (39.7%) died during the study. There was a significant relationship between chronic GvHD and chimerism analysis including whole blood on day 60 (P=0.001), PMN on day 60 (p= 0.05) and T-cell on days 15 (p=0.028), 30(p=0.01) and 60 (p=0.004). Patients with chronic GvHD showed a long-term survival as compared with those without chronic GvHD (P=0.0013).
    Conclusion
    Conducting continuous analysis of chimerism provides an opportunity to initiate immediate measures to prevent complications.
    Keywords: Hematopoietic Stem Cell Transplantation, Chronic GvHD, chimerism, polymerase chain reaction
  • Franceli Carvalho, Joice Zuckermann, Alessandra Paz, Gustavo Fischer, Liane Esteves Daudt, Lisandra Della Costa Rigonil., Uacute, Cia Silla, Laura Fogliatto, Simone Martins De Castro, Diogo AndrÉ Pilger Pages 30-36
    Background
    Tyrosine kinase inhibitors (TKIs) were the first drugs to use an intracellular signaling molecule as a therapeutic target. Unresponsiveness to TKIs limits therapeutic options, making allogeneic hematopoietic stem cell transplantation (HSCT) the only option leading to molecular remission. The aim of this study is to characterize CML patients unresponsive to first- and/or second-generation TKI therapy who underwent HSCT and to describe the main factors associated with treatment failure.
    Subjects and
    Methods
    Twenty one CML patients who underwent allogeneic HSCT and had previously used first- and/or second-generation TKIs from January 2005 to May 2014.
    Results
    Of the 21 patients, 52.4% were male, with a median age of 49 years (23-65 years) and 85.7% had chronic phase CML at the time of diagnosis; 28.6% showed inadequate treatment adherence to TKI therapy. Thirteen patients were resistant and eight were intolerant to TKIs; additionally, nine did not have T315I mutation. Ten transplantations involved related donors, and more than a half of patients (11) died, three of which due to graft failure. Most patients who survived transplantation were in the chronic phase of disease at the time of HSCT.
    Conclusion
    The population was composed mainly of young age patients at diagnosis, male, white, and coming from areas in the state of Rio Grande do Sul other than Porto Alegre and metropolitan region. Low adherence to TKI therapy may be related to unresponsiveness to treatment, especially in patients with acquired resistance, or this low adherence, together with the presence of molecular changes, may have led to the need for HSCT.
    Keywords: Chronic myeloid leukemia, Tyrosine kinase inhibitors, Resistance, Intolerance
  • Mehrzad Mirzania, Seyed Reza Safaee, Farhad Shahi, Issa Jahanzad, Ghazal Zahedi, Reza Mehdizadeh Pages 37-42
    Background
    Triple-negative breast cancers (TNBC) have a more aggressive course and are associated with poorer prognosis in comparison with other subtypes of breast cancer. One of the most common subtypes of TNBC is basal-like. The aim of this study was to investigate clinicopathological characteristics and clinical course of TNBC in Iranian women and compare them with other studies.
    Subjects and
    Methods
    Between March 2009 and February 2011, patients with breast cancer in Cancer Institute of Iran were selected and then followed-up for 2 years. Paraffin-embedded tumor block of all TNBC patients were evaluated for CK5/6 and EGFR using IHC method.
    Results
    Among 267 breast cancer patients, 60 cases with TNBC were identified (22.5%), 31 patients (51.7%) had basal-like and 29 patients (48.3%) had non-basal-like tumors. The median age of participants with TNBC was 49.6 years. Among our patients, 70% had positive lymph nodes.93.4% of all patients at the time of diagnosis were stage II or III and tumor size was at least 3 centimeters. No grade 1 TNBC was found in this study. During the follow-up period, there were 26 recurrences and 7 deaths.
    Conclusion
    The percentage of basal-like subtype among Iranian women with TNBC was lower compared to other studies, while bone metastases, clinical stage, lymph node involvement and tumor size were higher. Clinicopathological findings in basal and non-basal-like subgroups were not different, but the probability of lymph node involvement was more common in patients who were EGFR positive.
    Keywords: Basal, like tumors, Triple, negative breast cancer, Iran
  • Mehrdad Payandeh, Masoud Sadeghi, Edris Sadeghi, Alireza Janbakhsh Pages 43-48
    Background
    In developed or developing countries, the most common cancer in women is breast cancer with a pick in 40–50 years in Asia. Herein, we compared the association between IHC with FISH in HER2-positive breast cancer patients and affection of trastuzumab on disease free survival and overall survival (OS).
    Subjects and
    Methods
    Immunohistochemical (IHC) analysis of hormone receptors and HER2 was performed in 133 patients with breast cancer between 2003 and 2014. Patients were selected for Herceptin adjuvant treatment, according to IHC 3 or FISH. The specimens for pathology reports were fixed at 10% neutral-buffered formalin (pH=7.4) for 24 hours, then sliced into 4 μm sections.
    Results
    The mean age of patients at diagnosis was 46.39 years (range, 24-78 years), 100% female. Concordance rates between IHC and FISH were 31.1% for IHC 2 and 84.1% for IHC 3 (p50 years. Of the 133 patients, 30 patients (22.6%) had metastasis and 72 (54.1%) had right involvement. Ninety three (69.9%) patients had lymph node invasion. 48 patients (36.1%) were treated with trastuzumab and 85 (63.9%) were treated without trsastuzumab. The 10-year survival rate was 70% and the mean survival was 49 months.
    Conclusions
    We recommend clinicians that FISH analysis is as a predictor in breast cancer patients with IHC score 2. In contrast, FISH analysis of IHC 3 samples was no useful. Trastuzumab therapy is effective and tolerated for breast cancer with IHC 3 and probably IHC 2ﱒሟ.
    Keywords: FISH, Hormone receptors, DFS, Trastuzumab
  • Nastaran Farzi, Zahra Abrehdari, Tafreshi, Omid Zarei, Leili Chamani, Tabriz Pages 49-53
    Background
    Legionella pneumophila (L. pneumophila) is a gram-negative bacterium which causes ýLegionnaires’ disease as well as Pontiac fever. The Legionella infections in patients suffering from ýneutropenia- as a common complication of cancer chemotherapy- can distribute rapidly. We ýaimed to detect of L. pneumophila in haematological malignancy suffering patients with ýneutropenic fever by targeting the (macrophage infectivity potentiator) mip gene.
    Subjects and
    Methods
    Serum and ýurine specimens were obtained from 80 patients and presence of mip gene of L. pneumophila in ýspecimens was investigated by PCR.
    Results
    The L. pneumophila infection was detected in 21 (26.2%) and 38 ýý(47.5%) of urine and serum specimens, respectively.
    Conclusion
    Our findings indicated that the relative high ýprevalence of L. pneumophila in the studied patients group which show the necessity of ýconsidering this microorganism in future studies from detection and treatment point of view in ýcancer patients.
    Keywords: Legionella pneumophila, Malignancy, Mip, Neutropenia
  • Nasrin Amirifard, Mehrdad Payandeh, Mehrnoush Aeinfar, Masoud Sadeghi, Edris Sadeghi, Somaye Ghafarpor Pages 54-47
    Background
    Emotional Intelligence (EQ) is positively associated with mental health and it can have a crucial role in mental disorder therapy by suitable coping mechanisms. The present study aimed to evaluate the relationship of EQ with anxiety and depression among the women with breast cancer.
    Subjects and
    Methods
    During 2013 and in a cross-sectional study, 98 breast cancer patients (14 to 21 years old) entered into the study. For data collection, the following instruments were the Bar-On EQ inventory, Beck Depression Inventory and Cattle Anxiety Inventory.
    Results
    There was an inverse relationship between anxiety with intrapersonal (p
    Conclusion
    The results of this present study confirmed the important role of EQ. Also, the results can be an inspiration for the future studies regarding the training of EQ skills in the treatment of mental disorder (anxiety and depression) among patients with breast cancer.
    Keywords: EQ, Anxiety, Depression, Breast cancer
  • Ipek Yonal, Hindilerden, Sevgi Kalayoglu, Besisik, Nuray Gurses, Koc, Fehmi Hindilerden, Deniz Sargin Pages 58-62
    Background
    For adult ALL patients, the indications and appropriate timing of allogeneic hematopoietic stem cell transplantation (AHSCT) continue to be debated. The primary aim of this single-institution study was to compare the results of our adult ALL patients that had been allografted with those reported in the current literature.
    Subjects and
    Methods
    This study included 53 consecutive adults with acute lymphoblastic leukemia (ALL) who underwent allogeneic hematopoietic stem cell transplantation (AHSCT) with myeloablative (92%) and reduced-intensity (8%) conditioning between 1993 and 2011.
    Results
    Mean patient age was 27 years (SD:8.62) and donor age was 33.7 years (SD:9.47). Fourteen patients were in first remission; 21 in ≥2nd remission, 15 in relapse and 3 had primary refractory leukemia. Thirty-four, 15 and 4 patients received busulfan plus cyclophosphamide, cyclophosphamide/total body irradiation and fludarabine-based regimens, respectively. For graft-versus-host disease (GVHD) prophylaxis, cyclosporine plus methotrexate were used. Forty-six donors were related and 7 were unrelated. Thirty patients received granulocyte-colony stimulating factor (G-CSF) mobilized peripheral blood and 23 received bone marrow as stem cell source. Twenty-six patients relapsed at a mean duration of 11.3 months (SD:19.1). Forty-four patients succumbed to their disease after a mean follow-up of 13.6 months (SD:19.5). The cause of mortality was relapse (n=24; 54.5%) and transplant-related etiologies (n=20; 45.5%). The estimated five year probabilities of overall survival (OS) and progression-free survival (PFS) were 37% and 12%, respectively.
    Conclusion
    By multivariate analyses, transplantation in first remission was the most important predictor of transplant success.
    Keywords: Acute lymphoblastic leukemia, Allogeneic hematopoietic stem cell transplantation, Overall survival, Progression, free survival
  • Roghayeh Hosseinikia, Mohammad Reza Nikbakht, Ali Asghar Moghaddam, Ahmad Tajehmiri, Mahboobe Hosseinikia, Farhad Oubari, Mahin Nikougoftar Zarif, Yahya Pasdar, Kamran Mansouri Pages 63-77
    Mesenchymal stem cells (MSCs), as major stem cells for cell therapy, have been studied from different aspects in preclinical and clinical settings for more than a decade. These cells modulate the immune system (humoral and cellular immune responses) in vitro by producing soluble factors (anti-inflammatory molecules) and/or making cell-cell contacts. Hence, they could be used in regenerative medicine, tissue engineering and immune therapy. MSCs-based therapy have been recently used for treatment of cancer regarding the migratory potential of these cells towards tumor cells which makes them considerable candidates, also for cell therapy in both allogeneic and autologous settings. So, this review attempts to focus on the factors secreted by MSCs such as cytokines, their functional role in mounting and controlling immune responses mediated by different immune cell subpopulations and their significance in regenerative medicine in clinical trials. Although, further studies remain to be done to increase our knowledge of regulating development mechanisms, homeostasis and tissue repair in order to provide new tools to implement the efficacy of cell therapy trials. Although MSCs have been proved safe and effective for cell therapy, there are still challenges to overcome before widely applying MSCs in clinic.
    Keywords: MSCs, Immunomodulation, Cell therapy, Regeneration medicine, Soluble factors
  • Saeed Mohammadi, Ashraf Malek Mohammadi, Mohsen Nikbakht, Amir Hossein Norooznezhad, Kamran Alimoghaddam, Ardeshir Ghavamzadeh Pages 78-88
    Peripheral blood stem cell transplantation (PBSCT) is an effective treatment for hematological malignancies. Mobilization of peripheral blood progenitor cells performs in different ways among transplantation centers. Forceful mobilization schedules are comprised of growth factor alone, chemotherapy along with growth factor and also, a newly combination of novel agent such as plerixafor with any approach. With the appearance of numerous modifications in stem cell mobilization field over the past decade and advent of novel stem cell mobilization techniques, it seems to be necessary to review recent publications about stem cell mobilization strategies to respond above cited issues. Relevant literature was identified by a PubMed search (1996–2016) of English-language literature using the terms mobilization, Allogeneic Stem Cells Transplantation, Autologous Stem Cells Transplantation and technical aspects of apheresis. Although many institutions have established their own procedures to improve stem cell mobilization success rates accompanying cost-effectiveness considerations, an optimal stem cell mobilization regimen and methods have not been well-defined, yet. Practical guidelines are required to address critical clinical issues including proper growth factor, the most Impressive chemotherapy and its dosage and appropriate time for leukapheresis initiation. Hence, based on literature, we prepared practical guidelines in this review.
    Keywords: Stem cell, Mobilization, Peripheral blood, Transplantation