Altered expression of MALAT1 lncRNA in chronic lymphocytic leukemia patients, correlation with cytogenetic findings

BACKGROUND: Recent studies have devoted much attention to non-protein-coding transcripts in relation to a wide range of malignancies. MALAT1, a long non-coding RNA, has been reported to be associated with cancer progression and prognosis. Thus, we here determined MALAT1 gene expression in chronic lymphocytic leukemia (CLL), a genetically heterogeneous disease, and explored its possible relationships with cytogenetic abnormalities. METHODS: MALAT1 expression level was evaluated using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) on blood mononuclear cells from 30 non-treated CLL patients and 30 matched healthy controls. Cytogenetic abnormalities were determined in patients by fluorescence in situ hybridization (FISH). RESULTS: MALAT1 expression level was up-regulated in the CLL group compared to healthy controls (P=0.008). Del13q14, followed by Del11q22, were the most prevalent cytogenetic abnormalities. We found no association between the FISH results and MALAT1 expression in patients. CONCLUSION: Altered expression of MALAT1 is associated with CLL development. Further investigations are required to assess the relationship between this long non-coding RNA and CLL patient survival and prognosis.

Sixteen years of experience with the treatment of advanced colorectal cancer in iran; A report from three institutions

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 clinico-pathological characteristics have yet the most important prognostic effect in advanced CRC

association between PARP1 and LIG3 expression levels and chromosomal translocations in acute myeloid leukemia patients

Objective: Chromosomal translocations are among the most common mutational events in cancer development, especially in hematologic malignancies. However, the precise molecular mechanism of these events is still not clear. It has been recently shown that alternative non-homologous end-joining [alt-NHEJ], a newly described pathway for double-stranded DNA break repair, mediates the formation of chromosomal translocations. Here, we examined the expression levels of the main components of alt-NHEJ [PARP1 and LIG3] in acute myeloid leukemia [AML] patients and assessed their potential correlation with the formation of chromosomal translocations

Materials and Methods: This experimental study used reverse transcription-quantitative polymerase chain reaction [RT- qPCR] to quantify the expression levels of PARP1 and LIG3 at the transcript level in AML patients [n=78] and healthy individuals [n=19]

Results: PARP1 was the only gene overexpressed in the AML group when compared with healthy individuals [P=0.0004], especially in the poor prognosis sub-group. Both genes were, however, found to be up-regulated in AML patients with chromosomal translocations [P=0.04 and 0.0004 respectively]. Moreover, patients with one isolated translocation showed an over-expression of only LIG3 [P=0.005], whereas those with two or more translocations over-expressed both LIG3 [P=0.002] and PARP1 [P=0.02]

Conclusion: The significant correlations observed between PARP1 and LIG3 expression and the rate of chromosomal translocations in AML patients provides a molecular context for further studies to investigate the causality of this association

Assessment of cyclosporine serum concentrations on the incidence of acute graft versus host disease post hematopoietic stem cell transplantation

Allogeneic hematopoietic stem cell transplantation [HSCT] is a curative treatment option for hematological disorders. Cyclosporine [CsA] is one of the major immunosuppressive agents for the prophylaxis against graft versus host disease [GvHD]. In this retrospective study, we evaluated the effects of CsA serum levels on the incidence of acute GvHD and transplant outcomes. 103 adult patients received Hematopoitic Stem Cell Transplantation[HSCT] in the Hematology-Oncology, Bone Marrow Transplantation center at Shariati Hospital in Tehran, Iran. All participants received prophylactic regimen of cyclosporine plus methotrexate. CsA dose titration was done according to patients' serum levels and drug toxicity. Serum levels tested on the twice weekly basis in first 4 weeks after transplantation.Acute GvHD [grades II-IV] developed in 44 patients [43%, 95%CI: 33%-52%]. The median time to ANC and PLT recovery was 13 days [range: 9-31 days] and 16 days [range: 0-38 days], respectively. Univariate analysis of risk factors related to aGvHD [grade II-IV] development showed a higher risk of incidence of aGvHD [grades II-IV] for patients having the lowest blood CSA concentration [<200ng/ml] in the third weeks after transplantation [36% vs. 12%, P=0.035]. The only risk factors related to incidence of aGvHD grades III-IV was also blood CsA concentration at 3rd week post transplant [15% vs. 3%, P=0.047]. The CsA concentration at 3rd week was not related to disease free survival and overall survival [P=0.913 vs. P=0.81] respectively. Higher CsA serum levels in the third week post HSCT significantly decreased incidence of acute GvHD.

Is supplementation efficacious in maintaining adequate plasma levels of vitamin A and E for thalassemic patients undergoing hematopoietic stem cell transplantation? a cross-sectional study

Thalassemia along with hematopoietic stem cell transplantation [HSCT] can lead to major oxidative stress. Vitamins A and E are antioxidants which protect membrane from lipid peroxidation. We sought to determine for the first time, whether vitamins A and E supplementation is efficacious in maintaining or increasing plasma level of these vitamins in thalassemic children undergoing HSCT. A cross-sectional study was performed on 50 children with beta-thalassemia major hospitalized for HSCT. Patients took a daily multivitamin. Plasma vitamins A and E levels were measured at four different times: on admission, HSCT day [day 0], day 7 and day 14 after HSCT. Plasma vitamin A and E were abnormal on admission in most patients [62.0% and 60.0% respectively]. Ratio of patient with normal to abnormal plasma level of the vitamins improved from baseline to a peak on day 7 then deteriorated afterward until day 14. There was an increasingly positive correlation between daily oral intake and plasma vitamin A at different times, but plasma vitamin E showed inverse correlation at first which tended towards no correlation subsequently. In multivariate analysis, supplementation significantly changed plasma level of vitamin A at different measurement time [P=0.001] within study subjects. But, plasma level of vitamin E showed no significant difference [P=0.2]. Our findings suggest that oral supplementation could have beneficial effects due to increasing plasma vitamin A level and preventing plasma vitamin E depletion

Evaluation of febrile neutropenia in patients undergoing hematopoietic stem cell transplantation

The aim of this study was to determine the incidence and causes of fever as a major problem contributing to transplantation related mortality among patients undergoing hematopoietic stem cell transplantation [HSCT] and evaluation of antibiotic use, according to reliable guidelines.We retrospectively reviewed hospital records of 195 adult patients who underwent HSCT between 2009-2011 at hematologyoncology and bone marrow transplantation research center. Baseline information and also data related to fever and neutropenia, patient's outcomes, duration of hospitalization and antibiotic use pattern were documented.A total of 195 patients were analyzed and a total of 268 febrile episodes in 180 patients were recorded [mean 1.5 episodes per patient]. About 222 episodes [82%] were associated with neutropenia which one-fourth of them were without any documented infection sources. Microbiologic documents showed that the relative frequencies of gram positive and gram negative bacteria were 62.5% and 37.5%, respectively. The hospital stay duration was directly related to the numbers of fever episodes [P<0.0001].The rate of febrile episodes in autologous stem cell transplantation was significantly higher compared to allogeneic type [P<0.05].It is necessary to determine not only the local profile of microbiologic pattern, but also antibiotic sensitivities in febrile neutropenic patients following hematopoietic stem cell transplantation, and reassess response to antibiotic treatment to establish any necessity for modifications to treatment guidelines in order to prevent any fatal complications from infection

Changes of bone density in pediatric patients with beta-thalassemia major after allogenic hematopoietic stem cell transplantation

Thalassemia major and its treatment by stem cell transplantation can have deleterious effects on bone integrity. This study assesses the adverse effects of transplantation on growing bones of pediatric thalassemic patients. Bone mineral density [BMD] of 20 patients from three thalassemia classes whose mean [SD] age was 7.4 [3.8] years were tested with a Norland XR-46 device at baseline [before transplantation], 6 and 12 months after transplantation. At 6 and 12 months after transplantation we observed no significant changes in mean BMD. There were no Z-scores less than -2 among patients. Class 3 thalassemia did not negatively impact BMD. Calcium [Ca], phosphorous [P] and ferritin levels were not significantly related to patients' BMD scores. Transfusion duration and chelation therapy showed positive significant relationships to BMD [g/ cm2], but no significant relation with the BMD Z-score. The deleterious relation between corticosteroid use and changes in BMD was not significant. In contrast, patients who developed acute graft versus host disease [aGVHD] after transplantation showed significant adverse effects on BMD of their femur [P = 0.020] and spine [P = 0.027]. Stem cell transplantation in pediatric thalassemic patients who do not develop aGVHD does not appear to have any significant positive or negative effects on BMD

Stem cell therapy in treatment of different diseases

Stem cells are undifferentiated cells with the ability of proliferation, regeneration, conversion to differentiated cells and producing various tissues. Stem cells are divided into two categories of embryonic and adult. In another categorization stem cells are divided to Totipotent, Multipotent and Unipotent cells. So far usage of stem cells in treatment of various blood diseases has been studied [such as lymphoblastic leukemia, myeloid leukemia, thalassemia, multiple myeloma and cycle cell anemia]. In this paper the goal is evaluation of cell therapy in treatment of Parkinson's disease, Amyotrophic lateral sclerosis, Alzheimer, Stroke, Spinal Cord Injury, Multiple Sclerosis, Radiation Induced Intestinal Injury, Inflammatory Bowel Disease, Liver Disease, Duchenne Muscular Dystrophy, Diabetes, Heart Disease, Bone Disease, Renal Disease, Chronic Wounds, Graft-Versus-Host Disease, Sepsis and Respiratory diseases. It should be mentioned that some disease that are the target of cell therapy are discussed in this article

Cytogenetic and FMS-like tyrosine kinase 3 mutation analyses in acute promyelocytic leukemia patients

The secondary genetic changes other than the promyelocytic leukemia-retinoic acid receptor [PML-RARA] fusion gene may contribute to the acute promyelocytic leukemogenesis. Chromosomal alterations and mutation of FLT3 [FMS-like tyrosine kinase 3] tyrosine kinase receptor are the frequent genetic alterations in acute myeloid leukemia. However, the prognostic significance of FLT3 mutations in acute promyelocytic leukemia [APL] is not firmly established. In this study, the chromosomal abnormalities were analyzed by bone marrow cytogenetic in 45 APL patients and FLT3 internal tandem duplications [ITD] screening by fragment length analysis and FLT3 D835 mutation by melting curve analysis were screened in 23 APL samples. Cytogenetic study showed 14.3% trisomy 8 and 17.1% chromosomal abnormalities other than t[15;17]. About 13% of the patients had FLT3 ITD, and 26% had D835 point mutation. FLT3 ITD mutation was associated with higher white blood cell count at presentation and poor prognosis. The PML-RARA translocation alone may not be sufficient to induce leukemia. Therefore, we assume that FLT3 mutations and the other genetic and chromosomal alterations may cooperate with PML-RARA in the development of APL disease

Surveillance for hepatocellular carcinoma after autologous stem cell transplantation in Cirrhosis

During the resent years there has been interest in using bone marrow stem cells to treat liver cirrhosis. However, there is a potential concern for malignant transformation after stem cell therapy. The aim of this study was to evaluate the development of hepatocellular carcinoma [HCC] after autologous bone marrow stem cell transplantation for liver cirrhosis. All the patients who underwent autologous stem cell transplantation for liver cirrhosis between 2005 and 2011 at our center were enrolled. Cellular infusion was made through peripheral vein, portal vein, or hepatic artery.The patients were invited to undergo screening for hepatocellular carcinoma. The screening was made with ultrasonography and alpha-feto protein [AFP] measurement. Thirty two patients [18 males] were included in the study. Mean age of patients was 45.7 years. Fifteen patients [47%] received mesenchymal stem cell [MSC], 9 [28%] received bone marrow mononuclear cells, 5 [16%] were given CD 133-positive bone marrow cells, and 3 [9%] patients received CD 34-positive bone marrow cells. Mean duration of follow up was 20.5months. Mean serum level of AFP was 2.8 ng/ml at baseline and 3.4ng/ml at the end of follow up [p= 0.3]. One patient was found to have hepatocellular carcinoma three months after infusion of bone marrow mononuclear cells. The incidence rate for HCC was 1.8 cases per 100 person-years in this study. Autologous bone marrow stem cell infusion does not appear to increase the risk of hepatocellular carcinoma. The incidence rate of HCC in this study is comparable or even less than the reported rates of HCC in cohort studies of cirrhotic patients

Hematopoietic stem cell transplantation in acute promyelocytic leukemia, experience in Iran

Acute promyelocytic leukemia is a rare indication for hematopoietic stem cell transplantation. Usually it is indicated as consolidation of salvage regimens following relpase. Here we report our experience with stem cell transplantation in acute promyelocytic leukemia patients. Between 1989 and 2011, we performed 40 hematopoietic stem cell transplantation in first complete remission or relapsed acute promyelocytic leukemia patients. Median age of patients was 23.5 years. Patients received 11 autologous and 29 allogeneic hematopoietic stem cell transplantation from their HLA fully-matched sibling donors. Different conditioning regimens were applied. A total of 24 patients received hematopoietic stem cell transplantation who were in first complete remission and the remainder with a second or more complete remission. Hematopoietic stem cell engraftment was observed in all cases. There were no deaths prior to 100 days after hematopoietic stem cell transplantation. Acute graft versus host disease was mild to moderate in the majority of patients, whereas it was grade III in 4 patients. Chronic graft versus host disease was extensive in 2 cases. With a 4-year median follow up, the relapse rate was 25%. A total of 26 patients are alive. Five year overall survival was 65.5% and 46.8% for allogeneic and autologous hematopoietic stem cell transplantation, respectively. Hematopoietic stem cell transplantation is an acceptable treatment for acute promyelocytic leukemia. Although there is a statistical difference for overall survival between allogeneic or autologous hematopoietic stem cell transplantation, the choice between autologous or allogeneic transplantation needs to have reliable methods for the detection of molecular remission before hematopoietic stem cell transplantation as well as close, reliable follow up of patients with clinical and molecular parameters

Hematopoietic stem cell transplantation in the eastern mediterranean region [EMRO] 2008-2009: report on behalf of the eastern mediterranean bone marrow transplantation [EMBMT] group

The Eastern Mediterranean Bone Marrow Transplantation [EMBMT] Group has accumulated over 25 years of data and experience in hematopoietic stem cell transplantation [HSCT], most particularly in he-moglobinopathies, severe aplastic anemia [SAA], and inherited metabolic and immune disorders, in addition to hematologic malignancies peculiar to the region and where recent updates in trends in activities are warranted. To study trends in HSCT activities in the World Health Organization-Eastern Mediterranean [EM] region surveyed by EMBMT between 2008 and 2009. STUDY DESIGN: Retrospective analysis of the survey data, mainly of the cumulative number of transplants, types of transplants [autologous vs. allogeneic], types of conditioning as myeloablative [MAC] vs. reduced intensity conditioning [RIC] and trends in leukemias, hemo-globinopathies, SAA, inherited bone marrow failure syndromes amongst others. Fourteen teams from ten Eastern Mediterranean Region Organization [EMRO] countries reported their data [100% return rate] to the EMBMT for the years 2008-2009 with a total of 2608 first HSCT [1286 in 2008; 1322 in 2009]. Allogeneic HSCT represented the majority [63%] in both years. The main indications for allogeneic HSCT were acute leukemias [732; 44%], bone marrow failure syndromes [331, 20%], hemoglobinopathies [255; 15%] and immune deficiencies [90; 5%]. There was a progressive increase in the proportions of chronic myeloid leukemia [CML] cases transplanted beyond the first chronic phase [3; 7% of all CML cases in 2008 vs 13; 29% in 2009]. The main indications for autologous transplants were plasma cell disorders [345; 36%] Hodgkin disease [256; 27%], non-Hodgkin lymphoma [207; 22%] and solid tumors [83; 9%]. RIC continued to show a progressive increase over the years [7% in 2007, 11% in 2008 and 13% in 2009], yet remained relatively low compared to contemporary practices in Europe published by EBMT. The vast majority [95%] of allo-HSCT sources were from sibling donors with a continued dominance of peripheral blood [PB] [1076; 63%], while cord blood transplant [CBT] increased to 83 [5% of allo-HSCT], matched unrelated donor [MUD] remained underutilized [1; 0%] and there were no haploidentical transplants reported. Large centers with >50 HSCT/year showed a plateau of the total number of allo-HSCT over the last 5 years that may be related to capacity issues and needs further study. There is an overall increased rate of HSCT in the EMRO region with a significant increase in utilization of CBT and allogeneic PB-HSCT as a valuable source. However, further research on outcome data and development of regional donor banks [CB and MUD] may help facilitate future planning to satisfy the regional needs and increase collaboration within the group and globally

Long-term results of non-fludarabine versus fludarabine-based stem cell transplantation without total body irradiation in Fanconi anemia patients

Hematopoietic cell transplantation [HCT] is the only therapeutic modality capable of correcting the hematologic manifestations of Fanconi anemia [FA]. The development of well-tolerated immunosuppressive conditioning regimens for FA patients undergoing HCT has proven to be a challenging task for hematologists. Retrospective, patients referred to the hematology, oncology and stem cell transplantation research center. We analyzed the outcome of 53 FA patients who had undergone HCT between 1992 and 2010. The median age at transplantation was 9 years. Patients received transplants from an HLA-identiccal sibling [n=39] or matched relative [n=9] and one-antigen locus mismatched other relative/sibling [n=5]. All of the patients underwent transplantation with fludarabine and non-fludarabine-based conditioning regimens. No radiation therapy was given. The median follow-up period for survivors was 13.5 months [range, 3 months-13.5 years]. The 3-year overall survival [OS] was 60.6%. The 3-year OS for patients who did or did not receive fludarabine-based preparative regimens for the allograft was 36.4%, and 70%, respectively. However, there were no statistically significant differences in OS rates between these two groups [P=.112]. Graft failure occurred in 4 patients [7.5%]. All of these 4 patients had received fludarabine-based conditioning regimens. The incidence of acute GVHD after fludarabine-based regimens was 45% versus 79% in non-fludarabine-based regimens [P=.03]. Despite the high incidence of acute GVHD [78.6%] in the non-fludarabine group, which ressulted in the death of some patients, the OS rate was significantly better than in fludarabine recipients. Therefore, in spite of the fact that recent studies advocate the fludarabine-based conditioning regimens, we propose to conduct a multicenter, prospective study to evaluate the outcomes of regimens employed in FA patients

Treatment of relapsed acute promyelocytic leukemia by arsenic trioxide in Iran

Although standard first line treatment of acute promyelocytic leukemia is All trans retinoic acid [ATRA] and chemotherapy, some patients relapse and need a second line of treatment. Relapsed cases of promyelocytic leukemia can be salvaged with arsenic trioxide. Between May 1999 and Jan. 2010, we treated 31 relapsed cases of promyelocytic leukemia with arsenic trioxide. These cases relapsed after previous treatment with ATRA and chemotherapy. We applied arsenic trioxide as 0.15 mg/kg iv infusion until complete remission. After achieving complete remission patients received 2-4 consolidation therapy in the same schedule as remission induction. The median age of patients was 27 years. Complete remission rate was 77.4%. We observed four mortalities during remission induction. With a median follow up of 32 months, ten more relapses occurred. Two year disease-free survival and overall survival for the entire cohort was 54.6% and 81.1%, respectively. Our result is the same as other studies. Thus, we suggest that arsenic trioxide can be used as salvage therapy in patients who relapsed. Despite a good complete remission rate, the relapse rate during the first two years of treatment is high and hematopoietic stem cell transplantation should be considered after achieving complete remission

KIR2DS3 is associated with protection against acute myeloid leukemia

Interaction between killer cell immunoglobulin-like receptors [KIR] and human leukocyte antigen [HLA] class I molecules is important for regulation of natural killer [NK] cell function. The aim of this study was to investigate the impact of compound KIR-HLA genotype on susceptibility to acute leukemia. Cohorts of Iranian patients with acute myeloid leukemia [AML; n=40] and acute lymphoid leukemia [ALL; n=38] were genotyped for seventeen KIR genes and their three major HLA class I ligand groups [C1, C2, Bw4] by a combined polymerase chain reaction-sequence-specific primers [PCR-SSP] assay. The results were compared with those of 200 healthy control individuals. We found a significantly decreased frequency of KIR2DS3 in AML patients compared to control group [12.5% vs. 38%, odds ratio=0.23, p=0.0018]. Also, the KIR3DS1 was less common in AML group than controls [27.5% vs. 44.5%, p=0.0465, not significant after correction]. Other analyses including KIR genotypes, distribution and balance of inhibitory and activating KIR+HLA combinations, and co-inheritance of activating KIR genes with inhibitory KIR+HLA pairs were not significantly different between leukemia patients and the control group. However, in AML patients a trend toward less activating and more inhibitory KIR-HLA state was observed. Interestingly, this situation was not found in ALL patients and inhibition enhancement through increase of HLA ligands and inhibitory combinations was the main feature in this group. Our findings may suggest a mechanism for escape of leukemic cells from NK cell immunity

Gibbon ape leukemia virus transduction of peripheral blood CD34+-derived dendritic cells

Dendritic cells [DCs] play a critical role in the immune response and are a candidate for immunotherapy in cancer. Since gibbon ape leukemia virus [GALV] transduction of CD34+ cells is reasonably efficacious, we assessed the efficacy of GALV transduction of CD34+ derived DCs as a possible approach to creating genetically modified DCs for immunotherapy. Peripheral blood CD34+ cells were transduced with retroviruses obtained from the PG13/LN C8 cell line, with the neomycin gene as a marker gene. After prestimulation of hematopoietic cells for 24 hours with 10 ng/mL interleukin [IL]-3, 10 ng/mL IL-6, 100 ng/mL stem cell factor, 100 ng/mL granulocyte-macrophage colony stimulating factor and 8 micro g/mL protamine sulfate, the cells were cultured in a transforming media prior to differentiating into DCs by GM-CSF, TNF-alpha and IL-4. Immunophenotyping analyses for confirmation of the generated DCs, colony formation assay and PCR were done for the expression of neomycin gene in the transduced cells. Titration of viral vectors indicated a transduction efficiency of 1 x10[5] CFU/mL Transduction efficiency for the CD34+ cells transformed to DCs was 45% and 38% before and after DC differentiation, respectively. Additionally, a mean [SEM] of 26.9% [11.4%] and 41.4% [11.8%] of the genetically modified DCs were positive forCD86+ HLA-DRand CD1alpha+CD14, respectively. This study showed that the majority of transduced CD34+ cells were successfully differentiated into cells identical to DCs according to morphology and immunophenotyping features, which could be a potential application in immunotherapy

Hematopoietic stem cell transplantation in Iran: 1991 to 2008

Since 1991, 2042 first hematopoietic stem cell transplants [HSCT] have been performed at the Hematology-Oncology and Stem Cell Transplantation Research Center at Tehran University of Medical Sciences. Acute myelogenous leukemia [548 patients], thalassemia major [335 patients] and acute lymphoblastic leukemia [275 patients] have been the most common transplanted disorders. There were 1418 cases that received allogeneic HSCT and 624 cases that have received autologous HSCT. The numbers of allogeneic and autologous HSCT have increased, but the allogeneic to autologous ratio has remained constant. The first peripheral blood hematopoietic stem cell transplantation was performed in 1996; since then, 1671 have been done. The donor types for 1418 allogeneic first HSCT were 1367 [96.4%] human leukocyte antigen [HLA] matched-identical siblings, 29 [2%] HLA-mismatched sibling/other relative, 13 [0.9%] syngeneic twins, 5 [0.4%] HLA-matched other relatives and 4 [0.3%] unrelated. The first cord blood hematopoietic stem cell transplantation was performed in 1998 and since then there have been 14 patients that have obtained cord blood transplantations. Recently, new methods have been used like donor lymphocyte infusion [DLI] and cellular therapy. There were 111 patients with cellular therapy for post-myocardial infarction, cirrhosis, thalassemia major, multiple sclerosis, head of femur necrosis and renal cell carcinoma

Does mesenchymal stem cell therapy help multiple sclerosis patients? report of a pilot study

Mesenchymal stem cells [MSCs] with their potential to differentiate into mesodermal and non-mesodermal lineages have several immunomodulatory characteristics. These properties make them promising tools in cell and gene therapy. To evaluate the potential therapeutic applications of autologous MSC in improving clinical manifestations of MS patients. Ten patients were included in this pilot study. All had progressive disease that had not responded to disease modifying agents including Mitoxantrone. Their Expanded Disability Status Scale [EDSS] score ranged from 3.5 to 6. Patients were injected intrathecally with culture expanded MSCs. They were followed with monthly neurological assessment and a MRI scan at the end of the first year. During 13 to 26 months of follow up [mean: 19 months], the EDSS of one patient improved from 5 to 2.5 score. Four patients showed no change in EDSS. Five patients' EDSS increased from 0.5 to 2.5. In the functional system assessment, six patients showed some degree of improvement in their sensory, pyramidal, and cerebellar functions. One showed no difference in clinical assessment and three deteriorated. The result of MRI assessment after 12 months was as following: seven patients with no difference, two showed an extra plaque, and one patient showed decrease in the number of plaques. This preliminary report emphasizes on the feasibility of autologous MSC for treatment of MS patients. However, in order to draw a definitive conclusion a larger sample size is required