bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differentiation and Hematopoietic-Support of Clonal Cells in Myelodysplastic Syndromes.
Authors: Li Xiao , Wu Lingyun , Ying Shaoxu , Chang Chunkang , He Qi , Pu Quan 
Published: October 2019

Abstract
Studies were performed to obtain evidences on differentiating and hematopoieting potential of marrow clone-original cells in patients with myelodysplastic syndromes (MDS). Firstly, results of correlation analysis between bone marrow clonal cells and blast percentages for total 51 MDS showed that almost all cases had higher clonal (mean 48.2%) than blast proportion (mean 6.7%) (P<0.001). Wheras in 11 AML patients, mean clone/blasts desparity was nearly zero. Secondary, amount of clone-original individual cells were defined in mature hematopoietic cells, mean 45.9% in segmented granulocytes, 46.0% in orthochromatic normoblasts and 38.0% in mature megakaryocytes. In addition, FISH examination presented approximative proportions of clonal cells in peripheral blood for all 16 tested cases (mean 37.3% in blood vs 48.6% in marrow). Moreover, the neutrophils in MDSs peripheral blood oxidazed dihydrorhodamine123 (DHR) nearly as the same as neutrophils in normal donor’s circulations did, while obviously poor function-exerting were observed in neutrophils from AML blood. Of note, researches on clonality appeared an unexpectedly outcome that most of the typical morphological dysplastic cells possessed normal karyotypes. Our discoveries proposed that the biological features of MDS clones is obviously distinguished to AML clone, which perhaps provide some new consideration for MDS pathogenesis and treatment tactics.
G-CSF Priming before HA Chemotherapy Increased Apoptosis and Chemotaxis in Myelodysplastic Syndromes Cell Line MUTZ-1 by Activating the MEK/ERK Dependent Signal Pathway.
Authors: Cai Zhen , He Dong Hua , Hu Jie , Gao Liang 
Published: October 2019

Abstract
Myelodysplastic syndrome (MDS) represents a heterogenous group of clonal stem cell disorders with qualitative and quantitative abnormalities of blood cells and a high probability of evolving to acute leukemia. Intensive induction chemotherapy in order to reduce the malignant clone and reconstruct normal hematopoiesis is a classic therapy for MDS, especially high risk MDS. Homoharringtonine (HHT), one of the alkaloids from a Chinese natural plant, Cephalotaxus, incombination with cytarabine (A-rac) (HA chemotherapy) has been used successfully in the treatment of MDS. It has been recently reported that the effect of HA chemotherapy could be enhanced by granulocyte colony stimulating factor (G-CSF) (HAG chemotherapy). But the mechanism underlying the enhanced effectiveness in HAG remains unknown. We investigated the effect and mechanism of HAG chemotherapy on the apoptosis and chemotaxis in MDS cell line MUTZ-1. Cells were divided into HA group (HHT + Ara-C) and HAG group (treated with G-CSF before HA). Growth inhibition was measured by MTT method and 50% inhibiting concentration (IC50) was calculated. Cell cycle and apoptosis were measured by flow cytometry. Mitochondria membrane electric potential was determined by confocal microscopy. The mRNA expression of the chemokine receptor CXCR4 and the cysteinyl leukotriene receptor Cys-LT1 were detected by RT-PCR. The protein expression of Cys-LT1 and signaling molecular in MUTZ-1 cells was detected by western blot. The chemotaxsis of MUTZ-1 cells was detected by transwell migration assay. We found that the percentage of apoptotic MUTZ-1 cells increased and the mitochondria membrane electric potential in the cells decreased significantly more in HAG group than in HA group. The percentage in S phase of the cell cycle increased after exposure to G-CSF for 4 hours, and at its peak after 6 hours. Cys-LT1 mRNA and protein expression and chemotactic migration increased more in HAG group than in HA group, while no significant change was observed in CXCR4 expression. G-CSF activated both mitogen activated protein kinase kinase (MEK1/2) and extracellular signal-regulated kinase (ERK1/2). Chemotactic migration was partly blocked by the MEK1/2 inhibitor U0126. These results indicated that G-CSF priming before HA chemotherapy increased apoptosis and chemotaxis in MDS cell line MUTZ-1, and MEK/ERK signaling pathway is involved in G-CSF-induced chemotaxis.
Screening of JAK2 V617F Mutation in 84 Patients with Thrombocythemia and Erythrocytosis. Is Necesary for Diagnosis of a Chronic Myeloproliferative Disorders?.
Authors: Sobas Marta A. , Martinez M. , Perez-Encinas M. , Gonzalez T. , Quinteiro C. , Barros F. , Bendana A. , Ansoar E. , Rabunal M. , Gonzalez S. , Alonso N. , Diaz J. , Bello J. 
Published: October 2019

Abstract
BACKGROUND: The diagnosis of BCR-ABL negative chronic myeloproliferative disorders (CMPD) according to WHO/PVSG criteria may be difficult. The V617F mutation has been reported in 65–97% of patients with polycythemia vera (PV), 23–57% with essential thrombocythemia (ET) and 35–57% with idiopathic myelofibrosis (IM). The value of JAK2 mutation in unclassifiable CMPD, idiopathic erythrocytosis (IE) and idiopathic thrombocythosis (IT) is unknown.
AIMS: We wished to evaluate the utility of the V617F screening in patients with known or suspected myeloproliferative diseases.
METHODS: We applied the screening assay for JAK2V617F described by Baxter (Lancet2005;365) in 84 patients from our Clinical Department with a previous or suspected diagnosis of CMPD (retrospective and prospective cohort study). The variables were obtained from clinical records and the diagnosis were made according to WHO or PVSG criteria when was possible. There was: 14 cases of PV, 34 of ET, 14 of unclassifiable CMPD, 3 of IM, 13 of IT and 6 of secondary disorders.
RESULTS: The V617F screening was positive in 11/14 (79 %) of PV, 14/34 (41 %) of ET, 10/14 (71%) of unclassifiable CMPD, 3/3 IM, 1/13 (8%) of IT and 0/6 secondary disorders. At diagnosis, patients with mutation had significantly higher leucocyte and neutrophil counts and hemoglobin, hematocrit and LDH level. No significant interaction was noted between V617F mutation and the clinical data (gender, rates of transformation, splenomegaly, thrombosis and hemorrhage). The unclassifiable CMPD group was compared with the ET and PV groups. The unclassifiable CMPD group compared with the ET group showed a lower platelet count, a higher HCT level, and a higher frequency of JAK2 mutation.
CONCLUSIONS:
In case of suspected CMPD the JAK2 mutation screening seems to be useful . Some patients with IT had the mutation and these patients may represent an early phase of ET. According to the literature the V617F mutation was associated with some laboratory parameters but we don’t find significant clinical associations. The JAK2 mutation is frequent in the unclassifiable CMPD and these patients had clinical features similar to the PV group. The WHO or PVSG criteria should be changed to incorporate the JAK2 screening to reach a higher sensibility.
CD31 Expression and Gene Polymorphisms in Patients with B-Cell Chronic Lymphocytic Leukemia (B-CLL).
Authors: Mainou-Fowler Tryfonia , Norden Jean , Porteous Alistair , Davies Sian , Middleton Peter , Nicolle Annette , Proctor Stephen , Dickinson Anne , Summerfield Geoffrey 
Published: October 2019

Abstract
The CD31 antigen is expressed by a variety of cells including B lymphocytes from patients with B-CLL. The CD31 gene is polymorphic and CD31 gene polymorphisms involving single nucleotide substitutions (SNPs) such as C+373G (Leu125Val) and G+1688A (Ser563Asn) have been implicated in the pathogenesis of a number of diseases. CD31 is the physiological ligand for the CD38, a powerfull and independent prognostic marker for patients with B-CLL. A recent published study reports that the percentage of CD31 expression does not predict for poor prognosis in B-CLL (Ibrahim S, et al. Cancer.2003;97:1914–1918). A previous study showed that quantification of CD38 expression by flow cytometry significantly improves its prognostic value (Mainou-Fowler T, et al. Br J Haematol.2002;118:755–761). To re-assess the predictive power of CD31 in B-CLL, we quantified its expression and correlated its intensity with clinical outcome in a cohort of 120 patients (70M, 50F, age 47–91). The role in B-CLL of CD31 SNPs was also examined.
We report that Binet stage A patients had a significantly higher density of CD31 compared with stage B/C patients. A low CD31 predicted for poor disease outcome and identified those Binet stage A patients, and patients with low CD38, who followed a more aggressive clinical course. Disease-specific survival of patients with both low CD31 and high CD38 was significantly shorter than all other groups. Low CD31 expression significantly related with the homozygous GG and AA genotypes of the Leu125Val and Ser563Asn polymorphisms, respectively. The alleles found to be in strong disequilibrium but this was not 100%. There was no significant difference between observed and expected allele frequencies and no significant association was observed between patient genotype and clinical outcome.
Statistical comparisons are as follows: All patients:survival:high CD31 vs low CD31: P=0.0087,high CD31, low CD38 vs low CD31, low CD38: P=0.0425,low CD31, low CD38 vs low CD31, high CD38: P=0.0013,time to treatment: high CD31 vs low CD31: P=0.0064.
In stage A patients:P=0.0353,P=0.0721,P=0.0214,P=0.0716.
Distribution of CD31 expression within the genotypes: Leu/Leu vs Leu/Val, P=0.1442; Leu/Leu vs Val/Val, P=0.0466; Leu/Val vs Val/Val, P=0.0466; Asn/Asn vs Asn/Ser, P=0.1850; Asn/Asn vs Ser/Ser, P=0.0251; Asn/Ser vs Ser/Ser, P=0.0439.
In conclusion, low level of CD31 expression is an adverse prognostic indicator in B-CLL. The role of CD31 SNPs in B-CLL requires further investigation.
Bone Marrow Mesenchymal Stem Cells Exhibit a Transdifferentiation and Therapeutic Effects in a Murine Model of Orthotopic Hepatocellular Carcinoma.
Authors: Ren Jun , Jiang Hanfang , Di Lijun , Song Guohong 
Published: October 2019

Abstract
Background and Aim: Bone marrow stem cells can differentiate into mature hepatocytes in vitro and in vivo. Moreover, recent study shown bone marrow mesenchymal stem cells (MSCs) are the most potent component in hepatic differentiation, suggesting that the transplantation of MSCs is a promising treatment for liver disease. However, little information is available about the therapeutic potential of MSCs transplantation in cases of hepatic cell carcinoma (HCC). Here, we transplanted bone marrow-derived MSCs to testify their effects in a murine model of orthotopic HCC.
Methods:MSCs were obtained from tow male strains of β-galactosidase (β-gal) transgenic mouse(Rosa 26) and BALB/c mouse. MSCs were injected into tumor in BALB/c femal murine models of orthotopic HCC. Tumor growths were assessed by MRI on 7 days and survival rates were observed. When mouse was dying, the liver was removed from each treated mouse and evaluated by x-gal staining, and immunohistochemisty as well.
Results: MSCs transplantation increased the survival of hepatocellular carcinoma-bearing mice(25.5±4.5days verus 21.3±1.7days, p=0.025) and decreased tumor diameter slightly (7.7±2.9mm versus 9.4±2.8mm, p=0.284). MSCs transplanted directly into the tumor and/ or normal hepatic parenchyma in the same liver lobe localized mainly at the border between the tumor cells and normal liver parenchyma, induced a large area of coagulative necrosis in the tumor bed. Some engrafted MSCs were positive for albumin. There are in the carcinoma bearing BALB/c mice with MSCs implanted, whether MSCs from BALB/c mice or from Rosa 26 transgenic mice.
Conclusion: Our results suggest that the therapeutical effects of MSCs might be mediated not only by their differentiation into hepatocyte, but also mainly by they possess intrinsic antineoplastic properties.
Outcome Comparisons between Two Cord Blood Banks on Different Continents Using Identical Procedures.
Authors: Lin Allen , Yang Steven , Wang Brian , Tseng Peggy , Wu Tina , Chan Wendy , Gindy Laura , Brown Dick , Tonai Richard , Olmstead Jay , Sotomayor Gerry , Gjertson David , Petz Lawrence , Jaing Tang-Her , Tan Patrick , Chow Robert 
Published: October 2019

Abstract
Theoretically, cord blood (CB) banked using identical procedures by different banks should yield similar outcome if standard operating procedures (SOP) and quality programs are followed rigorously. To compare and validate the quality of the CB products, we studied whether all CB with available engraftment and/or survival transplant data from two banks, one in the USA and one in Taiwan, banked using virtually identical procedures, yielded similar transplantation outcome. Unadjusted engraftment of ANC500 were 91±3% for US (n=144) and 79±6% for Taiwan (n=49), while 1-year overall survival (OS) were 56±4% for US (n=153) vs. 68±7% for Taiwan (n=50). A number of obvious differences in transplants for the two banks were identified, for example, CB Transplants from the Taiwan CB bank (CBB) had more patients with benign diseases versus US (54% vs. 22%), which also influenced the proportion of pediatric patients and cell dose. Moreover, the Taiwan CBB had most units transplanted outside of the USA, whereas the USA CBB shipped most of its products within the USA. Another difference was that a higher proportion of CB were washed post-thaw for the USA CBB because USA transplant centers were more likely to practice post-thaw washing. We also analyzed the benign and malignant groups separately. For malignant patients, unadjusted engraftment of ANC500 were 92±3% for USA (n=114) and 73±10% for Taiwan (n=22), while 1-year OS were 50±5% for USA (n=120) vs. 40±11% for Taiwan (n=23). For benign indications, unadjusted engraftment of ANC500 were 89±6% for USA (n=30) and 85±7% for Taiwan (n=27), while 1-year OS were 66±9% for USA (n=33) vs. 92±5% for Taiwan (n=27). To adjust for some of these differences, a multivariate analysis was performed adjusting for malignancy, TNC dose, CD34+ dose, #HLA matches, recipient age, recipient sex, and washed status of CBU. Collectively, these data suggest that most of the apparent differences in outcome between the two banks may be explained by factors such as % malignant indications, and use of post-thaw wash. Overall, after adjustment for the differences between transplants using CB from the two banks, outcomes were quite similar, suggesting that if SOPs and quality programs were followed rigorously, results can be reproducible for CBB at disparate locations.
Association between Polyoma BK Virus Infection and Hemorraghic Cystitis in Allogenic Hematopoietic Stem Cell Transplantation Recipients.
Authors: Bouabdallah Kamal , Gomez Aurélie , Lafon Marie-Edith , Tabrizi Reza , Milpied Noel-Jean 
Published: October 2019

Abstract
BK Virus (BKV) infection is a common and benign infection occuring in childhood and resulting in viral latency. Because of immunosuppression, acute graft-versus-host disease (a-GVHD), and co infection with other viruses BKV infection often occurs after allogenic hematopoietic stem cell transplantation (HSCT) resulting, in some cases, in hemorraghic cystitis (HC).
We reviewed 258 patients who underwent allogenic HSCT in our institution between january 2001 and december 2005. One hundred and seven patients had a myeloablative conditioning regimen based on cyclophosphomide in combination with either total-body-irradiation (TBI/Cy) or Busulfan (Bus/Cy) with prophylaxis by MESNA. One hundred and fifty-one patients had a Fludarabine based reduced intensity conditioning regimen. BKV was detected by real-time PCR on urinary samples in most cases.
Macroscopic HC occured in 17 patients and BKV was detected in 15 patients out of 17. Among patients with HC and BKV viruria 11 (out of 107) received a conventional regimen compared with only 4 patients out of 151) positive for BKV in the non-myeloablative regimen group.
Although the number of patients is small, these data suggest strongly the role of the myeloablative regimen in the occurence of BKV induced HC. The high immunosuppression level induced by the conditioning regimen and the bladder injuries could explain this high frequency compared with the relative low frequency in patients with the less intensive regimen.
A prospective work is ongoing to better characterize the incidence, risk factors, clinical outcome and management of BKV induced HC after allogenic stem cell transplantation.
Preliminary Results from a Phase II Study of Lenalidomide Monotherapy in Relapsed/Refractory Aggressive Non-Hodgkin’s Lymphoma.
Authors: Wiernik Peter H. , Lossos Izidore , Tuscano Joseph , Justice Glen , Vose Julie M. , Pietronigro Dennis , Takeshita Kenichi , Ervin-Haynes Annette , Zeldis Jerome B. , Habermann Thomas M. 
Published: October 2019

Abstract
Background: Lenalidomide (Revlimid®), an immunomodulatory drug (IMiD®), was recently approved in the US for treatment of relapsed/refractory multiple myeloma and myelodysplastic syndromes associated with a deletion 5q[31] cytogenetic abnormality. Lenalidomide also has demonstrated activity in chronic lymphocytic leukemia and cutaneous T-cell lymphoma while thalidomide, a less potent IMiD®, has activity in non-Hodgkin’s lymphoma as both monotherapy and in combination with rituximab.
Aim: To assess the safety and activity of lenalidomide monotherapy in subjects with relapsed/refractory aggressive non-Hodgkin’s lymphoma (NHL).
Methods: Subjects with relapsed/refractory aggressive NHL following at least 1 prior treatment regimen with measurable disease are eligible. Subjects receive 25 mg lenalidomide orally once daily on Days 1–21 every 28 days and continue therapy for 52 weeks as tolerated or until disease progression. Response and progression are evaluated using the IWLRC methodology.
Results: As of July 25, 2006, 32 subjects of a planned 40 have enrolled and 31 have received drug. Twenty-two subjects are currently evaluable for tumor response. The median age of the 22 response-evaluable subjects is 65 (46–83) and 13 are female. Histology is diffuse large B-cell lymphoma [DLBCL] (n=12), follicular center lymphoma grade 3 [FL] (n=3), mantle cell lymphoma [MCL] (n=5) and transformed [TSF] (n=2). Median time from diagnosis to lenalidomide monotherapy is 2.3 (0.7–7) years and median number of prior treatment regimens per subject is 2 (1–6). Seven subjects (32%) exhibited an objective response (2 complete responses unconfirmed (CRu) and 5 partial responses (PR)), 6 had stable disease (SD) for a tumor control rate (TCR) of 59% and 9 progressive disease (PD). Responses were produced in each of the aggressive histologic subtypes studied: DLBCL (3/12), FL (1/3), MCL (2/5) and TSF (1/2). Five of 11 subjects (45%) with 1–2 prior treatment regimens had an objective response, as did 2 of 3 subjects (67%) who had received a prior stem cell transplant. Median time-to-response was 2 months. Grade 3 or 4 adverse events occurred in 18 of 31 (58%) subjects receiving drug. These were predominantly Grade 3 hematological events (neutropenia, thrombocytopenia) with only 4 subjects (13%) experiencing a Grade 4 adverse reaction.
Conclusion: Preliminary results indicate that lenalidomide monotherapy is active with manageable side effects in relapsed/refractory aggressive NHL.
Outcome of Invasive Aspergillosis (IA) in 30 Patients with Hematological Cancer (Hem-Ca): Immunity Is (Almost) Everything.
Authors: Miceli Marisa H. , Grazziutti Monica L. , Woods Gail L. , Diaz Jose A. , Krishna Somashekar G. , Kiwan Elias N. , Syed Nayyar , Barlogie Bart , Anaissie Elias J. 
Published: October 2019

Abstract
Background: Among IA pts receiving antifungal therapy, a strong relationship exists between outcome of IA and resolution of immunosuppression. Determining the respective contributions of immune reconstitution and antifungal therapy to response has not been attempted. Yet, treatment strategies for IA have focused almost exclusively on antifungal agents to the detriment of immune therapies. Galactomannan (GM) is an Aspergillus-specific polysaccharide released during aspergillosis and detected by the serum GM test. This FDA-approved test is an accepted diagnostic marker for aspergillosis and preliminary data suggest a correlation between GM index (GMI) and outcome.
Purpose: using GMI, to describe the contribution of immune recovery to outcome of IA in pts with hematological cancer (Hem-Ca).
Patients and Methods: From 11/03–2/06, pts at risk for IA underwent GMI screening during periods at risk. The clinical and radiological findings of pts with ≥ 2 positive (+) GMI (optical density ≥ 0.5) were reviewed.
Results: 30 pts had GMI (+) aspergillosis of the respiratory tract [myeloma 92%; median age: 59 years (27–75); 15 males]. Aspergillosis developed following stem cell transplant (SCT) [autologous (11), allogeneic (1)], or conventional chemotherapy (18). 25 pts were neutropenic (<1000/ml). The critical role of immune reconstitution was evident in 15/30 pts (50%). 7 of 25 (28%) neutropenic pts developed transient clinical and radiological worsening coinciding with immune recovery and rapid decline in GMI. All 7 responded without treatment modifications, suggesting an immune reconstitution inflammatory syndrome (IRIS). 6 pts had spontaneous clinical response with GMI normalization before commencing antifungal therapy (4 after neutrophil recovery, and 2 non-neutropenic pts after tapering immunosuppressants). 2 pts with IA refractory to prolonged and maximal antifungal therapy rapidly responded to interferon γ (1) and leukocyte transfusions (1) with GMI normalization within 48 h and subsequent clinical response.
Overall, all 3 pts who remained neutropenic died compared to 2 of 22 pts whose myelosuppression resolved and 1/5 non-neutropenic pts (p=0.005).
Conclusion: In addition to the strong association between neutrophil recovery and IA response, the critical role of immunity in IA is supported by common development of IRIS, spontaneous resolution of IA and response to immunomodulatory therapies. Daily GMI testing should be performed to accurately assess aspergillosis response. Declining GMI index obviates the need for invasive procedures and / or therapy modification. Immune therapies should be explored in IA.