bluuebunny/crossref_metadata_2025_split huggingface dataset:
Minoriting Cvtomegalovirus after Hematopoietic Stem Cell Transplantation for Seven Years-a Single Center Study
Authors: Wu Xiaojin , Depei Wu , Sun Aining , Tang Xiaowen , Fu Zhengzheng , MA Xiao 
Published: April 2020

Abstract
Objective: To investigate the incidence, risk factor and management of CMV reactivation in patients revived hematopoietic stem cell transplantation(HSCT).
Methods: 374 patients including 275 consecutive allogeneic and 99 autologous patients after bone marrow/stem cell transplantation from May 2001 to December 2007 were studied at our institution with nest-PCR and pp65 antigen assay. Anticoagulant blood samples were obtained from the recipients once weekly after days 14. After three months the CMV monitoring was performed every one month or every three months. If the patients catch CMV again after three year, the CMV monitoring was performed again.
Results:
The incidence of CMV positive in autologous patients was 3.03% and was 54.91% in allogeneic patients with a median onset of 48 days post transplants during 1 to 81 months. The difference between them is significant; The infection rate in the nonmyeloablative allogeneic peripheral stem cell transplantation (NST) group was 61.76%, in the group of HLA—identical sibling donor HSCT(sib-HSCT) was 47.10%, in haploidentical hematopoietic stem cell transplantation (Hi-HSCT) group was 75.00% and in the group of unrelated bone marrow transplantation (UR-BMT) was 57.45%. The infection rate of CMV in the Hi-HSCT group was higher than that in the group of sib-HSCT with significant difference (P&lt;0.05); The incidence rate of CMV infection in patients with regimen including ATG was higher than that without ATG ((65%&47.1%, P&lt;0.05); The incidence rate of CMV infection in patients with III–IV grade aGVHD and patients without III–IV aGVHD had not significant difference (P&gt;0.05).
There was not significant difference in the occurance of aGVHD between the patients with and without CMV infection (P&gt;0.05).5.87.8% patients are effective on antiviral therapy, incidence of CMV disease is very low, 0.65% patients catch CMV more than once.
Conclusion FCMV infection is common in our study, Minoriting CMV for long time is necessary, which benefit to antiviral therapy and judging of prognosis.
The Influence of Disease-Specific Prognostic Factors on the Outcome of Allogeneic Hematopoietic Stem Cell Transplantation in Myeloma
Authors: Singhal S. , Vickrey E. , Allen S. , Krishnamurthy J. , Duffey S. , Williams S. , Mehta J. 
Published: April 2020

Abstract
Although allogeneic HSCT is potentially curative in myeloma, series reporting encouraging results with submyeloablative regimens suffer from limited follow-up and incomplete information on prognostic factors known to be relevant in myeloma. The outcome of 24 myeloma patients (50–66 years, median 52) undergoing reduced-intensity allogeneic HSCT after 100 mg/m2 melphalan from related (n=21) or unrelated (n=3) donors. The 9 patients who had not relapsed after preceding autotransplantation received 50 mg/kg cyclophosphamide in addition. No patient underwent a planned sequential autograft-allograft procedure.
Complete prognostic factor information was available on each patient. High-risk disease (n=16) was defined by one or more of the following: del(13) on conventional karyotyping, t(4;14), del(17p), plasma cell labeling index &gt;1%, elevated LDH, plasmablastic morphology. The disease was refractory to therapy in 16 patients. Three patients (13%) had disease that was neither high-risk nor progressive, 10 had disease that was either high-risk or refractory, and 11 had refractory, high-risk disease.
Four patients died of toxicity (3 GVHD, 1 multiorgan failure) and 19 relapsed. 18 of 19 relapsing patients died of progressive disease and 1 is alive in CR after a second allograft. High-risk (RR 0.11, P=0.0007) disease and refractoriness to therapy (RR=0.10, P=0.0006) were associated with poorer event-free survival. High-risk (RR 0.16, P=0.002) disease and refractoriness to therapy (RR=0.23, P=0.007) were associated with poorer event-free survival.
The combination of the two factors resulted in the identification of 3 categories of patients with highly disparate outcomes as shown in Figure 2.
Figure 1 shows the effect of the biological nature of the disease on EFS and OS. Figure 1. shows the effect of the biological nature of the disease on EFS and OS. Figure Figure
Our data suggest that the outcome of allogeneic HSCT in myeloma is disappointing unless the disease is sensitive to therapy and biologically low-risk. However, such disease responds exceedingly well to autotransplantation–and is associated with prolonged survival that can rival that seen after allogeneic HSCT. Alternative strategies are needed to improve the outcome of patients with refractory or high-risk disease–and may include elective post-allograft maintenance therapy with novel agents such as thalidomide, lenalidomide or bortezomib.
Reduced-Intensity Unrelated Cord Blood Transplantation for Adult Patients with Severe Aplastic Anemia
Authors: Yamamoto Hisashi , Kato Daisuke , Uchida Naoyuki , Ishiwata Kazuya , Takagi Shinsuke , Tsuji Masanori , Araoka Hideki , Yoshimi Mayumi , Narita Madoka , Sagawa Kimiko , Matsuno Naofumi , Masuoka Kazuhiro , Wake Atsushi , Yoneyama Akiko , Makino Shigeyoshi , Taniguchi Shuichi 
Published: April 2020

Abstract
Although unrelated cord blood transplantation (UCBT) has become a viable therapeutic option widely applicable for adult patients with hematological diseases, UCBT for severe aplastic anemia (SAA) remains to be controversial due to higher incidence of graft failure (GF) relative to the other stem cell sources. To evaluate the feasibility of UCBT for SAA, we retrospectively analyzed results for 11 adult patients with SAA who received first UCBT after reduced-intensity conditioning regimen (RI-UCBT) in Toranomon Hospital. Median age was 49 years (range, 20–70). Nine of them were non-responders to intensive immunosuppressive therapy and were multiply transfused, and two patients were fulminant type with no neutrophils in peripheral blood at diagnosis. The conditioning regimen consisted of fludarabine 125mg/m2, melphalan 80mg/m2, and 4 Gy of total body irradiation. Graft-versus-host disease prophylaxis was composed of cyclosporine alone (n=2), tacrolimus alone (n=2), and tacrolimus plus mycophenolate mofetil (n=7). Median total nucleated cell number and median CD34+ cell number were 2.65 × 107/kg (range, 1.83–4.39) and 0.70 × 105/kg (range, 0.27–1.52), respectively. Serological HLA disparities were as follows; 6/6 (n=3), 5/6 (n=2), and 4/6 (n=6). Ten of the 11 patients achieved primary neutrophil and platelet engraftment. Median time to an absolute neutrophil count &gt; 0.5×109/liter and an unsupported platelet count &gt; 20×109/liter were 18 days (range, 12–28) and 42.5 days (range, 26–64) respectively. All patients who achieved engraftment resulted in complete hematological recovery with complete donor chimerism, except for one patient who developed late GF at three years after UCBT. All 2 who experienced GF (1: primary GF, 1: late GF) were rescued by second RI-UCBT. Two of the 11 patients died from IPS (n=2), and remaining 9 patients are alive, having survived for 18.7 months (range, 2–71 months). Six out of 7 patients who survived more than 6 months were free from immunosuppressant. The probabilities of overall survival and event-free survival at 2 years after UCBT were 77.8% and 68.2%, respectively. Our results here strongly indicated feasibility and effectiveness of RI-UCBT for adult SAA patients with high engraftment rate and low treatment-related mortality. RI-UCBT could be considered as a viable therapeutic option for those who lack suitable HLA-matched sibling donors and failed immunosuppressive therapy.
Detection of Pre-Transplant Clonal Cytogenetic Abnormalities in Stem Cells Used for Autologous Stem Cell Transplant in Relapsed Non-Hodgkin Lymphoma Is a Predictor of Relapse
Authors: Rojas Ana Maria , Pinter-Brown Lauren , De Vos Sven , Paquette Ronald , Schiller Gary J , Territo Mary Carol 
Published: April 2020

Abstract
Autologous stem cell transplant is used for chemotherapy sensitive relapsed Non-Hodgkin Lymphoma (NHL). Patients who receive an autologous stem cell transplant after high dose chemotherapy for relapsed NHL have significantly superior survival compared to those receiving conventional chemotherapy. Relapsed patients who achieve a second remission are treated with myeloablative chemotherapy followed by autologous stem cell transplant. These patients can achieve 5-year event free survival close to 50% and 5-year overall survival of greater than 50%. We performed a retrospective analysis of our center’s transplant data and reviewed pre-transplant cytogenetic analysis on the patient’s collected stem cells. 259 patients underwent autologous stem cell transplant from 1998 through 2007 for relapsed NHL. Cytogenetic evaluations of the patient’s pre-transplant stem cells had been done to look for evidence of MDS or characteristics of their lymphoma. Clonal cytogenetic abnormalities were found in 12 of the 259 patients. Two of these patients died within 45 days of transplant without evidence of relapse. One from infection and a second from non-treatment related causes. Nine of the remaining 11 (81%) patients with clonal cytogenetic abnormalities have relapsed and died. All patients relapsed with their original lymphoma. The cytogenetic abnormalities were varied. Out of the 9 relapses, 3 had cytogenetic abnormalities in the stem cells that are associated with lymphoma, 2 that are associated with AML, 1 that is associated with MDS, and 2 were abnormalities whose significance was unknown. In one patient cytogenetic changes of the original lymphoma were identified. The patients that had clonal cytogenetic abnormalities in their collected stem cells had an 81% relapse rate as opposed to 30% in the patients whose stem cells had a normal karyotype. Our findings show that cytogenetic changes in the collected stem cells are associated with a higher rate of lymphoma relapse.
Role of Brain-Type Natriuretic Peptide and Cardiac Troponins as Predictors of Outcome in Multiple Myeloma
Authors: Koca Ebru , Parikh Gaurav , Amjad Ali Imran , Mendoza Floralyn L , Hosing Chitra M , Popat Uday , Champlin Richard E , Giralt Sergio , Qazilbash Muzaffar H. 
Published: April 2020

Abstract
BACKGROUND: High circulating levels of cardiac troponins, T and I (cTnT and cTnI) and brain-type natriuretic peptide (BNP) are associated with shorter overall survival and increased transplant-related mortality (TRM) in patients with amyloidosis undergoing high-dose chemotherapy and autologous stem cell transplantation (auto SCT). Their role as prognostic markers in myeloma is not clearly defined. We evaluated the utility of BNP, cTnT and cTnI as prognostic markers in patients undergoing auto SCT for myeloma.
METHODS: We retrospectively analyzed patients who received high-dose chemotherapy followed by auto SCT at MD Anderson Cancer Center between January 1 and December 31, 2006. Pre auto SCT levels of BNP, cTnT and cTnI were available in all patients. The upper limit of BNP was 100 ng/L, cTnT 0.01 ng/ml and cTnI 0.03 ng/ml.
RESULTS: A total of 105 patients (68 male and 37 female) with a median age of 57 (31–73) received auto SCT during the study period. Seventy-seven patients received high-dose melphalan 200 mg/m2 as preparative regimen, while 28 patients received a combination of melphalan 140 mg/m2 + busulfan 130 mg/m2 × 4 days. Median follow up of surviving patients was 21 months (1–30). Twenty-four (23%) patients had a high BNP level (&gt;100 ng/L) prior to transplantation, 7 patients had a high cTnT level (&gt;0.01ng/ml) and 12 patients had a high cTnI level (&gt;0.03 ng/ml). In 101 evaluable patients, responses (complete 22 + partial 53) were seen in 75 (74%) patients. Overall survival (OS) and progression-free survival (PFS) at 24 months was 86 and 58%, respectively. There was no significant difference in 24-month OS in the high BNP group (p=0.7). Eight patients died of non-relapse causes, with only one death in patients with high BNP (p=0.67). Grade 3–4 cardiac adverse events were reported in 2 patients only, one of whom had elevated BNP (p=0.54). An increase in either BNP, cTnT or cTNI was seen in 30 patients. These patients did not have a significant increase in TRM (p=0.68) or cardiac toxicity, or a decrease in OS.
CONCLUSION: High pretransplant levels of BNP, cTnT or cTnI levels, either individually or together, did not adversely impact cardiac events, TRM or OS.
The Cation Transporter SLC22A16 Is Expressed in Pediatric Acute Lymphoblastic Leukemia
Authors: Moscow Jeffrey A. , Horton Terzah M. , Daily Abigail , Su Xiaoping 
Published: April 2020

Abstract
Hydrophilic drugs require transport proteins to traverse the cell membrane, and the selective expression of these membrane transporters can confer selective sensitivity to their toxic substrates. Therefore, identification of a transport gene with restricted expression on tumor cells represents an opportunity to target that transporter with a selective, toxic substrate. We previously have demonstrated that the organic cation transport gene SLC22A16 (OCT6) is highly expressed in the leukemia cell line HL-60, and its RNA levels were at least 2 orders of magnitude higher in 25 unique specimens of adult leukemic blasts than in liver, placenta and kidney, the tissues that usually have high expression of SLC22 transporters (Gong, S. et al. Experimental Hematology, 30, 1–8, 2002). To determine the relevance of SLC22A16 gene expression in pediatric acute lymphoblastic leukemia (ALL), we examined its expression using an Affymetrix U133B gene expression microarray in 132 primary pediatric ALL specimens. SLC22A16 was broadly and highly expressed in these pediatric ALL primary specimens. The gene was represented by 2 probesets, with average expression levels of 922 ± 344 in one probeset and 1715 ± 857 in the other. Analysis of subgroups revealed that overall expression was highest in hyperdiploid (&gt;50) ALL specimens (n=17), and lowest in T cell ALL (n=14). The gene with highest correlation with SLC22A16 on the U133B array was ERG (Pearson p=2.4 × 10−8; False Discovery Rate (FDR) =5.2 × 10−5), a member of the Ets family of transcription factors that are implicated in leukemogenesis. MLL gene expression correlated with SLC22A16 expression with a Pearson p=3.3 × 10−5 and FDR=0.005. Other genes of special interest in leukemia biology with significant expression correlation to SLC22A16 included LIMD1, a member of the ZYXIN family (Pearson p=2.3 × 10−6, FDR=0.001), PPAR-alpha (Pearson p=4.5 × 10−7, FDR=0.0004), and STS-1 (Pearson p=7 × 10−7, FDR=0.0005). To examine protein expression of SLC22A16 in pediatric ALL, a polyclonal antibody to SLC22A16, that recognizes a protein of expected size in HL-60 cells, demonstrated expression of this protein at a level comparable to HL-60 cells in 3 of 6 primary pediatric B-precursor ALL specimens. These results suggest that an SLC22A16 substrate plays a physiologic role in pediatric ALL, and that SLC22A16 is a new therapeutic target for pediatric ALL that could be exploited by SLC22A16-specific toxins and antibodies.
BAFF-R Receptor Functions in Transcription Regulation in Genes Critical to Survival and Proliferation in Normal and Neoplastic Human B Lymphocytes
Authors: Fu Lingchen , Lin-Lee Yen-Chiu , Pham Lan , Tamayo Archie , Ford Richard J. 
Published: April 2020

Abstract
B-lymphocyte stimulator (BLyS also called BAFF), is a potent cell survival factor expressed in many hematopoietic cells. However, many aspects of BLyS signaling pathway remain unclear. In order to investigate BLyS signaling pathway, we studied the function of BAFF-R (also called BR3), a major BLyS receptor, in normal and neoplastic B cell survival and proliferation. In our initial study, we found that BAFF-R was also present in nucleus, in addition to its presence in the plasma membrane of B cells. A candidate nuclear localization sequence was identified in the BAFF-R protein sequence. We also found BAFF-R mediated transcriptional activity, that could be increased through over expression of a NF-κB family member c-rel. Further study showed that BAFF-R co-localized with, c-rel in the nucleus and bound to the NF-κB binding site on the promoters of NF-κB target genes such as BLyS, CD154, Bcl-xL, Bfl-1/A1 and IL-8. The IκB kinase (IKK) protein complex is critical for regulating NF-κB pathway activation. The IKK complex includes three important subunits: the catalytic subunits IKKα and IKKβ (also known as IKK1 and IKK2) and the regulatory subunit IKKγ (also known as NEMO). In the cytoplasm, activation of the IKK complex induces processing of precursors p105 and p100 into p50 and p52 respectively, resulting in NF-κB subunit dimeric partners that migrate from the cytoplasm into the nucleus. In recent studies, IKKα has also been identified in the cell nucleus, functioning in histone H3 phosphorylation. Although IKKβ was also previously observed in the cell nucleus, its nuclear function has been obscure. Besides functioning as a transcriptional co-factor with c-rel, we also found BAFF-R interacted with IKKβ in the nucleus of normal and neoplastic (lymphoma) B cells, enhancing histone H3 phosphorylation through IKKβ by immuno precipitation experiments and in vitro kinase assays. Inhibition of BAFF-R entry into the nucleus by BAFF-R NLS mutant transfection, decreased the level of phosphorylated histone H3 compared to the controls in NHL-B cells. These findings not only demonstrate a novel nuclear function of IKKβ, but also determine a new mechanism of how BAFF-R promotes survival and proliferation of normal B cells and NHL-B cells. In addition to activating NF-κB pathways in the plasma membrane, BAFF-R also functions as a transcriptional regulator binding to NF-κB targeted gene promoters possibly through a chromatin remodeling mechanism(s).
Inverse Correlation of NM23 Expression with Lysophosphatidic Acid Receptor EDG2/lpa1 Expression of Human Leukemia Cells during Myeloid Differentiation Induced by All-Trans Retinoic Acid
Authors: Okabe-Kado Junko , Kasukabe Takashi , Honma Yoshio , Kaneko Yasuhiko 
Published: April 2020

Abstract
Overexpression of the nm23 gene is found in many hematological malignancies, and predicts poor treatment outcome. Because the amount of intracellular NM23-H1 protein is inversely correlated with differentiation and exogenous over expression of the nm23-H1 in myeloid leukemia cells reduced the sensitivity to induction of myeloid differentiation, nm23-overexpression is considered to function as a differentiation-suppressor. However, the molecular mechanism of this phenomenon is unknown. Recently, lysophosphatidic acid (LPA) receptor EDG2/lpa1 was identified as a gene down-regulated by nm23-H1 and associated with cell motility/metastasis suppressor functions in breast cancer cells. Although the clinical significance of nm23-H1 overexpression in leukemia is completely opposite to that in breast cancer, there might be a common molecular mechanism between the metastasis-suppressing activity and differentiation-inhibiting activity of nm23-H1 overexpression, because many functional characteristics of macrophages/neutrophils are similar to those of motile and metastatic tumor cells. Here, we examined the EDG2/lpa1 expression level and its association with NM23 expression level and myeloid differentiation of leukemia cells. EDG2 and NM23 proteins were expressed at different levels in all leukemia cells tested (HL-60, NB4, THP-1, U937, K562, HEL, BALM-1, BALM-3, MOLT4, Jurkat). During all-trans retinoic acid (ATRA)-induced myeloid differentiation of HL-60 cells, the NM23 expression decreased and EDG2 expression inversely increased. Similar effects of ATRA were observed in myeloid differentiation of NB4 and THP-1 cells. NM23 expression levels and EDG2 expression levels modulated by ATRA treatment were inversely correlated (Spearman’s correlation coefficient, rs = −0.7538, p = 0.0237). However, these correlations were not found in the erythroid differentiation of ATRA-treated HEL and K562 cells. Cell motility is required for myeloid differentiation; therefore, there might be a common mechanism, the inhibition of cell motility thorough EDG2 down-regulation by NM23-H1 overexpression, between differentiation-inhibiting activity in leukemia cells and motility-inhibiting activity in breast cancer cells. The discrepancy in the clinical significance of NM23-H1 overexpression between leukemia and breast cancer might be resolved.
Absence of FLT3 and JAK2 (V617F) Mutations in Langerhans Cell Histiocytosis
Authors: Abedalthagafi Malak , Guo Huimin , Hartmann Dan-Paul , Ozdemirli Metin 
Published: April 2020

Abstract
Langerhans cell histocytosis (LCH) is a neoplasm of histiocytic cells believed to be derived from cells of the dendritic system, but the disease pathogenesis is unknown. FMS-like tyrosine kinase 3 (FLT3) is a type III receptor tyrosine kinase that is expressed on the surface of hematopoietic stem cells and plays an important role in normal hematopoiesis. Recently, FLT3 has been shown to play a role in regulating dendritic cell development and elevated levels FLT3-ligand was found in the serum of LCH patients. Therefore we evaluated 14 cases of LCH for FLT3 mutations by PCR analysis of genomic DNA, obtained from formalin-fixed paraffin-embedded tissue samples, followed by PAGE for deletions or internal tandem duplications using a commercially available kit (InVivoScrib Technologies, San Diego, CA). There were 7 males and 7 females with a mean age of 25.1. The tissues involved included bones, lymph nodes, bone marrow, breast, lungs and various soft tissues. No mutations in FLT3 were identified in any of the 14 patient samples. In the same patient population we also looked at the JAK2 (V617F) mutation, which has been found in patients with myeloproliferative disorders other than chronic myeloid leukemia and which has not yet been evaluated in LCH by a single strand conformation polymorphism assay using a commercially available kit (Ipsogen, New Haven, CT). There was no JAK2 V617F mutation in any of the 14 cases. These results suggest that FLT3 and JAK2 V617F mutations do not play a role in the pathogenesis of LCH.
Quantitate Detect of the Methylation of Three Hematopathy Patients’ P16 Gene
Authors: Chen Bao-An , Shou Bei-ming , Zhou Dong-rui , Liu De-long , Ding Jia-hua , Gao Chong , Sun Yun-Yu , Wang Jun , Cheng Jian , Zhao Gang , Song Hui-hui , Bao Wen , Wang Jue-qiong , Yuan Peng , Pei Xiao-ping , Chen Ning-na , Ma Xu-dong , Lu Zu-hong 
Published: April 2020

Abstract
Objective: The changes of methylation of CpG Island are the frequent changes in epigenetic. Nowadays, there are many methods to detect the changes of methylation, but all these method are hard to quantitate precisely. In our experiment, we will establish a new precise method.
Methods: Use hydrosulfite to handle the DNA, and then do PCR. The cytosine will change to thymine, if it hasn’t been methylation. On the other side, the cytosine will maintain its state if it has been methylation. Design a pair of probe, which contain one methylation probe and one un methylation probe. This pair of probe will detect three consecutive sites of CpG island in P16. Our experiment will use gene chip. Mix the the DNA of methylation and unmethylation with different ratio, then build the standard curve. Contrast the patient sample with standard curve will get the quantitate result.
Results: We detected three patients, the methylation degree of the patients is 84.3%, 0%, 17.7%.
Conclusion: The method we used can detect methylation degree of three consecutive sites of P16 quantitate precisely. Solve the problem of quantitate precisely.