bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long Term Results of Allogeneic Stem Cell Transplant for CML in Pediatric Patients: A Study of 50 Cases Transplanted over 20 Years in a Single Institution.
Authors: Funke Vaneuza A.M. , Pettengil Claudia , Bonfim Carmem M.S. , Ruiz Jefferson , Bitencourt Marco A. , Setubal Daniela C. , Nunes Elenaide C. , Oliveira Michel M. , Azambuja Ana Paula , Lima Denise H. , Kojo Keiko T. , Datamanager Heliz Regina A. Neves , Neto Jose Zanis , Medeiros Carlos R. , Pasquini Ricardo 
Published: October 2019

Abstract
Introduction: Chronic myeloid leukemia (CML) accounts for 2–3% of the leukemias in childhood. The only potential curative treatment is allogeneic hematopoietic stem cell transplantation (HSCT), although promising results achieved with imatinib mesylate in adults substantiate its use as a therapeutic alternative for children. The aim of this study is to analyze the outcomes of HSCT in pediatric patients regarding overall survival (OS) and main causes of death.
Materials and methods: Retrospective analysis of children aged 1–17 years, diagnosed with CML who underwent HSCT in a single institution in Brazil between jan/1984 and aug/2005. Survival was estimated by Kaplan-Meier curves. Log Rank test was used for comparison of continuous variables.
Results: Fifty patients were assessed, 31 male and 19 female. Median age of 13,5 years (1–17). Forty one patients (82%) were in first chronic phase (CP1) and 9 in advanced phases. The interval between diagnosis and HSCT had a median time of 17,5 months (5–84). The source of stem cells was bone marrow in 44 patients (88%), umbilical cord blood in 5 (10%) and peripheral blood stem cell in 1 (2%). Thirty nine patients (78%) underwent related HSCT and 11 (22%) unrelated donor HSCT. Conditioning regimens: busulfan and cyclophosphamide in 35 patients (70%) and TBI containing regimens in 15 (30%). Complete engraftment occurred in 82% of the transplants. Acute (a) graft-versus-host-disease (GVHD) grades II–IV occurred in 44% of the patients, with 20% grade IV. Extensive chronic (c) GVHD occurred in 15/40 patients (38%). Fifteen patients (32%) relapsed after HSCT. Mortality in the study population was 48% and the main causes of death were: relapse in 6 patients (25%), a-GVHD in 6 (25%) and c-GVHD in 4 (17%). Estimated OS in 20 years was 50%, with a median survival of 1926 days. When analyzed separately, patients in CP1 who received related HSCT and immuneprophilaxis with three drugs (steroids, cyclosporine and methotrexate) had an estimated OS in 20 years of 70%.
Conclusions:
Long term follow up of these children with CML who underwent allogeneic HSCT demonstrate an OS of 50%, reaching 70% in low risk patients. Main causes of death were relapse, acute and chronic GVHD.
Autologous Non-Myeloablative Hematopoietic Stem Cell Transplantation for Refractory Systemic Vasculitis.
Authors: Statkute Laisvyde , Oyama Yu , Barr Walter G. , Satkus Jolita , Loh Yvonne , Verda Larissa , Burt Richard K. 
Published: October 2019

Abstract
Background
Current mortality rate in systemic vasculitis (SV) patients with the use of cytotoxic / immunosuppressive therapy is over 20 % at 5 years in some studies. For patients refractory to conventional therapy new strategies aimed at aggressive induction of remission and relapse prevention are being sought. We here report our single center experience in treating 4 patients with refractory SV employing non-myeloablative autologous hematopoietic stem cell transplantation (HSCT).
Patients and Methods
Four patients with refractory SV (2 - with neurovascular Behcet’s disease, 1 - with neurovascular Sjogren’s syndrome, and 1 - with Wegener’s granulomatosis) were involved in an IRB and FDA approved phase I clinical trial of high dose chemotherapy and autologous HSCT. Peripheral blood stem cells were mobilized with cyclophosphamide (Cy) 2g/m2 IV and granulocyte-colony stimulating factor 10 mcg/kg/day SQ and were CD34+ enriched. Conditioning regimen consisted of Cy 200 mg/kg and rabbit anti-thymocyte globulin 5.5 mg/kg IV. Disease activity and cumulative organ damage were assessed using Birmingham Vasculitis Activity Score (BVAS) and Vasculitis Damage Index (VDI), respectively. Primary and secondary endpoints were transplant-related toxicity, survival and change in BVAS and VDI after the transplant.
Results
All 4 patients tolerated HSCT well without transplant related mortality or any significant toxicity. At median follow up of 28 (range 22–35) months all patients are alive. Three patients (1 each with Behcet’s, Sjogren’s, and Wegener’s) entered a sustained remission at 6, 6 and 24 months after the transplant. Both, BVAS and VDI, markedly decreased within 6 months post-transplant. In a patient with WG C-ANCA levels became undetectable at 24 month evaluation corresponding to clinical and radiological improvement. All 3 patients who achieved remission discontinued immunosuppressive therapy at the time of transplant and have not required since. Two patients with pre-transplant steroid dependency discontinued prednisone at 6 and 14 months after HSCT. One patient with BD who is positive HLA-B51, now 22 months since HSCT, has never achieved remission and is still requiring immunosuppressive therapy.
Conclusion
We suggest autologous HSCT utilizing a non-myeloablative regimen is a safe and effective treatment for select patients with SV refractory to conventional immunosuppressive therapies. However, in patients with significant genetic predisposition, more aggressive approach such as allogeneic HSCT or cord blood transplantation might be considered.
Highly Efficient mRNA- and cDNA-Based Transient Gene Delivery into Human Progenitor Cells.
Authors: Greiner Jochen , Torzewski Jan , Ponsaerts Peter , Rojewski Markus T. , Kronawitter Desiree , Schrezenmeier Hubert , Hombach Vinzenz , Dohner Hartmut , Schmitt Michael , Wiesneth Markus , Zimmermann Oliver , Wiehe Juliane M. 
Published: October 2019

Abstract
The method of gene transfer into progenitor cells is critical as viral vector transduction involves the risk of tumor induction by non-specific genomic integration. Non-viral transfection systems often fail due to low transfection efficiency. However, gene transfer into human CD34+ hematopoietic progenitor (HPC) and mesenchymal stem cells (MSC) is an essential tool for in vitro- and in vivo-applications and therapeutic strategies such as tissue engineering and gene therapy. We recently reported an transient genetic labelling of human CD34+ HPC with deltaLNGFR-plasmid-DNA for in vivo application: Transient transfection was efficient for both, CD34+ HSC (41% ± 2%) and leukemia cell lines (55% ± 4.9%) using the method of nucleofection. Moreover, mature myeloid cells (CD66b+) derived from transfected human CD34+ HPC and leukemia cells maintained deltaLNGFR expression at a high percentage (70% ± 1.6% and 58% ± 2% respectively). In this work, we investigated labelling of CD34+ HPC with mRNA. Human CD34+ HPC and human MSC were transfected with in vitro-transcribed mRNA for deltaLNGFR, a marker gene approved for human in vivo-application, using nucleofection. EGFP was used as a control. 24h after nucleofection, FACS-analysis showed a higher transfection efficiency compared to plasmid transfected CD34+ HPC and MSC: A high transfection frequency was found for mRNA-transfected HPCs using deltaLNGFR (82.4±9.7%) and EGFP (88.7±2.6%). We found also a high transfection rate for MSC using the marker genes deltaLNGFR (92.4±3.6%) and EGFP (83.3±4.1%). Cell viability was not affected by mRNA-transfection. Moreover, differentiation assays of deltaLNGFR-selected MSC after transfection, showed that differentiation of MSC into mesenchymal cells like chondrocytes, adipocytes and osteoblasts was not affected by mRNA nucleofection. Taken together, mRNA based nucleofection is a powerful, highly efficient and non-toxic approach for transient labelling of human progenitor cells or, via transfection of selective proteins, for transient manipulation of stem cell function. It may thus be useful to transiently manipulate stem cell characteristics and combine principles of gene therapy and tissue engineering.
Therapeutic Efficacy of Engineered T Cells Targeting CD19 in a B-Cell Lymphoma Model.
Authors: Hawkins Robert E. , Gilham David E. , Thistlethwaite Fiona C. , Radford John A. , Cheadle Eleanor J. 
Published: October 2019

Abstract
The success of monoclonal antibodies in the treatment of certain cancers demonstrates that immune based therapies can work and are particularly effective in B cell malignancies. However, tumours can still avoid antibody mediate mechanisms of attack and there is currently no estalbished method of effectively recruiting T cells to harness their potential anti-tumour effects. We are exploring gene therapy approaches to endow T cells with antibody type specificity in order to more efficiently target and lyse tumours and thereby improve the overall immune therapy of cancer
T cells grafted with a CD19 specific receptor consisting of a CD19 scFv linked to human CD3zeta (CD19z) were tested for their potency against B cell lymphoma lines in vivo. T cells were engineered using retroviral vestors to possess a CD19 specific receptor which endows the T cells with specificity for B cell lymphoma. The vector incorporates a truncated hCD34 gene as a marker to facilitate assessment of transduced cells using as clinically applicable, non-immunogenic marker gene. Mice bearing B cell lymphoma were treated with a systemic infusion of targeted T cells with or without non-myeloablative chemotherapy. Human T cells targeting CD19 cured 40% of SCID/beige mice with 6 day established metastatic tumour but only in conjunction with a single dose of cyclophosphamide. Murine T cells expressing the CD19z receptor were also effective with cure of 24hr established s.c human CD19+ tumour in SCID/beige and immunocompetent mice. Pretreatment with cyclophosphamide did not affect T cell engraftment or efficacy in immuno-compromised animals but was necessary for T cell engraftment in immuno-competent animals.
These results which parallel the approach successfully used with tumour infiltrating lymhocytes in melanoma patients conclusively demonstrate that the combination of engineered T cells with “pre-conditioning” chemotherapy significantly impacts upon tumour growth in vivo and this evidence supports the development of phase I clinical trials targeting B cell lymphoma.
Significance of Laminar Air Flow Room for the Reverse Isolation in Neutropenic Cancer Patients.
Authors: Lee Ji Hye , Kim Hae Sook , Yoon Hwi-Joong , Lee Kun Soo 
Published: October 2019

Abstract
Infection is one of the most important causes of death in cancer patients. So many physicians make every effort to control the infection, especially in neutropenic cancer patients. The aim of this study is to find out the role of HEPA filter equipped laminar air flow room reverse isolation for the management of chemotherapy induced febrile neutropenic children with cancer. We evaluated febrile neutropenic patients following chemotherapy from January 2003 to April 2006 at the Department of Pediatrics, Kyungpook National University Hospital, Daegu, Korea. They were promptly managed by antibiotics and antifungal agents and if possible, they were isolated in the aseptic room. They were allocated to three groups of standard ward care, isolation after onset of fever and isolation before onset of fever. Profiles of infection, clinical courses and survival rate were compared among three groups. One hundred and nine episodes of febrile neutropenia from thirty eight cancer patients were observed. Twenty nine were boys and nine were girls with their median age were 5.5 years. The diagnoses included acute leukemia (36.8%), malignant lymphoma (15.8%), and other solid tumor (47.4%). Fifty five episodes were included to standard ward care, forty four episodes to isolation after onset of fever and thirteen episodes to isolation before onset of fever. We found out that one in thirteen episodes of isolation before onset of fever (8%) and twenty six in ninety six episodes in other groups (27%) were microbiologically or clinically defined infections. Fifty six episodes recovered and only one died of infectious cause both isolation after and before onset of fever group, especially all recovered in isolation before onset of fever group. Forty eight episodes recovered and four died in general ward care group, but there was no statistical difference among three groups (p=0.93). Age, sexual difference, underlying disease, absolute neutrophil count (ANC), duration of ANC recovery and incidence of disseminated intravascular coagulation were no difference among three groups. In early isolated group, duration of fever and antibiotics medication were significantly shorter (p=0.002, 0.009) and CRP level was lower than other two groups (p=0.04). Reverse isolation in laminar air flow room for neutropenic cancer children before onset of fever affect the durations of fever and antibiotics treatment with beneficial effect.
Assessment of Quality of Life, Psychological Distress, and Alexithymia in Patients with Cutaneous Lymphoma.
Authors: Sampogna Francesca , Frontani Marina , Baliva Giannandrea , Lombardo Giuseppe , Di Pietro D Stat Cristina , Alvetreti Gabriele , Tabolli Stefano , Abeni Damiano , Russo Giandomenico 
Published: October 2019

Abstract
Cutaneous lymphoma is a visible cutaneous malignancy, which especially in the more severe forms may have a profound effect on patients lives. The aim of this study was to evaluate quality of life (QoL), psychological distress, and alexithymia in patients with cutaneous lymphoma referring to a dermatological hospital, and to correlate these results with clinical parameters. QoL was evaluated with the Skindex-29, that measures QoL in skin conditions on three scale (symptoms, emotions, and functioning), and the EORTC QLQ-C30, that assesses the QoL of cancer patients. Presence of minor non-psychotic psychiatric disorders was assessed using the GHQ-12, defining as case patients scoring 4 or more; alexithymia was evaluated using the TAS-20 questionnaire. In our ongoing study, we analysed data from the first 66 patients. Of them, 67% were men, the mean age was 58 years (range: 26–85y), and there were 15 patients (23%) with cutaneous B-cell lymphoma (CTBL), and 51 with T-cell lymphoma (CTCL), 6 of them with Sézary Syndrome. In our population, 31.3% of patients were GHQ-cases, 18.6% had alexithymia, and another 22% possible alexithymia. Dermatology-specific QoL was particularly impaired in the symptoms and the emotions scales. QoL was always significantly more impaired in patients with CTCL than in those with CBCL. Also, the prevalence of GHQ-cases was higher (35% in CTCL vs 13% in CBCL), as well as the prevalence of people with alexithymia (48% vs 20%). Skindex-29 and TAS-20 scores significantly correlated with the T stage of lymphoma (i.e., the higher the stage, the lower the QoL and the higher the prevalence of alexithymia). The evaluation of quality of life and psychological problems in patients with cutaneous lymphomas may help clinicians to better manage the disease and its burden on patients life. Also, the relation between quality of life impairment and clinical variables may give important information on the course of the disease as well as the possible effect of treatment.
Epidemiology of Transfusion Related Acute Lung Injury in e-FIT, the French Hemovigilance Database: 1994 to 2006. A Study of the French Hemovigilance Network.
Authors: Renaudier Philippe , Vo Mai Mai Phuong , Ounnoughene Nadra , Willaert Beatrice , Caldani Cyril 
Published: October 2019

Abstract
Background: Transfusion Related Acute Lung Injury (TRALI) is a life-threatening complication of allogenic blood transfusion, manifested typically by a non-cardiogenic pulmonary edema. However, the magnitude of the risk of TRALI remains unknown at this time, all the more so as a variety of other clinically similar respiratory complications can be associated with transfusion. Hemovigilance had been implemented in France since 1994. All adverse effects (AE) regardless of their severity should be notified on a normalized form to AFSSaPS, the French health products safety agency, as required by the French law.
Objective : to describe TRALI observed in e-FIT, the French hemovigilance database.
Population and methods: AE possibly, probably or definitely associated with transfusion were considered for inclusion. As the item “ TRALI” was explicitly present since 09/01/2001, we screened the database from 07/01/1994 to 09/01/2001 with “ pulmonary edema AND fluid overload excluded” , or with free comments including the words “TRALI ” , “ anti-granulocyte antibodies ”, “ non-cardiogenic pulmonary edema ” , “ white lung syndrome ” . The subsequent AE were considered for inclusion only if TRALI was the final diagnostic.
Results: From 07/01/1994 to 06/01/2006, 82,436 AE were registered in e-FIT, corresponding to about 30,000,000 labile blood products (LBP) transfused. 117 AE fulfilled the above criteria (3.9/1,000,000 LBP transfused). There were 59 men and 58 women, age = 0 to 86 (median 58); 34 men and 21 women were 60 years old or more. 107 patients presented with pulmonary symptoms, 93 with dyspnea, 63 with chills and/or hyperthermia and 53 with a typical pulmonary edema. 13 TRALI were fatal, 85 were life-threatening and 19 were benign. 42 patients received only packed red cells, 4 only fresh frozen plasma and 40 only platelet concentrates ; among the 31 remainders, 14 received platelets concentrates associated with an other LBP.
Conclusion:
Although the initial French database was not adapted to detect TRALI cases until 2001, the dynamics of notification is of interest ; TRALI is more frequent in elderly patients, as noted in other reports ; Platelets concentrates remains the more frequently LBP involved, but packed red cells also contribute to nearly half of the TRALI reported ; Besides the classical life-threatening presentation, a benign form of TRALI seems to exist ; A national working party is implementing new ways to define and investigate TRALI, which will provide more accurate information on TRALI in France.
The Anti-Apoptotic Role of the Unfolded Protein Response in Bcr-Abl Positive Leukemia Cells.
Authors: Tanimura Atsuko , Yujiri Toshiaki , Tanaka Yoshinori , Tanizawa Yukio 
Published: October 2019

Abstract
Accumulation of unfolded or misfolded proteins within the endoplasmic reticulum triggers the unfolded protein response (UPR). Evidence from several studies suggests that the UPR is activated in various tumors and might play a crucial role in tumor growth. However, the role of the UPR in leukemia remains unclear. Therefore, to define the role of the UPR in leukemogenesis, we used p210 Bcr-Abl-expressing 32D myeloid cell lines (p210 32D). The mRNA expression of UPR-related genes, namely, a spliced form of X-box DNA-binding protein (XBP1) and glucose regulated protein 78 (GRP78), was increased in p210 32D. Luciferase assay indicated that p210 Bcr-Abl induced high levels of the transcriptional activity of the UPR element. Moreover, levels of the phosphorylated eIF2 alpha protein increased in p210 32D. Inhibition of the UPR using IRE1 and ATF6 dominant-negative mutants diminished the ability of Bcr-Abl to protect the cells from etoposide- and imatinib-induced apoptosis, but had no effect on the proliferation of p210 Bcr-Abl-transformed cells. We also evaluated the expression of UPR-related genes in primary leukemic cells from Ph chromosome-positive cells by real-time RT-PCR; it was found that these cells showed higher expression levels than the control cells. Taken together, these results for the first time suggested that UPR is a downstream target of the Bcr-Abl oncoprotein, and it plays the anti-apoptotic role of Bcr-Abl in Ph chromosome-positive leukemia cells.
Efficacy and Tolerability of Pregabalin in Decreasing Pain Associated with High Dose of Imatinib in Newly Diagnosed Philadelphia Chromosome-Positive Chronic Phase CML.
Authors: Iuliano Francesco , Maio Massimo DI , Infusino Stefania , Perricelli Alessia , Pomillo Angelo , Cilloni Daniela , Saglio Giuseppe 
Published: October 2019

Abstract
Background Recently published data suggest that high doses of imatinib mesylate (IHD) (800 mg/daily) may be more effective than standard dose (400 mg/daily) in newly diagnosed Philadelphia chromosome-positive chronic phase CML. Furthermore escalating the dose of imatinib to 800 mg per day can overcome some cases of resistance to imatinib but tolerability of high-dose imatinib continues to be an issue.
Aims To evaluate the efficacy and safety of pregabalin dosed twice daily (BID) for relief of musculoskletal and neuropathic pain associated with IHD.
Methods 13 patients in chronic phase (CP) were enrolled because complained of severe, persistent pain, requiring nonoppioid analgesics. Patients were asked to quantify their pain using a visual analogue scale (VAS) (numeric range 0–10). QoL assessment was based on Therapy Impact Questionnaire. At baseline, the median pain-rate was 5 (range 3–8). Pts received pregabalin in doses ranging from 75 to 300 mg twice daily for 12 weeks.
Results Despite a short study duration, a significant reduction was seen in weekly pain score (p < 0.0001), as well as VAS score (p < 0.0001) allowed pts to receive the scheduled dose of imatinib. Pregabalin was well tolerated, and the most common adverse event was only somnolence. The short study duration precluded the assessment of longer term safety issues such as weight gain.
Conclusions Pregabalin was safe and effective in decreasing pain associated with high dose of imatinib, and also improved mood, sleep disturbance, and quality of life.
Examination of Point Mutations within the ABL Kinase Domain of Bcr-Abl Fusion Gene in Chinese Patients with Chronic Myeloid Leukemia Who Develop Imatinib Resistance.
Authors: Yang Dongguang , Zhang Ri , Gang Honglin , Gu Jian , Cen Jian Nong 
Published: October 2019

Abstract
Objective: To investigate the point mutations within the ABL kinase domain (KD) of Bcr-Abl fusion gene in Chinese patients with chronic myeloid leukemia who develop IM resistance and investigate the mutation.
Method: We collect a total of 17 bone marrow samples obtained from 11 patients who showed hematology resistance(n=7) or cytogenetic refractoriness(n=4). A long semi-nest PCR method was used to amplify the ABL KD of the Bcr-Abl fusion gene. After two cycles of PCR reaction, we get a fragment including 863 bases, purified and sequenced it.
Result: The ABL point mutation was detected in 45.45% of patients. The mutation rate of hematology resistance is 57.14% and the mutation rate of cytogenetic refractoriness is 25%. In total, we find three point mutation in all of our patients tested, ie, G250E(2), E255K(1) and T315I(2). In patients who develop hematology resistance, the earliest time to detect mutation is 4 months later after the therapy of IM and the longest time to detect mutation is 9 months later after the therapy of IM. In patients who develop cytogenetic refractoriness, the time to detect mutation is 12 months later after the therapy of IM .For the patients whose samples are available, no single mutation happens before IM thearpy.
Conclusion: There is high frequency of point mutations clustered within the adenosine triphosphate-binding region of Bcr-Abl fusion gene in Chinese patients with chronic myeloid leukemia, and the mutation is related to IM therapy. It’s good for patients to switch to another therapeutic strategy when the mutations were detected earlier.
Figure Figure