bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rapid Infusion of Rituximab with or without Steroid Containing Chemotherapy. A Single Centre Experience.
Authors: Salar Antonio , Casao Dolors , Pedro Carmen , Abella Eugenia , Calafell Montserrat , Alverez Alberto , Besses Carlos 
Published: October 2019

Abstract
Introduction: Infusion-related toxicity is frequent after the administration of Rituximab despite the fact that strict guidelines have been recommended. Recently, a rapid rituximab infusion schedule in combination with a steroid containing chemotherapy regimen was well tolerated and safe.
Purpose: To investigate the feasibility of a rapid infusion of rituximab with or without steroid containing chemotherapy.
Methods: Inclusion criteria: lymphoproliferative disorder CD20+ and having been treated with a first infusion of rituximab according to the product monograph. Exclusion criteria: lymphocytosis > 5 x 109/L, toxicity grade 3/4 in the previous infusion of rituximab or dose > 375 mg/m2. Schedule: First infusion of rituximab according to the product monograph; Further infusions over a total time of 90 minutes (20% in the first 30 minutes and the remaining 80% over 60 minutes). Premedication: acetaminophen and diphenhidramine, plus methylprednisolone only in those patients receiving steroid containing chemotherapy.
Results: A total of 50 patients were treated for a total of 165 infusions. Patient characteristics: median age 62 yr (range 28–83), 49 % males, DLBCL 36%, follicular 47%, mantle 6%, MALT 7%, other 4%. Chemotherapy regimens: R-CHOP 28%, R-EPOCH 9%, R-ESHAP 4%, R-other chemotherapy 8%, rituximab monotherapy 10%, rituximab maintenance 41%. Number of rituximab administrations with and without steroids: 68 and 97 infusions, respectively. Median time from previous rituximab infusion was 29 days (range 7–272). Sixteen rapid infusions were administered with an interval greater than 90 days from the previous standard infusions. This rapid rituximab administration schedule was very well tolerated. No grade 3/4 adverse events were seen. Two patients referred symptoms during rituximab infusion (both grade 1): abdominal discomfort that disappeared spontaneously and sore throat that required to slow down the infusion speed. All these reactions occurred in patients who did not receive premedication with steroids.
Conclusions: Rituximab administration in a 90-minute infusion schedule is well tolerated and safe in this group of patients. This approach is beneficial, both in patients who are administered steroids and in patients who are not.
Proliferative Activity of Megakaryocytes in Myelo- and Lymphoproliferative Diseases.
Authors: Gawronski Krzysztof , Sulek Kazimierz , Sidor Malgorzata , Domagala Maria 
Published: October 2019

Abstract
Aim of the study: Evaluation of significance of investigation of Ki67 and AgNOR staining as an indices of proliferative activity of megakaryocytes.
Material and methods: Bone marrow smears from 151 patients suffering from hematological malignancies: polycythemia vera (PV) − 14 cases, myelofibrosis (MF) − 14, essential thrombocythemia (ET) − 15, chronic myeloid leukemia (CML) − 11, myelodysplastic syndromes (MDS) − 18; acute myeloid leukemia (AML) − 30, acute lymphoblastic leukemia (ALL) − 10, low grade non-Hodgkin’s lymphomas (NHL) with bone marrow infiltration − 20, multiple myeloma (MM) − 19. Cytological slides were stored in the room temperature more than 24 hours and then stained using immunocytochemical method for Ki67 and cytochemical method for AgNOR. Slides were analyzed using illuminating microscope with digital image analysis (software LUCIA). Mean particles area, mean nuclear area and maturity of nucleus in AgNOR staining as well as intensity of Ki67 expression were evaluated, according to arbitrary scale (strong, medium, light, no reaction).
Results: Look at the table 1 and table 2.
Conclusions:There is a good correlation between expression of Ki-67 and AgNOR’s in megakaryocytes as well as between nuclear maturity and indices of Ki-67 and AgNOR in myeloproliferative disorders. Differences in AgNOR’s and Ki 67 staining area between myeloproliferative diseases and another hematological malignancies are also significant.
Table 1: Values of indices of the Ki67 and AgNOR in megakaryocytes Diseases Mean nucleus surface μm2 Mean AgNOR particle area in nucleus of megakaryocytes μm2 Mean Ki67 particle area in nucleus of megakaryocytes μm2 Intensity of Ki67 expression in megakaryocytes Grade of megakaryocytes maturity PV 667,29 0,68 0,19 Medium III and IV ET 812,32 0,82 0,29 Strong / Medium III and IV MF 767,92 0,55 0,26 Strong / Medium III / IV CML 734,30 0,57 0,15 Medium / Light III / IV MDS 645,67 0,06 0,03 Light III / IV AML 679,04 0,04 No reaction No reaction IV ALL 712,23 0,03 No reaction No reaction IV NHL 798,56 0,04 No reaction No reaction IV MM 629,49 0,04 No reaction No reaction IV
Table 2: Intensity of Ki67 expression in megakaryocytes in hematological disorders Diseases Strong – % of cells Medium – % of cells Light – % of cells No reaction – % of cells PV 36 43 14 7 ET 56 33 11 0 MF 51 32 16 1 CML 16 43 34 7 MDS 9 12 68 11 AML 0 0 0 0 ALL 0 0 0 0 NHL 0 0 0 0 MM 0 0 0 0
Population-Based Risk Assessment for Multiple Myeloma: A Novel Approach for Identifying Potential Environmental Associations.
Authors: Ojha Rohit P. , Phillips Martha M. , Thertulien Raymond 
Published: October 2019

Abstract
Given the continued uncertainty of multiple myeloma (MM) etiology, environmental epidemiologic investigations remain an important approach for generating hypotheses regarding potentially significant exposures. We assessed MM incidence in Arkansas using a novel population-based approach that combines county agricultural and industrial characteristics with environmental hazard mapping techniques to determine case distribution throughout the state and to identify significant trends associated with case distribution. Our investigation revealed a significant association between manufacturing-dependent counties and MM incidence (OR = 1.26, p = 0.004), a significant inverse association between non-specialized counties and MM incidence (OR = 0.62, p < 0.00001), and no significant association between agriculture-dependent counties and MM incidence (OR=0.92, p=0.636). Analyses of sixteen selected industries and their associations with MM incidence revealed primarily wood-related industries (paper mills, sawmills, wood preservation, and softwood, veneer and plywood manufacturing) exhibited significant associations with MM incidence (OR= 1.79 – 2.02, p< 0.05). Trend analyses demonstrated increasing MM incidence with increasing proportion of the population employed in the aforementioned wood-related industries. This is the first such statewide assessment of associations between general environmental exposure and MM incidence within counties. The methods developed in this study can be applied to data from other states or regions to produce a larger body of information from several geographic areas regarding MM incidence or other disorders with suspected environmental associations. Subsequently, meta-analysis can be performed to support or refute the existence of apparent associations, provide insight regarding national trends of MM incidence, and potentially suggest additional sources of exposure for further investigation.
Prognostic Significance of Ki-67 Expression in Extranodal NK/T Cell Lymphoma, Nasal Type: A Proposed Prognostic Index, KLABS Index.
Authors: Kim Seok Jin , Yoon Soo-Young , Kim Byung Soo , Choi Chul Won , Choi Jungwoo , Kim In Sun , Lee Young-Hen , Kim Jun Suk 
Published: October 2019

Abstract
Ki-67 is a nuclear antigen expressed by dividing cells, therefore, the percentage of Ki-67-positive cells reflects the proportion of tumor cells actively proliferating. However, the prognostic value of Ki-67 expression is still controversial in non-Hodgkin’s lymphoma. Although a recent study in peripheral T-cell lymphoma showed a positive correlation with poor prognosis, the prognostic value of Ki-67 has never been studied in patients with extranodal NK/T cell lymphoma. Therefore, we performed this study to determine the value of Ki-67 expression in predicting prognosis and to propose a new prognostic model involving Ki-67 expression in patients with extranodal NK/T cell lymphoma. We studied 65 patients who were diagnosed with extranodal NK/T cell lymphoma from 1999 to 2005. All patients were treated with combination chemotherapy alone or followed by radiotherapy. We analyzed the percentage of Ki-67 expressing cells and determined its prognostic significance in terms of overall survival (OS) and disease-free survival (DFS). The immunohistochemical staining of Ki-67 was available for this study in fifty-five patients. The median age was 41 (range: 19 – 74 years), 89.1 percent of the patients (49/55) had an ambulatory performance status: Eastern Cooperative Oncology Group (ECOG) 0–1. Fifty-one patients presented as a localized disease: Ann Arbor stage I or II, and elevated level of serum lactate dehydrogenase (LDH) was observed in 14 patients. Thus, most patients showed the low or low-intermediate international prognostic index (IPI): low risk (74.5%, 41/55) or low intermediate risk (18.2%, 10/55). The percentage of Ki-67 expressing tumor cells was ranged from 5% to 95%, and the patients were separated into two groups: low Ki-67 (< 50%) versus high (≥ 50%). The patients in the high Ki-67 group had a shorter OS (95% CI 1.0-6.3, P = 0.046) and DFS (95% CI 1.1-5.5, P = 0.024) while the IPI failed to predict worse OS. Ki-67 expression could also predict the group with worse prognosis in 51 patients of low and low-intermediate IPI risk. Age, serum LDH, B symptoms, and tumor size were also associated with worse OS or DFS. Thus, based on the univariate and mutivariate analysis, we proposed a new prognostic index (KLABS index) with high Ki-67 expression, increased serum LDH, Age (≥ 60 years), presence of B symptoms, and bulky Size of tumors (≥ 10cm2) as follows: low risk, none or one of the above-mentioned factors; intermediate risk, presence of two factors; high risk, presence of three or more factors. This new index showed a high degree of correlation with survival outcomes in terms of OS and DFS (Figure A, B). This study demonstrated the prognostic significance of Ki-67 expression, and our new prognostic index may become a useful tool for predicting prognosis in extranodal NK/T cell lymphoma, nasal type.
Figure Figure
Immunodominant Minor Histocompatibility Antigen-Specific T Lymphocytes Eradicate BCR-ABL-Induced B-ALL and CML without Causing Graft-Versus-Host Disease in Mice.
Authors: Hu Yiguo , Sproule Thomas , Peng Cong , Kong Linghong , Goodrich Ami , Roopenian Derry , Li Shaoguang 
Published: October 2019

Abstract
Adoptive immunotherapy of human Philadelphia chromosome-positive (Ph+) leukemia has not been effective due to difficulties of identifying tumor-specific antigens for the disease. It has been reported that T lymphocytes activated by some minor histocompatibility antigens (mHAs) can efficiently treat mice receiving HL4 cells (a leukemia cell line) without causing graft-versus-host disease (GVHD). We investigated whether this anti-mHA immunotherapeutic strategy is applicable to treating Ph+ leukemia that includes B-ALL (B-cell acute lymphoblastic leukemia) and CML (chronic myeloid leukemia). Because the mHA, H60, is an immunodominant mHA among H7, H28, and H58 in mice (Choi et al, Immunity 17:593–603, 2002), we tested whether H60 can serve as an immunotherapeutic target in the treatment of B-ALL and CML in our retroviral bone marrow transduction/transplantation disease models (Li et al, J Exp Med189:1399–1412, 1999). We used C57BL/6-H60 congenic mouse splenocytes to immunize wild type C57BL/6 (B6) mice that do not have the H60 gene, and the activated T lymphocytes from the immunized B6 mice were injected into mice with BCR-ABL-induced B-ALL or CML (3×107 cells/mouse). We found that H60-specific T lymphocytes at a single dose completely eliminated leukemic cells within 10 days after the injection of the cells and cured B-ALL and CML, however, in mice receiving donor bone marrow cells transduced with empty vector and treated with H60-specific T lymphocytes, the non-BCR-ABL-expressing donor marrow cells lasted for more than 4 weeks, suggesting that H60-activated T lymphocytes have much stronger inhibitory effect on BCR-ABL-expressing leukemic cells than on normal marrow cells. In contrast, leukemia mice receiving naïve T lymphocytes died within 3 to 4 weeks post BCR-ABL induction of leukemia. Six months later, no residual leukemia cells were detected in the spleen and bone morrow of the leukemia mice receiving H60-activated T lymphocytes. In addition, no GVHD was observed in the mice. We also use H7/H28/H60 triple congenic B6 mice in our study, and found that H7/H28/H60-primed T lymphocytes were more effective in elimination of leukemia cells in mice compared with when the single H60 antigen was used in similar experiment. Especially, the H7/H28/H60-primed T lymphocytes were highly effective in treating B-ALL mice, and did not induce GVHD. These results indicate that mHAs are promising targets for immunotherapy of BCR-ABL-induced B-ALL and CML.
Investigating the Role of Dendritic Cells in Extracorporeal Photopheresis Using an In Vitro Model.
Authors: Holtick Udo , Marshall Scott R. , Haniffa Muzlifah , Hilkens Catharien M. , Wang Xiao N. , Dickinson Anne M. 
Published: October 2019

Abstract
Graft versus Host disease (GvHD) is the major limitation to successful allogeneic hematopoietic stem cell transplantation and contributes significantly to transplant related mortality and morbidity. Steroid refractory or steroid depending GvHD in particular is linked to poor survival or life quality. Conventional immunosuppression has very limited success in these conditions and increases susceptability for infection and relapse.
Extracorporeal Photopheresis (ECP) is a promising therapy for acute and chronic GvHD not responding to conventional immunosuppressive therapy. ECP treatment seems not to result in a pan-immunosuppression but has quite selective effects on the pathogenic process in GvHD.
The mechanisms of action of ECP in GvHD known so far include lymphocyte apoptosis, cytokine modulation and increased regulatory T cell numbers. It has been suggested that monocytes and dendritic cells (DC) were more resistant to ECP induced apoptosis, so that they might either be directly modulated by ECP or modulated by encounter with apoptotic cells and this way aquiring immunomodulating properties. Here we tested the first hypothesis analysing direct effects of ECP on monocyte derived dendritic cells in vitro.
Direct in vitro PUVA treatment leads to activation of monocyte derived immature DCs (upregulation of CD83, CD86, HLA-DR, reduced endocytosis capacity, increased migratory capacity), whereas mature DCs are not affected. However, immature and mature DCs undergo apoptosis later on within 24h-72h. Prestimualtion with either antigen (KLH), IL-12 or co-culture with CD40L expressing cells could not prevent apoptosis. Further DC stimulation through CD40L is abrogated 24h after treatment. DC cytokine analysis (IL-12, TNFα) is pending. After in vitro PUVA primary dermal DCs and Langerhans Cells migrated from skin biopsies undergo apoptosis similarly to monocyte derived DCs.
Going along with the early activation, the stimulatory capacity of in vitro PUVA treated immature DCs is enhanced in an MLR on naive T cells. IL-10 levels are decreased as compared to untreated or UVA treated cells. Secondary stimulation through either CD3/CD28 beads or mature DCs leads to reduced proliferation of naive T cells that were primarily stimulated with in vitro PUVA treated as compared to untreated immature DCs. Cytokine analysis after secondary stimulation is pending.
We conclude that in our model in vitro PUVA modulates the character especially of immature dendritic cells. However, immunostimulating and immunosuppressive characteristics could be described depending on the assay. Cytokine results after second stimulation (Th1/Th2) are pending. Apoptosis is a major finding and occurs both in monocytes and DCs after 24–72h. Our findings indicate that there might be direct ECP effects on monocytes and DCs going beyond the process of merely depleting antigen presenting cells. Further relevance is currently being investigated.
Generation of Dendritic Cells from Human Cell Expressed Cytokines.
Authors: Newman Rosie , Simpson Raina , Domagala Teresa , Lim Mei , Crofts Linda , Pilkington Glenn , Marks Denese 
Published: October 2019

Abstract
Traditionally, human cytokines have been expressed in non-human cells, including bacteria, yeast and mouse cells. However, the biological importance of species-specific post-translational modifications, in particular glycosylation, is increasingly being implicated as pivotal to protein function. Glycosylation is important for solubility, resistance to proteolysis, immunogenicity, biological recognition, biological activity, in vivo stability and clearance of glycoproteins including cytokines and growth factors, as up to 75% of their mass may consist of carbohydrate moieties. Clinical trials in cancer immunotherapy have attempted to benefit from the ability of autologous dendritic cells to boost antigen specific T-cell immunity. To date most clinical trials have generated dendritic cells using cytokines expressed in non-human cells. We have purified recombinant human cytokines expressed in modified human 293 cells. Human cell expressed human cytokines including IL-4, GM-CSF and TNF-alpha were used to generate dendritic cells from human peripheral blood mononuclear cells. The resulting cells exhibited a typical mature dendritic cell phenotype including expression of CD209, HLA-DR, CD40, CD80, CD83 and CD86, and were able to generate a T-cell response. In vitro comparisons of the biological activity of human cell expressed cytokines, in particular IL-4, with those expressed in other species has demonstrated that human cell expressed cytokines are more stable.
It is proposed that the enhanced biological stability of human cytokines derived from a human cell expression system would make these cytokines ideal for ex vivo derivation of immune cells such as dendritic cells for cancer therapy.
Comparison of Two Re-Freezing Methods on Previously Thawed Peripheral Blood Progenitor Cells.
Authors: Israel Donald S. , Rodriguez Federico , Hunt Stephen , Kitchen Kirk , Torloni Sergio , Wiltbank Thomas B. 
Published: October 2019

Abstract
Background: Peripheral Blood Progenitor Cells (PBPC) cryopreserved in DMSO are thawed at the patient’s bedside and infused immediately. Usually the infusions are completed without incident. There are occasions when mild/severe transfusion related reactions occur. When this does occur, the infusion is either slowed or paused for a short period of time. When reactions are severe enough to warrant stoppage of the infusion, transplant facilities maybe faced with discarding any remaining thawed cells. We have explored the question of salvaging the remaining cells by re-cryopreservation using two cryopreservation methods.
Study Design: Twenty PBPC were thawed in a 37C water bath until the internal temperature of the cells was approx 2-6C. The PBPC were not washed and allowed to remain at room temperature for 15 minutes. Ten PBPC were then placed on ice for 45 minutes. This simulated the transfer of cells to an off-site cryopreservation lab. These cells were then transferred to a new cryo bag, no change in the cryoprotectant solutions, and placed into a rate controlled freezer (RCF) bringing their temperature back to <−160C. The remaining 10 PBPC were allowed to remain at room temperature for an additional 10 minutes. The PBPC were then transferred to a −80C mechanical freezer. This simulated the transfer of cells to an internal laboratory without cryopreservation capabilities. All 20 PBPC were thawed after a minimum of 24 hours after return to their respective storage freezer conditions. We measured total nucleated cell count, viability by trypan blue, and CFU after the initial thaw and after the second thaw.
Results: The median viability of all PBPC after the first thaw was 69.5% (n=20; range= 35–83%). The median post thaw viability of the PBPC frozen by the RCF was 55.5% (n=10; range= 18–73%). Whereas, the median post thaw viability of the PBPC frozen in the −80C freezer was 25% (n=10; range 8–37%). Additionally, the median percent of viable cell loss from the initial pre-freeze data to the second thaw data for the RCF PBPC was 66.1% (n=10; range= 0 – 94.6%) and for the −80C PBPC was 94.1% (n=10; range= 91.3–97.8%. CFU growth was present for the RCF PBPC. No growth was demonstrated for the −80C PBPC.
Conclusion: Though neither method provided outstanding results, if faced with the dilemma of losing cells or attempting to save by re-cryopreservation, a transplant facility should consider RCF over −80C freezing.
Post-That Washing Prior to Transplantation of Umbilical Cord Blood (UCB) That Were Depleted of Plasma but Not of Red Blood Cells.
Authors: Chow Robert , Tan Patrick , Jaing Tang-Her , Rosenthal Joseph , Nademanee Auayporn , Karanes Chatchada , Graham Michael , Eames Gretchen , Chan Lee Lee , Wang Brian , Chow Tiffany , Wu Tina , Tan Ah Moy , Tan Poh-Lin , Lin Hai-Peng , Gjertson David , Petz Lawrence 
Published: October 2019

Abstract
Washing after thawing of frozen UCB used for hematopoietic stem cell transplantation (HSCT) is widely practiced for the purpose of removal of the cryoprotectant DMSO and free hemoglobin from lysed red cells. An updated retrospective audited analysis was performed on the outcomes of 208 PD UCB used in 186 patients with known thaw conditions that have engraftment and/or survival data −106 washed (W) and 80 non-washed (NW). When the DMSO dose was kept under the recommended 1 g per kg of recipient weight, the only severe adverse reaction was a seizure and encephalopathy following infusion of a NW PD UCB that resolved without any sequelae. Total nucleated cell recovery after thawing as reported by transplant centers was higher for NW (median 89% vs. 75%). The Kaplan-Meier estimate of 3-month neutrophil (ANC500) engraftment were 91±4% for NW versus 88±4% for W with median time to neutrophil of 21 versus 24 days (p = 0.02). The K-M estimate for 6-month platelet 20K engraftment were 86±6% for NW and 78±5% for W with median time to engraftment at 46 days for NW and 55 days for W (p = 0.002). Acute grade III–IV GvHD were similar at 12% (NW) and 13% (W), but extensive chronic GvHD were 4% (NW) and 19% (W). 1-year TRM were 25±5% for NW and 34±5% for W (p=0.75), with relapse rate at 16±5% for NW and 28±5% for W (p=0.09). K-M estimates of 1-year OS were 63±6% versus 53±5% (p = 0.54), and for 1-year DFS were 62±6% versus 48±5% (p = 0.23) for NW and W respectively. To our knowledge, this was the largest transplant outcome study comparing no post-thaw wash versus wash for UCB, though the conclusions are confined to PD CBU. No clear benefits of post-thaw washing were seen for PD UCB. HSCT with NW PD UCB was at least as efficacious as that using W PD UCB with respect to GvHD, TRM, relapse rate, 1-year OS and DFS. Moreover, washing may have a negative impact on neutrophil and platelet engraftment of PD UCB.