bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcome of Elderly Patients with Hodgkin's Disease-Single Centre Experience from Riyadh, Saudi Arabia
Authors: Tailor Imran Khan , Zaidi Syed Ziauddin A. , Motabi Ibraheem H , Alshehry N F , Elghazaly Assem A , Almudaibigh Samer Homoud S , AlGhamdi Mubarak S. , Gill Atta Munawar , Iqbal Shahid , Murtaza G , Butt A 
Published: October 2019

Abstract
Background: Hodgkin's disease accounts for approximately 10% of all lymphoma cases. There is a bimodal distribution with initial peak in second decade and a later peak in sixth decade. There is paucity of date on outcome of elderly patients with Hodgkin's disease. There is hardly any data from middle eastern patients.
Materials and Methods: We retrospectively analyzed 168 consecutive patients diagnosed with Hodgkin's disease at our centre from 2006 to 2015 (age>14 years) and found 16 patients to be over the age of 60 years.
Results: Out of 16 patients 6 were females, 10 were males and the median age was 70 years (range 61-86).All patients had classical Hodgkin's disease out of which 12 had nodular sclerosis subtype, 2 had mixed cellularity subtype and 1 had lymphocyte rich subtype. 4 patients had early stage disease (IA-IIA) while rest 12 had advanced stage disease. 15 were treated with ABVD based regimen, the other was treated with chlorambucil based regimen.3 out of 16 were given radiation in addition to chemotherapy. Out of the 14 evaluable patients (two were lost to follow up) 13 completed treatment and all of them achieved complete remission (93%).9 of 16 patients were given reduced dose doxorubicin. Three patients died (one due to sepsis, the other due cardiomyopathy 2 years after treatment, third one due secondary cancer).None of the alive patients have relapsed yet. One patient developed secondary cancer who later died with the same. At a median follow up of 35 months (range 1-72) even free survival and overall survival were 79% and 86% respectively.
Discussion: As per our study unlike in western world, older patients are less frequently affected with Hodgkin's disease. The remission rates and survival data are very encouraging despite dose reductions, however further data from this part of the world is needed to confirm our results. ABVD appears feasible, effective treatment option for elderly patients although frail patients who cannot tolerate ABVD may be candidates for anti CD30 antibody based regimens.

Disclosures
No relevant conflicts of interest to declare.
R-COMP Regimen in B Cell Non Hodgkin Lymphoma Patients with Cardiovascular Comorbidities
Authors: Annibali Ombretta , Chiodi Francesca , Sarlo Chiara , Cenfra Natalia , Tomassini Simona , Mecarocci Sergio , Cimino Giuseppe , Avvisati Giuseppe 
Published: October 2019

Abstract
Backgroung: Anthracyclines-based regimens remain the gold standard for the treatment of Lymphomas, although the associated cardiac toxicity may limit their use, especially in frail and elderly patients.
Patients and Methods: From October 2008 to January 2015 we treated 51 newly diagnosed patients B cell with poor-risk non Hodgkin lymphoma and cardiovascular comorbidities using the R-COMP regimen (rituximab, cyclophosphamide, non-pegylated liposome-encapsulated doxorubicin, vincristine and prednisone). Median age was 72 years (range:46-82 yrs ; 62% ≥ 70 years). As for histology, 26/51 (50%) were Diffuse Large B-cell Lymphoma; 10/51 (20%) Follicular Lymphoma; 8/51 (16%)mantle cell lymphoma; 5/51 (10%) Nodal Marginal Zone Lymphoma; 2/51 (4%) other B-cell indolent Lymphoma. IPI and FLIPI prognostic scores were Intermediate to High in the majority (39/51 = 76%) of the patients. Stage III and IV according to Ann-Arbor staging system was present in 40/51 patients (78%). The median age adjusted Charlsons comorbidity index was 6 (range: 3 to 11). Cardiovascular risk factors were considered: hypertension (39/51pts = 76%), a history or recent acute myocardial infarction (9/51 pts = 17%) and Atrial fibrillation (4/51 = 8%). According to National Institute of Aging/National Cancer Institute (NIA/NCI index), a large portion of patients (39%) presented high-impact conditions mainly consisting of ischemic and arrhythmic diseases, under active treatment. Treatment was well tolerated and toxicities were limited grade III/IV cytopenia.
RESULTS: Complete remission was achieved in 37/51 (72%) and partial response in 8/51 (15%). The remaining 12% of patients had a progressive disease . As of July 2015, after a median follow up period of 25 months (range 3-79), the OS, RD, EFS, TTF were not reached ( Figure 1, panel A,B,C respectively). In particular, at 5 years from the treatment starting, OS and RD are both 70% and EFS is 54% .Cardiac toxicity was observed in one patients who died for pulmonary edema, while two patients developed arrhythmias.
Conclusions: This study confirm the efficacy and tolerability of R-COMP regimen in elderly patients with cardiovascular comorbidities.
Figure 1. Figure 1.

Disclosures
No relevant conflicts of interest to declare.
Up-Regulation of CAR-T Cells after G-CSF and Dexamethasone Treatment in a Defuse Large B Cell Lymphoma Patient Receiving 4SCAR19 T Cell Therapy
Authors: Jing Hongmei , Chang Lung-Ji , Chen Mingyi , Bao Fang , Wang Jing , Wang Wenming , Liu Yuanyuan , Kuo Hao-Hsian , Liu Yuchen , Dong Lujia 
Published: October 2019

Abstract
A 37-year-old woman was diagnosed with DLBCL, GCB origin, positive with CD20, Bcl-2, Bcl-6, CD10 and negative with CD3, CD5, ,D21, CD23, CyclinD1. PET-CT scan showed that her lymph nodes were broadly involved. Based on PET-CT, the stage was IIIA and aaIPI score was 1. After eight cycles of R-CHOP (rituximab, cyclophosphamide, epirubicin, vincristine, and prednisone), the tumor regressed to a small retroperitoneum lesion with SUV 2.0, and she received another four cycles of rituximab for maintenance. The tumor relapsed one year later with resistance to ESHAP after she had failed multiple alternative treatments including GA101 trial, 3x DICE, MTX1g, 2x GEMOX, and 2x EPOCH. She was enrolled in a CD19-CAR (chimeric antigen receptor) T cell pilot study in January 2015. Her T cells were apheresis collected and transduced with a 4th generation, apoptosis-inducible, safety-engineered lentiviral CAR: CD19- scFv/CD28/CD137/CD27/CD3ζ-iCasp9 (4SCAR19). A personalized conditioning regimen was given based on the patient's history to chemotherapy: cyclophosphamide 500mg/d d1-3, and fludarabine 50mg/d d1-4, 40mg d5. Two days later, she received infusions of a total dose of 1.27×108 of the 4SCAR19 T cells (2x106/kg). At day 7 (D7) after infusion, she developed a fever over 39o C, which lasted for 7 days; this was controlled with NSAIDs (Non-Steroidal Anti-inflammatory Drugs). The tumor in her lymph nodes began to shrink 5 days after CAR-T infusion and she achieved nCR (near complete response) after 30 days. In a follow up PET/CT 3 months after CAR-T infusion, there was only one suspected retroperitoneum lesion (SUV 3.8) in the whole body, but it was indiscernable whether the SUV signal was tumor or T cell related. We monitored the peripheral blood CAR-T cell counts by qPCR and detected 0.03%, 0.07%, 0.3%, 9.3%, 0.01%, 1.57% on D7, D13, D48, D69, D84 and D112, respectively. In attempt to perform an autotransplantation to pursue a cure, she was mobilized twice with G-CSF on D68-D72, D110-112, plus dexamethasone 20mg/d on D101-102 and 15 mg/d on D110-111. Unexpectedly, the CAR-T cells in the patient peripheral blood increased to 9% after the first mobilization, and to 18% after the second mobilization. To this date, the patient has remained in nCR after 4SCAR19 therapy (January 23 to July 23, 2015). To our knowledge, this is the first report of evident CAR-T cell boost associated with G-CSF plus dexamethasone treatment. Further investigation is warranted to understand the molecular mechanisms behind such a favorable CAR-T therapy outcome in a terminal DLBCL disease.

Disclosures
Kuo: America Yuva Biomed: Employment. Liu:America Yuva Biomed: Employment. Dong:America Yuva Biomed: Consultancy.
Correlation Between Tumor-Associated Macrophage and Inflammatory Factors in Lymphoma Patients
Authors: Sun Xiaolin , Ni Jun , Wang Hong , Sun Xin , Wang Cuimei , Wu Wei , Gu Jian , Depei Wu 
Published: October 2019

Abstract
Introduction
To study the expression of tumor associated macrophage (TAMs), inflammatory cytokines IL-1β (interleukin-lβ), TNF-α (tumor necrosis factor-α), IL-6 (interleukin 6) and IL-10 (interleukin 10) and its significance in different types of lymphoma in lymph node pathological tissue.
Methods
106 cases of clinical pathology specimens of patients were collected from different types and different staging classifications. The expressions of tumor-associated macrophage and interleukin-1β (IL-1β), tumor nec.rosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-10 (IL-10) in lymphoma tissues were detected by immunohistochemical staining;
Results
Both CD68 and CSF-1R showed high expression in lymphoma tumor tissues. The positive rates of CD68 and CSF-1R in Ⅳ period patients was higher than Ⅱperiod (P <0.05), and the level of CSF-1R in high-risk group was higher than low-risk group (P <0.05). The expression of CD68 was positively correlated with CSF-1R. The inflammatory cytokines such as IL-1β, TNF-α, IL-6, IL-10 were highly expressed in tumor tissues; the positive rate of IL-1β in lymphoma IV period was higher than periodⅡ(P <0.05) and the level of IL- 6 in high-risk group were significantly higher than the low-risk group (P <0.05).The expression of tumor-associated macrophage phenotype CD68 in lymphoma tissues was positively correlated with inflammatory cytokines IL-1β, TNF-α, and IL-6 (P <0.05).
Conclusion
1.CD68, tumor-associated macrophage phenotype, and CSF-1R were highly expressed in lymphoma tissues
2.The expression of CD68 was positively correlated with inflammatory cytokines.
3.TAMs were involved in tumor inflammatory microenvironment.
Funded by Jiangsu Provincial Special Program of Medical Science (BL2012005)

Disclosures
No relevant conflicts of interest to declare.
Survey of Qol (quality of life) on Patients Receiving Tyrosine Kinase Inhibitors for Chronic Myeloid Leukemia: Korean CML Working Party Group
Authors: Kim Kyoung Ha , Kim Dae-Young , Kim Sung-Hyun , Kim Yeo-Kyeoung , Kim Inho , Kim Hee-Jin , Sohn Sang Kyun , Lee Jeon-Ok , Cheong June-Won , Jung Chul Won , Cho Young-Uk 
Published: October 2019

Abstract

Background
With imatinib therapy, the survival of patients with CML has improved dramatically. In recent years, second generation TKI (2G TKI) led to more increased responses. Despite the demonstrated superiority of efficacy and toxicities as previous treatments, several adverse events of TKIs remain. Because CML treatment is lifelong, it is important for patients to maintain adherent to treatment. Correlations between poor adherence to TKI treatment and adverse events and quality of life (QoL) have been demonstrated among CML patients in clinical settings. The FACT-leu is a validated tool that measures leukemia-specific and more general QoL concerns. However, there are few studies about QoL of CML patients in Korea. Therefore, we evaluated the QoL of CML patients treated with TKIs.
Methods
The CML working party of the Korean society of Hematology was produced by the questionnaire included the questions of FACT-leu. We distributed the questionnaire over the online or offline. QoL of patients with CML was analyzed using these questionnaires.
Results
A total of 384 patients were surveyed between March 2014 and June 2014. Male was 234 (60.94%) patients. Median age was 47 (range 12-71) years. Current taking medication at survey were imatinib (n=197), dasatinib (n=71), nilitinib (n=88), radotinib (n=28). Patients with high compliance of TKI (taking 90% or more drugs) were 88.28% and lower compliance (taking 70% or less drugs) were 1.82%. In queries about poor adherence to TKI therapy, common causes were forgetfulness (18.49%) and adverse events (8.59%). FACT-Leu scale was higher in patients with 2G TKIs than imatinib (122.9 ± 22.65 vs 116.0 ± 25.00 (p=0.005)). Female, older patients, patients with CML in longer time showed meaningful worse QoL in FACT-leu scale. There was no significant difference between dasatinib (122.2±25.5) and nilotinib (124.6±22.06) in FACT-leu scale.
Conclusion
In 2G TKI era, QoL of CML patients seemed that is better than before. Additional prospective studies are warranted using adequate measuring tool of QoL.

Disclosures
No relevant conflicts of interest to declare.
Labile Plasma Iron (LPI), More Practical and More Sensitive to Iron Overload in Myelodysplastic Syndromes
Authors: Chang Chunkang , Gu Shucheng , Guo Juan , Zhao Youshan , Fei Chengming , Li Xiao 
Published: October 2019

Abstract
Background: In order to gain an insight into LPI in iron metabolism microenvironment in MDS.
Materials and Methods: We performed ELISA, quantitative RT-PCR, flow cytometry, MRI T2* assays to test LPI, iron biochemical parameters and LIC among 22 MDS patients.
Results: LPI has a statistical difference (P<0.001 by ANOVA), which decreased gradually, among three groups, while no difference was found in ASF (P=0.086 by ANOVA). After DFO treatment, serum hepcidin expression increased from 301.26±59.78¦Ìg/L to 340.33±49.78¦Ìg/L (P=0.032), while hepcidin/ASF was up-regulated gradually from 0.16±0.08 to 0.22±0.03 (P=0.045). APAF-1 expression (P=0.047) and erythroid apoptosis rate (P=0.009) decreased significantly, respectively. No statistical difference was found in EPO (P=0.247) and GDF15 expression (P=0.172). LIC dropped from 9.83±4.84mg/g dry weight to 6.28±4.01mg/g dry weight (P<0.001). No significant difference was found in cardiac T2* (P=0.594). LPI has a closer connection to LIC than ASF (r=0.739, P<0.001 vs. r=0.321, P=0.034). (Figure1)
Conclusion: LPI seems to be a real-time indicator which reflects body iron loading status instantaneously. Despite the limited knowledge available on LPI speciation in different types and degrees of IO, LPI measurements can be and are in fact used for identifying systemic IO and for initiating/adjusting chelation regimens.
Before DFO treatment, a patient had an abnormal liver function. Along with iron chelation therapy, his LPI decreased rapidly. Meanwhile, his ALT dropped and his hemoglobin increased gradually. Furthmore, his LIC decreased after receiving DFO treatment.
Lane a: LIC was 9.97mg/g dry weight on week 0.
Lane b: LIC was 5.81mg/g dry weight on week 26.
Figure 1. The improvement of ALT, hemoglobin and LIC Figure 1. The improvement of ALT, hemoglobin and LIC Figure 2. Figure 2.

Disclosures
No relevant conflicts of interest to declare.
Invasive Fungal Infections in Patients with High-Risk MDS and AML Treated with Azacitidine
Authors: Pomares Helena , Arnan Montserrat , Sánchez-Ortega Isabel , Sureda Anna , Duarte Rafael F. 
Published: October 2019

Abstract
Introduction: The incidence of invasive fungal infections (IFI) and need for antifungal prophylaxis in patients with high-risk myelodysplastic syndromes and acute myeloid leukemia (MDS/AML) treated with hypomethylating agents is currently unknown.
Methods: We retrospectively analyzed the incidence of IFI in all MDS/AML patients receiving azacitidine (75 mg/m2/day 7 days every 28-day cycle) in our center between June 2007 and June 2015. IFI diagnosis follows the European Organization for Research and Treatment of Cancer and Mycosis Study Group (EORTC/MSG) 2008 Criteria. Patients did not receive antifungal prophylaxis.
Results: One hundred and twenty one consecutive unselected patients (86 MDS and 35 AML; Table 1) received a total of 948 cycles of azacitidine in this series (median 5, range 1-43). One hundred and ten (91%) received azacitidine frontline and 11 (9%) following refractoriness or relapse after previous intensive chemotherapy. Seventy one patients received ≥4 azacitidine cycles. Forty two (35 %) patients had complete medullar and cytogenetic responses. Two hundred and seventy four azacitidine cycles (28%) in 49 patients (40%) were administered during and/or led to prolonged grade IV neutropenia (<0.5x109/L ³10 days), and caused febrile neutropenia episodes in 121 cycles (12% of total, 44% of neutropenic cycles) in 45 patients (37%), range 1-6 per patient. Four IFI occurred in these patients: one possible, two probable and one proven (Table 2). The incidence of IFI was 0.42% per treatment cycle and 3.3% per patient treated for the overall series, and 0.72% per treatment cycle and 4.1% per patient treated among those with prolonged severe neutropenia. Of note, all cases of IFI occurred in either the first or the second azacitidine courses. Two patients died from IFI, leading to an IFI-related mortality rate of 1.65% per patient treated and 0.21% per treatment cycle. The numbers needed to treat with primary prophylaxis, even for an ideal agent that could potentially prevent all IFI, are well in excess of 100 courses of azacitidine and well over 20 patients throughout their treatment course, to prevent one single IFI in these patients, even among those with neutropenia.
Conclusion: Our data show that patients with MDS/AML treated with azacitidine have a very low risk of IFI, including those with concurrent severe prolonged neutropenia. Primary antifungal prophylaxis should not be recommended for this subset of patients. This very low risk of IFI is a potential additional benefit from treatment of MDS/AML with hypomethylating agents, compared to conventional intensive chemotherapy. Prospective studies are needed to better address this issue.

Disclosures
Sureda: Takeda: Consultancy, Speakers Bureau.
The Retinoid Derivative Drug, Acitretin, Modulates CD38 Expression on MEC-1 Cells and Primary Chronic Lymphocytic Leukemia (CLL) Cells and Reduces Migration in Response to the Chemokine CXCL12
Authors: Elsir Mohammed Sally , Murphy Philip , Quinn John , Thornton Patrick , Bergin Stephen , Hennessy Bryan 
Published: October 2019

Abstract
Background: CD38 is a cell surface receptor and ectoenzyme expressed in a variety of haematological malignancies. In CLL, CD38 expression is a marker of poor prognostic disease and is now attracting growing interest as a target molecule for anti CLL therapy.
Retinoids modulate CD38 expression due to the presence of the Retinoic Acid Response Element (RARE) DNA sequence in the promotor region of the CD38 gene. In this study we demonstrate that the retinoic acid derivative, acitretin, upregulates the expression of CD38 on the MEC-1 cell line and on primary CLL cells from CD38 positive patients. We propose that, by doing so, Acitretin may render these cells more susceptible to the actions of anti CD38 monoclonal antibody drugs and thus have a potential role as an adjunct to such therapies.
Methods: Primary CLL cells were freshly isolated from whole blood of CLL patients using the FICOLL density centrifugation technique. The CLL like cell line MEC-1 was obtained from DSMZ, Germany.
MEC-1 cells and cells from three CD38 negative and five CD38 positive patients were treated with 10micM acitretin for 24, 48 and 72hrs. CD38 expression was measured by FACS analysis at baseline and at the different time points. Results are expressed as fold increase in Mean Fluorescence Intensity (MFI).
Migration assays were performed using 2x10^6 cells per well incubated with 10microM acitretin overnight in 1%FBS. Cells were subsequently transferred to chamber inserts overlying 10%FBS media containing 200ng/ml CXCL12 in all wells, except negative controls. Cells were then allowed to migrate for 4hrs. Migration was calculated as percentage of cells in lower chamber to upper chamber.
Results: Acitretin increased the expression of CD38 on MEC-1 cells by a mean of 7.4 fold and on cells from CD38 positive patients by a mean of 3.4 folds (n=5). Acitretin, however, did not modulate CD38 expression levels on primary CLL cells from CD38 negative patients (n=3).
Migration of primary CLL cells from 11/14 patients toward the CXCL12 chemokine was reduced in response to Acitretin treatment as compared to untreated controls. Mean migration of treated cells was 12.3% versus 27.3% mean migration in untreated controls.
Conclusion: Our findings re-affirm the potent effect of retinoid drugs as upregulators of CD38 expression and suggest that their use in CLL therapeutics in conjunction with anti CD38 monoclonal antibodies should be explored. We also propose that acitretin appears to exert a favourable blocking effect on CLL cell migration towards micro-environmental chemokines such as CXCL12, warranting further evaluation.

Disclosures
Murphy: Celgene: Honoraria.
Mutations in the Second Linker of KLF1 Cause Congenital Non-Spherocytic Hemolytic Anemia Due to Global Reduction of In Vivo DNA-Binding Affinity
Authors: Huang Stephen , Gillinder Kevin R. , Sorolla Annabel , Whitelaw Emma , Perkins Andrew C 
Published: October 2019

Abstract
The mommeD45 mutation generates an amino acid transversion (H350R) within a conserved linker peptide between zinc fingers two and three of Klf1 (linker 2). Klf1H350R/H350R mice have mild compensated microcytic anaemia 1. Mice Carrying the H350R mutation were interbred with Klf1+/- mice. Klf1H350R/-mice have severe perinatal haemolytic anaemia, jaundice and marked splenomegaly. Haematological evaluation of these mice shows similar phenotypes to human patients who are compound heterozygotes for null and linker 2 mutations in KLF12. Analysis of Klf1H350R/- fetal liver by flow cytometry showed an increase in circulating immature CD71+ Ter119+ erythroblasts. In the bone marrow, a marked reduction in mature (Cd71- Ter119+) red blood cells was observed. Flow cytometric analysis of the spleen from Klf1H350R/- animals revealed an expansion of erythroid cells consistent with extramedullary erythropoiesis. ChIP-seq for Klf1 in 14.5DPC fetal liver from Klf1H350R/H350R mice revealed no loss in specificity when compared to wildtype Klf1, but a global reduction in affinity. Affinity measurements of recombinant zinc finger domains in vitro will be presented. By RNA-seq, we observed significantly lower expression of Klf1 target genes in mice homozygous for the H350R mutation compared to mice carrying a wildtype allele. And this correlates with reduced DNA binding observed in ChIP-seq and in vitro assays. Previous studies of the linkers in C2H2 zinc finger transcription factors have revealed their necessity as structural and regulatory components for the C2H2 class of transcription factors. Our results show the second linker of Klf1 plays an indirect role in DNA-binding and does not act just as a spacer for the zinc fingers.
References:
1. Sorolla A, Tallack MR, Oey H, et al. Identification of novel hypomorphic and null mutations in Klf1 derived from a genetic screen for modifiers of alpha-globin transgene variegation. Genomics. 2015;105(2):116-122.
2. Viprakasit V, Ekwattanakit S, Riolueang S, et al. Mutations in Kruppel-like factor 1 cause transfusion-dependent hemolytic anemia and persistence of embryonic globin gene expression. Blood. 2014;123(10):1586-1595.

Disclosures
Perkins: Novartis Oncology: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Honoraria.