bluuebunny/crossref_metadata_2025_split huggingface dataset:
Superior Survival of Combined Gastrointestinal and Skin GvHD Compared to Isolated Gastrointestinal GvHD in Children Post Allogeneic Stem Cell Transplantation
Authors: Gassas Adam , Ali Muhammad , Dupuis Annie , Doyle John J , Schechter Tal 
Published: October 2019

Abstract
Abstract 4535

Objective:
To compare the prognosis of isolated gastrointestinal (GI) graft versus host disease (GvHD) vs combined (GI and skin) GvHD in children post allogeneic stem cell transplantation (SCT).

Methods:
Allogeneic SCT recipients from January 2000-Dec 2009 were included and patients who were diagnosed with skin and GI GVHD were identified. Demographics and outcome data were collected and analyzed.

Results:
Four hundred and fifty children (0–18 years) underwent allogeneic SCT in the study period. Seventy-nine (17.5%) patient underwent endoscopy and GI biopsy for GI GvHD. Of the seventy-nine patients, 49 had isolated GI GvHD and 30 had combined GvHD. Fifty-one patients received SCT for a malignant indication and 28 for a non-malignant cause. Donor sources were; isolated GI group, related 10, unrelated 20: combined group, related 20, unrelated 29). All patients received myeloablative conditioning regimens and the majority received cyclosporine A and methotrexate for GvHD prophylaxis. Sixty-seven percent of patients with combined GvHD had grade III-IV while only 31% had grade III-IV in patients with isolated GI GvHD. To ensure there was no bias in a quicker initiation of anti GvHD therapy in children with skin involvement, we included only children who had a GI scope and GI biopsy looking for GI GvHD and also we compared if GvHD therapy initiation was different in patients with or without skin involvement [In the combined group 16 patients (53%), therapy was started prior to GI biopsy versus 16 patients (33%) in the isolated GIT group P=0.2]. Interestingly, 40% of children with combined GvHD had also liver GvHD while only 6% of patients with isolated GI GvHD had liver involvement (p≤0.0001). Overall response to GvHD therapy was similar in both groups (83% vs 87%). However, despite having less patients in the isolated GI group with severe (grade III-IV GvHD), there was a significant increase in non-relapse mortality (NRM) in the isolated GI group compared to the combined group (37% vs 16%) resulting in a statistically significant superior overall survival for those children with combined GvHD (79% vs 49% P= 0.02). Disease relapse was similar in both groups (8% and 6% for combined and isolated GIT group, respectively).

Conclusion:
Children with GI GvHD has better prognosis when there is skin involvement. Further research is warranted to examine if there is certain biological features that make GI GvHD extends to skin and other organs and why isolated GI GVHD is associated with worse prognosis?

Disclosures:
No relevant conflicts of interest to declare.
First Reported Use of a Biosimilar G-CSF in Allogeneic Stem Cell Mobilisation
Authors: Azar Nabih , Choquet Sylvain , Garnier Alice , Roos-Weil Damien , Leblond Véronique 
Published: October 2019

Abstract
Abstract 4571

OBJECTIVES:
Biosimilar granulocyte colony-stimulating factor (G-CSF) has been approved on the basis of comparable quality, safety and efficacy as the originator product. Approval of biosimilar G-CSF is in the same indications as the originator, including autologous and allogeneic peripheral blood stem cell (PBSC) mobilisation, for which it is being used throughout our large hospital group in Paris, France. Concerns have been raised by professional bodies over use of biosimilar G-CSF in allogeneic transplants. To our knowledge, this is the first reported use of biosimilar G-CSF in healthy donors for allogeneic transplantation.

METHODS:
Healthy related donors received biosimilar G-CSF (EP-2006, Sandoz Biopharmaceuticals) 10 μg/kg/day for PBSC mobilisation. G-CSF was administered on days 1–4 with the first leukapheresis performed on day 5. If the required number of CD34+ cells per recipient body weight (4 × 106 CD34+ cells/kg) was not collected, G-CSF administration was continued and a second PBSC collection was performed on day 6. Further G-CSF administration and a third leukapheresis was done on day 7 if required.

RESULTS:
Twelve healthy donors (7 male, 5 female; mean ± SD age 61.0 ± 7.8 years, range 51–73) received biosimilar G-CSF for PBSC mobilisation. Median donor body weight was 82 kg (range 55–115 kg). Median CD34+ cell count on day 5 was 75/ml (range 23–140). A single leukapheresis after 4 injections of biosimilar G-CSF was sufficient to collect the CD34+ cell dose required in six donors with peripheral blood (PB) CD34+ counts ranging from 80–140 ml. Six donors underwent a second leukapheresis after 5 days of biosimilar G-CSF, one of whom (a 73-year old female) underwent a third leukaphereses on day 7 (PB CD34+ at first apheresis 23 ml). Median number of CD34+ cells per recipient bodyweight was 5.5 × 106 cells/kg (range 2.6–8.9). Five donors reported bone pain (4 mild, 1 moderate severity) which was effectively treated with paracetamol. No other adverse events were reported. Blood measurements were normal in all donors when assessed one week after the end of mobilisation. These findings are consistent with our previous use of originator G-CSF (Neupogen®) in allogeneic stem cell mobilisation.

CONCLUSION:
These preliminary findings suggest biosimilar G-CSF is effective and well-tolerated in allogeneic stem cell mobilisation. Further studies are required to assess longer-term safety outcomes. The use of biosimilar G-CSF may provide important cost-savings when compared with the originator product.

Disclosures:
No relevant conflicts of interest to declare.
PRMT1 Interacts with AML1-ETO to Promote Its Transcriptional Activation and Progenitor Cell Proliferative Potential
Authors: Shia Wei-Jong , Okumura Akiko J. , Yan Ming , Sarkeshik Ali , Lo Miao-Chia , Matsuura Shinobu , Komeno Yukiko , Zhao Xinyang , Nimer Stephen D. , Yates John R. , Zhang Dong-Er 
Published: October 2019

Abstract
Abstract 4621
Fusion protein AML1-ETO resulting from t(8;21) translocation is highly related to leukemia development. It has been demonstrated that full-length AML1-ETO blocks AML1 function and requires additional mutagenic events to promote leukemia. We have previously shown that the expression of AE9a, a splice isoform of AML1-ETO, can rapidly cause leukemia in mice. To understand how AML1-ETO is involved in leukemia development, we took advantage of our AE9a leukemia model and sought to identify its interacting proteins from primary leukemic cells. Here we report the discovery of a novel AE9a binding partner PRMT1 (protein arginine methyltransferase 1). PRMT1 not only interacts with but also weakly methylates Arginine 142 of AE9a. Knockdown of PRMT1 affects expression of a specific group of AE9a-activated genes. We also show that AE9a recruits PRMT1 to promoters of AE9a activated genes, resulting in enrichment of H4 Arg3 methylation, H3 Lys9/14 acetylation, and transcription activation. More importantly, knockdown of PRMT1 suppresses AE9a’s self-renewal capability, suggesting a potential role of PRMT1 in regulating leukemia development.

Disclosures:
No relevant conflicts of interest to declare.
Monitoring the Chimerism Status of Subpopulation in HLA Haplo-Identical Stem Cell Transplantation Using the Anti HLA Antibodies: Based on the Study of HLA Distribution in Korean Population
Authors: Choe Won Ho , Jang Seongsoo , Chi Hyun-Sook , Park Chan-Jeoung , Im Ho Joon 
Published: October 2019

Abstract
Abstract 4706

Background:
Determining the chimerism in stem cell transplantation (SCT) is important in the monitoring of engraftment. Conventional monitoring methods such as short tandem repeat (STR) PCR are labor intensive and difficult in showing the changes of cell subpopulations. Nowadays, HLA-haploidentical SCT is performed actively and flow cytometric analysis using anti HLA antibody targeted for the different HLA between donor and recipient in HLA-haploidentical SCT can be useful by observing changes of cell subpopulations and determining the chimerism.

Methods:
Based on the study of HLA distribution in Korean population, we designed the panel of HLA monoclonal antibody that can detect and differentiate major HLA of Korean population. This panel was verified against 23 cases of HLA-haploidentical SCT. Flow cytometric analysis was performed using anti-HLA-antibodies on one pediatric patient with aplastic anemia who underwent HLA-haploidentical SCT. Tests were performed every day since SCT. The appearance or disappearance of donor and/or recipient HLA was observed using antibodies against mismatched HLA. Donor and/or recipient T cells, B cells, NK cells, and monocytes were observed using CD3, CD19, CD56, and CD13 respectively. The flow cytometric results were interpreted by observing the changes in subpopulations of detected cells and determining the engraftment status of patients.

Results:
A total of 11 anti-HLA-A-antibodies and anti-HLA-B-antibodies were selected. They cover 97.9% of HLA-A and 8.6% of HLA-B in Korean population. In the verification of our panel of HLA monoclonal antibody, we distinguished donor and recipient cells in 21 of 23 HLA-haploidentical SCT cases. In our case, the patient had HLA-A2/A24 while the donor had HLA-A2/A33. Recipient type of CD3(+) and HLA-A33(-) T cells appeared in first few days but donor type CD3(+) and HLA-A33(+) T cells appeared at day 20 and were increased. Donor type CD56(+) and HLA-A33(+) cells were seen at analysis done in day 8 and continued to appear. HLA-A33(+) cells were consistently observed and increased throughout the follow up period, showing the process of engraftment of donor stem cells.

Conclusion:
We were able to apply our flow cytometric analysis design using HLA monoclonal antibody for the detection of chimerism in HLA-haploidentical SCT. This method was more simple and sensitive than conventional monitoring techniques. Moreover, this method allowed us to observe the dynamics of changes in cell subpopulations after HLA-haploidentical SCT. Flow cytometric analysis can be considered as a strong tool for observing the changes in cell subpopulations and the monitoring the engraftment of HLA-haploidentical SCT.

Disclosures:
No relevant conflicts of interest to declare.
Upregulation of TCRζ Chain Overcome T Cell Immunodeficiency in Patients with Chronic Myeloid Leukemia
Authors: Zha Xianfeng , Chen Shaohua , Yang Lijian , Li Bo , Chen Yu , Yan Xiaojuan , Li Yangqiu 
Published: October 2019

Abstract
Abstract 4719
TCRζ chain is the key molecular of TCR signaling, the defective TCRζ chain not only decreases the expression of TCR on the T cell surface and the quantity of circulation T cells, but also influences T cell activation and proliferation. Previous studies indicated that the obvious downregulation of TCRζ chain was one of main factors which caused T cell immunodeficiency in patients with chronic myeloid leukemia (CML), which lead to dysfunction of immune supervision to tumor. This study was undertaken to explore the possibility that forced expression of TCRζ chain may restored the T cell immune function. In present study, the freshly CD3 + T cells were isolated by MACS from de novo CML patients; freshly T cells were transfected with TCRζ chain recombinant vector (TCRζ-IRES-EGFP) and control vector (pIRES2-EGFP) by nucleoporation technique. The transfection efficiency was detected by FCM at 18 hours post-transfection, and TCRζ chain protein and its phosphorylation were detected by Western blotting after activation with OKT3 antibody for 1 minute. The supernatants and RNA were collected from transfected cells stimulated with OKT3 and anti-CD28 antibody, for analysis of IL-2 levels and the mRNA expression of ZAP70 and NF-κB. The results showed the transfection efficiency of TCRζ chain vector and control vector construct was 72.16±6.95% and 73.4±7.90% in CML T cells from different patients respectively. In T cells transfected with TCRζ chain, the expression of TCR chain was increased, the IL-2 production induced by OKT3 and anti-CD28 antibody in TCRζ chain transfected T cells (175.1±66.3pg/mL) were higher than that from control group (107.6±65.5pg/mL) (n=6, p=0.039). The bother expression levels of ZAP-70 and NF-κ B in the experimental group was higher than the control group (n = 4, p < 0.05), moreover the expression level between ZAP-70 and NF-κB showed linear correlation (n = 4, p = 0.013, r = 0.98). In conclusion, the results indicate that upregulation of deficient TCRζ chain may reverse the TCR/CD3-mediated signaling abnormalities, which may improve the T cell immune function in patients with CML.
This study was supported by grant from the Key project of Natural Science Foundation of Guangdong Province, China (No. 9251063201000001).

Disclosures:
Zha: This study was supported by grant from the Key project of Natural Science Foundation of Guangdong Province, China (No. 9251063201000001): Research Funding. Li:the Key project of Natural Science Foundation of Guangdong Province: Research Funding.
The Feature of SALL4 and BMI-1 Expression in Placenta and Umbilical Cord Blood
Authors: Chen Shaohua , Shen Qi , Yang Lijian , Li Bo , Ma Yupo , Li Yangqiu 
Published: October 2019

Abstract
Abstract 4800
The SALL4 is a newly discovered pluripotency stem cell factor involved in the self-renewing, hematopoietic stem cells (HSCs) and leukemic stem cells. Its important role in normal HSCs and leukemic stem cells is supported by its interactions with several key players, like BMI-1, a putative oncogene of the Polycomb group family, controlling specific target genes involved in development, cell differentiation, proliferation, and senescence. Little is known the expression feature of SALL4 and BMI-1 mRNA in placenta and umbilical cord blood (UCB). In this study, the mRNA expression level of SALL4 and BMI-1 in 10 cases placenta tissues and the mononuclear cells from the corresponding UCB (CBMCs) were measured by real-time PCR with SYBR Green I technique, β2-microglobulin gene (β2M) was used as an endogenous reference, mononuclear cells from 10 healthy adults peripheral blood (PBMCs) and 2 cases of adult thymic cells served as control. The result showed that the expression level of both SALL4 and BMI-1 in placenta (Median: 34.36 and 17.55 respectively) were significantly higher than those from CBMCs (Median: 11.3 and 2.07 respectively) (p=0.007, p=0.001) and PBMCs (Median: 0.64 and 0.03 respectively) (P<0.001, P<0.001). Moreover, both SALL4 and BMI-1 expression levels in CBMCs were significant higher than those from PBMCs (P=0.002, P=0.001). And the expression of SALL4 could be detected in thymic cells. Correlation analysis was performed among the relative expression levels of SALL4 and BMI-1. The results showed that significant positive correlation between the expression levels of SALL4 and BMI-1 was observed in placenta tissues and CBMCs, as well as in PBMCs (rs=0.648, P=0.043, rs=0.721, P=0.019, rs=-0.697, P=0.025). In conclusions, the expression level of SALL4 and BMI-1 might be related to the numbers of hematopoietic stem cells, placenta tissues may be as an appropriate model for investigating gene regulation of SALL4 and BMI-1, while the significance of expression both genes in PBMCs and thymic cells is needed further investigation.

Disclosures:
Chen: National Natural Science Foundation of China(no. 30871091): Research Funding; the Fundamental Research Funds for the Central Universities (No. 21610603): Research Funding.
Hypoxic Induction of Vascular Endothelial Growth Factor Regulates Fetal Erythropoiesis but Not Stem Cell Function
Authors: Rehn Matilda , Cammenga Jorg 
Published: October 2019

Abstract
Abstract 4823
It has recently become apparent that hypoxia is an important factor in the hematopoietic stem cell (HSC) niche in the bone marrow (BM) but whether hypoxic niches also plays a role in regulation of fetal liver (FL) HSCs is not clear. Vascular endothelial growth factor A (VEGFA) is a key molecule in angiogenesis but is also known to be essential for adult HSC survival, mediated by a cell-intrinsic, autocrine mechanism. Vegfa expression can be induced by hypoxia-inducible factors (HIF), transcription factors that are stabilized in low-oxygen conditions and that activate transcription by binding to hypoxia-response elements (HRE). We have previously shown that hypoxic induction of Vegfa in adult HSCs is needed for proper function, using the mouse model Vegfaδ/δ, where the HRE in the Vegfa promoter is deleted. Here we have investigated the role of hypoxic Vegfa in fetal hematopoiesis. The Vegfaδ/δ genotype is partly embryonic lethal and we established that the major part of lethality in utero takes place between day 15.5 of development and birth. However, the exact reason for the lethality is not known. We speculated that the function of FL HSC might be reduced, and therefore BM seeding is inefficient and a cause of prenatal deaths. In contrary to our hypothesis, we now show that HSCs from Vegfaδ/δ FL have a normal capacity to competitively repopulate adult recipients. On the other hand, fetal erythropoiesis is severely impaired in absence of hypoxia-induced Vegfa, possibly explaining the embryonic lethality of Vegfaδ/δ mice. Fetuses at day 15.5 are pale and have significantly lower amounts of Ter119+ CD71low erythrocytes in the FL compared to wild type controls. Our findings indicate that hypoxic regulation of Vegfa expression is important in fetal erythropoiesis, suggesting that hypoxic areas exist within the FL. However, HSCs are affected by such hypoxic areas only to a small extent and hypoxic Vegfa expression is not highly important in FL HSCs.

Disclosures:
No relevant conflicts of interest to declare.
Treatment of Burkitt's Like Lymphoma: A Single Institution Case Series
Authors: Ranpura Vishal , Shah Shilpan S. 
Published: October 2019

Abstract
Abstract 4962
Background: Burkits's like (BL) lymphoma is a new pathologic entity with features partially resembling to Burkitt's lymphoma and diffuse large B cell lymphoma. The incidence of BL lymphoma is infrequent and may present with lymph node enlargement, involvement of bone marrow and peripheral blood. The natural history of BL lymphoma and its treatment remains unclear. Here we present a single institution case series of five patients diagnosed with BL lymphoma and their treatment. Methods: We searched the pathology reports of all patients diagnosed with lymphoma over the last one year. No inclusion or exclusion criteria were used. Results: We identified a total of five patients with diagnosis of BL lymphoma. All patients presented with lymphadenopathy and with no involvement of bone marrow, central nervous system or peripheral blood. Table 1 summarizes characteristics of all patients, their chemotherapy regimen and subsequent response to treatment. Conclusion: BL lymphoma is a new pathologic entity with low incidence. Treatment with DA-EPOCH and R-HyperCVAD has very good response rate. The data is limited by single institution case series and limited follow up time. Further studies are recommended to evaluate optimal chemotherapy regimen. Table 1: Characteristics, presentation, treatment and response in patients with BL lymphoma
No Age Sex LDH, Presentation Treatment Response Duration of response 1 68 F 386 Parotid and abdominal lymphadenopathy DA-R-EPOCH CR 16months 2^ 44 M 536 Neck, Axillary, media, abdomen pelvis and sacral mets R-HyperCVAD PR 3months 3* 66 F 310 Inguinal and pelvic lymphadenopathy R-HyperCVAD f/b Autologus BMT, CR 14months 4** 71 M 237 Parotid mass 3 cycles of DA-EPOCH f/b 3 cycles of R-CHOP CR 9months 5^ 52 M 186 Neck Lymphadenopathy R-HyperCVAD CR 3months DOX, DOXOL, and anthracenediones in soluble fractions of human myocardial strips after sequential DOX loading/clearance and anthracenedione treatment Notes: DA-REPOCH: Dose Adjusted Rituximab-Etoposide, Vincristine, Cyclophosphamide, Doxorubicine, Prednisone, R-HyperCVAD: Rituximab, hyperfractionated Cyclophosphamide, Vincristine, Doxorubicin, Dexamethasone, CR: complete remission, BMT: bone marrow transplantation, R-CHOP: rituximab, doxorubicin, cyclophosphamide, vincristine and prednisone. CNS: central nervous system * patient underwent bone marrow transplant because of relapse at current presentation. ** patient was changed from DA EPOCH to R-CHOP as patient was not able to tolerate EPOCH ^ Epatients are halfway through their treatment cycles and are actively getting treatment

Disclosures:
No relevant conflicts of interest to declare.
The Vitamin B12 Content of Human Liver Tissue and Its Nutritional Significance
Authors: SWENDSEID MARIAN E. , HVOLBOLL ELIZABETH , SCHICK GERALDINE , HALSTED JAMES A. 
Published: October 2019

Abstract
Range and average values are reported for the vitamin B12 content of liver tissue obtained at autopsy from 132 individuals. Th average value for all age groups was approximately 0.70 γ per Gm. of wet tissues. In cirrhosis the average value was 0.26 γ per Gm. It was concluded that there are no apparent differences in vitamin B12 stores in the various age groups. Also, the amount of vitamin stored is relatively large in terms of requirement and is probably sufficient to last for a period of several years.
Specific and Cross-reacting Antibodies in ABO Heterospecific Twin Pregnancy
Authors: ZUELZER WOLF W. , COHEN FLOSSIE , ROBINSON ABNER R. , BEATTIE KATHRYN 
Published: October 2019

Abstract
A "study in depth" is reported concerning the case of hemolytic disease of a group B infant born to a group O mother, whose group A twin was apparently unaffected. It was shown that the hemolytic disease of the affected infant was due to a specific anti-B antibody. The study included parallel examinations of the antibodies in the sera of the three individuals.
The specificity of the B-anti-B reaction was demonstrated in vitro and in vivo. The powerful anti-B antibody of the mother had no effect on the group A twin, in whose serum anti-B was present in large amounts.
In vitro, studied by the usual technics of cross absorption the maternal and the fetal anti-A and anti-B serum antibodies behaved as if strictly specific. By applying successive absorption, elution and neutralization techniques, however, it was possible to demonstrate additional cross-reacting antibodies in the maternal serum which could be separated from one another and from the specific anti-A and anti-B antibodies. From the erythrocytes of the normal group A twin such cross-reacting antibody could be eluted.
The cross-reacting anti-B antibody, isolated in pure form in eluates, could be shown to be loosely attached to group A erythrocytes without producing visible agglutination reactions while after elution from A cells it did visibly agglutinate group B cells. It could be eluted from A cells, absorbed by fresh A cells and reeluted while retaining its anti-B effect. It was neutralized by group B saliva only. A separate anti-A antibody with similar properties was eluted from B cells and specifically neutralized by group A saliva.
A partial affinity of these antibodies for heterologous erythrocytes but not for specific soluble substances was thus demonstrated. These findings support neither the linkage hypothesis of cross reactions between anti-A and anti-B nor the C-anti-C hypothesis of hemolytic disease. They are in keeping with the view that group O sera contain variable complexes of anti-A and anti-B antibodies, composed of multiple fractions with different partial specificities. It is suggested that the occurrence or non-occurrence of cross-reacting antibodies found in sera of group O mothers whose infants develop hemolytic disease is best explained on this basis. It is further stressed that the demonstration of an antibody in mother or child in ABO hemolytic disease does not necessarily indicate its pathologic significance.