bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of Enteral Versus Parenteral Feeding As Nutritional Support In Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Lemal Richard , Guièze Romain , Moluçon-Chabrot Cécile , Hermet Eric , Ravinet Aurélie , Combal Cécile , Cabrespine Aurélie , Bay Jacques-Olivier , Corinne Bouteloup 
Published: October 2019

Abstract
Abstract 4576

Introduction
Allo-HSCT procedure is associated with a frequent and potentially severe malnutrition which could highly participate to the transplant-related morbidity (TRM). Optimal nutritional management is still poorly known while both enteral nutrition (EN) and parenteral nutrition (PN) are effective. We proposed to retrospectively evaluate the impact of EN versus PN as nutritional support on early outcome of allo-HSCT.

Patients and methods
We retrospectively analyzed all the successive patients who needed a nutritional support during their first allo-HSCT in our center from January 2009 to October 2010, excepting whose who had a progressive disease at time of transplant. Datas were compared in an intent to treat analysis according the EN or PN initial nutritional support strategy.

Results
We analysed early outcome of 56 successive patients. Twenty of them received a myeloablative conditioning regimen and 36 a reduced intensity one. A total of 28 agreed to receive EN via a nasogastric feeding tube and the remaining 28 received PN. No significant difference in terms of age, diagnosis, disease status at transplant, conditioning regimens, stem cell source, GVHD nor antifungal secondary prophylaxis could be observed between the EN and PN groups. We found a lower median duration of fever in EN (2[0–8] vs. 5[0–17] (days); p=0.0026) and a lower need for antifungal therapy in EN group (7/28 vs. 17/28; p=0.0069), with a lower median duration of intravenous antifungal use (0 day [0–99] in EN vs. 7 days [0–93] in PN; p=0.00034) while incidence of bacteriemiae was not different. We observed a lower rate of replacement of central veinous catheter in EN group (3/28 in EN vs. 9/28 in PN; p=0.05) and a lower rate of transfer to ICU in the EN group (2/28 in EN vs. 8/28 in PN, p=0.036) but early death rate (<100 days) was the same in each group (4/28 vs. 4/28, p=NS). Median neutropenia and thrombopenia duration and median transfusion requirements were not significantly different. Fourteen patients in EN group and 18 in PN group presented a grade 3–4 oral mucositis (p=NS). Grade III-IV GVHD incidence was comparable in both groups (4/28 vs. 8/28; p=0.19).

Conclusion
Compared with PN, EN directly decreases the infectious risk, particularly the fungal risk, and its complications in allo-HSCT, without influencing hematopoietic toxicity nor GVHD incidence. Based on these encouraging results, we are now conducting a prospective, multicentric and randomized trial to confirm EN benefice in allo-HSCT.

Disclosures:
No relevant conflicts of interest to declare.
Morphological Atypia Represents Favorable Prognosis of Chronic Lymphocytic Leukemia in Japanese Patients
Authors: Suzumiya Junji , Aoki Sadao , Isobe Yasushi , Ohta Masatsugu , Takizawa Jun , Izutsu Koji , Suzuki Ritsuro , Tsukasaki Kunihiro , Kuriyama Kazutaka , Ohshima Koichi , Tamura Kazuo 
Published: October 2019

Abstract
Abstract 4594

Background:
B-chronic lymphocytic leukemia (B-CLL) is rare in Japan. Therefore, only a few data are available on the clinical characteristics of B-CLL for Japanese patients (pts). We reported that the rate of atypical CLL appeared to be higher in Japanese pts than that of Caucasians.

Patients and Methods:
This nation-wide study was performed from Oct. 2003 to March 2008, and was supported by Japanese Elderly Leukemia and Lymphoma Study Group. The study was conducted in accordance with the Declaration of Helsinki and was approved by the Institutional Review Boards of the core members' hospitals. The pts with CLL and CLL-like disease were registered. Precursor leukemia and adult T-cell leukemia/lymphoma were excluded. The smears of peripheral blood and bone marrow of all the registered pts were examined by the Diagnosis Committee by using the 4th edition of WHO classification and FAB classification. FAB classification defines typical CLL as prolymphocytes≤10% and atypical CLL including CLL/PLL as 11%≤prolymphocyte<55% and CLL mixed as prolymphocytes<10% and pleomorphic lymphocyte>15%. Mantle cell lymphoma was excluded by means of cytogenetics, fluorescent in situ hybridization of CCND1-IGH, and immunohistochemistry of CCND1.

Results:
One hundred and thirty-one evaluable pts were registered. There were 96 pts with B-CLL, 2 SLL, 1 B-PLL, 3 hairy cell leukemia, 16 leukemic phase of other B-cell lymphomas. Thirteen pts had NK or T cell leukemia/lymphoma with 7 T-LGL, 4 T-PLL, 1 NK-LGL, and 1 Sezary syndrome. Among B-CLL, there were 62 pts with typical morphology (typical CLL), 18 with atypical morphology (atypical CLL), 16 with intermediate morphology between typical and atypical CLL (intermediate CLL). The differences among 3 subgroups are shown in Table. No differences were found between the 3 morphological subgroups for age, sex, stage (modified Rai and Binet classification), hemoglobin level, platelet counts, the presence of hepatomegaly, splenomegaly and lympoadenopathy, ECOG-PS and the rate of treatment requirement. However, the incidence of CD5 and CD23 expression was higher in typical CLL than in atypical/intermediate morphology groups (P<0.001), i.e. 7% of the pts with atypical CLL showed co-expression of CD5 and CD23. The overall survival (OS) of typical CLL pts was lower than that of intermediate or atypical CLL pts (Figure).

Conclusion:
Morphological atypia was more frequent in Japanese B-CLL pts, partly because of the low incidence of typical CLL. The atypical/intermediate CLLs were associated with atypical immunophenotype (absence of CD5 and/or CD23) and favorable prognosis. Prospective study is ongoing to evaluate other prognositic factors including the implication of IgVH gene mutation status and ZAP-70 expression in Japan.

Disclosures:
No relevant conflicts of interest to declare.
Primary Localized Laryngeal Amyloidosis (LA)
Authors: Richards Matthew , Le Kim , Lorenzo-Medina Mercedes , Dane Langsjoen , Arango Carmen , Gupta Anuradha , Garcia Rafael , Campos-Gines Angel F , Landeros Mark M , Herrada Juan 
Published: October 2019

Abstract
Abstract 4596

Background:
Localized Laryngeal Amyloidosis (LA) is a rare condition. There is limited understanding of its natural history. Our aim is to report the clinical evolution of a patient diagnosed with localized LA.

Methods:
Case report.

Results:
In May 2002, a 43-year-old gentleman presented with hoarseness and a CT scan of the neck showed a thickening of the right vocal cord with a mass that measured 2.9 × 1.2 cm in widest diameter. The patient had this mass removed surgically and the pathology showed a positive Congo red staining and a positive birefringence under polarized light, diagnostic of amyloidosis. No evidence of systemic amyloidosis or an overt B-cell lymphoma was found in this patient.
Patient lost follow-up until October 2008 when he was found to have soft tissue induration around the left false vocal cord area. The biopsy showed again amyloidosis.

Conclusions:
LA recurrences can manifest several years after initial diagnosis. Long-term follow-up is essential.

Disclosures:
No relevant conflicts of interest to declare.
Common Fragile Site Gene FRA16D WWOX (WW domain containing oxidoreductase) Is Frequently Altered in Plasma Cells of Multiple Myeloma and MGUS, Possibly Related to Disease Development
Authors: Sasaki Yoshiko , Handa Hiroshi , Takahashi Noriyuki , Hattori Hikaru , Saitoh Takayuki , Osaki Yohei , Matsumoto Morio , Isoda Atsushi , Sawamura Morio , Saito Akio , Yokohama Akihiko , Koiso Hiromi , Mitsui Takeki , Tsukamoto Norifumi , Nojima Yoshihisa , Murakami Hirokazu 
Published: October 2019

Abstract
Abstract 4646
The common fragile sites (CFSs) are regions of profound genomic instability, and hot-spots for deletions and other alterations in cancer cells. We have previously shown that promoter of FHIT is frequently methylated in multiple myeloma (MM) and correlated with worse prognosis. WWOX is located at a CFS region on chromosome 16q23.3, this gene is also a target of alterations in multiple cancers. The objective of current study is to find if this tumor suppressor gene is altered in MM and MGUS. Six myeloma cell lines, bone marrow mononuclear cells (BMMNC) of 165 MM and 25 MGUS patients were subjected to this study after obtaining informed consent. Isolated CD138 positive plasma cells (PC) of 24 MM were examined to see if the alteration occurred really in myeloma cells. Using methylation specific PCR, WWOX promoter methylation was detected in 2 of 6 cell lines, 35% of MM patients and 8% of MGUS patients (p=0.01). The overall survival of the MM patients with methylated WWOX tended to be worse than with unmethylated WWOX (p=0.2). Using nested RT-PCR, aberrant short transcripts of WWOX lacking exons coding SDR domain were detected in 4 cell lines, 68% of MM and 60% of MGUS (p=0.51) In isolated PC, aberrant transcripts of WWOX were detected in 58% of MM and 25% of MGUS (p=0.02). Real time PCR demonstrated higher WWOX expression in isolated PC of MM and MGUS than of BMMNC other than plasma cells (p=0.0001), and those higher WWOX were aberrant type (p=0.001). As aberrant WWOX is known to function as dominant negative for wild type, our results imply that this aberrant WWOX is an oncogene as well as losing tumor suppressor function. Since WWOX is demonstrated to regulate beta-catenin and NF-kB pathway, high frequency of aberrant WWOX expression indicates an important role in myeloma development.

Disclosures:
No relevant conflicts of interest to declare.
Expression of PIM-2 and NF-κB Is Increased in Patients with Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia (ALL) and Correlates with Complete Remission Rate
Authors: Kapelko-Slowik Katarzyna , Urbaniak-Kujda Donata , Wolowiec Dariusz , Dybko Jaroslaw , Jazwiec Bozena , Slowik Miroslaw , Jakubaszko Jacek , Owczarek Tomasz , Grzymajlo Krzysztof , Kuliczkowski Kazimierz 
Published: October 2019

Abstract
Abstract 4648

Background.
PIM-2 is a proto-oncogene that encodes for serine/threonine kinase which interacts with various signalling molecules. PIM-2 is highly expressed in neoplastic tissues and in leukaemic and lymphoma cell lines which is consistent with a its role during oncogenic transformation. The nuclear factor kappa B (NF-κB) pathway appears to be deregulated in variety of tumors, with sustained activity of NF-κB leading to apoptotic resistance in tumor cells

The aim.
The aim of this study was to investigate whether the PIM-2 and NF-κB expression is altered in acute myeloid leukaemia (AML) and acute lymphoblastic leukaemia (ALL). Patients and methods. One hundred fourty-three patients were included: 91 with AML and 52 with ALL (42 with B-ALL and 10 with T-ALL), aged 18–84 (median=41). Seventy-five patients reached complete remission (CR): 50 in AML and 25 in ALL. Bone marrow samples were collected at the time of diagnosis. Control samples were obtained from 24 healthy donors. We analysed PIM-2 and NF-κB expression by RQ-PCR analysis.

Results.
Expression of both PIM-2 and NF-κB in all leukaemic patients and in subgroups: AML and ALL was significantly higher than in controls. In AML group patients who reached CR expressed PIM-2 and NF-κB at significantly lower levels than patients with primary resistance to chemotherapy (with no CR, NCR). Moreover in AML, we have found the correlation between PIM-2, NF-κB expression and blasts in myelogram and PIM-2 and patients‘ age.

Summary.
Our data indicate that PIM-2 and NF-κB genes expression is increased in patients with AML and ALL and correlates with CR rate in AML patients.

Disclosures:
No relevant conflicts of interest to declare.
Molecular Diagnosis of Haemophilia B Leyden In a Chinese Pedigree: C>G Transition At Position +9 of the FIX Gene
Authors: Zhou Rong-Fu , Zhang Xian , Ouyang Jian , Tao Hong , Shao Xiao-Yan , Xu Jingyan , Li Ping 
Published: October 2019

Abstract
Abstract 4651

Objective
To investigate the molecular change causing Haemophilia B in a Chinese family.

Methods
The peripheral blood samples had been extracted from proband and his family members. The activated partial thromboplastin time (APTT), prothrombin time (PT) and FIX activity (FIX:C) were adopted for phenotype diagnosis. All the 8 exons and their flank boundaries were amplified by polymerase chain reaction (PCR). The PCR products were sequenced directly. The corresponding DNA fragments of their famliy members were amplified by PCR and then screeded by direct sequencing.

Results
The 3-year-old Chinese boy had persistent nose swelling for 10 days from an injury. He had a long APTT of 96.6s which could be corrected to 30.2s with mixed normal plasma. PT, TT and fibrogen level was in normal range, respectively. FVIII:C was 54%, FIX:C was 1.6% and AT:C was 115%. DNA sequencing of the proband’s F9 gene revealed that there was a C>G mutation at nt +9 in the promoter region. His mother, maternal grandmother and two maternal grandmother’s sisters all had the same C/G genotype, with FIX:C 44%, 89%, 81% and 67%, respectively. His maternal uncle, aged 30, had the C>G mutation with FIX:C 40% and another maternal uncle, aged 12, had the same mutation with FIX:C 4.2%.
To date, there are only two cases with Haemophilia B Leyden reported from Asia, one from Thailand (nt +8 T>C) and the other from HongKong (nt +6 T>A). The mutation at nt +9 C>G lies in the binding sites for transactivating factors, such as CCAAT/enhancer binding protein (C/EBP), affects the first (site 1: nt +1 to +18) of five known cisacting sites in the FIX promoter. The clinical picture of the proband reported herein and his maternal uncle with the same genetic defect conforms to the Leyden phenotype, because the uncle now has a relatively normal FIX level (40%) and no recent bleeding episodes.

Conclusion
The mutation at nt +9 C>G in FIX promoter might be the causative one leading to FIX deficiency in this Chinese pedigree.To the best of our knowledge, this is the first time to report the mutation at this site of FIX promoter.

Disclosures:
No relevant conflicts of interest to declare.
Acute Hemolytic Reactions Reported in ITP Patients Treated with Rho (D) Immune Globulin: Symptom Onset and Does Prior Exposure Lessen the Risk?
Authors: Muller Carmen , Little Gregg , Hess Kristen , Sinclair Chris 
Published: October 2019

Abstract
Abstract 4670

BACKGROUND:
Acute hemolytic reactions (AHR) associated with administration of Rho (D) Immune Globulin (RhIG; WinRho® SDF, Cangene Corporation, Winnipeg, Canada) have been infrequently reported during the previous 16 years. AHR were defined as any case reported with signs of hemolysis (hemoglobin decrease, haptoglobin decrease, LDH increase, elevation of bilirubin, etc.) occurring within hours to a number of days after RhIG administration irrespective of the degree of change from baseline. Intravascular hemolysis (IVH) was defined as a specific type of AHR in which plasma or urinary hemoglobin were positive. The reporting rate of AHR (including IVH) among RhIG-treated patients was previously estimated as 1/946 doses (0.11%), while the estimated reporting rate of IVH was 1/3,271 doses (0.03%).1 Reports surrounding the clinical monitoring of such patients have led to the analysis of AHR post-marketing data.

AIMS/PURPOSE:
Identify the onset of AHR/IVH symptoms relative to RhIG and determine if prior exposure to RhIG mitigates the risk of such events.

METHODS:
Retrospective evaluation of AHR (AEs reported with signs of hemolysis; including IVH) from the Cangene post-marketing surveillance database.

RESULTS:

CONCLUSION:
Of the ITP patients who developed IVH, 40% reported an onset of symptoms within 4 hours of RhIG infusion; an additional 10% reported symptoms within 8 hours. The symptom onset was unidentified in 18% of IVH cases. In addition, previous uneventful administration of RhIG did not preclude the possibility of an occurrence of IVH and its complications following subsequent administration of RhIG; however, the majority (approx 84%) of reports of IVH were among RhIG naïve patients.

Disclosures:
Muller: Cangene: Employment. Little:Cangene: Employment. Hess:Cangene: Employment. Sinclair:Cangene: Employment.
HIV-Associated Thrombotic Thrombocytopenic Purpura
Authors: Boro Jordana , Pavenski Katerina , Ambler Kimberley L.S. , Leitch Heather A , Hicks Lisa K 
Published: October 2019

Abstract
Abstract 4677
Thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening form of microangiopathic hemolysis that can be associated with HIV infection, and has previously been reported to be associated with low CD4 counts. The existing literature on HIV-TTP is very small and largely made up of small case series generated through databases of patients with HIV. As a result, reports have tended to focus on HIV parameters with limited information available regarding the presentation, management and outcome of the TTP itself. We conducted a retrospective review of TTP cases referred to the pheresis units St. Michael’s Hospital and Vancouver General Hospital in Vancouver between July 1993 and May 2011. Ten cases of HIV associated TTP were identified (8 male; 2 female). Median age at presentation was 38 years. One patient had been previously diagnosed and treated for TTP at a different institution. Average duration of HIV infection prior to TTP diagnosis was 5 years (range 0 to 11). Median CD4 count at TTP diagnosis was 79 × 106/ml (range 2 to 326). Median platelet count at presentation was 14 × 106/ml (range 5 to 233), median haemoglobin was 74 g/L (range 61 to 133), all patients had an LDH > 2x the upper limit of normal, and all for whom data was available (8/10) had fragmentation on blood film. Creatinine was elevated in 9 of 10 patients. ADAMTS13 was assessed in 3 of 10 patients and was deficient in one. Five of 10 patients had fever. At presentation, 6 of 10 patients had neurological symptoms (most commonly seizures and/or confusion), but none suffered permanent neurological deficits. All patients were treated with plasmapheresis and received a median of 16 exchanges (2-56). Four patients received concurrent steroids, two patients received IVIG, and one patient received pheresis, steroids IVIG, vincristine and rituximab. Eight of 10 patients achieved complete remissions, one patient achieved a partial response, and one died on treatment. Four of the responding patients subsequently relapsed (0.6 to 13.8 months after the initial episode of TTP); two achieved second remissions, and two died on treatment. In conclusion, our series of HIV associated-TTP confirms previous reports that HIV-TTP tends to occur in patients with CD4 counts less than 200. Complete remissions can be achieved with standard management. However, based on our small series, relapses may be more common and mortality greater than in the general TTP population.

Disclosures:
Leitch: Novartis Pharmaceuticals: Honoraria, Membership on an entity’s Board of Directors or advisory committees.
Generation of Induced Pluripotent Stem Cells From the Peripheral Blood of a Pyruvate Kinase Decifient Patient
Authors: Quintana-Bustamante Oscar , Garate Zita , Segovia Jose Carlos , Cerrato Laura , Güenechea Guillermo , Bueren Juan 
Published: October 2019

Abstract
Abstract 4713
The generation of induced pluripotent stem cells (IPSCs) from patients with specific diseases has improved the possibilities of dissecting the etiology of human pathological conditions and has opened potential new therapeutic options for the treatment of human diseases. One of the major safety concerns in the generation of hiPSCs is the persistence of copies of the reprogramming genes in the genome of iPSCs. Additionally, the use of cells from accessible tissues, like peripheral blood, constitutes preferential options for cell reprogramming, compared to other cells whose collection would require a more aggressive intervention. Here we have selected Pyruvate Kinase Deficiency (PKD) as a human disease affordable to be modeled and genetically corrected using hiPSC technology. PKD is an autosomal recessive disease that affects the erythrocyte R-type Pyruvate Kinase (RPK) enzyme by mutations in the PKLR gene, causing chronic nonspherocytic hemolytic anemia. Deficiency in the RPK, the last enzyme of the glycolisis, reduces the energetic balance of red blood cells and therefore affects the viability and function of the erythrocytes. Clinical symptoms of PKD can progress from mild to severe anemia and can be lethal in the most severe cases. Peripheral blood mononuclear cells (PB-MNC) from healthy donors and from a PKD patient were infected with five independent recombinant non integrative RNA Sendai viruses (SeV) encoding four human reprogramming factors (OCT3/4, SOX2, KLF4, c-MYC) and the Azami green protein as reporter. After infection with SeVs, no differences in the reprogramming efficiency of healthy and PKD PB-MNC were observed (1 hES-like colony per 6,000 transduced healthy or PKD PB-MNC). Integrated SeVs were not found in PBMNC-hiPS lines, as deduced from the lost of Azami green expression and also from RT-PCR analyses of the reprogramming factors. Healthy and PKD PBMNC-hiPSCs could be cultured for more than 15 passages, indicating their self-renewal ability. The pluripotent characteristics of these PBMNC-hiPS were confirmed by the analysis of expression of endogenous pluripotent genes by Q-RT-PCR and immunofluorescence. This study confirms the feasibility to generate integration-free hiPS lines from healthy and PKD PB-MNC. These hiPSC lines constitute an invaluable tool for the development of a human model of PKD and for applying new gene therapy strategies.

Disclosures:
No relevant conflicts of interest to declare.
Severe Neutropenia in Patients with Chronic Hepatitis C Not on Antiviral Therapy At the Memphis Veteran's Affairs Medical Center
Authors: Sheehan Vivien , Waters Bradford , Weir Alva B. 
Published: October 2019

Abstract
Abstract 4733
Abstract: We reviewed the records of 685 patients evaluated for treatment of chronic hepatitis C virus (HCV) at the Veteran's Affairs Medical Center in Memphis, TN in 2010. We identified six cases of severe neutropenia (defined as an absolute neutrophil count <500 x103/dL), in the absence of medications known to cause neutropenia such as interferon. None had concomitant HIV infections. Bone marrow biopsies were performed in three of the six patients and were negative for malignancy or abnormal myelopoesis. In this case series report, we compare laboratory parameters and clinical histories of these six patients to a similar cohort of chronic hepatitis C patients with at least one documented absolute neutrophil count (ANC) between 1000 x103/dL and 1500 × 103/dL. The two groups differed only in ANC and frequency of anti-nuclear antibody positivity. There was no significant difference in race, MELD scores, viral load, viral type, hemoglobin levels or platelet levels. Neither group suffered serious systemic infections. There was no evidence that the severe neutropenia was related to portal hypertension or splenomegaly. In our series, patients with severe neutropenia in the setting of chronic HCV had a benign course that did not lead to severe infections and responded to granulocyte colony stimulating factor. This opens the question of whether these patients may be candidates for antiviral therapy.

Disclosures:
No relevant conflicts of interest to declare.