bluuebunny/crossref_metadata_2025_split huggingface dataset:
Some Leukemia Cells Are Dependent on Glutamine as Energy Source
Authors: Miwa Hiroshi , Shikami Masato , Imai Norikazu , Suganuma Kazuto , Goto Mineaki , Mizuno Shohei , Takahashi Miyuki , Nitta Masakazu 
Published: October 2019

Abstract
Abstract 4861
In cancer cells, glucose uptake is elevated and glycolysis persists even under aerobic conditions (Warburg effect). Glutamine metabolism is another target for alteration in cancer development. Glutaminolysis (catabolism of glutamine to generate ATP) is known to increase in tumors. We examined the dependency of the leukemia cells (Kasumi-1, THP-1, HL-60 and NB4) on glucose or glutamine by measuring the growth (MTS count) in glucose- or glutamine-deprived condition. Glucose withdrawal greatly suppressed the growth of all 4 cell lines. However, glutamine withdrawal showed different growth suppressive effects among the cell lines (Kasumi-1: 55% of control, THP-1: 60%, HL-60: 39%, NB4: 70%). HL-60 was most sensitive to glutamine deprivation. The growth suppression of HL-60 due to glutamine withdrawal was partially rescued by oxaloacetate (OAA), a TCA cycle metabolite, while the growth of other cell lines was not rescued by OAA. In the course of glutamine catabolism, ammonia is liberated. Although basal level of the ammonia concentration was not so different among each cell line, glycolysis inhibitor (2-deoxyglucose) treatment enhanced the ammonia generation in HL-60 (Kasumi-1: 2.8% increased, THP-1: 1.7%, HL-60: 6.1%, NB4: 2.8%). Glutaminase, an enzyme converting glutamine to glutamate, is most abundantly expressed in HL-60 in western blot analysis. In addition, HL-60 was most sensitive to the treatment with aminooxyacetate, an inhibitor of glutamate-dependent transaminases that convert glutamate into a-ketoglutarate in the glutaminolytic pathway (Kasumi-1: 86% of control, THP-1: 97%, HL-60: 79%, NB4: 83%). Taken together, HL-60 was considered as glutamine dependent cell line. Therapies targeting glutamine metabolism, such as glutamine depletion or use of inhibitor of glutaminolytic pathway, might be effective against some leukemia.

Disclosures:
No relevant conflicts of interest to declare.
Acute Tumor Lysis Syndrome. Modulation of Cyclooxygenase-2, Alpha V Beta Integrin and Microsomal Prostaglandin E Synthase-1 In Human Immunodeficiency Virus-1 (HIV-1) Squamous Cell Carcinoma (SCC) of the Penis with Selenomethionine/Nsaids
Authors: McPherson Eugene 
Published: October 2019

Abstract
Abstract 4880
Invasive squamous cell carcinoma of the penis overexpress Cyclooxygenase-2 (cox-2), Microsomal Prostaglandin E Synthase-1 and Alpha V Beta Integrins. Trace minerals selenium (selenomethionine) is deficient in many neoplasia conditions especially SCC of the penis in HIV-1 patients. Selenium, an essential trace element, has been shown to inhibit tumorigenesis. Hence, selenium and arachidonic acid metabolism may be linked to SCC. Penile cancer (SCC histology) displays elevated COX-2 and PGE2 can be regulated by selenium supplementation.
We present a 47 We present a 47 yo male with HIV-1, CD4-133/cumm, VL of 95,000 copies/ml with T4 advanced stage SCC of the penis post XRT, surgical skin graft with extensive lymphedema, pain and KPS score of 40–50%. CT scan of Abdomen/Pelvis was c/w extensive disease of his right inguinal region, bladder compressed and displaced into left pelvis and tissue massof the right and left groin with ill defined nodular densities within RLL and left hepatic lobe. Bone marrow was hypocellular, M:E ratio of 8:1 with foamy macrophages. When treated for selenium deficient level and pain with selenomethionine and COX-2 inhibitor, acute tumor lysis syndrome developed with hyperkalemia, hyperuricemia and hypocalcemia defervesing with aggressive therapy with hydration, alkalinization and allopurinol.

Conclusion:
Overexpression of COX-2, mPEGS-1, alpha V beta integrin leads to phenotypic changes in epithelial cells that could enhance tumorigenesis. Selenium supplementation and COX-2 inhibition may help regulate COX-2 alternating cellular adhesion and promote apoptosis in SCC of the penis and upon treatment of these HIV-1 patients, with heavy tumor burden, tumor lysis syndrome along with disease Invasive squamous cell carcinoma of the penis overexpress Cyclooxygenase-2 (cox-2), Microsomal Prostaglandin E Synthase-1 and Alpha V Beta Integrins. Trace minerals selenium (selenomethionine) is deficient in many neoplasia conditions and PGE2 can be regulated by selenium supplementation. especially SCC of the penis in HIV-1 patients. Selenium, an essential trace element, has been shown to inhibit tumorigenesis. Hence, selenium and arachidonic acid metabolism may be linked to SCC. Penile cancer (SCC histology) displays elevated COX-2.

Disclosures:
No relevant conflicts of interest to declare.
Does Upfront Therapy with Fludarabine Increase the Risk of Histological Transformation In Patients with Follicular Lymphoma?
Authors: Yaqub Sobia , Gress Todd W. , Ballester Oscar 
Published: October 2019

Abstract
Abstract 4885

Introduction:
Fludarabine has been reported to increase the incidence of relapse and histological transformation in chronic lymphocytic leukemia (Thornton PD, Leukemia research, 2005) and Waldenstrom macroglobulinemia (Leleu X, J Clincal Oncology, 2009). The purpose of our study was to investigate the role of Fludarabine and the risk of transformation and relapse in follicular lymphoma (FL).

Patients and Methods:
This is a retrospective single institution study. We included 50 patients consecutively diagnosed with FL Grade I and II based on WHO classification of lymphoid malignancies. Grade III patients were excluded from the study. Median follow up is 2.86 years. Patients were grouped according to the initial therapy chosen by their treating physicians: Group 1(n=14) included patients on observation and radiation therapy, Group 2 (n=6) included patients on Fludarabine based regimens, Group 3(n=13) included CVP-R and other rituximab regimens and Group 4(n=17) included R-CHOP. Data collected included time to the onset of biopsy proven transformation, time to relapse, mortality and overall survival. Level of significance was set at <0.05.

Results:
Median age of the patients was 56.5 and it was not significantly different for the various groups. High risk FLIPI score was seen in 66% of patients treated with Fludarabine regimens as compared to 61% of R-CHOP treated patients. Overall, relapse occurred in 38% patients and transformation occurred in 16% patients during the follow up period. Fludarabine treated patients had the highest relapse rate: 50% (p=0.03). R-CHOP group has lowest relapse rate: 11%. Transformation rate was highest in the Fludarabine group: 33%, as compared to 13% to 17% in other groups (p=0.10). Mortality rate was 7% in group 1, 16% in group 2, 23% for group 3 and 5% in group 4 (p=0.44). Time to relapse/progression in group 1 was 2.9 years; in group 2 was 2.1 years; in group 3 was 2.7 years and in group 4 was 5.8 years.

Conclusions:
In our study, Fludarabine treated patients appear to be at higher risk for relapse and transformation compared to patients treated with R-CHOP. The differences can not be explained on the basis of known prognostic factors such as age or FLIPI score. The retrospective nature of the study and the small numbers of patients preclude more definitive conclusions. Further research is needed with large number of patients.

Disclosures:
No relevant conflicts of interest to declare.
Treatment of Sezary Syndrome with Combined Therapy
Authors: Corinaldesi Giorgio 
Published: October 2019

Abstract
Abstract 4928
The Sezary syndrome (SS) is an erythrodermic cutaneous T-cell lymphoma with a leukemic component and lymphadenopathy, characterized by atypical T-lymphocytes, and a CD4 + T-helper/memory; these cells may express the markers CD45RO, and CD25 with frequent loss of the CD26, CD7, CD2, CD3, and with cerebriform nuclei.
The strategies for patients with SS in early stage, when the disease is limited to the skin, includes topical therapies with corticosteroids (clobetasol), carmustine, retinoids (bexarotene, tazarotene) and phototherapy with PUVA (psoralen and ultraviolet light), in the refractory or relapsed patients polychemotherapies (CMED/AB, Pegylated liposomal doxorubicin, gemcitabine) may reduce tumor burden, as well as the symptoms, and most interestingly, it may delay tumor progression and preserve significantly the quality of life; the most typical approach might be constituted by a high dose of chemotherapy followed by allogenic bone marrow transplantation.
We have studied 2 patients with advanced stage IIB. One of them was a 52-year old patient (T3, NP0, M0, B0), and the other one was a 62-year old patient (T3, NP1, M0, B1); both of them were treated with the following drug-combination: bexarotene 150 mg os daily, and vorinostat 400 mg os once daily, and localized treatment with clobetasol. This scheme had a significantly high clinical response and little side effects (fatigue, lethargy, thrombocytopenia, headache), and the patients remained in remission the first for 4 years DFS and the latter for 3 years DFS; both of them were initially treated with PUVA, MTX 50 mg, and INF-alfa 3 MU per day.

Disclosures:
No relevant conflicts of interest to declare.
Clinical Safety of Long-Term Intravenous Itraconazole for the Treatment of Invasive Fungal Infection In Severely Ill Patients with Hematological Malignancies
Authors: Xie Yaping , Qian Shenxian , Gao Daquan , Huang Xilian , Shi Pengfei , Chen Kuang , Tan Junfeng , Liu Lirong 
Published: October 2019

Abstract
Abstract 4943
The clinical safety of intravenous itraconazole use exceeding 14 days is unknown. However, many cases need further treatment, but the absorption of itraconazole oral in severely ill patients is variable and unpredictable. Gastric acidity and food influence the absorption of oral formulation. The intravenous formulation, on the other hand, achieves adequate blood levels more rapidly and its bioavailability is predictable and invariable compared to the oral formulation. We performed this study to investigate the clinical safety of long-term intravenous itraconazole for the treatment of invasive fungal infection (IFI) in severely ill patients with hematological malignancies. 20 patients (median age, 70 years; range, 38–82 years) with hematological malignancies who had met the IFI inclusion criteria were enrolled. All the infection sites were the lung. These patients were given intravenous itraconazole for 14 days. There were significant effective but the lesions were not fully absorbed and no severe adverse events were found. So the long-term intravenous itraconazole therapy was enabled. Clinical efficacy and adverse events were recorded. Itraconazole 200 mg via intravenous infusion (administered over 1 hour) twice a day for 4 doses followed by 200 mg once a day until the lesions was fully absorbed. The treatment median time was 27(18-58) days. During this period, closely monitor changes in vital signs, chest CT, liver enzymes, renal function, electrocardiogram and electrolytes were assessed. We found that the patients achieved composite endpoints including survival, defervescence and undetectable lesions, except one patient died of primary disease - acute myeloid leukemia. Treatment-related adverse events were found in 7 patients (35%) during the study and none of them were severe adverse events. Such as hypokalemia (10.0%), gastrointestinal disorders (10.0%), elevation of liver enzymes (10.0%) and pleural effusion (5.0%). All the adverse events occurred during the first two weeks of the treatment and no significant exacerbation in the following days.
In conclusion, long-term intravenous itraconazole therapy was effective for IFI and the drug-related adverse events have been shown to be generally predictable and manageable.

Disclosures:
No relevant conflicts of interest to declare.
Concomitant Usage of Rasburicase and Allopurinol May Augment Toxic Epidermal Necrolysis Syndrome TEN
Authors: Jajeh Ahmad 
Published: October 2019

Abstract
Abstract 4949
Rasburicase is used succesfully in conjunction with Allopurinol in the tratment and prevention of tumor lysis syndrrome. Rasburicase is a recombinant form of urate oxidase, which is an enzyme present in primates but not humans and convert uric acid to allantoin, which is five to ten time soluble than uric acid. This abstract represent our experience in four males patients, mean age is thirty five years, two with Acute Lymphoblastic Leukemia ALL and two patients with Burkitt's Lymphoma. Three patients has successful outcome in the treatment with Rasburicase followed by allopurinol. Only one patient with Burkitt's Lymphoma arising from congenital combined immunodeficiency syndrome who developed fatal Toxic Epidermal Necrolysis syndrome TEN. TEN is a relatively rare incidence and can be deadly. The mechanism of action is different for both drugs. In this patient Rasburicase was used initially with excellent reduction of uric acid levels, then patient was put latter on allopurinol. The TEN syndrome appeared after three days of initiating the drug and progressed rapidly. High dose Methotrexate and sever neutropenia may contributed to the fast progression and not respoding to steriods after allopurinol was stopped. Since this patient has combined humoral and cellular immunodeficiency with no recent administartion of immunoglobulins therapy, it is difficult to explain the allopurinol reaction based on any type of immune response, particulary type IV hypersensitivity reaction.
In conclusion: This particular case may draw the light on Rasburicase possible role in contribution or augumentation of TEN syndrome induced by allopurinol.

Disclosures:
No relevant conflicts of interest to declare.
A 2-Year Single Center Experience of Decitabine Treatment for the Patients with MDS and CMML
Authors: Yi Jun Ho , Jung Chul Won , Kim Dong Hwan (Dennis) , Kim Kihyun , Jang Jun Ho 
Published: October 2019

Abstract
Abstract 4952

Purpose:
Decitabine is effective to MDS and CMML patients. However few long term follow up data has been reported. We report a 2 year, single-institutional data of decitabine treatment in patients with MDS and CMML.
Patients and Methods: Patients were treated with decitabine 20 mg/m2 by IV infusion daily for 5 consecutive days every 4 weeks. Bone marrow examination was performed every 2 cycles. The response was evaluated according to IWG 2006 criteria.
Results: Fifty-four patients were evaluated. The median age was 63.5 years (range, 23–80) and the median cycle was four. (range 2–15). Among 54 patients, 13 were complete responses(CR), 1 partial response, 10 marrow CRs(mCR), 6 hematologic improvements, respectively. The overall response rate was 44.3% and overall improvement rate was 55.6% which included six patients with hematologic improvement. Among responders, 28 (93.4%) patients showed response at least in two cycles. Out of 18 patients with intermediate or poor cytogenetic abnormalities, only one patient had demonstrated cytogenetic CR. Out of total 326 cycles, 24 events of febrile neutropenia, nine events of bacterial pneumonia, eight events of fungal pneumonia, four events of bleeding and two events of hepatic dysfunction were occurred, and most complications were medically manageable. 10 out of 13 CR patients were maintained CR with decitabine treatment. The median overall survival duration was 20.2 months (95% CI 14.6 – 25.8). Stopping decitabine treatment had led to leukemic progression within 3 to 5 months in four patients who had achieved mCR and three patients who had achieved CR.
Conclusion: Five day scheduled decitabine treatment demonstrated rapid and durable response in patients with MDS. However, even after achieving clinical response, keeping decitabine treatment seems to be necessary to prevent leukemic progression. Further study for role of maintenance therapy is needed.

Disclosures:
No relevant conflicts of interest to declare.
Expression of CD123 and CD114 on the Bone Marrow Cells of Patients with Myelodysplastic Syndromes
Authors: Shao Zonghong , Yue Lanzhu , Fu Rong , Wang Huaquan , Li Lijuan , Hu Haoran , Fu Lin 
Published: October 2019

Abstract
Abstract 4966

Background
Recent studies have shown that interleukin-3 receptor α(CD123) is highly expressed on leukemia stem cells of patients with acute myeloid leukemia, and is correlated with tumor load and poor prognosis. The expression of CD123 may also be high in patients with myelodysplastic syndromes (MDS). In this study, the expression of CD123 as well as granulocyte colony stimulating factor (G-CSF) receptor (CD114) on the bone marrow cells of patients with MDS was investigated in order to explore the molecular marker of the malignant clone of MDS.

Methods
Forty-two patients with MDS, who were diagnosed in the hematological department of General Hospital of Tianjin Medical University from 2008 to 2009, and twelve normal controls were enrolled in this study. FACS was used to measure the expression of CD123 on CD34+CD38- cells and CD114 on CD34+ cells of the bone marrow of these patients and controls and the clinical significance was analyzed. The expression of CD114 on CD123+CD34+CD38- cells was further measured to explore the molecular marker of the malignant clone in MDS.

Results
The ratio of CD34+CD38-/CD34+ in the bone marrow cells of MDS patients was [(14.03±5.27)%], significantly higher than that of normal controls [(7.70±4.36)%] (P<0.01); The ratio of CD123+CD34+CD38-/CD34+CD38- in the bone marrow cells of MDS patients[(48.39±28.15)%]was significantly higher than that of normal controls [(8.75±11.71)%] (P<0.01), and was significantly positively correlated with the proportion of bone marrow blasts(r=0.457, P<0.05). The ratio of CD114+CD34+/CD34+ in the bone marrow cells of MDS patients [(33.05±21.71)%] was lower than that of normal controls [(38.99±19.07)%], but with no significance(P>0.05). The expression of CD114 on CD123+CD34+CD38-cells [(34.82±29.58)%] was significantly lower than that on CD123-CD34+CD38-cells [(53.48±27.41)%] of MDS patients (P<0.05).

Conclusions
MDS patients displayed higher proportion of CD34+CD38-/CD34+ than normal controls. CD123 was highly expressed in the bone marrow of patients with MDS, significantly correlated with the proportion of bone marrow blasts, thus might be the marker of MDS malignant clone. CD123+CD34+CD38-cells exhibited lower expression of G-CSF receptors, which might partly explain why MDS clone responsed worse to G-CSF in vitro and in vivo.

Disclosures:
No relevant conflicts of interest to declare.
Activated Protein C Resistance (APC-R) Analyzed as a Continuous Variable Is Significantly Decreased In Patients with Multiple Myeloma (MM) Compared to Normal Individuals
Authors: Berno Tamara , Boucher Kenneth , Zhan Fenghuang , Fink Louis M. , Tricot Guido J. , Mughal Benjamin , Zangari Maurizio 
Published: October 2019

Abstract
Abstract 4988

Background:
Increased risk of venous thromboembolism (VTE) has been described in multiple myeloma (MM) patients, particularly when exposed to immunomodulatory drugs. Epidemiological studies have showed that monoclonal gammopathy of undetermined significance (MGUS) patients also have an increased risk of VTE compared with normal subjects. Acquired activated protein C resistance (APC-R) is an independent risk factor for VTE in hematologic malignancies.

Methods:
We reviewed the records of patients with MM and MGUS for APC resistance by PREFAKIT APC-R test. We excluded from the analysis patients with a documented Factor V Leiden mutation. The PREFAKIT APC-R is a plasma-based functional clotting assay based on the ratio of patient clotting time with and without APC which is standardized and reported as normalized ratio (normalized to results obtained on pooled normal plasma which is performed on each run).

Results:
APC-R results from 33 MGUS and 75 MM patients were compared with 39 normal subjects. The median APC-R for MM, MGUS and normal subjects were 1, 1.05 and 1.1 respectively. MM patients compared to normal subjects, had significantly lower APC-R (P = 0.0016). No significant difference was observed between MGUS and normal subjects (P= 0.11) (Figure 1). Baseline characteristics from the three groups were similar in terms of age, sex, and performance status.

Conclusion:
APC-R measured as continuous variable shows a statistically significant decrement in patients with paraproteinemias compared to normal subject and correlates to the underline hypercoagulability observed in patients with MGUS and MM.

Disclosures:
No relevant conflicts of interest to declare.
Direct Myeloma Cell Invasion as One of the Major Causes of Renal Impairment In Myeloma A Pathological Analysis of Renal Findings In 41 Autopsied Cases
Authors: Tagashira Amane , Takano Junichiro , Hagiwara Shotaro , Mochizuki Makoto , Endo Hisako , Hirai Risen , Tanimura Akira , Takeshita Masataka , Murakami Hirokazu , Miwa Akiyoshi 
Published: October 2019

Abstract
Abstract 5001

Background:
Renal insufficiency is one of the main complications in myeloma patients. Various causes were reported to be responsible for renal damage. Through analysis of an autopsied cases we would show the diversity of the renal diseases in myeloma.

Methods:
We studied 41 autopsied myeloma cases from 1979 to 2008 at the National Center for Global Health and Medicine. The kidneys were evaluated by light microscopy using hematoxilin-eosin-stained sections, as well as Congo-red stain when amyloidosis was suspected.

Results:
There were 21 men and 20 women. Mean age at autopsy was 64.5 years old. The most common lesion was cast nephropathy (41.5%). The giant cell invasion was found in 35.3% of patients with cast nephropathy. Plasma cell tumor involvement was detected in 29.3% of all 41 autopsied cases. Fourteen per cent of cases had both cast nephropathy and plasma cell tumor involvement. In 75.6% of the patients, arteriosclerosis was found. In addition, 32% of the patients had the glomerular sclerosis which involved more than 20% of the glomerulus. Other findings include acute tubular necrosis (31.7%), AL-amyloidosis (19.5%), renal calcification (17.1%), bacterial and fungal infection (7.7%), micro thrombo-embolism (7.7%), mesangial proliferation (4.9%). At least one of above findings were detected in all cases and combined findings were detected in 65.9% cases.

Conclusion:
We evaluated the renal manifestations in 41 autopsied cases in detail. In all cases, at least one pathological finding was detected. Cast nephropathy was the most common renal manifestation. However, direct myeloma cell invasion was found in 29.3% and combined pathologic findings were common.

Disclosures:
No relevant conflicts of interest to declare.