bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pediatric Myelodysplastic Syndrome In Japan and China According to 2008 WHO Classification
Authors: Yang Wenyu , Zhang Peihong , Hama Asahito , Ito Masafumi , Kojima Seiji , Zhu Xiaofan 
Published: October 2019

Abstract
Abstract 5030
Unlike adult myelodysplastic syndrome (MDS), most of children with MDS have hypocellular bone marrow. Thus, distinguishing MDS from aplastic anemia (AA) can be diagnostically challenging in these patients. To clarify the frequency of pediatric MDS and AA with hypocellular bone marrow in eastern Asia, Japanese and Chinese pediatric hematologists and pathologists conducted a review of 100 patients with cytopenia (50 from Japan, 50 from China). Films stained with both peripheral blood (PB) and bone marrow (BM) along with specimens of BM trephine biopsy were available for all of the patients examined. Patients included 45 males and 55 females, with a median age at diagnosis of 9 years (range: 1 to 19 years). A total of 76 patients had pancytopenia at the time of diagnosis, while 23 had bi-cytopenia and 1 had isolated thrombocytopenia. The medium internal from onset to diagnosis was 319(1–4165) days. Most children present with nonspecific symptoms as a result of cytopenia, including pallor(24%), fatigue(11%), petechiae (27%), bleeding (31%), fever (19%) and infections (10%). Hepatosplenomegaly is uncommon. Before diagnosed, 7% of patients had idiopathic thrombocytopenic purpura (ITP) and 8% of patients had other diseases such as asthma, pneumonia and etc. Cytogenetic analyses performed in 75 patients indicated the karyotype was normal in 45 patients, while 4 had trisomy 8, 1 had monosomy 19, and 2 had trisomy 2. Other abnormalities found included t(X;3)(p11.2;q13), add(6)(p21), and +6. The final diagnoses reached by consensus among the hematologists for the 100 patients included AA in 30 cases, refractory cytopenia of childhood (RCC) in 59 cases, and refractory cytopenia with multi lineage dysplasia (RCMD) in 11 cases. The distribution of the subtypes in the Japanese and Chinese cases were 14:16 for AA, 33:26 for RCC, and 3:8 for RCMD, respectively. In 9 of the patients, the hematologists and pathologists could not agree on the final diagnosis. In 5 of these cases, the hematologists diagnosed the patients as AA, while the pathologists diagnosed RCC. We analyzed the difference between pediatric hematologists and pathologists are the quality of bone marrow and biopsy samples' disparity. Overall, our results suggest that there is no difference in the distribution of the MDS subtypes between Japanese and Chinese children. In order to ensure there is a correct diagnosis of childhood MDS, cooperation between hematologists and pathologists is indispensable.

Disclosures:
No relevant conflicts of interest to declare.
Impact of Age on Physician's Decision to Pursue Active Treatment in Elderly Patients with Myelodysplastic Syndromes: Results from an Internet-Based Survey
Authors: Smith B. Douglas , Santini Valeria , Kurtin Sandra E. , Huber John , Campbell Kenneth , Waldman Anita 
Published: October 2019

Abstract
Abstract 5045

PURPOSE:
Myelodysplastic syndromes (MDS) are a group of hematological disorders predominantly affecting older patients. A patient's age influences the treating physician's decision to proceed with active treatment in MDS, with older patients being less likely than younger patients to receive active treatment, irrespective of their physical status.

DESIGN:
This study is an internet-based survey of hematologists and oncologists who treat patients with MDS consisting of a 47-item questionnaire designed to assess 1) factors physicians consider when determining treatment recommendations for MDS patients, 2) the impact of patient age on treatment decisions and 3) views on tools available to physicians to guide their treatment plans. Respondents were given hypothetical patient scenarios and asked to select their recommended treatment based on the available information.

RESULTS:
A total of 310 online interviews were conducted in North America and Europe. Although physicians cited biological age and disease performance status as more important, chronological age nevertheless emerged as a strong influencing factor on their treatment recommendations for MDS patients aged 65 years and older. For instance, physicians were significantly more likely to prescribe active therapy to a 70-year-old patient with secondary MDS and an intermediate International Prognostic Scoring System level than to an 80-year-old patient with otherwise identical characteristics (32% vs. 12%; p<0.05). Concerns regarding treatment toxicity influenced the recommendations of 66% of physicians, and 29% expressed dissatisfaction with the amount of data available to help guide treatment recommendations. A majority (62%) agreed that better guidelines would prevent under-treatment of older patients.

CONCLUSION:
Chronological age can influence physicians' treatment recommendations for MDS patients. The findings suggest that some older patients may be denied appropriate treatment options due to age and support the need for additional clinical evidence for older patients with MDS, such as validated comprehensive geriatric assessment tools to support treatment decisions regarding active treatment.

Disclosures:
Smith: Celgene: Honoraria. Santini:Celgene: Honoraria. Kurtin:Celgene: Honoraria. Huber:Celgene: Honoraria. Campbell:Celgene: Honoraria. Waldman:Celgene: Honoraria.
The Limited Screening Value of Insulin-Like Growth Factor-I in 610 Very Long Term Adult Survivors of Leukemia and Other Types of Childhood Cancer
Authors: Blijdorp Karin , van den Heuvel Marry M. , Pieters Rob , Boot Annemieke , van der Lely Aartjan , Neggers Sebastian J.C.M.M. 
Published: October 2019

Abstract
Abstract 506FN2

Introduction
Over the last decades childhood cancer survival rates have improved significantly. Currently, 70–80% of patients become long term cancer survivors. It has been estimated that 1 out of 640 young adults in the U.S. is a survivor of childhood cancer. Consequently, the incidence of late, treatment-related complications is increasing. Endocrine sequelae, such as the metabolic syndrome, osteopenia, sub fertility, thyroid dysfunction and growth hormone deficiency represent an important category of such late effects. Growth hormone deficiency (GHD) in childhood cancer survivors, mainly caused by cranial radiotherapy, is reflected by low levels of insulin like growth factor 1 (IGF-I). Whereas the value of IGF-I measurement for the diagnosis of GHD is controversial, low IGF-I levels are associated with high body mass index and high visceral fat percentage. However the clinical relevance of low IGF-I levels in long term childhood cancer survivors is not extensively studied. In this study we evaluated whether IGF-I is useful as a marker for altered body composition and growth hormone deficiency in this group.

Methods
We retrospectively analyzed data of 610 adult childhood cancer survivors, retrieved from the Rotterdam late effects clinic, which starts 5 years after cessation of therapy. Median age at diagnosis was 6 years (interquartile range (IQR) 3–11) and follow up time was 18 years (13–24). We assessed IGF-I Z-scores, anthropometrical measures, growth hormone stimulation tests in patients with clinical suspicion of GHD and measures of body composition (assessed by dual X-ray absorptiometry, Lunar Prodigy).

Results
Cranial irradiated acute leukaemia survivors (25 Gy (24–25)) and locally irradiated brain tumour survivors (42 Gy (35–54)) had significantly lower IGF-I Z-scores (p<0.001), lower height SDS (p<0.001), higher body mass index (p=0.01), higher waist-hip ratio (p=0.001), higher visceral fat percentage (p<0.001), higher total fat percentage (p<0.001) and lower lean body mass (p<0.001), compared to non cranial irradiated survivors. IGF-I did not show a strong correlation with BMI (r=-0.12, p=0.04), waist hip ratio (r=-0.15, p=0.01), total fat percentage (r=-0.14, p=0.02) and lean body mass (r=0.15, p=0.01). In the patients with low IGF-I levels who had growth hormone stimulation, IGF-I Z-scores did not significantly differ between the patients with and without severe GHD (p = 0.39).

Conclusion
This study shows that there is a limited value of IGF-I as marker for alterations in body composition, and confirms the fact that low IGF-I levels are not predictive for GHD, in a large cohort of childhood cancer survivors. Therefore the use of IGF-I should not be encouraged in adult childhood cancer survivors.

Disclosures:
No relevant conflicts of interest to declare.
Gynecomastia In Multiple Myeloma Patient Treated with Cytoxan
Authors: Jajeh Ahmad 
Published: October 2019

Abstract 5131
Cytoxan is an active drug in the treatment of multiple myeloma. It is commonly reserved for patients who became refractory to common active drug therapy or in combination with other active agents such as bortezomib, pegylated liposmal doxorubicin, vincristine, melphalan and decadron in patients who are not eligible for autologous bone marrow transplant. This abstract is intended to present interesting side effect of cytoxan that seen only in multiple myeloma and not seen in other hematological malignancies or solid tumors. Gynecomastia is defined as hypertrophy of breast tissue in male which can be seen in various medical condition associated with endocrine disturbances. In this abstract will describe five cases of significant degree of gynecomastia that seen exclusively in african american males and not seen in white males. Median age of patients is 57 years, range 40–68. Three has failed tandem autologus bone marrow transplant and has been exposed to lenalidomide and bortezomib. The other two have failed many lines of therapy including melphalan and prednisone. Gynecomastia has not been seen in other white males who received cytoxan in the treatment of multiple myeloma. The degree of gynecomastia was very significant in all of the five african american males. Also this is a limited number of patients but it is interesting enough to draw attention on possible endocrine disturbances seen particularly in multiple myeloma and other plasma cell dyscrasia such as Poems syndrome. The fact that gynecomastia is exclusively seen in african american males who all denied abusing marijuana is of scientific interest that needed further study and attention.

Disclosures:
No relevant conflicts of interest to declare.
Alternative Dosing of Cyclophosphamide, Bortezomib and Corticosteroids (CyBorD) for Relapsed/Refractory Multiple Myeloma
Authors: Ho Viet Q. , Finley-Oliver Elizabeth , Shain Kenneth H. , Alsina Melissa , Ochoa Leonel , Nishihori Taiga , Djulbegovic Benjamin , Baz Rachid 
Published: October 2019

Abstract
Abstract 5142

Background:
The combination of an alkylating agent and bortezomib has been shown to be synergistic both preclinically and in the clinical arena. Although the combination of cyclophosphamide, bortezomib and corticosteroids (CyBorD) has been evaluated by several investigators, many have used different doses and schedule of cyclophosphamide and an optimal schedule has not been established. Herein, we report the safety and efficacy of this combination in patients with relapsed and refractory multiple myeloma.

Methods:
All patients with myeloma that received this schedule of CyBorD at the Moffitt Cancer Center were included. CyBorD was comprised of cyclophosphamide 1000 mg/2 IV on Day 1, Bortezomib 1.3 mg/m2 IV on Days 1, 4, 8, and 11 and either low dose dexamethasone (equivalent of 120– 160mg/cycle) or prednisone (100 mg PO day 1–5). Demographic, laboratory and clinical data was collected and evaluated via descriptive statistics. Response and progression are defined as per the IMWG uniform response criteria.

Results:
A total of 20 patients were identified and included for analysis. Demographic data is shown in table 1. At baseline, 35% of patients were platelet transfusion dependent, and the median ß2m was 6.2mg/L. 8 patients (40%) received prophylactic GCSF and 9 patients (45%) received secondary GCSF after significant neutropenia was noted. Overall response rate (PR and better) was 50% (70% minimal response and better), including 1 complete response (CR) and 5 very good partial response (VGPR). Median progression free survival was 3.4 months (95% CI 0–7.5 months) and median overall survival was 11.9 months (95% CI 3.3–20.0). The incidence of grade 3/4 neutropenia and thrombocytopenia was 80% and 75%, respectively. Grade 2 and 3 peripheral neuropahty developed in 1 and 1 patient respectively. Nine patients required dose reductions of cyclophosphamide (only 2 of the 8 who received prophylactic GCSF therapy) and 3 patients required dose reductions of the bortezomib.

Conclusion:
In this cohort of patients with high burden of disease, intermediate dose cyclophosphamide administered once every 3 weeks in combination with standard dose and schedule of bortezomib results in a meaningful response rate (albeit short PFS) with mainly hematologic toxicities that are manageable with growth factor support.

Disclosures:
Off Label Use: Cyclophosphamide in combination with bortezomib for relapsed/refractory multiple myeloma. Finley-Oliver:Millenium: Speakers Bureau. Alsina:Millennium: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Allergan: Research Funding. Djulbegovic:Millenium: Research Funding. Baz:Millenium: Research Funding, Speakers Bureau; Celgene: Research Funding.
The Phenotypic Profile of Circulating Microparticles Is Different in Polycythemia Vera and Secondary Erythrocytosis
Authors: Charpentier Agnès , Devaux Stéphanie , Bruge-Debreu Judith , Cambier Nathalie , Rose Christian , Demory Jean-Loup 
Published: October 2019

Abstract
Abstract 5166

Rationale:
In Ph1 myeloproliferative neoplasms (MPN), the blood stream carries a variety of microparticles and exosomes released by cells from myeloid lineages and endothelium; we had already demonstrated an excess of platelet microparticles (PMP) in ET and PV patients (ASH Annual Meeting 2009, Abstr. 1906). A further step has been to characterize five categories of MP depending on their origin. Then we used this method to compare the sub-populations found in Polycythemia vera (PV) and secondary erythrocytosis (SE).

Patients and methods:
We analyzed plasma samples from 20 PV diagnosed in accordance to WHO classification and 20 SE patients. SE was defined by elevated hematocrit, normal or increased serum EPO, Jak2V617F negative and a presumable cause, mainly respiratory. The 2 groups were comparable for age and sex-ratio. Mean Hb level was 18.0g/dl in the PV group and 18.1g/dl in the SE group. The concentration of MP was measured by flow cytometry using a FC500 cytometer (BeckmanCoulter™). All the MP subtypes express Annexin V thus defining the total MP. Additional co-expression of either CD41, CD144, CD14, CD11b or GPA identify MP populations originating respectively from platelets (PMP), endothelial cells (EMP), monocytes (MoMP), granulocytes (GrMP) and red cells (EryMP). Pre-analytical and testing procedures complied with the recommendations of the ISTH Standardization Sub-committee.

Results:
MP from endothelial cells (EMP) and leukocytes (GrMP and MoMP) are minor populations whose proportions are similar in both groups of patients (7%, 4% and 2% respectively). Conversely, EryMP and PMP are significantly different (p<0.001 Kursall-Wallis test) in PV and SE as shown in the following table.
So, in PV most of the MP are PMP while EryMP widely predominate in SE; in an attempt to explain such unexpected results we postulate that the cells generating MP are more or less mature depending on the physiopathology: clonal hematopoietic progenitors in MPN and well-differentiated cells in reactive conditions. However, even in SE, the EryMP concentration does not correlate with RBC count, haemoglobin or hematocrit.

Conclusion:
This study demonstrates a different phenotypic profile of circulating MP in PV and SE, possibly helpful to precise the origin of an elevated hematocrit, especially when molecular markers are negative. The significance of the MP subtype pattern observed in PV and SE remains unclear, calling for further studies.

Disclosures:
No relevant conflicts of interest to declare.
Tubastatin A, a Selective HDAC6 Inhibitor, Enhances Antigen-Presenting Cell (APC) Function and Restores the Responsiveness of Anergic CD4+ T Cells
Authors: Wang Hongwei , Wang Zi , Cheng Fengdong , Woan Karrune V. , Rock-Klotz Jennifer , Sahakian Eva , Powers John , Javier Pinilla , Bergman Joel , Villagra Alejandro , Kozikowski Alan , Sotomayor Eduardo M. 
Published: October 2019

Abstract
Abstract 520
Histones play a critical role in transcriptional regulation, cell cycle progression and developmental events. Histone acetylation/deacetylation alters chromatin structure and affects transcription factor access to DNA. Histone deacetylase inhibitors (HDI) induce growth arrest, cellular differentiation, and apoptosis and are being pursued as anticancer drugs. Interestingly, in addition to their antitumor properties, HDI have also been shown to modulate inflammatory responses.
Recently, we have found that HDAC6 is required for the production of the immunosuppressive cytokine IL-10 by APCs. Given the role of this cytokine in T-cell tolerance induction we asked whether inhibition of HDAC6 with Tubastatin A, a potent and selective HDAC6 inhibitor would influence the inflammatory status of APCs and their ability to determine activation versus tolerance of antigen-specific CD4+ T cells in vitro. First, treatment of peritoneal elicited macrophages (PEM) with increasing concentration of Tubastatin A resulted in enhanced tubulin acetylation which was accompanied by enhanced expression of co-stimulatory molecules in treated cells. In addition, Tubastatin-A treated PEM were unable to produce IL-10 and TNF-a in response to LPS stimulation. In sharp contrast, Tubastatin-A treated PEM produce higher level of the pro-inflammatory cytokines IL-12 and IL-6. Next, we evaluated the ability of Tubastatin A-treated APCs to present cognate antigen to naïve and tolerant CD4+ T-cells specific for a MHC class II restricted epitope of influenza hemagglutinin (HA). We found that treatment of PEM with Tubastatin A significantly enhanced their antigen-presenting capabilities leading to effective priming of naïve CD4+ T-cells confirmed by their increased production of IL-2 and IFN-g in response to cognate antigen. More importantly, Tubastatin-A treated APCs were able to restore the responsiveness of tolerant CD4+ T cells isolated from lymphoma bearing mice.
Taken together, selective HDAC6 inhibition with Tubastatin A provides a novel therapeutic approach to induce inflammatory APCs and overcome the significant barrier that T-cell tolerance has imposed to effective lymphoma immunotherapy.

Disclosures:
No relevant conflicts of interest to declare.
Establishment of An Angioimmunoblastic T-Cell Lymphoma (AITL) Model in the NOG Mouse
Authors: Ito Asahi , Ishida Takashi , Sato Fumihiko , Mori Fumiko , Masaki Ayako , Ri Masaki , Kusumoto Shigeru , Komatsu Hirokazu , Inagaki Hiroshi , Iida Shinsuke , Ueda Ryuzo 
Published: October 2019

Abstract
Abstract 5207
The aim of the present study was to establish a murine AITL model. We inoculated cells from affected LN of an AITL patient intraperitoneally into NOG mice. Hepatosplenomegaly developed in these animals about 2 months later, and normal splenic architecture was replaced by multi-focal deposit of lymphocytes and numerous blood vessels. Some of the former consisted of AITL cells characterized by small to medium size, and clear to pale cytoplasm. The remaining lymphocytes were non-neoplastic reactive cells including CD8-positive cells, B cells, and plasma cells. Double immunostaining revealed that the neoplastic cells were positive for both UCHL-1 (CD45RO) and BCL-6. In addition, significant levels of human IgG/A/M were detected in these animals. The AITL cells engrafted in the NOG mice indeed functioned as follicular helper T (Tfh) cells and induced antibody production by B-cells, consistent with recent evidence that AITL is a neoplasm originating from Tfh cells. These clinical and histological features in the mice are almost identical to those seen in AITL patients. Cells from spleens of affected animals could be serially transplanted, with enrichment of the AITL cells together with reduction of the reactive cells at each passage. This phenomenon might reflect the progressive nature of AITL. TCRB analysis demonstrated that the AITL clone in the mice was identical to that from the donating patient. This is the first mouse model of AITL, and could be a powerful tool for investigating, and developing novel treatment modalities for this type of lymphoma.

Disclosures:
No relevant conflicts of interest to declare.
Stage I or II Marginal Zone B-Cell Lymphoma; Multicenter Retrospective Analysis of 217 Cases
Authors: Oh Sung Yong , Kim Won Seog , Suh Cheolwon , Hong Junshik , Lee Soon Il , Song Moo-Kon , Kim Jung Han 
Published: October 2019

Abstract
Abstract 5219

Background:
Local stage- Ann Arbor stage I/II- Marginal zone B-cell lymphoma (MZL) was occupied 50∼70% of all MZL patients. Even though almost of them were well controlled with local treatment based therapy, But there is no data about risk factors and role of additional chemotherapy in stage II after local treatment. In this study, we conducted multicenter retrospective analyses of local stage MZL in order to assess their clinical features, optimal treatments, and prognoses.

Methods:
Between May 1992 and Jan. 2011, a total of 217 patients with biopsy-confirmed Ann Arbor stage I/II -MZL from 7 different institutions in Korea were included for analysis in this study.

Results:
The median age of our subjects was 48 (range: 14–82) years. This study involved 102 males (47%) and 115 females (53%). The most common primary sites of involvement were the orbit and ocular adnexa (43%) followed by small or large bowel (14%), and nodal MZL (10%). 190 patients (88%) and 27 patients (12%) were stage I and II, respectively. Of 217 patients with stage I or II, 213 patients were available for treatment outcome analysis. 167 (77%) were treated with local modality such as radiation therapy or surgery alone, 24 patients (11%) received additional systemic chemotherapy after local treatment. 26 patients (12%) were treated with chemotherapy alone. The overall response rate was 98% (95% CI, 96–100%) with 188 CRs and 20 PRs. Median progression free survivals (PFS) was 10.5 years (95% CI, 7.5–13.4 years). Overall survival (OS) did not reach the median value. 5 year and 10 year OS rates were 94% and 88%, respectively. During the follow-up 38 relapse events were observed. Poor prognostic factors influence to PFS were stage II (P=0.007) and chemotherapy alone treatment (P=0.002).

Conclusion:
Local stage- Ann Arbor stage I/II- MZL had been observed a good clinical course and well controlled with local treatment modality without additional chemotherapy. But, stage II MZL patients who need chemotherapy had relatively poor survival.

Disclosures:
No relevant conflicts of interest to declare.