bluuebunny/crossref_metadata_2025_split huggingface dataset:
Normal Blood and Bone Marrow Wt1 Expression Level in Extramedullary Relapse in AML Patient
Authors: Girshova Larisa , Romanova Ekaterina , Gorunova Elena , Kholopova Irina , Nikulina Tatiana , Mirolubova Julia , Ivanov Vladimir , Zaritskey Andrey 
Published: October 2019

Abstract
Abstract 4825
Wilms' tumor gene 1 (WT1) that encodes a transcription factor has elevated expression in 90% of AML. High level of WT1 gene expression in bone marrow and peripheral blood of patients with AML indicates the presence of leukemia tumor burden. Thus, quantifying assessment of the level of WT1 could predict relapse. It is important to monitor a universal marker in the absence of target molecular genetic abnormalities in the disease onset. There are few data related to extramedullary relapses. Here we describe the patient with extramedullary relapse without concomitant elevation of WT1 expression.
The patient is 22 year old male with the first early bone marrow and CNS relapse of AML. Cytogenetics- (45XY, t (3, 5) (q29; q15), −7, der (7), add (11) (p15)). Blast cells immunophenotype was CD45 + CD34 + CD38 + CD117 +. There was high blast count with high expression of WT1 level (Tabl 1). And there was no expression of other molecular genetic prognostic markers. Therapy with high dose of cytarabine with intrathecal administration of cytotoxic drugs was conducted. The complete hematological and cytogenetic remission was achieved after the first induction. Also there was no any blast cell in the CSF, WT1 expression decreased by 1,87 log (WT1 level became normal). Consolidation of remission with three similar courses with high doses of cytarabine was conducted. Extramedullary relapse during bone marrow and CNS remission with unilateral lesion of the lacrimal gland and the periorbital area( 2.8 × 3.4×4.6 cm )was diagnosed in 6 month. Relapse was confirmed by histological and immunochemical study of the left lacrimal gland biopsy, blasts phenotype was similar to the phenotype of bone marrow blasts at AML onset. WT1 level in bone marrow and peripheral blood remained within normal limits: 15.5 WT1/104 ABL copies and 13.4 WT1/104 ABL copies respectively. Therapy with high dose cytarabine and mitoxantrone was used as an induction. After this therapy a local remission was diagnosed according to MRI. Consolidation courses were followed by a course of radiotherapy to the area of the left orbit. Bone marrow remission and low-level expression of WT1 remained to be normal. Thereafter the patient has undergone unrelated allogeneic bone marrow transplantation.

Conclusion.
We have described isolated AML relapse without elevation of WT1. A possible reason for normal level of expression of WT1 in patients with extramedullary relapse may be a small amount of the extramedullary formation, its location and features of blood supply of the body area.

Disclosures:
No relevant conflicts of interest to declare.
Outcome of Nodular Lymphocyte Predominant Hodgkin Lymphoma Patients Treated with or without Rituximab
Authors: Mocikova Heidi , Michalka Jozef , Koren Jan , Stepankova Pavla , Wild Alexander , Raida Ludek , Markova Jana , Kral Zdenek , Trneny Marek , Indrak Karel , Mayer Jiri , Kozak Tomas 
Published: October 2019

Abstract
Abstract 4878

Background.
Strong CD20 expression in nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) suggests the feasibility of rituximab in the treatment of this disease.

Methods.
We analysed the outcome of 102 patients with NLPHL treated with or without rituximab in combination with conventional treatment: chemotherapy and/or radiotherapy. Histologies were reviewed for the purpose of this study. Rituximab was administered in 26 of 102 NLPHL patients (13 in the first line treatment and in 13 of 20 relapsed patients). Additionally, rituximab with chemotherapy was administered in 11 patients with histologic transformation to diffuse large-B cell lymphoma. Median follow-up was 7.1 years. Median patient age was 34.2 years.

Results.
The 10-year overall survival (OS) rate and progression - free survival (PFS) of the whole group was 88% and 65%, respectively. There was no difference in OS and PFS in patients with clinical stage IA without risk factors treated without or with rituximab (30 vs 3 patients) and conventional treatment, however the follow-up in the rituximab group was short. The addition of rituximab to conventional treatment did not affect the OS in the group of patients with more advanced disease: 58 patients without vs 10 with rituximab (94% [95% CI: 88 – 100%] vs 100% [-], P=0.566). PFS in both groups did not differ significantly in the first line treatment (69% [95% CI: 57 – 82%] vs 100% [-], P=0.165), however when all lines of treatment were analysed, PFS was significantly better in patients treated without rituximab (92% [95% CI: 84 – 100%] vs 38% [95% CI: 22 – 65%], P< 0.001). Histologic transformation to diffuse large B - cell lymphoma was diagnosed in 11 rituximab naive patients, but this was not statistically significant when compared to 0 patients after rituximab treatment (14,5% vs 0%, P=0.061). Histologic transformation was the only poor prognostic factor that influenced OS (HR 7.936, P=0.004).

Conclusions.
Rituximab does not prevent relapses in NLPHL. This study confirms favorable OS of NLPHL patients regardless whether rituximab was used or not. The absence of histologic transformation in NLPHL patients treated with rituximab deserves further investigation.

Disclosures:
No relevant conflicts of interest to declare.
High Incidence of tMDS in Elderly Lymphoma Patients Subjected to Radioimmunotherapy
Authors: Zimowska-Curylo Dagmara , Jurczak Wojciech , Giza Agnieszka , Jakobczyk Malgorzata , Krawczyk Katarzyna , Skotnicki Aleksander B 
Published: October 2019

Abstract
Abstract 4882

Background:
Conventional therapies with cytotoxic agents for disseminated NHL are associated with a high risk of therapy related myeloid neoplasm (tMN). The latency period between exposure to this agents and development of tMN ranges from one to 10 years.
Radioimmunotherapy (RIT) uses monoclonal antibodies, specifically binding to antigens of tumor cells, as a carrier for the radioisotope. The radiation is delivered not only to the antibody –bound tumor cell, but also neighboring cells.

Methods:
In the years 2005–2011 radioimmunotherapy with ibritumomab tiuxetan was used in 102 patients with FL (during consolidation therapy), MCL (as consolidation of the first-line treatment and after achieving PR in the first- or second-line therapy), DLBCL and MCL (in the HDT supported by auto-SCT). 5 patients (4,9%) ( 4 with MCL/ 1 with FL) subjected to RIT developed tMDS. All patients with MCL in previous treatment were exposed to alkylating agents, antymetabolites and inhibitors of II topoisomerase. All patients had hypoplastic bone marrow year after RIT.

Results:
Median time to diagnosis of tMDS after treatment with RIT was 2,3 years. 4/5 during 6 month transformed into tAML. In peripheral blood of all patients anemia, thrombocytopenia or pancytopenia was observed. All patient in histophatology had dysplastic changes in 3 hematopoetic lines with 5% blast cells, without elevated percentage of ring sideroblasts. Each patient had typical for tMDS complex abnormalities with monosomy of chromosome 5 or 7, or abnormalities of this chromosome [table 1]. Three of this patients was treated with azacitidine, one of this patients was prepared to RIC allo BMT but developed tAML and died during induction therapy. All patients received supportive care.

Conclusion:
The development of secondary hematological malignancies (tMDS and tAML) after RIT is very closely related to the drugs applied in the induction treatment especially purine analogues. Higher incidence of tMDS in patients with MCL confirm the relationship of occurrence of secondary MDS and AML after radioimmunotherapy with the earlier use of purine analogs (fludarabine) and cumulative damage to bone marrow cells rather than exclusively associated with administration of RIT.

Disclosures:
No relevant conflicts of interest to declare.
Activity of Rituximab-Bendamustine (RB) Combination in Nodular Lymphocyte Predominant Hodgkins Lymphoma (NLPHL)
Authors: Devarakonda Srinivas S , Haddad Philip A 
Published: October 2019

Abstract
Abstract 4894
Nodular Lymphocyte Predominant Hodgkin's Lymphoma (NLPHL) is an uncommon subtype of Hodgkin's lymphoma. NLPHL represents a more indolent disease than classical Hodgkin's lymphoma. It has unique clinicopathological features that resemble indolent Non Hodgkin's Lymphomas and hence, the tendency to manage it as such.
We reviewed the activity of Rituximab-Bendamustine (RB) combination in 2 cases of relapsed NLPHL. The first patient is a 53 year old African American man who was diagnosed with Ann-Arbor Stage IIA NLPHL in 2005. He was initially treated with 3 cycles of ABVD after which he was lost to follow up. He sought medical attention in 2008 and a repeat PET/CT showed persistent cervical lymphadenopathy consistent with his known disease but the patient refused therapy at that time. Three years later, he presented with weight loss and enlarging cervical lymph nodes. A repeat biopsy of these nodes confirmed his initial diagnosis of NLPHL. He was reluctant to undergo any chemotherapy similar to the initial treatment because of the side effects. He was then treated with 4 cycles of RB followed by involved field radiation therapy, which he tolerated well. Post therapy PET/CT scan revealed a complete remission. The second patient is a 62 year old white man who was initially diagnosed with IE DLBCL of the proximal jejunum in 2004 which was successfully treated with R-CHOP. After five years he was found to have diffuse lymphadenopathy. Excisional biopsy revealed NLPHL. The patient refused to take adriamycin containing regimen or combination therapy since he poorly tolerated it before and agreed to try RB instead. He was treated with 6 cycles of RB. Re-staging PET/CT scans revealed near complete resolution. The patient was referred for autologous stem cell consolidation. He underwent adequate stem cell collection and successfully engrafted. Both patients continue to be disease free as of their last clinic visit.
Rituximab –Bendamustine combination seems to have significant activity in NLPHL, reminiscent of its activity in indolent non-Hodgkin's lymphomas. Incorporation of the regimen into front line treatment of patients with this disease needs further study and evaluation.

Disclosures:
Off Label Use: Rituximab and Bendamustine are not FDA approved for NLPHL. Haddad:Cephalon: Honoraria, Speakers Bureau.
B Cell Receptor (BCR) Signal Pathways Confer Microenvironment-Mediated Drug Resistance and Are Promising Therapeutic Targets for B Cell Lymphomas
Authors: Tao Jiangchuan , Lwin Tint , Zhao Xiaohong , Zhang Ling , Moscinski Lynn , Sotomayor Eduardo M. , Dalton William S. , Tao Jianguo 
Published: October 2019

Abstract
Abstract 4918
Despite intensive efforts in developing new therapies, B-cell lymphoma remains essentially incurable with standard therapeutic approaches. Dynamic interactions between the lymphoma cell and its microenvironment play a critical role in lymphoma development and response to therapy. There is accumulating evidence pointing to an essential role of BCR signaling in B-cell lymphomas. Recently, inhibitors of BCR signaling have become an area of substantial clinical interest. We therefore studied the role of BCR signal pathways in stroma-mediated lymphoma cell survival. We demonstrated that adhesion of the various B-cell lymphoma cell lines to lymph node stromal cells enhanced activation of BCR signaling pathways: activation of phosphatidylinositol 3-kinase (PI3K), Bruton's tyrosine kinase (Btk) and extracellular signal-regulated kinase (ERK) pathways. Inhibition of Btk by PCI 32765 or PI3K by CAL101 significantly blocked BCR signal pathways, triggered lymphoma cell apoptosis and overcame stroma-mediated drug resistance. Furthermore, targeting BCR signal pathway disrupted microenvironmental stroma-lymphoma interaction through regulation of CXCR4 expression. Collectively, these data support that BCR activation not only controls intrinsic survival pathway related to B lymphoma cell but also regulates stroma-mediated extrinsic lymphoma cell survival as well as lymphoma cell homing and interplay with its microenvironment. As a result, this study suggests that targeting BCR signal pathway molecules is a promising therapeutic strategy to lymphoma therapy.

Disclosures:
No relevant conflicts of interest to declare.
The Impact of Comorbidity in Myelodysplastic Syndromes
Authors: Huang Yu-Chung , Chen Kuo-Wei , Hong Ying-Chung , Liu Chia-Jen , Yu Yuan-Bin , Tzeng Cheng-Hwai 
Published: October 2019

Abstract
Abstract 4940

Introduction
Myelodysplastic syndrome (MDS) is a heterogeneous clonal hematopoietic cell disorder. The prognostic implication of comorbidities at diagnosis of MDS is emerging.

Objective
We aimed to investigate the impact of comorbidity on the patients with MDS.

Method
Totally 263 MDS patients during a 15-year period in single institute were collected.
The clinical characteristics and the extra-hematological systemic diseases at diagnosis were all registered in this database. Well established prognostic models, including original International Prognostic Scoring System (IPSS), WHO classification-based Prognostic Scoring System (WPSS), and total MDACC scores were evaluated in our cohort.

Results
Comorbidity was present in 76. 4% of patients. In univariate and multivariate analysis, HCT-CI ≥ 3 was significantly associated with poor outcome. IPSS, WPSS and MDACC were informative to discriminate between risk groups of patients with MDS. By comparing AIC values in the Cox proportional hazards analysis, MDACC had superior prognostic value followed by IPSS and WPSS. A modified score incorporating HCT-CI and MDACC divided patients into four risk groups. The 3 year-survival rate was 72%, 40%, 31%, 4%, respectively.

Conclusion
Building new models incorporating comorbidities to current prognostic score help to predict survival in patients with MDS.

Disclosures:
No relevant conflicts of interest to declare.
Extreme Thrombocytosis Under Azacitidine in Patients with Myelodysplastic Syndrome
Authors: Kelaidi Charikleia , Kokkinidis Dimitrios , Protopappa Maria , Papaioannou Georgios , Batsis Ioannis , Apostolou Chrysa , Stamatopoulos Kostas , Athanasiadou Anastasia , Anagnostopoulos Achilles , Vadikoliou Chrysanthi 
Published: October 2019

Abstract
Abstract 4961

Background:
Platelet increase under azacitidine in patients with myelodysplastic syndrome (MDS) has been acknowledged as an early predictive factor of response to treatment. However, extreme thrombocytosis under azacitidine has not been reported.

Methods:
We studied consecutive patients with MDS or MDS/myeloproliferative neoplasm (MDS/MPN) who had platelet counts near or over 1, 000 G/L under azacitidine.

Results:
Four patients, sex ratio 1:1, with median age of 65 years, had extreme thrombocytosis under azacitidine. Baseline characteristics were: WHO classification RAEB-2/CMML-1/CMML-2 in 2/1/1 patients, median platelet count 248 G/L (<400 G/L in all), normal karyotype/+8, −9/−7 in 2/1/1 patients, IPSS low/int-2/high in 1/2/1 patients. None had reticulinic fibrosis or ring sideroblasts>15% at baseline. A median number of 8 cycles of azacitidine was administered. Individual platelet counts reached 2, 960 G/L, 800 G/L, 1, 188 G/L and 2, 740 G/L. Thrombocytosis occured early after treatment onset or resumption (Figure 1). Histologic findings under treatment were: Increased cellularity (N=4), micromegakaryocytes and other signs of megakaryocytic dysplasia (N=4), reticulinic fibrosis grade I and II in 1 and 2 patients, respectively. JAK2 V617F mutation was detected in 1 patient (with maximum platelet count of 2, 900 G/L) and was undetectable in the remaining patients. None had a thrombotic or hemorrhagic event. Two patients had a concomitant increase of WBC count. Response to azacitidine was CR, PR and stable disease in 1/1/2 patients. Three patients received hydroxyurea (HU) in addition to azacitidine and one patient underwent hematopoietic stem cell transplantation (HCT). AML transformation occurred in 1 patient 25 months after azacitidine onset. Median overall survival after azacitidine onset was 25 months.

Conclusion:
Extreme thrombocytosis of the range of essential thrombocytosis, with megakaryocytic dysplasia and hyperplasia, was noted under azacitidine in 4 patients with MDS-MDS/MPN and normal baseline platelet count. Hypothetically, azacitidine may induce the expression of critical genes of megakaryopoiesis or platelet release in patients with rare mutations. Notably, JAK2 mutation was detected in only one patient. Alternatively, demethylation could unmask an underlying unclassified MDS/MPN similar to RARS-T.

Disclosures:
No relevant conflicts of interest to declare.
Multiple Myeloma, Detection of Four Unfavorable Genetic Pronostic Factor by Interphase Two-Color Fluorescence in Situ Hybridization Analyses: A Study of 33 Patients At Diagnosis or Relapse
Authors: Barragan Carlo Sergio , Hansson Silvia B. , Cicchini Silvina A , Hidalgo Federico J , Ochoa Claudia E , Nunez Gabriela , Flores María Gabriela , Salvador Teresa , Saba Silvia 
Published: October 2019

Abstract
Abstract 5004

Background:
Interphase Fluorescence in situ hybridization (FISH) has improved the detection of early bad prognostic genomic aberrations in Myeloma (MM) is a fast and reliable method. We used this assay in myeloma patients at diagnosis, after relapse or treatment failure.

Methods:
Interphase Mononuclear cells from Bone Marrow of 36 Caucasian patients, 13 men and 23 women, age ranged from 40 to 84 years (median, 64) with MM. were analyzed by LEXEL Live FISH probes, for deletions in chromosome band 13q14. 3, 17p13. 1; IGH/CCND1 translocation dual fusion and cMYC breakapart 8 Chromosome.

Results:
Chromosomal aberrations were detected in 16 of 33 evaluable patient samples of a total 36 patients population. The most frequent aberrations were 7/16 in 13p14. 3 band deletion (43. 75%) 7/33 (21%); 5/16 (31, 25%)patients with deletion had 17p13. 15/33 (15, 15%); 3 cMYC breakapart 3/16 (18. 75%) 3/33 (9%); IGH/CCND1 translocation in 3 patients 3/16 (18. 75%) 3/33 (9%), two of them associated one with cMYC and the other with 13p14. 3. We found other association: A)13p14. 3; 17p13. 1 and cMYC in (1/33). B) 13p14. 3 and cMYC (1/33) C) 17p13. 1; cMYC (1/33). Two patients had 8 chromosome trisomy 2/33 (6%). We foun that 13p14. 3, 17p13. 1 and cMYC association was correlated with a worst and fast evolution. Who had 13p14. 3 band deletion had a worst evolution in our patients. cMyc was associated with a poor prognosis.

Conclusions:
Genomic aberrations are independent prognosis factors of disease progression, chemotherapy respond and survival in Myeloma. Novel DNA molecular target and bone marrow micro environment modification drugs such as bortezomib and thalidomide or lenalidomide must be use in first line associated perhaps with standar chemotherapy drugs for improving result and consolidate this patients with autologous bone marrow transplantation avoiding the dilate of this strategic in patient with poor prognosis. Future trials must be performed to include a more complete panel of probes in Myeloma.

Disclosures:
No relevant conflicts of interest to declare.
Multiple Myeloma Associated GI Polyposis
Authors: Nabbout Nassim , Hawari Mohamad El , Schulz Thomas K. 
Published: October 2019

Abstract
Abstract 5009
Multiple myeloma is a neoplastic proliferation of monoclonal plasma cells that can result in osteolytic bone lesions, hypercalcemia, renal impairment, bone marrow failure, and the production of monoclonal gammopathy. The gastrointestinal tract is rarely involved in myeloma. GI polyposis is a rare manifestation of extra-medullary disease in multiple myeloma. Such cases usually present as gastrointestinal hemorrhage or intestinal obstruction.
A 53-year-old African American male recently diagnosed with multiple myeloma presented with three-day history of rectal bleed and fatigue. EGD showed multiple raised, polypoid, rounded lesions with a superficial central ulceration in the stomach. Colonoscopy showed similar lesions in the ascending and transverse areas of the colon that ranged in size from 5 to 16 mm in diameter. Biopsies showed that these polyps were made of plasma cells. A bone marrow biopsy showed diffuse involvement (greater than 90%) of bone marrow with multiple myeloma with anaplastic features. The patient was started on bortezomib at diagnosis, however, he passed away a few weeks later.
This type of metastatic disease has been described in isolated case reports in the literature, while solitary GI plasmacytoma has been reported more frequently. In rare cases, multiple myeloma can involve the GI tract which may lead to bleed or obstruction. This involvement is likely a marker of aggressivity. This example of extra-medullary disease in myeloma is an uncommon variant with features of poor prognosis and dedifferentiation.

Disclosures:
No relevant conflicts of interest to declare.
Baicalein Inhibites Multiple Myeloma Cells Proliferation and Migration by Interfering Wnt Signaling Pathway
Authors: Xu Chaoping , Liu Shangqin , Huang Jianying , Zhang Yicheng , He Li , Cai Huili , Zhang Ruibo , Ji Jinna , Zhou Dingxin , Ma Zi 
Published: October 2019

Abstract
Abstract 5019

Background:
The Wnt/β-catenin signaling pathway has been implicated in a variety of tumor cell survival and proliferation, including myeloma cells. It can facilitate myeloma cell proliferation by upregulating the expression of many related genes, such as c-myc, cyclin D1, MMP and so on. We have previously demonstrated that Baicalein, a important component of Scutellaria radix from Huang-Lian-Jie-Du-Tang(HLJDT), can inhibit cell proliferation and induce cell death in myeloma cell through suppressing NF-κB activation (Ma Z, et al., Blood, 2005, 105(8): 3312–3318). In clinic, we found that HLJDT had a very good effective in multiple myeloma(MM) patients treatment (data not show). But, the precise molecular mechanism of HLJDT exerts its anti-tumor effects remains poorly understood. Here we further evaluated alternative mechanisms which is responsible for inhibition myeloma cell proliferation and migration by baicalein.

Methods:
Myeloma cell lines, RPMI8226 and U266 cells, were used for the analysis. MTT assay was used to assess cell viability in RPMI8226 and U266 cells which were exposed to baicalein with different concentrations and time period. Immunofluorescence assay and western blot analysis were used to assess β-catenin protein expression in MM cell lines. Transwell chamber migration assay was used to assess migration ability of myeloma cells treated with different concentrations of baicalein. RT-PCR analysis was used to assess β-catenin, c-myc, cyclin D1 and integrin β7 mRNA expression.

Results:
Baicalein can inhibit the MM cell lines proliferation in a dose- and time-dependent manner as measured by MTT assay. Immunofluorescence images and western bloting revealed that treatment of baicalein decreased the β-catenin protein expression level in myeloma cells. The mRNA expression level of β-catenin, c-myc and cyclin D1 was also decreased by baicalein treatment. In addition, we found that baicalein has an ability to inhibit the migration of MM cell llines, RPMI8226 and U266 cell, by decreasing the integrin β7 mRNA expression in a dose-dependent manner.

Conclusion:
Baicalein can inhibit myeloma cell proliferation is related to downregulation of β-catenin, c-myc and cyclin D1 genes expression, and the inhibition of myeloma ia associated with suppression of integrin β7 gene expression. Thus, HLJDT may have a potential of clinical applications in MM patient treatment.

Disclosures:
No relevant conflicts of interest to declare.