bluuebunny/crossref_metadata_2025_split huggingface dataset:
Despite Tolerance of Imatinib Prior to Transplant, Imatinib Induces Prolonged Exanthematous Pustulosis in a Patient with Sclerodermatous Graft-Versus-Host Disease: A Case Report.
Authors: Bishara Michael , Hamm Caroline 
Published: October 2019

Abstract
Abstract 4670
Treatment of sclerodermatous chronic graft versus host disease (cGVHD) remains a daunting challenge. Despite developments in prophylaxis for cGVHD, supportive care measures remain as the primary mode of therapy, with little evidence of treatments that reverse the process. Steroids and immunosuppressants are often ineffective, and extracorporeal photopheresis has been used with varying success. Recently, case reports have reported on the successful use of imatinib in treating sclerodermatous GVHD (Moreno-Romero et al, 2008; Leonardo Magro et al., 2009). We report a case of a 40-year-old male patient with extensive sclerodermatous cGVHD. In 2005 he underwent an unrelated stem cell transplant (SCT) for chronic myeloid leukemia. His transplant course was complicated by thrombotic thrombocytopenic purpura (TTP) associated with all standard immunosuppressive drugs (cyclosporine, tacrolimus and sirolimus). Two years later, the patient developed sclerodermatous GVHD and was given plaquenil, steroids, and photopheresis to manage this complication. Unfortunately, after months of treatment, he showed progressive disease, including increased contractures, and difficulties with inspiration. Based on case reports, and the patient's tolerance of imatinib prior to SCT, he was started on imatinib for his sclerodermatous GVHD. Within 5 days he developed generalized erythema, pustular rash, and skin sloughing (Figure 1). He was hospitalized for this severe reaction and was treated with high dose steroids after which, his symptoms began to improve. Resolution of erythema did not occur until months following initial exposure. Histological differential diagnosis included pustular psoariasis and Sneedon-Wilkinson syndrome. The skin biopsy revealed subcorneal pustular dermatosis (Figure 2). In view of this history, it is suggested that the exanthematous pustulosis was induced by imatinib in this patient. We recommend that close attention is paid to patients with cGHVD who are treated with imatinib and to intervene early in those who develop severe cutaneous reactions by stopping imatinib and starting appropriate therapy.
Figure 1 SEQ – Imatinib induced generalized erythema, pustular rash, and skin sloughing developed five days into treatment. Figure 1. SEQ – Imatinib induced generalized erythema, pustular rash, and skin sloughing developed five days into treatment. Figure 2 SEQ - skin biopsy revealing subcorneal pustular dermatosis Figure 2. SEQ - skin biopsy revealing subcorneal pustular dermatosis

Disclosures:
No relevant conflicts of interest to declare.
Prognostic Significance of Beta-2 Microglobulin (B2M) in Adult Acute Lymphoblastic Leukemia (ALL).
Authors: Thomas Deborah A. , O'Brien Susan , Faderl Stefan , Cortes Jorge , Borthakur Gautam , Burger Jan A. , Garris Rebecca , Wierda William G. , Keating Michael J. , Kantarjian Hagop M. 
Published: October 2019

Abstract
Abstract 4679
Beta-2 microglobulin (B2M) is 12-kDa light chain protein that binds to the alpha chain of class 1 MHC molecules, dissociated into extracellular fluids after degradation of HLA. Elevated levels of serum B2M have historically been associated with a poor prognosis in several lymphoproliferative disorders. The prognostic relevance of B2M in myeloid disorders such as acute myelogenous leukemia and myelodysplastic syndrome has also been noted, in some cases providing further refinement of existing prognostic models. The significance of pretreatment serum B2M levels has not been extensively studied in adult ALL. In our historical experience with the conventional VAD (vincristine, doxorubicin, dexamethasone) regimen, elevated levels of B2M were associated with a lower complete remission (CR) rate, worse survival (OS), and higher propensity for development of CNS leukemia, after adjusting for renal dysfunction and older age [Kantarjian, Am J Med 93:599, 1992]. The analysis was somewhat limited by the strong negative impact of the mature B-cell ALL subset were the significantly high levels of B2M were associated with poor prognosis in the era prior to intensive multi-agent chemotherapy regimens. We assessed the associations of pretreatment B2M levels with outcome in 320 adolescents and adults with de novo ALL (Burkitt leukemia/lymphoma, Philadelphia chromosome positive ALL, and lymphoblastic lymphoma subtypes were excluded from the analysis) treated with the more intensive hyper-CVAD regimen (fractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone alternating with methotrexate and cytarabine) and its variants (modified hyper-CVAD with or without anthracycline intensification and with or without rituximab). Median serum B2M level was 3 mg/L (range 0-14.7). As observed previously, the CR rate was lower for patients (pts) with elevated levels of B2M, an effect which persisted after excluding the elderly subset and accounting for renal dysfunction (93% versus 98%, p=.02). The 3-yr rates for CRD and OS were also worse if B2M was elevated above the median, 55% vs 70% (p=0.09) and 60% vs 70% (p=.01), respectively. These findings confirm the prior observations in a larger more homogenous population of de novo ALL treated with intensive chemotherapy. A limited multivariate analysis identified the independent prognostic influence of B2M on survival. Additional analyses will be conducted to determine how these observations can be best incorporated into clinical practice.

Disclosures:
No relevant conflicts of interest to declare.
Utility of Gene Scan for Detection of MRD in Precursor B-Cell Neoplasm.
Authors: Abdel-ghaffar Hasan Ahmed , Salem Dalia A. , Evans Paul , El-deen Omar Sharaf , Shamaa Sameh S. 
Published: October 2019

Abstract
Abstract 4720
Reliable Techniques are needed for detection of MRD to evaluate the effectiveness of the treatment in patients with precursor B-cell leukemia/lymphoma and to predict impending relapse prior to clinical manifestations. Currently, PCR analysis of Ag receptor gene rearrangements and flowcytometry (FC) represent the most clinically useful techniques for MRD analysis in ALL. In this study, we assessed the applicability of a non–sequence based PCR technique for the detection of MRD namely gene scan (GS) as compared to multicolor FC and real time quantitative PCR (RQ PCR). As a pilot study, results of MRD using the three techniques were assessed in 8 follow-up bone marrow samples of patients with precursor B-Cell leukemia/lymphoma. MRD detection using fluorescent GS was positive in 87.5% of samples compared to 37.5% using four colour FC. RQ-PCR was applied on 4 samples using patient-specific allele-specific oligonucleotide and revealed the presence of MRD in all of them. Only 3 of those sample gave positive result for MRD using both 4-colour FC and GS. Fluorescent GS technique as a known simple, rapid, and cost effective method might be a reliable technique for detection of MRD in precursor B-Cell leukemia/lymphoma as it showed a considerable sensitivity compared to four colour FC. However, a large-scale study for accurate assessment of sensitivity and specificity of Fluorescent GS in comparison with RQ-PCR as a gold standard technique is now undergoing.

Disclosures:
No relevant conflicts of interest to declare.
Distribution of Cytoskeleton Protein Nestin in Acute Leukemia.
Authors: Du Xin , Yang Xuhui , Ling Wei , Tian Xia , Zou Maoxian , Chen Zhengguang , Wang Tao , Weng Jianyu , Wu Suijing , Guo Rong , Zhang Xiuming , Lahn Bruce T. , Xiang Andy Peng 
Published: October 2019

Abstract
Abstract 4721

Objective
Nestin was detected in some tumor cells and nestin expression was positive relative with malignancy of glioma, angioma and melanoma. Nestin maybe was considered as marker of tumor malignancy and cell proliferation. There was no report about nestin expression in acute myeloid leukemia (AML) and acute lymphoblast leukemia (ALL). Herein, we describe the clinicopathological and immunohistochemical features of 48 patients with acute leukemia, introducing nestin as an additional marker that identifies these tumors .Meanwhile, Nestin and ki67 antigen expression were done to identify the relation of nestin and cell proliferation in AML, and the correlation between histoscore of nestin expression on leukemic blasts and patients' complete remission rate (CR) and overall survival (OS) was analyzed in AML.

Methods
Nestin and ki67 antigen expression in a series of 37 AML samples, 11 ALL samples, 2 multiple myeloma samples (MM) and 2 chronically myeloid leukemia samples (CML) were done with immunohistochemistry. Histoscore of nestin expression on leukemic blasts with AML and ALL was done and analyzed with independent t-test. The correlation of histoscore of nestin expression with patients' CR rate in AML was analyzed by the method of chi-square test. Patients' OS analysis was determined by the method of Kaplan and Meier, with log-rank analysis to estimate statistical significance in AML. P values of <0.05 were considered significant.

Results
Among 37 cases with AML, Nestin expression was observed in most leukemic blasts, and matural granulocytic cell also expressed nestin in 30 cases .The ratio of tumor cell expressing nestin and total tumor cells was over fifty percents in AML in 14 patients. The ratio of tumor cell expressing nestin and total tumor cells was over ten percents in AML in 7 patients. The ratio of tumor cell expressing nestin and total tumor cells was less ten percents in AML in 9 patients. Nestin expression was not observed in 8 patients. Where ki67 expressed in AML, nestin expressed intensely in 7 cases with AML. But other cases did not express ki67. However, histoscore of nestin expression on leukemic blasts in AML was not correlated with patients' CR (p=0.701) and OS (p=0.245). Nestin immune-reactivity in ALL mainly focused on matural granulocytic cells, matural lymphocytic cells and tumor cells did not express nestin. Compared with AML, there was significant statistical significance (p=0.007).

Conclusions
These findings constitute the first conclusive evidence that stem cell marker nestin expression in leukemic blasts with AML, CML, MM, but nestin did not express in leukemic blasts with ALL. Nestin may be a useful immunohistochemical marker for identifying AML and ALL. Nestin expression was not correlated with cell proliferation, patients' CR and OS in AML.

Disclosures:
No relevant conflicts of interest to declare.
Leukemic Presentation Is Predictive Indicator for Relapse for Patients with Follicular Lymphoma Treated with Rituximab Containing Initial Therapy.
Authors: Kodaira Makoto , Takeuchi Kengo , Nara Eriko , Nakano Kenji , Ueda Kyoko , Yamada Shuhei , Mishima Yuko , Yokoyama Masahiro , Terui Yasuhito , Hatake Kiyohiko 
Published: October 2019

Abstract
Abstract 4763

INTRODUCTION
Peripheral blood involvement (leukemic presentation) is considered as a part of bone marrow involvement and detected about 18% of bone marrow (BM) involvement of follicular lymphoma (FL). It is not known whether leukemic presentation is an adverse prognostic factor in rituximab era.

METHOD
We retrospectively evaluate prognostic value of peripheral blood involvement in patients with follicular lymphoma received rituximab containing regimen as an initial therapy from October 2000 to January 2009. Leukemic presentation was defined by morphologic identification of an abnormal lymphoid population in the peripheral blood.

RESULT
Total 129 patients were treated with rituximab containing initial therapy. Bone marrow involvement was detected in 39 /108 (36.1%) patients and leukemic presentation was identified in 8 / 39 (20.5%) of patients with BM involvement. Leukemic presentation shows significant poorer progression free survival than BM involvement without peripheral blood involvement. (2yr PFS 23.4% vs 73.3% p=0.015) Multivariate analysis conducted by Cox proportional hazard analysis including five variables of FLIPI revealed Hb <12g/dl (HR 2.769 95% CI: 1.111-6.902 p=0.029) and leukemic presentation (HR 5.127 95% CI: 1.898-13.853 p=0.001) were significant independent adverse prognostic factor for PFS.

CONCLUSION
Leukemic presentation is a significant adverse prognostic factor of FL in rituximab era. Prognostic value of leukemic presentation should be validated in further study.

Disclosures:
No relevant conflicts of interest to declare.
Phase I Trial Examining Addition of Gemcitabine to CHOP in Intermediate Grade NHL.
Authors: Reagan John L. , Butera James N. , Rosmarin Alan G. , Nadeem Ahmed , Schiffman Fred J. , Sikov William , Winer Eric , Mega Anthony 
Published: October 2019

Abstract
Abstract 4765

BACKGROUND
Gemcitabine induces a 20% response as single agent therapy in patients with relapsed or refractory NHL. We report phase I findings of gemcitabine in combination with standard CHOP chemotherapy with G-CSF support for intermediate grade NHL. The protocol was modified during enrollment to include rituximab in CD 20+ lymphomas.

METHODS
Patients received CHOP plus gemcitabine at 500 mg/m2 (Cohort 1) or 750 mg/m2 (Cohort 2) on days 1,4 of each 21 day cycle. Accrual was suspended once each cohort was filled. Dose escalation occurred after all patients in the cohort were determined to not have a dose limiting toxicity.

RESULTS
Between 4/02 and 5/04 10 patients were enrolled and completed the study treatment (6 in cohort 1, 4 in cohort 2). In Cohort 1, grade 3 toxicities included neutropenia, anemia, neuropathy, and constipation. Grade 4 toxicities were febrile neutropenia, and thrombocytopenia. In Cohort 2, grade 3 toxicities included neutropenia, thrombocytopenia, mucositis, anemia and intestinal obstruction. Grade 4 toxicities included febrile neutropenia, neutropenia, and thrombocytopenia. One patient developed MDS 36 months after chemotherapy. Three of four patients in Cohort 2 developed dose limiting toxicities (mucositis and thrombocytopenia) requiring dose reduction of gemcitabine after cycle 1. Overall, the survival rate at 2.5 years was 71%.

CONCLUSIONS
This Phase I trial concludes that gemcitabine 500mg/m2 on days 1 and 4 of each 21 day cycle is the maximum tolerated dose when combined with standard CHOP chemotherapy with G-CSF support for intermediate grade NHL. Response rates are encouraging for this novel chemotherapeutic regimen.

Disclosures:
Off Label Use: Gemcitabine was added to standard CHOP chemotherapy in this trial.. Sikov:Eli Lilly: Honoraria.
Extranodal NK/T-Cell Lymphoma, Nasal Type: Experience of Management in a Referral Hospital in a Development Country.
Authors: Castellanos-Sinco Humberto , Rivas-Vera Silvia , Argote Victoria E. Ferrer , Peñafiel Christian Omar Ramos , Salinas-Torres Ana Carmen , Romo-Jiménez Angélica , Hernández-Sánchez Merit , Martínez-Murillo Carlos 
Published: October 2019

Abstract
Abstract 4767

Introduction
Extranodal NK/T-cell lymphoma, nasal type is an entity of difficult diagnosis. It is characterized by damage and vascular destruction, necrosis, cytotoxic phenotype and Epstein Barr virus association. It is prominent in Asia, Mexico, Central and South America, predominantly in men.

Material and methods
It is an observational, descriptive and retrospective study, based on medical records of NK/T-cell lymphoma patients of the General Hospital of Mexico between 1992-2009.

Results
Of 632 non-Hodgkin lymphomas (NHL), 113 had a T cell lymphoma. Only 32 cases (28.3%) were eligible for the study. The age range was 19-56 years with a media of 42. The male:female ratio was 2.2:1. The most frequent clinical presentation symptoms were nasal obstruction, facial swelling and pain. Central nervous system involvement was present only in two cases and bone marrow infiltration in one. Seventy eight percent were on clinical stages I or II and 56% had B symptoms. In 7/10 patients the Epstein Barr association was documented by hystopathological study. The treatment was completed in 31/32 individuals. Fifty five percent showed some response, regardless of the therapy used. The CHOP regimen was the first line treatment in 80.6% of cases and only 13% received fractionated radiotherapy as initial treatment. The CHOP arm had an overall response rate of 60% (complete remissions, unconfirmed complete remissions, partial remissions), and 100% of the patients in the radiotherapy arm presented complete response. Most patients of the radiotherapy arm were on stage IE. The overall survival rate was 63% at 36 months. The average follow-up was 40 months. There were no differences in overall survival rates between the two arms, but the radiotherapy arm had a higher rate of complete remissions.

Conclusions
In this study we report the clinical features and response to treatment of the patient population treated at the General Hospital of Mexico. The results are similar to other international reports. Although the incidence of NK/T-cell lymphoma is low, it is necessary to standardize its treatment and these preliminary data warrant further trial of radiotherapy as the initial treatment and chemotherapy as consolidation for advanced stages of the disease.

Disclosures:
No relevant conflicts of interest to declare.
Inhibition of Fatty Acid Synthase Suppresses c-Met Receptor Kinase and Induces Apoptosis in Diffuse Large B Cell Lymphoma.
Authors: Uddin Shahab , Hussain Azhar , Bavi Prashant , Al-Kuraya Khawla 
Published: October 2019

Abstract
Abstract 4787
Targeted approaches are expected to revolutionize cancer treatment in near future. Fatty acid synthase (FASN), the enzyme responsible for de novo synthesis of fatty acids has emerged as a potential therapeutic target for several cancers however its role in diffuse large B-cell lymphoma (DLBCL) has not been fully elucidated.. Therefore, we investigated the expression of FASN in tissue micro array cohort of 301 DLBCL patients. FASN was found to be expressed in 62.6% (162/259) DLBCL samples and was seen in highly proliferative tumors manifested by high Ki67 (p<0.0001). Significant association was found between tumors expressing high FASN and c-Met tyrosine kinase (p<0.0002) as well as p-AKT (p=0.0309). In vitro, pharmacological FASN inhibition and SiRNA targeted against FASN triggered caspase dependent apoptosis and suppressed expression of c-Met kinase in DLBCL cell lines which further highlighted the molecular link between FASN and c-Met kinase. Finally, simultaneous targeting of FASN and c-Met with specific chemical inhibitors induced a synergistically stimulated apoptotic response in DLBCL cell lines. These findings provide evidence of an active role of FASN in DLBCL evolution by specifically regulating tyrosine kinases related to malignant transformation strongly suggest that targeting FASN may have therapeutic value in treatment of DLBCL.

Disclosures:
No relevant conflicts of interest to declare.
Transient Laboratory Findings Upon First Dosing with T-Cell Engaging BiTE® Antibody Blinatumomab in Non-Hodgkin Lymphoma Patients.
Authors: Nagorsen Dirk , Zugmaier Gerhard , Kufer Peter , Klinger Matthias , Viardot Andreas , Goebeler Mariele , Schmidt Margit , Klappers Petra , Wolf Andreas , Brandl Christian , Baeuerle Patrick A , Bargou Ralf C 
Published: October 2019

Abstract
Abstract 4798
Blinatumomab is a single-chain bispecific antibody construct with specificity for CD19 and CD3 belonging to the class of bispecific T cell engager (BiTE®). It has shown high response rates as single agent after treatment of patients with indolent and mantle cell lymphoma and B-precursor acute lymphocytic leukemia. We here report from an ongoing phase 1 trial in non-Hodgkin lymphoma patients on transient laboratory findings seen upon start of continuous i.v. infusion of blinatumomab. The vast majority of adverse events (AEs) during 4-8 weeks of infusion occurred within the first two days of treatment. Lymphopenia (up to CTCAE grade 4) was the most frequent early laboratory AE, and can be explained by rapid B cell depletion and initial redistribution of T cells. Except for B cell decline, all laboratory parameters were transient and normalized within days during continued treatment. Dose-dependent increases were seen for AST and ALT (maximally grade 1/2), CRP, and D-dimer during the first days of treatment. Dose-dependent declines during the first days of treatment were observed for platelets and hemoglobin, which normalized after a few days. Of note, no drug-related thromboembolic events were observed. Serum levels of cytokines IL-6, IL-2, IFNγ, and IL-10 showed small dose-dependent increases, which reversed to baseline within hours. No association between cytokine levels and thrombocytopenia was found. Moreover, there was no evident correlation between any laboratory abnormality and clinical adverse event observed during the first days of treatment. The laboratory AEs induced by blinatumomab appear to reflect consequences of the onset of redirected target cell lysis, T cell activation and bystander effects. In conclusion, blinatumomab causes characteristic laboratory findings during the first days of treatment, which are transient, not associated with clinically relevant AEs and do not require treatment interruption. Compared to AEs caused by chemotherapy regimens, the laboratory findings observed after start of blinatumomab treatment are considered rather mild.

Disclosures:
Nagorsen: Micromet: Employment, Equity Ownership. Zugmaier:Micromet: Employment, Equity Ownership. Kufer:Micromet: Employment, Equity Ownership, Patents & Royalties. Klinger:Micromet: Employment, Equity Ownership. Schmidt:Micromet: Employment, Equity Ownership. Klappers:Micromat: Employment, Equity Ownership. Wolf:Micromet: Employment, Equity Ownership. Brandl:Micromet: Employment, Equity Ownership. Baeuerle:Micromet: Employment, Equity Ownership. Bargou:Micromet: Consultancy, Patents & Royalties.