bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effect of Tacrolimus on Time to Development of Post-Transplant Lymphoproliferative Disorder (PTLD).
Authors: Maitland Hillary S , Stukenborg George , Williams Michael E. 
Published: October 2019

Abstract
Abstract 4500

Background:
Post Transplant Lymphoproliferative Disorder (PTLD) is a rare but potentially fatal complication occurring after solid organ transplant. PTLD is divided pathologically into three subgroups: early lesions, polymorphic PTLD, and monomorphic PTLD. The severity of these complications ranges from reactive lymphoid hyperplasia to aggressive non-Hodgkin lymphoma and Hodgkin-like lymphoma. Most PTLD are of B cell lineage associated with infection or reactivation of Epstein Barr virus (EBV). Post-transplant patients on immunosuppressive therapy may lack sufficient cytotoxic T cells to clear EBV-infected B cells, allowing unchecked polyclonal B cell proliferation and infection of other cells with EBV. Immunosuppression with cyclosporine and tacrolimus has been associated with a higher risk for development of PTLD. This study examines the relationship between tacrolimus and PTLD among solid-organ transplant patients.

Methods:
Differences in time to PTLD between patients with and without exposure to tacrolimus were assessed using a retrospective, case-control design. University of Virginia Health System registry records were searched to identify all patients in the post- solid organ transplant population diagnosed with malignancy in the years 1998–2009. Bone marrow transplant patients were excluded. Following IRB approval, data was collected on the type of transplant, immunosuppressive regimen, time from transplant to development of PTLD, and lymphoma treatment; from electronic charts and pathology reports were reviewed.

Results:
A total of 2841 patients with solid organ transplants were identified, including1486 patients who received tacrolimus for immunosuppression. There were 26 cases of PTLD: 19 with exposure to tacrolimus (1.3%), and 8 without exposure (0.6%). The mean time to PTLD was 2.52 years (SD = 0.65) in the tacrolimus group, and was 6.75 years (SD = 1.80) among those not exposed. This difference in time to event was stat istically significant (Log-Rank = 5.347, p = .0208).

Conclusion:
In our population of post solid organ transplant patients with PTLD, exposure to tacrolimus was associated with significantly shorter time to development. Prospective studies are needed to better elucidate the relationship between type of immunosuppression and development of PTLD. These results suggest that immunosuppressive regimens using tacrolimus may be associated with increased risk of developing PTLD.

Disclosures:
No relevant conflicts of interest to declare.
The Impact of ABO Major Incompatibility In Hematopoietic Stem Cell Transplantation Using Reduced Intensity Conditioning.
Authors: Nakamura Kazuhiro , Kamata Aya , Miki Mizuka , Kajiume Teruyuki , Sera Yasuhiko , Sato Takashi , Kobayashi Masao 
Published: October 2019

Abstract
Abstract 4520
The impact of ABO major incompatibility in hematopoietic stem cell transplantation (SCT) using conventional myeloablative conditioning has been reported to be negligible in clinical settings. To date, there are scant studies about its clinical significance using reduced-intensity nonmyeloablative SCT (RISCT). In this study we analyzed 32 cases performed HSCT using fludarabine-based RISCT (median age was 15 years old ranged from 7 months to 35 years old, 10 cases with and 22 cases without ABO major incompatibility) and 19 cases using conventional myeloablative SCT (median age was 8 years old ranged from 1 to 16 years old, 6 cases with and 13 cases without ABO major incompatibility) in our institution from January, 2005 to April, 2010. All patients using RISCT were non-malignant disorders including 13 patients with chronic granulomatous disease, 11 with aplastic anemia, and 5 with severe congenital neutropenia. On the other hand, all patients with conventional myeloablative SCT were pediatric malignant disorders including 8 patients with acute lymphoblastic leukemia, and 7 with acute myelogenic leukemia. As shown in Table, in RISCT, the number of red blood cell (RBC) transfusion after SCT was significantly higher and the last day of RBC transfusion was also significantly longer in patients with ABO major incompatibility than those in patients with ABO compatibility. Notably, two patients with ABO major incompatibility had prolonged delay of RBC engraftment and pure red cell aplasia due to the presence of high titer of anti-A antibody. Furthermore, the prolonged recovery of platelet and neutrophil were also observed in patients with ABO major incompatibility (Table). On the other hand, in HSCT using conventional myeloablative conditioning, no differences in the recovery of RBC and platelet were noted irrespective of ABO incompatibility. These data suggest that RISCT with ABO major incompatibility affects the engraftment and recovery of multi-lineage blood cells. Thus, the alternatives of donors may be an important role in transplant-related morbidity of RISCT with ABO incompatibility.TablePatients using RISCTABO major incompatibilityCompatibleIncompatibleP valuesPatients NumbersN=22N=10The number of RBC transfusion* (time)2.1 ± 3.113.6 ± 26.7<0.01The last day of RBC transfusion* (day)16.4 ± 14.7117.9 ± 203.8<0.01The number of Platelet transfusion* (time)14.0 ± 10.717.6 ± 13.2NSThe last day of Platelet transfusion* (day)29.1 ± 15.451.8 ± 42.10.05The day of ANC recovery above 500/ml* (day)18.2 ± 3.723.8 ± 8.8<0.05*After hematopoietic stem cell transplantationRBC: red blood cell ANC: absolute neutrophil count NS: not significant

Disclosures:
No relevant conflicts of interest to declare.
Is Antifungal Prophylaxis Useful In Stem Cell Transplantation (SCT) During Hospitalization?.
Authors: Irrera Giuseppe , Giuseppe Messina , Console Giuseppe , Martino Massimo , Maria Cuzzola , Meliadò Antonella , Iacopino Pasquale 
Published: October 2019

Abstract
Abstract 4541

Introduction:
Limited data demonstrate to what extent preventing fungal exposures is effective in preventing infection and disease. Further studies are needed to determine the optimal duration of fluconazole prophylaxis in allogeneic recipients to prevent invasive disease with fluconazole-susceptible Candida species during neutropenia. Oral, nonabsorbable antifungal drugs might reduce superficial colonization and control local mucosal candidiasis, but have not been demonstrated to reduce invasive candidiasis. Anti-fungal prophylaxis is recommended in a subpopulation of autologous recipients with underlying hematologic malignancies with prolonged neutropenia and mucosal damage.

Methods:
This is a retrospective study of 1007 SCT performed in our center between 1992 and 2009 in 809 consecutive patients, irrespective of diagnosis. HEPA filter and environmental monitoring (air, water, surfaces) are attributes of our transplant center.

Results:
The main characteristics of the patients are reported in Table 1. Systemic prophylaxis was used according to the guidelines (Table 2): fluconazole in the nineties, then itraconazole and from 2004 was either abolished or substituted with non-adsorbable prophylaxis in transplants with standard risk. Secondary prophylaxis was prescribed for high risk patients (with infectious fungal history, suggestive iconography, positive fungal biomarker). In 17 years our Center has never been colonized by mould. Only 3 probable aspergillosis infections and 4 proven fungal infections (fusarium, mucor and 2 aspergillosis) were diagnosed, all in allogeneic patients (2 haplotipical, 1 singenic, 1 sibiling, 1 MUD and 2 mismatched), resulting in death in all cases. No infection was documented in autologous setting, while the infection rate in allogenic setting was 3.6% with an incidence rate of 1.1 infection per 10000 transplants/year. These results are significantly lower than published reports.

Conclusion:
Systemic antifungal prophylaxis should not be performed in autologous SCT patients. The abuse of systemic prophylaxis targeting yeasts has influenced the change of epidemiology in the transplant setting with prevalence of mould infections. The identification of high risk patients is useful to select patients for systemic antifungal or secondary prophylaxis to reducing overtreatment, incidence of resistant strains and costs.

Disclosures:
No relevant conflicts of interest to declare.
Refractory NK/T Cell Lymphoma Treated with Bortezomib+Chemotherapy and APBSCT.
Authors: Fu Chengcheng , Wang Juan , He Xuefeng , Xu Ting , Zhang Ri , Depei Wu 
Published: October 2019

Abstract
Abstract 4602

Backgrouds:
NK/T cell lymphoma is a rare disease, but usually shows a highly aggressive clinical course and its prognosis is poor due to the stumbling block in early diagnosis and effective management. Until present, there are no consensus treatments especially for recurrent patients. Bortezomib, and other new drugs are subject to active investigation, although only limited preliminary information is available. Here, 3 cases of refractory disseminated NK/T cell lymphoma were treated with Bortezomib plus high dose chemotherapy as salvage therapy.

Patients and methods:
From 2008–2010, 3 cases of refractory NK/T cell lymphoma, 2 males, 1 female, aged from 26–35, PS 0–1 were enrolled. Former treatments included at least 2–9 months of chemotherapy (CHOP or CHOP like) and local radiotherapy. The stage of patients was III in 2, IV in 1. IPI scores were all in high risk.

Result:
3 patients received high dose chemotherapy combined with bortezomib as re-induction treatment. 2 patients received hyperCVAD as induction therapy with bortezomib given 1.3mg/m2 on d2, 5, 9 and 12. 1 patient received bortezomib and SMILE protocol, included bortezomib 1.3 mg/m2 on days1, 4, 8, 11, dexamethasone 20 mg twice a day on days 1 through 4, etoposide 100 mg/m2 on days 1 through 3, ifosphamide 1.0 g/m2 on days 1 through 5, methotrexate 30 mg/m2 on days 4, 11, L-asparaginase 6000U/m2 on days 7, 9, 11, 13, 15. All 3 patients had response to the treatment. HyperCVAD, HDAC+MTX and SMILE protocol combined with bortezomib were also given to the patients as consolidation therapy for 1–4 courses. After 2 course of treatment, 1 patient got CR, 2 got PR. Then ASCT was performed. Condition protocol was SEAM+Bz1.3 mg/m2 on days-4, -1. At a median follow-up for 15 months, the median duration of PFS was 12 months. No PN was found in all patients. SAE were neutropenia and thrombocytopenia grade 4, mucositis grade 3, increase AST grade 2 in 3 patients and HZV infection in 1.

Conclusion:
Bortezomib combined with high dose therapy may be effective salvage therapy in some refractory disseminated NK/T cell lymphoma, especially in young adults. More cases need to be carefully investigated to explore the effect and side effect in bortezomib plus high dose therapy in this special disease.

Disclosures:
No relevant conflicts of interest to declare.
Splenic Volume Can Be a Novel Predictive Parameter for the Prognosis of Chronic Lymphocytic Leukemia?
Authors: Song Moo-Kon , Chung Jooseop , Shin Ho-Jin , Seol Young Mi , Choi Young Jin , Lee Ho Sup , Kim Sung Hyun , Cho Goon Jae 
Published: October 2019

Abstract
Abstract 4623
Recently, clinical importance of disease status by computed tomography (CT) before treatment in chronic lymphocytic leukemia (CLL) is increasing. The present study was conducted to evaluate whether splenic volume (SV) by CT would predict the clinical outcome in CLL patients.
SV were measured in 61 Rai II-IV CLL patients who underwent CT scan before chlorambucil therapy. SV was reconstructed and measured from the cross-sectional CT images by using 3 dimensional Voxar analytical volume software.
Median SV was 721.3 cm3 (223.7-3576.6 cm3) is the most significant separated cut-off point on progression-free survival (PFS) and overall survival (OS). Low SV group was associated with longer PFS and OS than high SV group (p<0.001; p<0.001). High SV (SV ≥ 721.3 cm3) was associated with higher Rai stage (SV between Rai II and III, p=0.005; Rai III and IV, p=0.026) and poorer response (SV between CR and PR, p=0.075; PR and SD, p=0.366; SD and PD, p=0.019). Univariate and multivariate analyses revealed that high SV was independent prognostic factor on PFS (HR, 2.924; 95%CI, 1.308–6.538; p=0.009) and OS (HR, 3.024; 95%CI, 1.106–8.270; p=0.031).
SV before therapy reflected the clinical outcome in CLL patients.

Disclosures:
No relevant conflicts of interest to declare.
Preclinical Evaluation of the Proteasome Inhibitor MLN9708 (MLN2238) In Chronic Lymphocytic Leukemia Cells
Authors: Masood Aisha , Miles Kiersten M , Khan Nazmul H , Akhtar Drusilla , Adelaiye Remi , Advani Pooja , Sher Taimur , Chitta Kasyapa , Chanan-Khan Asher A. 
Published: October 2019

Abstract
Abstract 4634
The proteasome is an important therapeutic target in multiple hematological malignancies. The proteasome inhibitor bortezomib has demonstrated significant clinical activity in multiple myeloma and mantle cell lymphoma. However, clinically bortezomib has failed to demonstrate efficacy in chronic lymphocytic leukemia (CLL); the exact reason for this remains unknown. MLN9708 (Millennium Pharmaceuticals, Inc., Cambridge, MA) is a proteasome inhibitor which has a shorter proteasome dissociation half life than bortezomib and is currently in Phase I clinical development. Upon exposure to aqueous solutions or plasma, MLN9708 rapidly hydrolyzes to MLN2238, the biologically active form. MLN2238 was used for all of the studies reported here, in which we evaluated the antileukemic effects of MLN2238 in primary CLL cells from 16 patients. MLN 2238 induced a time and dose dependent decrease in CLL cell viability in 12 (75%) patient cells in vitro. Cell death was shown to be due to the induction of apoptosis confirmed by Annexin V staining of CLL cells and cleavage of PARP-1, an indicator of apoptosis. Biochemical analysis showed that caspase 3 and 9 were activated in these cells, indicating that MLN2238 induces cell death through the intrinsic apoptosis pathway. We noted increased mitochondrial outer membrane permeability (MOMP) in the presence of MLN2238, which suggests the engagement of the mitochondria in MLN2238 induced apoptosis in CLL cells. Evaluation of non-responding CLL patient samples demonstrated that increased expression of PSMB5 is associated with lack of sensitivity to MLN2238. Furthermore, incremental addition of autologous serum in responding CLL samples resulted in upregulation of PSMB5 levels, resulting in protection against MLN2238 induced cell death. Our preclinical observations demonstrate for the first time that MLN2238 can induce death in primary CLL cells, and support further investigation in CLL.

Disclosures:
No relevant conflicts of interest to declare.
Expression of C/EBPα and PU.1 Gene In MDS and Their Significance Analysis
Authors: Ji Wencan , Ding Kaiyang , Sun Zimin 
Published: October 2019

Abstract
Abstract 4649

Objective
This study was aimed to investigate the expression levels and significance of CCAAT/enhancer binding protein alpha gene and transcription factor PU.1 gene in myelodysplasyic syndromes (MDS).

Methods
A real time quantitative reverse transcriptase polymerase chain reaction (Real-time PCR) method was used to detect the expression levels of C/EBPα mRNA in bone marrow mononuclear cells (BMMNCs) of 33 patients with MDS and 14 normal controls, Reverse transcription polymerase chain reaction (RT-PCR) was established for detecting PU.1 mRNA expression levels in BMMNCs of above-mentioned samples.

Results
The expression of C/EBPα was significantly lower in low-risk and high-risk MDS than those of normal controls (P<0.01, P<0.001, respectively), moreover, high-risk MDS showed lower C/EBPα expression than those of low-risk MDS (P<0.05). The expression level of PU.1 significantly decreased in low-risk MDS, as compared with normal controls and high-risk MDS (P<0.001), but there was no significant difference in expression level of PU.1 between high-risk MDS and normal controls (P>0.05).

Conclusion
reduced C/EBPα and PU.1 expression level have closely associated with the pathogenesis of MDS, they may be important molecular biological markers of MDS; The degree of down-regulated C/EBPα has closely related to the progression of MDS, the detection of C/EBPα gene expression level may be useful for assessing disease progress and prognostic of patients with MDS.

Disclosures:
Ding: Anhui Provincial Natural Science Foundation (070413257X): Research Funding; Fund of Anhui Provincial “115” Industrial Innovation Program: Research Funding.
The Role of Mir-150 as a Tumor Suppressor In Malignant Lymphoma
Authors: Watanabe, Atsushi , Tagawa Hiroyuki , Teshima Kazuaki , Kameoka Yoshihiro , Takahashi Naoto , Sawada Kenichi 
Published: October 2019

Abstract
Abstract 465
Disease specific genetic alteration or translocation have not been identified in NK/T cell lymphoma. We recently demonstrated that over expressions of miR-21 and/or miR-155 are frequently occurring in natural killer (NK) cell lymphoma/leukemia and deeply associated with their lymphomagenesis by deregulation of AKT signaling. In this study, we tried to identify tumor suppressor miRNA(s) in malignant lymphomas including B-cell, NK-cell and CD4+T-cell lymphoma, by using quantitative PCR and/or Northern blot analysis. We found that miR-150 in both cell lines and primary samples of NK and T-cell lymphoma showed significantly lower expression than those of normal natural killer cells and CD4+T cells. To examine the role for lymphomagenesis, we stably transduced miR-150 into lymphoma cell lines. Enforced expression of miR-150 in NK/T cell lymphoma cell lines showed increased levels of susceptibility of apoptosis, and showed senescence with reduced levels of telomerase activity and telomere DNA shortening. We further demonstrated that miR-150 directly down regulate AKT2, leading to reduced expression of phosphorylated AKTser473/474 with upregulation of tumor suppressors, Bim, p27 and p53. Since it has been proven that AKT kinase phosphorylate hTERT (human telomerase reverse transcript), downregulation of miR-150 in lymphomas lead to activate telomerase activity, resulting immortalization of the cancer cells. These results suggest that miR-150 play as a role of tumor suppressor in NK/T-cell lymphoma. Our recent and previous report demonstrate that downregulation of miR-150 and upregulation of miR-21/miR-155 collaborately contribute to NK/T-cell lymphomagenesis by deregulating AKT signaling. These findings will give a new insight into the pathogenesis of NK/T cell lymphoma and the miR-150 itself and/or AKT targeting therapy can be a useful against aggressive lymphoma.

Disclosures:
No relevant conflicts of interest to declare.
Sequential Infusion of rFVIIa and Plasma-Derived Activated Prothrombin Complex Concentrate In Haemophilia A Paediatric Patient with Inhibitors
Authors: Lassandro Giuseppe , Scaraggi Francesco Antonio , Scaraggi Rosanna , Capriati Teresa , De Mattia Domenico , Giordano Paola 
Published: October 2019

Abstract
Abstract 4660
One of the serious complication in hemophilia therapy is the development of high titre inhibitors to FVIII and less often to others coagulation factors. It makes treatment of bleeds very challenging. We report a case of hemarthrosis in hemophilia A pediatric patient with inhibitors, treated with sequential infuson of rFVIIa (rFVIIa, NOVOSEVEN; Novo Nordisk A/S, Bagsvaerd, Denmark) and plasma activated prothrombin complex concentrate (pd- aPCC, FEIBA; Baxter AG Vienna Austria). rFVIIa and plasma activated prothrombin complex concentrate are, indeed, used as haemostatic bypassing agents to prevent eaemorrages, with the goal of limiting sequelae as arthropathy, or to control quickly heamostasis as intensive on–demand treatment. A 3 years old male patient affected by haemophilia A with inhibitors came to our observation for a traumatic hemarthrosis of the left knee. Clinic examination showed swelling and pain. His inhibitor titre was 29 Bethesda Units. First we infused rFVIIa for seven consecutive days at the dose of 90 ug/kg every 3 hours. This therapy didn't determinate any clinical improvement. Then we infused plasma activated prothrombin complex concentrate for the next consecutive seven days at the dose of 60 UI/kg every 12 hours. At the end of treatment we noticed pain disappearance and reducing swelling. Medical literature recently describes similar paediatric cases treated with sequential infusion of rFVIIa and plasma activated prothrombin complex concentrate. Our positive experience could stimulate to use haemostatic bypassing agents because apparently safe. We encourage to use this therapeutic scheme because it seem to reduce healing times of acute events.

Disclosures:
No relevant conflicts of interest to declare.
Pregnancy-associated Thrombotic Thrombocytopenic Purpura: A Single Institution's Experience
Authors: Boro Jordana , Pavenski Katerina , Freedman John J. , Garvey Marie B. , Hicks Lisa K 
Published: October 2019

Abstract
Abstract 4675
Thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening form of microangiopathic hemolysis that can be associated with pregnancy. Although the association between TTP and pregnancy is well recognized, the presentation, natural history, and ideal treatment of TTP in this population remain poorly understood. St. Michael's Hospital is a regional referral centre for TTP in Ontario, Canada. We conducted a retrospective review of all cases of TTP referred to our pheresis unit between July 1993 and May 2010. Ninety-four cases were identified, of these, ten patients were pregnant or up to one week post-partum at the time of TTP diagnosis. Median age at presentation was 34 (29-36). Only one patient had been previously diagnosed with TTP and then developed a TTP relapse while pregnant. At presentation, all patients had thrombocytopenia (platelets: < 3 to 124 × 106/ml), anemia (hemoglobin: 60 to 99 mg/L), elevated LDH (1.3 to 12.5 × ULN), and fragmentation on blood film. ADAMTS13 was assessed in six of ten patients. It was normal in four patients, and deficient in two patients. Seven patients had neurological symptoms at presentation, one of whom suffered permanent right sided paralysis. Six patients had depressed glomerular filtration ratio (GFR) at presentation, four of these six recovered normal GFR. Hypertension was present in only one patient, and no patients had abnormal coagulation parameters at presentation. ALT was normal in six patients, mildly elevated in two patients, and unavailable in two patients. There were no patient deaths in this series. Patients were treated with a median of 17 plasma exchanges (range: 9 to 55) using either fresh frozen plasma or cryosupernatant. Eight patients achieved complete remission with plasma exchange. Two patients had refractory disease which ultimately responded to splenectomy and rituximab respectively. There were two fetal deaths, one a first trimester miscarriage, and the second an intrauterine death in the second trimester. In conclusion, in our series of pregnancy associated-TTP, there were no maternal deaths and most women responded to a short course of plasma exchange. ADAMTS13 deficiency was uncommon in our series. Nonetheless, in our series, TTP was not difficult to distinguish from preeclampsia and/or disseminated intravascular coagulation using routine laboratory parameters.

Disclosures:
No relevant conflicts of interest to declare.