bluuebunny/crossref_metadata_2025_split huggingface dataset:
Allogeneic Stem Cell Transplantation Overcomes the Negative Prognostic Impact of TP53 Alterations in Mantle Cell Lymphoma
Authors: Lin Richard J , Ho Caleb , Hilden Patrick , Barker Juliet , Giralt Sergio , Hamlin Paul A. , Jakubowski Ann A. , Castro-Malaspina H.R. , Papadopoulos Esperanza B. , Perales Miguel-Angel , Sauter Craig S. 
Published: October 2019

Abstract
TP53 alterations detected by chromosome 17p deletion, oncogenic mutation, or p53 protein overexpression portend extremely poor prognosis for patients with mantle cell lymphoma (MCL), despite aggressive upfront therapy including consolidative high-dose therapy autologous stem cell transplant and; more recently, novel agents such as ibrutinib or lenalidomide. We reviewed outcomes of 42 patients with available TP53 status who had received reduced-intensity/non-myeloablative conditioning (RIC/NMA) allogeneic hematopoietic cell transplant (allo-HCT) for MCL at our institution and examined the impact of TP53 alteration and other clinical factors on outcomes.
Nineteen patients had TP53 alterations including 17p deletion (n=3), oncogenic mutation (n=7), and strong p53 protein overexpression by immunohistochemistry (n=9). There were no differences in demographic or clinical characteristics among patients with and without TP53 alterations (Table 1). With a median follow-up for survivors of 23 months (range 4-119), the one-year overall survival (OS) and progression-free survival (PFS) is 87% (95% CI 72-94) and 74% (95% CI 57-85), respectively (Figure 1A). The one-year cumulative incidence of relapse and non-relapse mortality is 16% (95% CI 6-29) and 10% (95% CI 3-22), respectively (Figure 1B). The cumulative incidences of grade II-IV acute GVHD is 38% at 180 days (95% CI 24-53), and of any chronic GVHD is 33% at three-year (95% CI 17-49).
Importantly, there is no statistically significant difference in OS (p=0.582, Figure 1C), and cumulative incidence of relapse (p=0.715, Figure 1D) among patients with and without TP53 alterations. In univariate and multivariate analyses, we find that only Ki67 >30% is a significant predictor of PFS (HR 4.1, 95% CI 1.1-15.5, p=0.024), and that only Karnofsky Performance Status (KPS) <90 is a significant predictor of OS (HR 4.9, 95% CI 1.4-17, p=0.01). This is the first report that RIC/NMA allo-HCT could overcome the negative prognostic impact of TP53 alterations in MCL with relatively low incidence of transplant-related mortality. While requiring prospective evaluation, our data supports the consideration of RIC/NMA allo-HCT for MCL patients with TP53 alterations.

Disclosures
Ho: Invivoscribe, Inc.: Honoraria. Hamlin:Portola: Consultancy. Perales:Novartis: Other: Personal fees; Incyte: Membership on an entity's Board of Directors or advisory committees, Other: Personal fees and Clinical trial support; Merck: Other: Personal fees; Takeda: Other: Personal fees; Abbvie: Other: Personal fees. Sauter:Juno Therapeutics: Consultancy, Research Funding; Sanofi-Genzyme: Consultancy, Research Funding; Spectrum Pharmaceuticals: Consultancy; Novartis: Consultancy; Precision Biosciences: Consultancy; Kite: Consultancy.
Varicella Zoster Virus Reactivation Can be Prevented Very Well By Valacyclovir in Patients with Multiple Myeloma Treated with Bortezomib
Authors: Wei Qi , Wei Yongqiang , Feng Ru , Wei Xiaolei 
Published: October 2019

Abstract
BACKGROUND:
Bortezomib is associated with a significant risk of Varicella zoster virus (VZV) reactivation in patients with multiple myeloma (MM). There are some reports that acyclovir or valacycclovir reduces the risk of VZV reactivation. We assessed whether VZV reactivation could be prevented by valacyclovir at a dose of 300 mg bid.
PATIENTS AND METHODS:
We retrospectively evaluated 108 patients with MM who received bortezomib and valacyclovir prophylaxis at the Nanfang Hospital from 2015 to 2017. Patients received valacyclovir prophylaxis orally at a dose of 300 mg bid, without cessation until finishing the whole course of bortezomib treatment.
RESULTS:
The median age was 56 years (range=37-84 years). 57 patients were male and 51 were female. The median bortezomib dose was 31.2 mg/m2(range=5.2-83.2 mg/m2). All patients also received corticosteroids. The median duration of valacyclovir prophylaxis was 333 days (range=38-724 days) and the median valacyclovir dose was 199.8 g (range=22.8-434.4 g). VZV reactivation did not develop in any patient during valacyclovir prophylaxis. Adverse events over grade 3 associated with valacyclovir were not observed.
CONCLUSION:
Valacyclovir at a dose of 300 mg bid appears to be effective at preventing VZV reactivation and was well-tolerated by patients with MM treated with bortezomib.

Disclosures
No relevant conflicts of interest to declare.
Intestinal Microbiota at Neutrophil Engraftment Can Predict Acute Graft-Versus-Host Disease in the Recipients of Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Han Lijie , Fan Zhiping , Jin Hua , Xuan Li , Dai Min , Huang Fen , Lin Ren , Sun Jing , Liu Qifa 
Published: October 2019

Abstract
Backgrounds: An increasing of researches have demonstrated that intestinal microbiome plays an important role in the development of acute graft-versus-host disease (aGVHD), and loss of microbiota diversity is associated with aGVHD. But whether microbiota might be as a biomarker to predict aGVHD is undetermined. This study investigates the prediction of intestinal microbiota at neutrophil engraftment for occurrence of aGVHD.
Methods: We prospectively collected stool and blood samples from 166 patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) at pre-conditioning, day 0 and day 15 post-transplantation. The microbiota in stool were detected by 16S rRNA gene sequencing; the inflammatory factors (TNF-α, IL-6, IL-17A, IL-1β and Lipopolysaccharide (LPS)) in blood by multiplex immunoassays and dynamic turbidimetric methods; and T lymphocyte subsets were tested by flow cytometry. AGVHD was determined by retrospective review of the clinical charts.
Results: 141 patients were enrolled into analysis, including 83 in grade 0-I aGVHD (non-aGVHD group) and 58 in grades II-IV aGVHD (aGVHD group). The microbiota diversity was lower in aGVHD group than that in non-aGVHD both at day 0 and day 15 post-transplantation (P = 0.018, 0.009, respectively). The diversity was associated with conditioning (Intensified vs. Standard: medain, 3.39 vs. 3.04 (P = 0.017, day 0); medain, 3.17 vs.1.89 (P = 0.045, day 15)) and β-lactam antibiotics (β-lactam vs. No β-lactam: medain, 3.33 vs. 2.48, P = 0.004 (day 15)). At day 15 post-transplantation, Treg/Th17 cells ratio in blood positively correlated with the microbial diversity(r = 0.217, P = 0.010), but negatively correlated with the levels of TNF-α, IL-17A and LPS (r = -0.226, -0.216, -0.291; P = 0.007, 0.010, &lt; 0.001, respectively). Based on the accumulated microbiota Score of the diversity and the special discriminated constitution (Enterobacteriaceae, Lachnospiraceae, Peptostreptococcaceae and Erysipelotrichaceae) between aGVHD and non-aGVHD groups at day 15, the area under the receiver operator characteristic curve (AUC) of the Score could be used to predict aGVHD (II-IV aGVHD: AUC = 0.75, P &lt; 0.001; III-IV aGVHD: AUC = 0.84, p &lt; 0.001). The Score also correlated with the grades of aGVHD (r = 0.481, P &lt; 0.001).
Conclusions: The intestinal microbiota diversity is affected by both conditioning and antibiotics. The constitution of microbiota at neutrophil engraftment was a predictive marker for the subsequent development and grades of aGVHD.
Keywords: intestinal microbiota, marker, acute graft-versus-host disease, hematopoietic stem cell transplantation

Disclosures
No relevant conflicts of interest to declare.
Marrow Blast Percentage Impact on High-Grade Myelodysplastic Syndrome By the Revised International Prognostic Scoring System
Authors: Alkharabsheh Omar , Patnaik Mrinal M. , Gangat Naseema , Begna Kebede H. , Alkhateeb Hassan B. , Shah Mithun Vinod , Hogan William J. , He Rong , Greipp Patricia , Nguyen Phuong L. , Litzow Mark R. , Al-Kali Aref 
Published: October 2019

Abstract
Introduction:
The revised international prognostic scoring system (IPSS-R) for myelodysplastic syndrome (MDS) is widely accepted and has been validated in multiple studies. Patients with adverse cytogenetics do poorly and that is reflected in this scoring system by having the highest score for cytogenetics; 2 for intermediate, 3 for poor and 4 for very poor. Little is known about the effect of marrow blasts in adverse cytogenetic in the high-grade MDS defined by IPSS-R intermediate (>3), high (>4.5) and very high (>5). The goal is to examine the effect of marrow blast percentage on outcome in patients with adverse cytogenetics that is present in the high-grade MDS.
Methods:
We performed data collection from the Mayo clinic records for patients with confirmed MDS after obtaining appropriate IRB approval. Patients were divided based on their total IPSS-R score and we extracted high-grade MDS cases with intermediate, high and very-high IPSS-R only. Cytogenetics and baseline CBC were available for analysis. We calculated the survival difference in patients with blasts <5% and patient with blasts of 5% to 19% for every group. Survival estimates were calculated by Kaplan-Meier method and compared by log-rank testing using JMP v.13.
Results:
Our database had 1300 patients with confirmed MDS, 41% (N=536) are high-grade MDS. From those, the median age was 70 and 70% were males. Median bone marrow blast was 6% (0-19). Baseline hemoglobin is 9.2 g/dL, WBC 2.7, ANC 1.05, and platelets 69. Their cytogenetics were 1% very good, 31% good, 23% intermediate, 16% poor and 29% very poor. The total IPSS-R groups were 39%,31%, and 30% for the intermediate, high, and very-high groups respectively. The overall survival (OS) for the high-grade MDS with marrow blast <5% was 12.3 months and for patients with marrow blasts ≥5% 11.4 months (P=.4). At each high-grade MDS; intermediate, high and very high, there were no statistically significant differences for patients with marrow blasts below or above 5%. In term of risk of progression to AML, patients with blasts ≥5% were at higher risk of progression compared with <5% (25% vs 10% , P<.001), with no statistically significant difference in term of time-to-AML progression.
Conclusion:
The percentages of bone marrow blasts had no impact on overall survival among patients with high grade MDS. However, patients with ≥5% marrow blasts are at a higher risk for progression to AML.

Disclosures
Al-Kali: Novartis: Research Funding.
The Analysis of HIV-Associated Lymphoma in Japan
Authors: Hagiwara Shotaro , Yoshinaga Kentaro , Shiseki Masayuki , Tanaka Junji , Okada Seiji 
Published: October 2019

Abstract
Background.
The recent advance of antiretroviral therapy decreased the morbidity of opportunistic infections. However, the incidence of HIV-associated lymphoma remains high. Also, the outcome of the HIV-associated lymphoma is unclear in the era of rituximab. In order to address these clinical questions, we performed a nation-wide epidemiological study.
Methods.
Patients with HIV-associated lymphoma were extracted from the database of Japanese society of hematology blood disease registry from January 2012 to December 2015. We analyzed the patient's age, sex, subtypes of lymphoma, the international prognostic index (IPI) for diffuse large B cell lymphoma, and overall survival.
Results. Eighty-one patients were extracted from the database. Eighty patients were available for the survival analysis. Seventy-six (93.8%) patients of them were male. The median age was 52.5(25-88) year-old. However, there were two peaks of age; the first peak was 38-40-year-old and the second was 59-62-year-old. Sub-types of lymphomas were diffuse large B cell lymphoma (DLBCL)(48.1%), Burkitt lymphoma(19.8%), primary CNS lymphoma(8.6%), plasmablastic lymphoma(7.4%), peripheral T cell lymphoma(3.7%), Hodgkin's lymphoma(3.7%), primary effusion lymphoma(2.5%), MALT lymphoma(1.2%), Follicular lymphoma(1.2%) and Adult T cell lymphoma/leukemia(1.2%). Extra-nodal involvement at the diagnosis was observed in 61.7%. The involved sites were the brain, stomach, small bowel, colon, thyroid and the others. In DLBCL, the patients with IPI high and high-intermediate risk was 51.3%. The median observation period was 26 months. Estimated 3 years overall survival (OS) in all cases was 68.8+/-0.63%. Although there was no statistical significance, however, the 3 years, OS of Burkitt lymphoma tended to be better than that of DLBCL (84.6%+/-10.0 versus 67.7+/-8.8%). Log-rank analysis showed the OS in DLBCL patients with IPI high-intermediate and high risk was significantly worse than the patients with low, and low-intermediate risk (p<0.001). Estimated 3 years OS was 90+/-9.5% vs. 38.0+/-13.0%, respectively. The outcome of patients with primary CNS lymphoma remains poor, estimated 3 years OS was 45.7+/-22.4%.
Conclusion.
Our study showed diversity in the pathological subtype of HIV lymphoma. In the era of rituximab, the outcome seemed to be improved in patients with DLBCL and Burkitt lymphoma. However, the survival remains short in patients with poor prognostic factors and primary CNS lymphoma.
Figure. Figure.

Disclosures
Hagiwara: Celgene: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees. Shiseki:NOVARTIS Pharma: Honoraria, Research Funding; Bristol-Myers Sqibb: Honoraria; Otsuka: Speakers Bureau. Tanaka:Novartis Pharma: Honoraria; Bristol-Myers Squibb: Honoraria, Research Funding; Otsuka: Honoraria; Pfizer: Honoraria.
The Expression of BTK/p-BTK Is Different between CD5+ and CD5- B Lymphocyte from Autoimmune Hemolytic Anemia/Evans Syndromes
Authors: Xing Limin , Qu Yingying , Duan Ningning , Shao Zonghong 
Published: October 2019

Abstract
Objective To investigate the expression level of Bruton's tyrosine kinase (Btk) on CD19+B lymphocytes in peripheral blood (PB) of autoimmune hemolytic anemia (AIHA)/Evans patients.
Methods The expression of Btk and Phosphorylated Btk(p-Btk) on CD5+CD19+B and CD5-CD19+B lymphocytes were detected using flow cytometry in AIHA/ Evans patients with different disease states, healthy controls (HC) and chronic lymphocytic leukemia (CLL) patients and analyzed its correlation with clinical parameters.
Results
36 AIHA/ES patients (16 hemolytic, 20 remission), 11 CLL patients and 15 healthy controls (HC) were enrolled in this study. The expression of Btk and p-Btk on CD5+B lymphocytes in AIHA/Evans patients were higher than those in HCs and CLL patients, the latter two groups had no significant difference, and were positively correlated with the quantity of IgE. The ratio of p-Btk to Btk on CD5+B lymphocytes of hemolytic group and remission group was obviously higher than that on CD5-B lymphocytes [(74.62±6.42)%, (29.63±10.19)%, P=0.001], [(77.95±9.57)%, (26.29±6.86)%, P=0.006]. The ratio of p-BTK to BTK on CD5+B lymphocytes [(54.89±9.56)%] and CD5-B lymphocytes [(30.86±12.47)%, P=0.109)] showed no significant difference in HCs. There was no significant difference of Btk on CD5+B and CD5- B lymphocytes in AIHA/Evans patients, but the expression of p-Btk on CD5+B lymphocytes significantly higher than that on CD5-B lymphocytes in AIHA/Evans patients.
Conclusion The expression levels of p-BTK in different B cell subsets of AIHA/Evans patients were significantly different, the expression levels of p-BTK in CD5+B cells were obviously higher than that in CD5-B cells, and higher than that in CD5+ B cells in CLL patients, and positively correlated with the number of serum IgE.
Key words: anemia hemolytic autoimmune; Bruton's tyrosine kinase, Phosphorylated Bruton's tyrosine kinase; B cell subsets

Disclosures
No relevant conflicts of interest to declare.
High PARP-1 expression Predicts Poor Survival in Acute Myeloid Leukemia and PARP-1 Inhibitor and SAHA-Bendamustine Hybrid Inhibitor Combination Treatment Synergistically Enhances Anti-Tumor Effects
Authors: Li Xia , Li Chenying , Jin Jingrui , Wang Jinghan , Jin Jie 
Published: October 2019

Abstract
PARP-1 plays a critical role in DNA damage repair and contributes to progression of cancer. To address the role of PARP-1 in AML, we analyzed the expression of PARP-1 in acute myeloid leukemia (AML) using RT-PCR. We found high expressers had higher levels of blast cells in bone marrow (P=0.003) and WBC in peripheral blood (P=0.008) and were associated with a more frequent FLT3-ITD mutation (28.2% vs 17.3%, P= 0.031). The overall survival (OS) and event free survival (EFS) of the high expression group were significantly shorter than those of the low expression group (P=0.005 and P=0.004, respectively). High PARP-1 expression predicts poor survival in AML patients. Then, we investigated the efficacy and mechanism of PARP inhibitor BMN673 (Talazoparib) combined with, NL101, a novel SAHA-bendamustine hybrid in vitro and in vivo. The combination significantly enhanced apoptosis of AML cells and induced G2/M cell cycle arrest. Mechanistically, BMN673 and NL101 combinatorial treatment promoted DNA damage. In vivo, the combination effectively delayed the development of AML and prolonged survival.The synergistic effects of PARP inhibitor BMN673 in combination with SAHA-bendamustine hybrid, NL101, provide a new therapeutic strategy against AML.

Disclosures
Jin: College of Medicine, Zhejiang University: Employment; The National Natural Science Foundation of China: Research Funding.
The Demographic, Clinical and Survival Rate of Classical Hogkings Lymphoma Patients in Oman, Retrospective Study
Authors: Al Hashmi Khalid Nasser , Alwahaibi Kamla , Al-Khabori Murtadha K. 
Published: October 2019

Abstract
Background and Objectives
Hodgkin's lymphoma (HL) is a B cell lymphoma characterized by the presence of Reed-Sternberg cells. HL comprises 1% of all cancer cases and 14% of all lymphoma cases. The clinical presentation and survival rate of these patients have not been described in Oman. We, therefore, aimed to describe the clinical characteristics and survival rate of patients with classical Hodgkin's lymphoma.
Methods
This is a retrospective study that was conducted in a tertiary care centers in the Sultanate of Oman. All Omani adults with histopathological confirmed diagnosis of classical Hodgkin's lymphoma from 2000 to 2016 were included in this study. The demographic, clinical, and survival rate were recorded and analyzed.
Results
A total of 273 patients (45 % females and 55% males, mean age 32) fulfilled the inclusion criteria with histopathological confirmed diagnosis of classical Hodgkin's lymphoma. The commonest presenting feature was lymph node enlargement (83%); followed by fever (48%). The most common classical HL histological subtype was nodular sclerosing HL (NSHL) (71%). The most common stage was II 34%. The most common chemotherapy regimen used as the first line was doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) (89%). Five and 10-year survival rates were 93.8 % and 99.2%, respectively.
Conclusions
This is the first study that demonstrates the demographic, clinical and survival rate of HL patients in Oman, and provides a general picture of the HL patients in our country.

Disclosures
No relevant conflicts of interest to declare.
Tandem Autologous Hematopoietic Stem Cell Transplantation Treatment for Adult T-Cell Lymphoblastic Lymphoma: A Multiple Center Prospective Study in Southwestern China
Authors: Liu Yao , Rao Jun , Li Jiali , Wen Qin , Lou Shifeng , Su Yi , Yang Tonghua , Wang Sanbin , Lei Gao , Zhang Cheng , Peiyan Kong , Gao Li , Mai-Hong Wang , Zhu Lidan , Xiang Xixi , Zhou Sha , Peng Xiangui , Zhong Jiangfan , Zeng Defu , Zhang Xi 
Published: October 2019

Abstract
Backgroud
T-cell lymphoblastic lymphoma (T-LBL) is a highly aggressive lymphoma with very poor clinical outcomes which has not standard treatment. This study evaluated the efficacy and safety of tandem autologous hematopoietic stem cell transplantation (auto-HSCT) treatment for adult T-LBL and assessed the factors that affect survival.
Methods
160 newly diagnosed adult T-LBL patients were divided into three groups: chemotherapy group (68 patients), single auto-HSCT group (46 patients), and tandem auto-HSCT group (46 patients). The primary outcome measure was failure-free survival. The intermediate primary outcomes were progression/relapse rate and overall survival. Factors influencing toxicity related to tandem auto-HSCT treatment and prognosis for the patients were analyzed as well.
Results
The 3-year progression/relapse rate of the tandem auto-HSCT group was significantly lower than that of the single auto-HSCT group and chemotherapy group (19.6% vs 45.7% and 70.6%, p < 0.05). The 3-year PFS rate and OS rate of the tandem auto-HSCT group (68.3% and 72.5%, respectively) were significantly higher than those of the single auto-HSCT group (41.5% and 55.4%, respectively, p < 0.05) and the chemotherapy group (23.3% and 43.3%, respectively, p < 0.05). In the tandem auto-HSCT group, age and disease status after the first transplant had an influence on the OS and PFS. Multivariate analysis identified disease status after the first transplant as the only independent prognostic factor for outcome in T-LBL.
Conclusions
Tandem auto-HSCT improves long-term survival of adult T-LBL patients. Disease status after the first transplant was an independent prognostic indicator for those patients.

Disclosures
No relevant conflicts of interest to declare.
Thalidomide Combined with Interferons for the Treatment of Recurrent or Refractory Non-Hodgkin's Lymphoma
Authors: Yuan Fangfang , Ai Hao , Yin Qingsong , Chen Lin , Mi Ruihua , Wei Xudong , Song Yongping , Liu Delong 
Published: October 2019

Abstract
This study examined the clinical efficacy and safety of thalidomide combined with interferons for the treatment of recurrent/refractory non-Hodgkin's lymphoma. We retrospectively analysed the clinical data of 42 patients with recurrent or refractory non-Hodgkin's lymphoma (NHL) who were treated with a regimen of thalidomide combined and interferon α-1b (IFNα-1b) at Henan Tumour Hospital from July 2007 to January 2017. Specifically, the patients initially received 100 mg thalidomide in tablet form once daily at bedtime. If the patient tolerated the drug, the dose was increased to 200 mg. Recombinant human interferon α-1b was subcutaneously injected at a dosage of 60 μg every other day over a period of four weeks. The efficacy was monitored throughout each treatment cycle, adverse reactions were evaluated, and the progress of the disease was assessed during follow-up visits. Relevant indicators, such as the overall response rate (ORR), the overall survival (OS), the progression-free survival (PFS) for all patients, and the safety of the regimen, were analysed. Forty-two patients were treated with a regimen of thalidomide combined with interferons for at least 1 period. The efficacy of the treatment was evaluated for each patient. The objective response rate (CR + PR) was 73.8%. The median overall survival time was 28 months and the median progression-free survival (PFS) time was 21 months. According to the standards of lymphoid malignancies classified by the WHO in 2001, 36 patients were diagnosed with B-cell lymphoma, 24 of whom suffered from recurrent or refractory mantle cell lymphoma (MCL). The combination of thalidomide and interferons improved the conditions of 16 MCL patients, 8 of whom experienced CR and 8 of whom experienced PR. The median OS was 28 months, and the median PFS was 19 months for the patients with MCL. The primary adverse effects of the regimen were drug-induced fever and joint pain caused by the IFN and neurotoxicity and constipation caused by the thalidomide. The adverse reactions ranged in severity from degree I~II and could be alleviated by symptomatic treatment. Serious adverse reactions, such as anaphylactic shock, deep vein thrombosis and bradycardia, did not occur.

Disclosures
No relevant conflicts of interest to declare.