bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Retrospective Study to Evaluate the Survival Rates in R-CHOP Chemotherapy Followed by Autologous Stem Cell Transplantation for the Treatment of Diffuse Large B Cell Lymphoma
Authors: Lee Mark H. , Kim Sung-Yong , Kim Inho , Park Seonyang , Kim Yeo-Kyeoung , Kim Yang Soo , Lee Ho Sup , Kim Jeong-A , Park Jinny , Kim Seok Jin , Park Sung Kyu , Park Byeong-Bae , Shim Hyeok , Eom Hyeon Seok , Lee Junglim 
Published: October 2019

Abstract
Abstract 4517
Prognosis in diffuse large B cell lymphoma (DLBCL) is highly associated with the International Prognostic Index (IPI) score, which was proposed to assign prognosis to patients with aggressive non-Hodgkin lymphoma undergoing treatment with doxorubicin-containing chemotherapy. The addition of rituximab to CHOP or CHOP-like regimens has resulted in significant improvements in the overall survival (OS) rate of CD20 positive DLBCL. In addition, the original IPI scoring system has been validated even in patients receiving rituximab-based chemotherapy. However, OS and progression-free survival (PFS) in patients with high-intermediate or high IPI DLBCL were not satisfactory, and the upfront autologous stem cell transplantation (ASCT) was reported to improve the survival rates in these patients subset. Therefore, we retrospectively evaluated the survival rates in patients with DLBCL with CD20+, who were treated with R-CHOP followed by ASCT.
We analyzed 40 DLBCL patients who underwent an ASCT, reported to the Korean Blood and Marrow Transplant Registry between 2005 and 2011 by 12 centers. Patients characteristics at diagnosis: 60% male, 5% stage II with bulky disease, 95% stage III or IV, 42.5% bone marrow involvement, 65% high-intermediate or high risk by IPI score. Patients characteristics at ASCT: median age 47 years (range, 23–66) and 82.5% of patients received ≥6 cycles of R-CHOP. Response to R-CHOP: 62.5% CR and 37.5% PR. 17.5% of patients received involved field radiotherapy prior to ASCT for bulky disease or residual lymphoma. Disease status at ASCT: 72.5% CR and 27.5% PR. Median time from diagnosis to ASCT was 7.85 months (range, 4.4–16.1).
Median follow-up period from diagnosis was 36.2 months (range, 6.3–84.8). 2-year estimates of PFS, OS and relapse from diagnosis were 73.8%, 86.4% and 24.3%, respectively. 5-year estimates of PFS, OS and relapse were 70.8%, 68.3% and 27.4%, respectively. 3-year estimates of PFS and OS according to IPI score were not significantly different among 4 risk groups (P=0.890 and P=0.855, respectively).
The upfront ASCT following R-CHOP induction therapy may improve survival for patients with advanced high risk DLBCL. Prospective evaluation of the treatment outcome of R-CHOP followed by ASCT is needed for high risk DLBCL on a large scale.

Disclosures:
No relevant conflicts of interest to declare.
Autologous Transplantation in Relapsed and Refractory Mantle Cell Lymphoma
Authors: Shah Bijal D. , Little Bryan J , Cultrera Jennifer , Bello Celeste M. , Sokol Lubomir , Sotomayor Eduardo M. , Tomblyn Marcie , Ayala Ernesto 
Published: October 2019

Abstract
Abstract 4542

Introduction:
Consolidation with autologous transplantation (AutoSCT) may extend progression free survival when administered following initial induction. There are limited data to support the role of AutoSCT in the relapsed or refractory setting.

Methods:
We retrospectively evaluated all patients with MCL transplanted at our institution before 2010. We identified 57 patients, among whom 42 were transplanted in first remission (CR1, n=32; PR1 n=10), 11 in second remission (CR2, n=4, PR2, n=7), and 4 with relapsed/refractory disease beyond first remission.

Results:
The median PFS are: CR1 37mo, PR1 24mo, CR2 not reached, and PR2 23mo. No statistically significant difference was observed between patients transplanted CR1 vs PR1 (p one-sided =0.08), CR2 vs PR2 (p one-sided =0.10), or in CR/PR1 vs CR/PR2 (p one-sided =0.39). The median PFS for those with refractory disease, and/or those transplanted beyond second remission was 6mo which is significantly inferior to the cohort of those transplanted in first or second remission (p one-sided =.01).
The median OS calculated from transplant are: CR1 63mo, PR1 50mo, CR2 not reached, PR2 45mo. No statistically significant difference was observed between patients transplanted CR1 vs PR1 (p one-sided =0.47), CR2 vs PR2 (p one-sided =0.46), or in CR/PR1 vs CR/PR2 (p one-sided =0.29). The median OS for those with refractory disease, and/or those transplanted beyond second remission was 16mo which is not statistically significantly inferior to the cohort of those transplanted in first or second remission (p one-sided =.067).
MIPI data collected at diagnosis were available for 30 patients, all transplanted in first or second remission with chemosensitive disease. These data were not predictive of survival or progression from transplantation. Simplified MIPI obtained at the time of transplant were available for 44 patients, all transplanted in first or second remission with chemosensitive disease. These data were similarly uninformative for prediction of progression or survival from transplantation.

Conclusions:
Consolidation with AutoSCT may be similarly effective for patients in first relapse with chemosensitive disease. MIPI at diagnosis and the simplified MIPI at transplant may failed to account for survival among highly selected patients considered eligible for transplantation.

Disclosures:
Sokol: Celgene: Honoraria, Speakers Bureau.
Identification of Differentially Expressed and Spliced Genes with RNA Sequencing Analysis of CLL Specimens
Authors: Liao Wei , Jordaan Gwen , Jaroszewicz Artur , Pellegrini Matteo , Sharma Sanjai 
Published: October 2019

Abstract
Abstract 4582
High throughput sequencing of cellular mRNA provides a comprehensive analysis of the transcriptome. Besides identifying differentially expressed genes in different cell types, it also provides information of mRNA isoforms and splicing alterations. We have analyzed two CLL specimens and a normal peripheral blood B cells mRNA by this approach and performed data analysis to identify differentially expressed and spliced genes. The result showed CLLs specimens express approximately 40% more transcripts compared to normal B cells. The FPKM data (fragment per kilobase of exon per million) revealed a higher transcript expression on chromosome 12 in CLL#1 indicating the presence of trisomy 12, which was confirmed by fluorescent in-situ hybridization assay. With a two-fold change in FPKM as a cutoff and a p value cutoff of 0.05 as compared to the normal B cell control, 415 genes and 174 genes in CLL#1 and 676 and 235 genes in CLL#2 were up and downregulated or differentially expressed. In these two CLL specimens, 45% to 75% of differentially expressed genes are common to both the CLL specimens indicating that genetically disparate CLL specimens have a high percentage of a core set of genes that are potentially important for CLL biology.
Selected differentially expressed genes with increased expression (selectin P ligand, SELPLG, and adhesion molecule interacts with CXADR antigen 1, AMICA) and decreased (Fos, Jun, CD69 and Rhob) expression based on the FPKM from RNA-sequencing data were also analyzed in additional CLL specimens by real time PCR analysis. The expression data from RNA-seq closely matches the fold-change in expression as measured by RT-PCR analysis and confirms the validity of the RNA-seq analysis. Interestingly, Fos was identified as one of the most downregulated gene in CLL. Using the Cufflinks and Cuffdiff software, the splicing patterns of genes in CLL specimens and normal B cells were analyzed. Approximately, 1100 to 1250 genes in the two CLL specimens were significantly differentially spliced as compared to normal B cells. In this analysis as well, there is a core set of 800 common genes which are differentially spliced in the two CLL specimens. The RNA-sequencing analysis accurately identifies differentially expressed novel genes and splicing variations that will help us understand the biology of CLL.

Disclosures:
No relevant conflicts of interest to declare.
Spontaneous Remission of Chronic Lymphocytic Leukemia, Possibly More Rare Then Previously Reported?
Authors: Nakhla Peter , Butera James N , Castillo Jorge J , Treaba Diana O , Quesenberry Peter J 
Published: October 2019

Abstract
Abstract 4589

Introduction:
Spontaneous remission of chronic lymphocytic leukemia (SRCLL) has occassionaly been reported since the 1950s. About 40–50 cases have been reported in the English literature. The often quoted incidence of such a phenomena is estimated to be 1% of all CLL cases (Table 1). However, a review of these reports which have determined this incidence suggests that many patients did not have a true SRCLL. The authors have conducted a systemic search within their own institution database to determine the true incidence of SRCLL.

Methods:
After obtaining appropriate IRB approval, a systemic search was performed within the our institution's hematopathology databases for the diagnosis of chronic lymphocytic leukemia from year 2000 to 2012. Records and laboratory findings were reviewed for all cases. Records for patients with laboratory data suggestive of remission were reviewed to determine if they had received any form of therapy. All cases were included in the review if the diagnosis of CLL was firmly established by flow cytometry. SRCLL was defined as: 1) the patient's elevated lymphocyte number at diagnosis was >5 × 109/L and persisted for >6 months confirming the initial diagnosis of CLL, 2) the lymphocyte number subsequently normalized to <5 × 109/L, the lymphocyte count remained normal for greater than 9 months, 3) resolution of other features of CLL such as lymphadenopathy, and 4) no intervening treatment was given to patients, including radiation therapy or steroids.

Results:
After reviewing 167 cases, only one case met our inclusion criteria, with an estimated incidence of 0.6%.

Conclusion:
Spontaneous remission of CLL is a rare phenomenon. This review suggests that the incidence of SRCLL is less then the previously often quoted incidence of 1% and may more appropriately approximate 0.6%.

Disclosures:
No relevant conflicts of interest to declare.
Plasmacytoid Transformation of Chronic Lymphocytic Leukemia CLL with Multiple Lytic Bony Lesions
Authors: Jajeh Ahmad 
Published: October 2019

Abstract
Abstract 4590
Richter transformattion in patients with Chronic Lymphocytic Leukemia CLL can happen in 3%- 15%. This involve transformation of relatively indolent CLL cells into higher grade and aggressive form of Lymphoma. Plasmcytoid transformation of CLL with paraprotinemia, multiple lytic lesions and hypercalcemia can occur. This abstract will describe six patients with CLL who presented with hypercalcemia and lytic bony lesions in the course of their disease. Mean age is 72 years old. All were males, four whites and two blacks. One patient had solitary bony lesion with solitary small lung lesion that biopsy showed moderately differentiated adenocarcinoma. Bone scan was negative and monoclonal IgG lambda was present. The second patient had multiple lytic lesions with nephrotic range proteinuria of five grams; kappa light chain with bone marrow biopsy showing plasma more than 10%. Two patients has progressive adenopathy with elevated IgM level more than 2 grams with increased LDH. One patient progressed to PLL and developed renal failure that required hemodialysis with lambda light chain in urine. One patient with progressive bony lesion involving the scapula and close vertebrae with IgG spike. All patients expired in a short period less than six months with therapy. Biopsy was available for four patients which showed plasmacytoid or plasmablastic morphology.
In conclusion: Plasmacytoid transformation in patient with CLL should be considered when hypercalcemia, lytic bony lesions and paraproteinemia is present.

Disclosures:
No relevant conflicts of interest to declare.
Assessment of Minimal Residual Disease Levels in B-CLL After Front-Line Treatment with FC-R and Rituximab Maintenance
Authors: Garcia-Vela Jose A. , Lopez Javier , Ferrer Secundino , Giraldo Pilar , González-Barca Eva , Conde Eulogio , González Marcos , Guzman Jose-Luis , De la Serna Javier , Osma Mar , Deben Guillermo , Monzo Encarna , De Paz Raquel , Penalver Francisco-Javier , Jarque Isidro , Martinez Rafael , Burgaleta Carmen , de Oteiza Jaime Perez , Andreu M.Angeles , Carbonell Felix , Garcia-Marco Jose A 
Published: October 2019

Abstract
Abstract 4599

Objective:
To prospectively analyze change over time in minimal residual disease (MRD) in a cohort of 84 untreated patients diagnosed with CD20+ B-CLL who received from October 2007 to December 2010 six cycles of R-FC (Rituximab 375 mg/m2 IV in cycle 1 and 500 mg/m2 in cycles 2–6; F: 25 mg/m2, and C: 250 mg/m2 on days 1–3; every 28 days). Patients who achieved response were treated with rituximab 375 mg/m2 every 2 months for 3 years.

Materials and methods:
EDTA-anticoagulated peripheral blood (PB) and bone marrow (BM) samples were taken at diagnosis, after 3 and 6 cycles of R-FC, and every 6 months during the maintenance phase. MRD was centrally assessed by four-color multiparameter flow cytometry using the following antibody combinations: CD22/CD23/CD19/CD5, CD81/CD22/CD19/CD5, CD20/CD38/CD19/CD5, and CD20/CD79b/CD19/CD5. An acquisition was performed by selection of CD19+ cells/SSC including at least 200,000 events, reaching a sensitivity level of 0.01% (10-4).

Results:
PB/BM samples for assessing MRD were available from 28 of the 84 patients after 3 cycles of R-FC and from 79 patients after the 6 induction cycles, and 43 (58%) of the 74 patients on maintenance reached the interim study at 18 months of maintenance (9 cycles). Correlation between PB and BM was 57%, 68%, and 86% at the three study time points. After three R-FC cycles, 16 patients (56.8%) had a MRD- in PB, but only 4 patients (14%) also had MRD- in BM. After six R-FC cycles, 58 patients (73.3%) had a negative study in PB, and 41.7% also in BM. Among the 24 patients analyzed after the third cycle with BM+, 11 achieved negativization after 6 cycles, and MRD was negative in PB in 10 of 12 patients. After 18 months of maintenance, 11 patients (26.2%) converted to MRD- in PB/BM, and a single patient (2.4%) converted to MRD+.

Conclusion:
Six cycles of R-FC achieved better MRD- rates in PB and BM as compared to 3 cycles. Addition of rituximab as maintenance after R-FC increased the number of MRD-negative in BM, and in consequence the MRD-negative CRs. A good correlation was not found between MRD values in blood and bone marrow in the induction phase. However, these levels improved in the maintenance phase due to an increase in the number of cases with RMD-negative in BM witch were negatives in PB during induction phase.

Disclosures:
Off Label Use: R in Maintenance.
Replication Timing and Pediatric Leukemia
Authors: Gilbert David M , Battaglia Dana , Chang Bill H , Buckley Quinton , Pope Benjamin D , Druker Brian J. , Ryba Tyrone 
Published: October 2019

Abstract
Abstract 4609
Abnormal temporal control of replication (“replication timing”) is a universal hallmark of cancer, but the significance of this relationship is not understood. During normal development, changes in replication timing are regulated in defined chromosomal units (“replication domains”) of 400–800 kb, with late replication generally associated with stable gene silencing. We have performed genome-wide replication timing mapping on pediatric acute leukemias and identified patterns of replication-timing mis-regulation (“leukemia fingerprints”) in common across multiple types of pediatric leukemia (“multi-lineage fingerprints”), as well as those linked to specific subtypes of acute leukemia and patient-specific fingerprints. Most of the mis-regulated regions are not associated with copy number variation or translocations and correspond to many of the same domains whose replication timing is regulated during normal development. The existence of multi-lineage fingerprints suggests an early origin of their mis-regulation while type-specific and patient-specific fingerprints suggest that mis-regulation continues to occur downstream of the initiating event. Our hypothesis is that there exists an hierarchy of replication-timing mis-regulation, initiating with frozen vestiges of normal hematopoiesis that are inappropriately maintained, followed by additional changes that evolve as the tumor differentiates. These changes may then affect the ability of downstream lineages to activate or silence genes. Since chromatin is assembled at the replication fork, and different types of chromatin are assembled at different times during S phase, changes in replication timing likely contribute to domain-wide changes in chromatin structure, similar to those observed in long range epigenetic silencing (LRES). In fact, we find that genes within leukemia fingerprint domains are significantly enriched for those transcribed during hematopoiesis and/or mis-regulated in cancers. Replication timing is an exceptionally stable epigenetic property that is not easily disturbed by loss or mis-expression of single master regulators of cell fate and is not directly related to transcription, but rather to the stability of gene silencing. Hence, events occurring early in hematopoiesis could have profound effects on the activation of transcriptional programs in downstream lineages. Elucidating the genesis and genealogy of leukemia-specific replication timing fingerprints and their relationship to transcriptional control will be fundamental to understanding their link to the development of acute leukemias.

Disclosures:
No relevant conflicts of interest to declare.
Patterns of Clinical Presenations of Thrombotic Thrombocytopenic Purpura in Plasma Exchange Era
Authors: Dawod Muath , Alhyari Mohammad , Kuriakose Philip 
Published: October 2019

Abstract
Abstract 4642
Thrombotic thrombocytopenic purpura (TTP) is a rare but serious disease in which early diagnosis and management has a major impact on outcome. TTP has been historically linked to a pentad of clinical features (mental status changes, fever, acute renal failure, anemia and thrombocytopenia). The frequency of the classical pentand in the pre plasma exchange era has been reported to be as high as 40 percent. With the introduction of plasma exchange and increased awareness of this disease a different pattern of clinical presentation of TTP might be forming based on early diagnosis. We reviewed the clinical presentation of 91 patients with a diagnosis of TTP in terms of pattern and duration of symptoms.
Only 9% of patients (n=8) presented with the pentad. Duration of symptoms in all patients ranged between 1 and 60 days, with a mean of 9.3 days. Statistical analysis showed no correlation between the duration of symptoms prior to diagnosis and the presence of the pentand (mean of symptom duration in the pentad and non-pentad groups were 9.4 and 9.3 days with range of (3–30) and (1–60), respectively).
The most common patterns of clinical presentation were in the form of constitutional symptoms (fatigue, malaise and generalized weakness), which were seen in 67% of patients (n=60), followed by neurological symptoms (mainly headache and confusion) in 51% of pateints (n=46). Gastrointestinal (GI) symptoms (nausea, vomiting or abdominal pain) were seen in 47% of patients (n=42).
The most common triad of symptoms was neurological (headache and confusion), constitutional (fatigue, weakness and anorexia) and GI(nausea, vomiting and abdominal pain), which was present in 14% of patients (n=13).
In terms of clinical outcome, there was also no correlation between the duration of symptoms and the clinical outcome (mean of symptom duration in the alive and dead groups were 9.2 and 10 days, with range of 1–60 and 1–21 days, respectively). There was no association between the presence or absence of the pentad and mortality, (25% (n=2/8) as compared to 11% (n=9/83), P-value of 0.248). On the other hand patients with poor outcome (defined as death) were less likely to present with constitutional and nonspecfic symptoms (27.3% (n=3/11) as compared to 72.5% (n=58/80), P-value of 0.005),
As a conclusion, the pentad is a very rare presentation in TTP and the duration of symptoms prior to diagnosis does not predict its presence. While nonspecific and/or constitutional symptoms are the most common presentation, patients who do not present with such symptoms tend to do worse. Our study highlights the importance of defining the clinical presentation of this disease in a new and pertinent form that could help clinicians in the diagnosis and timely management. It also raises the question of prognsotic value of the clinical presentation in this potentially lethal disease.

Disclosures:
No relevant conflicts of interest to declare.
Patterns of Clinical Presentation of Thrombotic Thromboxytopenic Purpura. Is There a Racial Difference?. A Single Institution Experience.)
Authors: Dawod Muath , Alhyari Mohammad , Kuriakose Philip 
Published: October 2019

Abstract
Abstract 4653

Background:
Thrombotic thrombocytopenic purpura (TTP) is a rare but serious disease that has been reported more frequently in African-Americans (AA). While recent reports have showed an increased incidence of TTP amongs AA patients, there is no data with regards to the patterns of clinical presentation in this racial subgroup and if there is any difference as compared to other racial subgroups.

Patients and methods:
In this retrospective study we reviewed characterstics and clinical presentation of 91 patients with the diagnosis of TTP. Sixty four patients were AAs (70%). The second largest racial subgroup was Caucasians (24 patients, 26%). Demographics, lab values and symptoms were compared between AAs and Caucasians. Continuous variables were compared using two-sided two-sample t-tests. Alternatively, the Wilcoxon rank-sum test was used if the data were not normally distributed. Categorical variables were compared using Chi-square tests.

Results:
AA patients were older [median age of 47.6 years as compared to 40 years, P-value of 0.057] and more likely to be females [68.8%, (n=44/64) as compared to 45.8%, (n=11/24), P-value of 0.048]. As for laboratory evaluation, AA patients were more likely to have positive ANA [44% (n=22/64) as compared to 14.3% (n=2/24), P-value of 0.042] and higher ESR (median of 75.5 as compared to 40.7, P-value 0.03). Other laboratory evaluation including hemoglobin, platelet counts and creatinine were comparable. The most common patterns of clinical presentation in AA patients were in the form of constitutional symptoms (fatigue, malaise and generalized weakness) which were seen in 67% of patients (n=43), followed by neurological symptoms (mainly headache and confusion) in 53% of pateints (n=34). Gastrointestinal (GI) symptoms (nausea, vomiting or abdominal pain) were seen in 44% of patients (n=28). This pattern was comparable to what is seen in Caucasian patients. Skin symptoms were reported less frequently in AA as compared to Caucasians (17.2% vs. 41.7%, p = 0.016).

Conclusion:
While AA patients are more likely to be females, older and have positive ANA, the clinical presentation of TTP is similar among different racial subgroups (African Americans and Caucasians).

Disclosures:
No relevant conflicts of interest to declare.