bluuebunny/crossref_metadata_2025_split huggingface dataset:
Frequency of Allogeneic Stem Cell Transplant(SCT) in Patients Presenting with Newly-Diagnosed AML or AML at Time of First Salvage Therapy.
Authors: Sandhu Ravinder , Petersdorf Stephen , Sandmaier Brenda M. , O'Donnell Paul , Becker Pamela S. , Deeg H. Joachim , Appelbaum Frederick R , Estey Elihu H. 
Published: October 2019

Abstract
Abstract 4332
Allogeneic SCT is widely considered the therapy most likely to prolong survival in pts with AML in first CR(CR1) or relapse (REL). Questions have arisen regarding the frequency with which the procedure is undertaken in a defined population of pts presenting with newly-diagnosed AML and subsequently followed through REL and after, or in pts presenting in REL. We first analyzed 26 consecutive UW pts age < 70 who did not have CBF AML, who were not NPM1+/FLT3,- and who achieved CR1 with at least 4 months have elapsing from presentation date. These patients would typically be considered candidates for SCT in CR1 Eleven of the 26(42%, 95% CI 23-63%) received SCT at a median of 3.5 months (range 0.5-9.0) from CR date. Rates of SCT were 42% both in pts age <60(8/19) and in pts ≥ 60 (3/ 7). In contrast to a report from another institute in which 14/99 pts age ≥50 received SCT in CR1 7/16 of the current pts did so (p=0.01). Rates of SCT were 6/13 in pts at highest risk based on cytogenetics and FLT3 status and 3/11 in pts at lower (i.e. “intermediate” risk; risk status not known in 2) Three of the 15 pts who did not receive SCT had available donors, but 12 were not HLA –typed. Age distribution was similar (p=0.31) in pts who were and were not HLA-typed and in only 2 non-typed pts were financial considerations or pt refusal an issue. Rather, notes suggested that physicians felt that pts were doing well and might not need SCT. We also examined our 21 consecutive pts who were under age 70, did not receive SCT in CR1, and were given first salvage therapy (S1) for relapse, again with at least 4 months follow-up from relapse date. These 21 included patients referred to us at initial diagnosis or only at time of S1. The frequency with which they were transplanted (8/21; 38% 95%CI 18-62%) did not differ from the frequency with which SCT was done in CR1. However SCT was most commonly done as 2nd salvage therapy (4 cases), with 3 pts transplanted in CR2 or CR and only 1 given SCT as S1.10 of the 13 S1 pts never given SCT had available donors (3 related, 3 unrelated, 4 cord) with SCT not done because of high blasts and/or poor performance status. We conclude that although older and younger pts may be equally likely to receive SCT in CR1, failure to HLA type may be a major impediment to increasing rates of SCT in CR1. Although relapsed pts are transplanted as often as pts in CR1, such transplants are only rarely used as initial therapy of relapse.

Disclosures:
No relevant conflicts of interest to declare.
High Risk Factors of Relapse After Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT) for Leukemia.
Authors: Chen Jia , Chen Feng , Depei Wu , Sun Aining , Qiu Huiying , Jin Zhengming , Tang Xiaowen , Miao Miao , Fu Chengcheng , He Guangsheng 
Published: October 2019

Abstract
Abstract 4345

Object
To screen the high risk factors of relapse after allo-HSCT in acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) respectively, then to compare the contribution to relapse of each risk factor and explore the mechanisms which the factors take part in. Furthermore, to discuss the subsequent surveillance and treatment strategy after transplantation.

Method
This is a retrospective study of single center experience. We conduct 262 evaluable cases of leukemia which accepted allo-HSCT between the November, 2001 and the December, 2008, with 69 cases in ALL, 90 cases in AML and 103 cases in CML. Cox proportional hazard regression model is applied in single and multiple analysis to screen the high risk factors. Donor lymphocyte infusions(DLI) were administrated in 18 patients who relapsed after transplantation, and we describe the characteristics of this approach.

Results
The risk factors which affect relapse significantly are: ALL: Cytogenetic risk classification, the cycles of initial induction chemotherapy; AML: Cytogenetic risk classification, minimal residual disease (MRD) level before transplant, reconstitution of WBC, CD4+/CD8+ lymphocyte ratio in the graft; CML: disease stage before transplant. 9 of the 18 patients who had a lower tumor load benefited from the DLI.

Conclusion
Cytogenetic risk classification is the most relevant predictor of relapse after transplantation. DLI hold great promise to overcome the barrier of relapse, especially for patients with lower disease burden.

Disclosures:
No relevant conflicts of interest to declare.
Excessive Toxicity of Once Daily Intravenous Busulfan, Melphalan, and Thiotepa Followed by Autologous Stem Cell Transplantation On Patients with Non-Hodgkin's Lymphoma.
Authors: Won Jong-Ho , Lee Sang-Cheol , Kim Seok Jin , Lee Dae Ho , Kim Won Seog , Suh Cheolwon , Park Hee-Sook 
Published: October 2019

Abstract
Abstract 4361
The busulfan, melphalan, and thiotepa (BuMelTT) regimen has shown high activity in the treatment of patient with breast cancer, ovarian cancer, aggressive lymphoma, and relapsed Hodgkin's disease. Given the limited toxicity observed with intravenous busulfan and the known activity of BuMelTT regimen in NHL, we developed a protocol utilizing once-daily intravenous busulfan/melphalan/thiotepa (ivB-MT) regimen as a conditioning for HDT in the patients with high risk or relapsed NHL.
Between March and December 2008, 13 patients with relapsed or primary refractory NHL but sensitive to salvage chemotherapy or chemo-sensitive high risk NHL underwent HDT with ivB-MT regimen followed by autologous SCT at the Soonchunhyang University Hospital, Asan Medical Center of Ulsan University, and Samsung Medical Center of Sungkyunkwan University, Seoul, Korea. The conditioning regimen consisted of busulfan 130mg/m2/day i.v. on day -8, -7, and -6, melphalan 50mg/m2/day i.v. on day -5 and -4, and thiotepa 250mg/m2/day i.v. on day -3 and -2. One patient did not recovered neutrophil and platelets and the disease relapsed on day 30 and another patient died on day 74 due to sepsis without recovery of platelets. The remaining patients achieved an ANC > 500/mm3 at a median of 10 days (range 9-30) and an unsupported platelet count of > 20,000/mm3 at a median 20 days (range 11-35) after infusion of peripheral blood stem cells(PBSC). Grade 3-4 regimen related toxicities (RRT) occurred in eight of 13 (61.5%) patients, mainly including mucositis, GI, and hepatic toxicity. Six patients (46%) developed hepatic VOD including one severe type and three patients documented infections (klebsiella pneumonia, streptococcal pneumonia, and sepsis due to MRSA and CMV bacteremia), one died of sepsis on post-transplant day 74. In all, one patient was not evaluable for response because of septic death. Four (80%) out of five patients with PR state before HDT achieved CR after HDT and one out of seven patients with CR state progressed during HDT, resulted 10 out of 12 patients achieved or maintained CR after HDT. During the follow up period (median 312 days, range 74-467), four patients were relapsed after CR and EFS were 60, 102, 104, and 203 days, respectively.
In the current study, grade 3 to 4 mucositis and liver toxicity occurred in 65% and VOD developed in 46%. It is assumed that such toxicities may be relevant to regimen with triple alkylating drugs. Despite of comparable efficacy, ivB-MT regimen was too toxic to apply to the patients with NHL undergoing HDT and autologous SCT.

Disclosures:
No relevant conflicts of interest to declare.
The Normal IGHV1-69-derived B Cell Repertoire Contains “Stereotypic” Patterns Characteristic of Unmutated CLL.
Authors: Forconi Francesco , Potter Kathleen N , Wheatley Isla , Darzentas Nikos , Sozzi Elisa , Lauria Francesco , Stamatopoulos Kostas , Mockridge Christopher Ian , Packham Graham , Stevenson Freda K 
Published: October 2019

Abstract
Abstract 4370
The cell of origin of chronic lymphocytic leukemia (CLL) has long been sought and immunoglobulin gene analysis provides new clues. The immunoglobulin heavy variable gene (IGHV) status has clinical relevance in CLL, where two subsets, delineated by the absence or presence of somatic mutation, have markedly different prognoses. The unmutated subset (U-CLL), of inferior prognosis, appears to derive from a pre-germinal center B cell. In U-CLL, there is strikingly increased usage of the 51p1-related alleles of the IGHV1-69 gene, often combined with selected IGHD genes and with IGHJ6. Shared sequence “stereotypic” characteristics of the HCDR3 result, and suggest antigen selection of the leukemic clones. In this study, we have analyzed 147 51p1/IGHJ6 rearrangements from 3 healthy individuals (>51yr) and sought sequence patterns parallel to those of U-CLL. A pre-established dataset of 313 51p1/IGHJ6 rearrangements from patients with U-CLL was used as a reference. A high proportion (49/147, 33.3%) of normal sequences revealed stereotypic patterns, several (22/147, 15%) being similar to those described in U-CLL. Additional CLL-associated stereotypes, not yet reported, were detected in 7/147 sequences (4.8%). Stereotypes (13.6%) not detected in CLL were also found in 20/147 (13.6%) 51p1/IGHJ6 combinations. The HCDR2-IGHJ6 sequences were almost exclusively unmutated (143/147, 97,3% sequences had ≥98% homology to germline). Junctional amino acids in normal B cells were heterogeneous, as in the cases of CLL with stereotyped 51p1/IGHJ6 B-cell receptors. Normal B cells expressing 51p1-derived IgM (4.8% of all B-cells) had a phenotype of naïve B-cells, similar to 51p1-negative (CD27-) B cells, i.e. IgM+ IgD+ CD23+ CD38+, with a small percentage of CD5+ B cells, not found in the memory B-cell subset. This snapshot of the naïve B-cell repertoire reveals subsets of B cells closely related to those characteristic of CLL. Conserved patterns in the 51p1-encoded IgM of normal B cells suggest a restricted sequence repertoire shaped by evolution to recognize common pathogens. Proliferative pressure on these cells is the likely route to U-CLL.

Disclosures:
No relevant conflicts of interest to declare.
DETECTION of CHROMOSOMAL 14q32 ABNORMALITIES IN B-CELL CHRONIC LYMPHOCYTIC LEUKEMIA.
Authors: Mura Mariangela , Trojani Alessandra , Soriani Silvia , Tedeschi Alessandra , Lodola Milena , Colombo Chiara , Ricci Francesca , Morra Enrica , Montillo Marco 
Published: October 2019

Abstract
Abstract 4385

Introduction
Conventional cytogenetic and FISH studies with the standard panel (13q14, 11q22.3, 17p13, 12, 6q23) are used to detect chromosomal abnormalities of clinical significance in patients with chronic lymphocytic leukemia (B-CLL). Recently, translocations and 5'IGH deletions involving chromosome14q32 are associated with B-CLL.

Aim
Our aim was to investigate the presence and the characteristics of chromosome 14q32 aberrations in a group of patients with B-CLL.

Patients and Methods
A total of 58 patients with B-CLL were investigated by conventional cytogenetic, in addition the cultures were stimulated with CpG oligodeoxynucleotide plus IL2. FISH studies with 14q32/IGH break-apart probe designed to detect chromosomal breakage of the IGH (14q32) locus, were done for 59 patients.

Results
Chromosomal abnormalities were detected in 60.3% of cases by cytogenetic. 14 patients showed complex cariotype while trisomy 12 was the most frequent anomaly found in 8 patients. Among the twelve other patients several chromosomal aberrations were noted: del(13)(q14), del(13)(q12q21),
del(13)(q12q14), del(13)(q13q32), +21, t(11;13)(q23;q14), +12 t(1;4)(q31;p14), t(3;14)(p21;q22), del (11)(q12) +21, del(6)(q21), inv3(?p13q21), del(11)(q12). Abnormalities of chromosome 14 were found in 23.8% of patients. Deletion of 5'IGH, corresponding to the variable IGH segment, was the most frequent anomaly found in 8 patients. Interesting, a 3'IGH deletion was detected in two patients, while only one patient showed a complete deletion of chromosome 14 (47,XXY,add14q32). Three patients showed 14q32 translocations involving the IGH locus.

Conclusions
Based on our findings, deletions of the variable region of the IGH gene (IGHv) and 14q32/IGH translocations are involved in B-CLL. As these preliminary data are based on small sample size, our goal will be to study the cytogenetic profile of a large number of CLL patients. Future studies will permit the identification of 14q32 translocations and the type and the frequency of IGH rearrangements. Finally, chromosome 14 abnormalities will be correlated to other cytogenetic and FISH abnormalities, and associations with known prognostic markers, such as IGVH mutation status and ZAP-70 expression, will be investigated.

Disclosures:
No relevant conflicts of interest to declare.
Palonosetron Uniquely Inhibits Substance P-Mediated Neuronal Responses in Rat Nodose Ganglia.
Authors: Li Ying , Wu Xiaoyin , Rojas Camilo , Cantoreggi Sergio , Sebastiani Silvia , Slusher Barbara 
Published: October 2019

Abstract
Abstract 4826

Introduction
Clinical studies have shown that palonosetron is more effective than first generation 5-HT3 receptor antagonists (5HT3RAs) for preventing chemotherapy induced nausea and vomiting (CINV). In addition, NK-1 receptor antagonists have been shown to augment the the antiemetic activity of the 5HT3RAs and dexamethasone to inhibit CINV. While palonosetron is effective in preventing delayed CINV, it does not directly bind to the NK-1 receptor. Recent data, however, has revealed significant receptor “cross-talk” between the NK-1 and 5HT3 signaling pathways. Alteration of 5HT3 receptor activity has been shown to cause downstream effects on NK-1 signaling, and vice versa. We postulated that if palonosetron differentially inhibited the NK-1/5HT3 crosstalk, this could help explain the differences observed in the clinic.

Methods
We carried out in vivo electrophysiology experiments in rats where single neuronal recordings of nodose ganglia expressing both NK-1 and 5HT3 receptors were collected.

Results
First, we showed that neuronal responses to substance P (SP), a known non-selective agonist of the NK-1 receptor, were significantly enhanced in the presence of cisplatin. Second, we found that palonosetron, but not ondansetron or granisetron (1st generation 5HT3RAs), could dose-dependently inhibit the cisplatin-induced SP enhancement. This inhibition was observed when palonosetron was administered 30 minutes before or 5 or 10 h after cisplatin administration.

Conclusion
The results are consistent with previous mechanism of action (MOA) experiments indicating that palonosetron uniquely exhibits allosteric binding, positive cooperativity and receptor internalization at the 5HT3 receptor. Taken together, the MOA studies may help explain the unique results observed with palonosetron in the clinic.

Disclosures
Li: Eisai, Inc: Research Funding. Wu:Eisai: Research Funding. Rojas:Eisai, Inc: Employment. Cantoreggi:Helsinn Healthcare: Employment. Sebastiani:Helsinn Healthcare: Employment. Slusher:Eisai, Inc: Employment.
Differential Protein Expression of Serum in Patients with RAEB Myelodysplastic Syndromes.
Authors: Zhong Liye , Liu Tianhao , Li Yangqiu , Geng Suxia , Lu Zesheng , Weng Jianyu , Wu Suijing , Du Xin 
Published: October 2019

Abstract
Abstract 4845

To screen molecular markers for refractory anemia with excess blasts in transformation (RAEB) in myelodysplastic syndromes (MDS) by serum proteome profiling.

Methods
Serum protein were isolated respectively from patients with RAEB, acute myeloid leukemia or normal person by 2-dimensional electrophoresis(2-DE). The imaging films were obtained and the differential reacting protein spots were recognized. Then the differential reacting proteins were obtained in the replica gel by matching analysis,and identified by peptide mass fingerprint based on matrix-assisted laser desorption/ionization time of-flight mass spectrometry (MALDI-TOF-MS) and database searching.

Results
Seven differentially expressed proteins in RAEB were found by 2-DE. Of the 7 proteins, 4 were identified with significantly statistical difference, including dipeptidyl peptidase (DPP/CD26), polymerase (DNA directed) kappa, PRO2044 and albumin-like.

Conclusion
2-DE-based serum proteome profile can help to identify serum proteomic biomarkers related to MDS. DDP/CD26 has increased serum levels in RAEB subtype MDS, suggesting significant action in advanced MDS.

Disclosures
No relevant conflicts of interest to declare.
Retrospective Analysis of Patients with Refractory Cytopenia with Unilineage Dysplasia.
Authors: Wang Yuchun , Du Xin , Geng Suxia 
Published: October 2019

Abstract
Abstract 4847

Background
Myelodysplastic syndromes (MDS) are a group of clonal heterogeneous bone marrow stem cell disorders characterized by dysplastic hypercellular marrows with peripheral cytopenias. Accurate diagnosis and classification are essential for subgroup identification and prognostic assessment of patients with MDS. Classification systems such as the World Health Organization (WHO) classification are widely used but do not always provide sufficient prognostic information. So WHO improved the classification systems last year(2008). The major change was that refractory anemia (RA) was substituted by refractory cytopenia with unilineage dysplasia (RCUD). The aim of this study was to apply the new WHO classification to re-evaluate MDS with RA.

Methods
MDS patients with RA diagnosed between 2000 and 2008 were retrospectively reclassified with WHO criteria (2008).

Results
According to the new WHO classification, RCUD is intended to encompass those myelodysplastic syndromes (MDS) which present with a refractory cytopenia with unilineage dysplasia and includes refractory anemia (RA), refractory neutropenia (RN) and refractory thrombocytopenia (RT), so in 34 cases diagnosed as RA, 12 cases (12/34,35%) still pertained to RA, 19 cases (56% ) to RN and 3 (9%) cases to RT. IPSS showed 94% of RCUD cases categorized as low or intermediate-I risk. The median survival of patients with RCUD was 84 months.

Conclusions
RA is the main subtypes of RCUD. Understanding the clinical features of RCUD accurately is helpful to determine the right subtype of RCUD. The new WHO classification system was improved to provide better diagnostic criteria.

Disclosures
No relevant conflicts of interest to declare.
Blood Product Use in Recently Diagnosed Persons with Myelodysplastic Syndrome: A Population Study.
Authors: Ramsey Scott D , McDermott Cara L , Beck Sara J , Lopez Jose A. , Dinwiddie Stephen C , McCune Jeannine S 
Published: October 2019

Abstract
Abstract 4849
Many patients with myelodysplastic syndrome (MDS) experience cytopenias that require blood product support. The extent to which MDS patients utilize blood products following diagnosis is unknown. The objective of this study was to characterize the use of blood products among recently diagnosed MDS patients in western Washington State. Records from the NCI's Surveillance, Epidemiology, and End

Results
(SEER) cancer registry for western Washington State were searched for patients diagnosed with MDS between 2001 and 2007. These records were linked to Puget Sound Blood Center (PSBC) database records. The PBSC is the major supplier of blood products for the Washington SEER region. SEER identified a total of 781 newly diagnosed patients during 2001-2007. The average age was 72.84, 76% were over age 65 and 55% were over age 75. Fifty-eight percent were male and 88% were white race. The most common MDS subtypes included refractory anemia (24%) and refractory anemia with excess blasts (21%); 33% had no specified subtype. Three hundred seventy-six patients (48%) received at least one blood product within 12 months of diagnosis; packed red blood cells (RBCs) (n=361 persons) and platelets (n=222 persons) were most commonly transfused. Among those receiving at least one transfusion of RBCs or one transfusion of platelets respectively, patients received an average of 15.40 units of RBCs and 15.37 units of platelets over 12 months from diagnosis; of these patients, the highest quartile used an average of 39.84 RBCs and 33.81 platelets per person. The proportion of MDS patients receiving any RBCs within 12 months of diagnosis increased from 24% in 2001 to 54% in 2007. Platelet use within 12 months of diagnosis increased from 12% of patients in 2001 to 39% in 2007. Among those receiving at least one platelet transfusion or at least one red blood cell transfusion within 12 months of diagnosis the number of products transfused increased over time, from an average of 8.00 platelet units (SD 5.77) and 8.85 units of RBCs (SD 11.21) in 2001 to 14.12 platelet units (SD 20.31) and 15.98 units RBCs (SD 19.35) in 2007 (p<0.0001, p<0.0001, respectively). Approximately half of newly diagnosed MDS patients receive at least one blood product in the first 12 months following diagnosis. Blood product use has increased substantially from 2001 to 2007, in terms of both the proportion of patients receiving them and the number of transfusions per person. Further study is needed to determine the factors leading to more aggressive use of blood products in these patients.

Disclosures
No relevant conflicts of interest to declare.