bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of Response Over 6 Years Between Patients with Chronic Myeloid Leukemia Who Received Imatinib as Initial Therapy and Those Who Received Imatinib as Secondary Therapy.
Authors: Jiang Hao , Huang Xiaojun , Chen Shanshan , Jiang Bin , Jiang Qian , Qin Yazhen , Lai Yueyun 
Published: October 2019

Abstract
Abstract 4281

Objective
To compare responses in a single center over 6 years between patients with Philadelphia-positive chronic myeloid leukemia (CML) who received imatinib as initial therapy and those who received imatinib as secondary therapy.

Patients and Methods
We reviewed 171 cases of patients with Philadelphia chromosome (Ph)-positive CML who received imatinib for 72 months: 73 patients in an initial therapy group (time from diagnosis of CML less than 6 months) and 98 patients in a secondary therapy group (time from diagnosis of CML greater than 6 months).

Results
Cumulative rates of complete cytogenetic response (CCyR) at 6, 12, and 36 months after imatinib treatment in the initial therapy group and secondary therapy group were 75%, 89% and 96%, and 48%, 77% and 84%, respectively (P=0.0002). The median time to CCyR in initial and secondary therapy groups was 6 months (95%CI, 3.3–8.3) and 9 months (95%CI, 6.4–11.6), respectively (P=0.0002). Cumulative rates of major molecular response (MMoR) at 9, 12 and 18 months after imatinib treatment in initial therapy and secondary therapy groups were 26%, 42% and 49%, and 16%, 25% and 36%, respectively (P=0.048). The median time to MMoR in initial and secondary therapy groups was 19 months (95%CI, 11.7–26.3) and 36 months (95%CI, 19.7–52.4), respectively (P=0.048). Estimated rates of freedom from progression to accelerated phase (AP) and blastic phase (BP) in initial and secondary therapy groups were 99% and 89%, respectively (P=0.08). Estimated 6-year progression-free survival (PFS) rates in cases with CCyR and without CCyR were 93% and 62%, respectively (P=0.0012). Estimated 6-year event-free survival (EFS) rates in initial and secondary therapy groups were 96% and 68%, respectively (P=0.04). The event was defined as progression to accelerated AP and BP, loss of CCyR or CHR.

Conclusion
The time to CCyR and MMoR in the initial therapy group was significantly shorter than that in the secondary therapy group. There was no difference in PFS rates between the two groups in the 72-month long-term follow-up. The EFS rates indicated that patients receiving imatinib as initial therapy achieved more stable remissions than those receiving it as secondary therapy.

Disclosures:
No relevant conflicts of interest to declare.
Monozygotic Twins Display Different Minor Histocompatibility Antigens.
Authors: Markiewicz Miroslaw , Siekiera Urszula , Mietla Monika Dzierzak , Karolczyk Agnieszka , Kruzel Tomasz , Helbig Grzegorz , Kyrcz-Krzemien Slawomira 
Published: October 2019

Abstract
Abstract 4324

Introduction
Albeit it is generally presumed that monozygotic twins are genetically identical and that phenotypic differences between twins are mainly due to environmental factors, large-scale variation in copy number of DNA segments recently evidenced by Bruder et al. (AJHG, 2008) showed presence of genotypic diversity in monozygotic twins. The rationale of this study was to test whether monozygotic twins display disparities of minor Histocompatibility antigens (mHags) which may play role in syngenic HCT. We and others have previously shown that mHags constitute an important immunogenetic factor influencing immune responses following transplantation from HLA-matched allogeneic donors.

Patients and Methods
mHags HA-1, HA-2, HA-3, HA-8, HB-1, ACC-1, ACC-2, HwA-9, HwA-10, UGT2B17, HY genotypes were defined with use of Dynal AllSet kits by PCR-SSP method in secured DNA samples from 3 monozygotic twins pairs aged 34, 24 and 28, who underwent syngenic allo-HCTs due to different hematological malignancies (NHL, CML, AML) in the Department of Hematology and BMT in Katowice, Poland in years 2000-2004.

Results
In 2 out of 3 syngenic pairs we have found differences in genes encoding mHags: different allele of EB-1 was present in one pair (NHL) (recipient HH, donor HY), and two different alleles of HwA-9 (RR, RG) and HwA-10 (**, R*) were present in second pair (CML). No differences in mHags were observed in the third pair (AML).

Conclusions
Our results question the long-standing belief that monozygotic twins are genetically identical and open up a possibility to further study the role of disparate mHags in disease and transplantation.

Disclosures:
No relevant conflicts of interest to declare.
Induction with New Drugs and Planned Autologous Followed by Non-Myeloablative Allogeneic Transplantation in Newly Diagnosed Myeloma.
Authors: Giaccone Luisa , Festuccia Moreno , Sorasio Roberto , Mordini Nicola , Schianca Fabrizio Carnevale , Patriarca Francesca , Casini Marco , Iori Anna Paola , Foà Robin , Boccadoro Mario , Bruno Benedetto 
Published: October 2019

Abstract
Abstract 4330

Introduction
Immunomodulatory drugs have recently changed the treatment options in multiple myeloma. Moreover, thalidomide, bortezomib and lenalidomide have also been used in the setting of allografting as post-transplant salvage therapy or as maintenance. We are currently evaluating the impact of new drugs as induction therapy in newly diagnosed multiple myeloma before a planned standard autograft followed by a non-myeloablative allograft (Tandem auto-allo).

Patients and methods
Twenty-five newly diagnosed patients (median age 55 years old, range 26-65) entered a recently designed prospective phase II program of tandem auto-allo which included the use of so-called new drugs during induction. Here, we report data on the first 11 evaluable patients with a follow up of at least 1 month after the allograft. Induction consisted of lenalidomide and dexamethasone (n=5), thalidomide and dexamethasone (n=4), or bortemomib-containing regimens (n=2), followed by G-CSF mobilized peripheral blood stem cell harvest. A standard autograft after melphalan 200 mg/m2 was planned 2-4 months before a low-dose (2 Gy) TBI-based allograft from an HLA-identical sibling. GVHD prophylaxis consisted of cyclosporin and mycophenolate mofetil. Disease status at allografting and post-transplant outcomes were compared to those of 22 patients pair-matched for beta2microglobulin and age, who underwent tandem auto-allo after induction with VAD-based regimens without new drugs (Blood, 2009).

Results
At the time of allografting after induction with new drugs and the autograft overall response rate was 81% (9/11), including a immunofixation-negative complete remission (CR). Following allografting, all patients promptly achieved donor engraftment. After a median follow-up of 11 months (2-26), all patients are alive and the overall response rate was 91% (10/11). Incidence of grade II-IV GVHD was 34% (4/11), including 1 patient with grade III GVHD. Chronic GVHD was observed in 40% (4/10) of patients with at least 3 months of follow-up. The induction with new drugs did not increase allotransplant-related toxicity or incidence of acute GVHD (Table 1). We observed a higher response disease before allografting in patients treated with new drugs.

Conclusions
Induction with lenalidomide, thalidomide or bortezomib does not impact feasibility and safety of tandem auto-allo. Longer follow up and a larger cohort of patients are necessary to evaluate the impact of new drugs in improving disease control post-tandem auto-allo.

Disclosures:
Patriarca: Janssen Cilag: Honoraria; Celgene: Honoraria. Boccadoro:Celgene: Consultancy, advisory committees, Research Funding; Pharmion: Consultancy, advisory committees, Research Funding; Janssen Cilag: Consultancy, advisory committees, Research Funding.
G-CSF Treatment May Prevent Telomere Attrition in CD34+ After Peripheral Blood Autologous Stem Cell Transplantation: Shortening Time to engrafting but Early Relapse in Non Hodgkin's Lymphoma. First Experience without Stem Cell Cryopreservation.
Authors: Silva-Moreno Mario , Murillo-Ortiz Blanca , Hernández-González Martha , Solorio-Meza Sergio , Martínez-Garza Sandra , Castillo-Valenzuela Rosa , Albarrán-Tamayo Froylán 
Published: October 2019

Abstract
Abstract 4358

Background
Hematopoietic reconstitution after stem cell transplantation requires excessive replicative activity because of the limited number of stem cells that are used for transplantation. Telomere shortening has been detected in hematopoietic cells after allogenic peripheral blood stem cell transplantation (PBSCT). Recent studies have demonstrated shortening of telomeres after chemotherapy, this shortening being equivalent to 15-40 years of ageing which has been related to genetic instability, increase risk of mutations, myelodysplastic syndromes, secondary malignancies and relapse.

Aims
To measure in vivo the effect of G-CSF administration, on the regulation of stem cells obtained from peripheral blood collected for autologous transplantation and to know its possible implications, on telomere dynamics following high-dose (HD) chemotherapy courses cyclophosphamide (CY) and HD-Ara-C for relapsed non Hodgkin's lymphoma.

Methods
Telomeric measurement was performed with real-time polymerase chain reaction (RT-PCR),in peripheral blood progenitor cells(PBPC) collected on day 5 and 10 of G-CSF administration from patients with Lymphoma, and day 0,+7,+14 and +17 post transplantation. For CD34+ cells selection, mononuclear cells were isolated from peripheral blood stem cell by Ficoll-Hypaque. The purity of CD34 selected cells was determined in a cell sorter (Becton Dickinson) using a fluorescein isothiocyanate (FICT)-conjugate monoclonal antibody (mAb).

Results
We have shown dynamic telomere length change during the immediate reconstitution, Telomere Lenght (TL) was shorter in PBPC collected after HD-Ara-C and CY compared to TL after G-CSF administration, 6526bp vs. 4582 bp (P < 0.01). This result was confirmed on CD34+ cells. Engraftment of granulocytes and platelets come on day +13 and +19 respectively An increase in telomere length to day +19 (5962 bp) was found. Unfortunately we face with an early relapse of the same non Hodgkin's lymphoma at day +60.

Conclusions
Administration of G-CSF increased TL in CD34+ prevents telomere attrition after allogenic peripheral blood stem cell transplantation. The size and composition of the transplanted stem cell pool determines the ultimate telomere length. Whether PBSCT with shortened telomeres has engraftment improvement with G-CSF but risking early relapse warrants more prospective studies. We suggest that measurement of telomere length in peripheral blood collected for transplantation could be useful as a prognostic marker for engraftment/relapse in non Hodgkin's lymphoma without stem cell cryopreservation.

Disclosures:
No relevant conflicts of interest to declare.
Multicenter Retrospective Analysis of High Dose Chemotherapy and Autologous PBSCT for Ovarian Cancer.
Authors: Kim Kyoung Ha , Won Jong-Ho , Park Hee-Sook , Jeong Seong Hyun , Lee Hyun Woo , Park Joon Seong , Cho Seok-Goo , Lee Joon Mo , Park Chong Won , Kim Dong Hwan (Dennis) , Jang Jun Ho , Lee Won Sik , Lee Jung Lim , Mun Yeung-Chul , Seong Chu-Myong , Kim Han Jo 
Published: October 2019

Abstract
Abstract 4365

Background
Ovarian cancer is one of the most chemotherapy sensitive solid tumors. However, the role of dose intensity in the chemotherapy of advanced epithelial ovarian cancer has remained controversial. Accordingly, the current study attempted to analyze the outcome of high dose chemotherapy and autologous peripheral blood stem cell transplantation for ovarian cancer retrospectively.

Methods
Clinical data were collected retrospectively from 6 transplant centers in Korea between January 1996 and July 2008.

Results
Twenty three patients of total 6 centers were analyzed. The median age of the patients was 52 years (40-62 years). Nineteen patients (82.6%) were platinum sensitive and 4 patients were not. The conditioning regimens were reported to be ICE (ifosfamide, carboplatin, and etoposide) in 43.5 %, CTM (cyclophospamide, thiotepa, and melphalan) in 26.1 %, melphalan in 13%, other in 17.4 %. The median time to attain a neutrophil count greater than 500/mm3, following the transplantation, was 13 days (4∼38), and to attain a platelet count greater than 20,000/mm3, was 13 days (4∼38 days). There was primary graft failure of platelet in 3 patients. The median duration of progression free survival and overall survival were 6.3 months (95% CI, 0-19.3) and 19.7 months (95% CI, 10-29.4). The median overall survival was 25.9 months in the platinum sensitive patients and 17.4 months in the platinum resistant patients, however, there was no statistically significant difference in PFS between two groups. Poor prognostic factor for survival which retained statistical significance at multivariate level were platinum resistance (p=0.06, RR 3.99; 95% CI, 0.94-16.97) and clear cell type (p=0.015, RR 9.63; 95% CI, 1.56-59.45).

Conclusion
Some subgroups (non clear cell types, platinum sensitive groups) of patients with ovarian cancer seem to have good outcomes after high dose chemotherapy with autologous stem cell transplantation, although several biases may have affected these observations.

Disclosures:
No relevant conflicts of interest to declare.
Multimodal Bcl-2 Sub-Populations in CLL.
Authors: Degheidy Heba A. , Gadalla Shahinaz M. , Raveche Elizabeth , Stetler-Stevenson MA , Marti Gerald E. 
Published: October 2019

Abstract
Abstract 4391

Introduction
The Recently described NZB miRNA15a/16-1 mutation is syntenic to 13q14 deletion in CLL. The mir15a/16-1 complex is thought to regulate bcl-2 expression. Therefore the level of bcl-2 expression was examined more closely as it might be used to differentiate mono-allelic deletion from the diploid CLL clone.

Patients and Methods
Multicolor flow-cytometry using a panel of anti-bcl-2 FITC (clone 124, DAKO Cytomation, Glostrup, Denmark) and CD19, CD20, CD5, CD23, CD38, kappa, lambda, and CD45 was used. Bcl-2 expression was evaluated using the conventional bcl-2 index (Mean fluorescence intensity (MFI) B cell/ MFI T cells) in 25 untreated CLL patients, and 10 normal donor controls. A modified ratio based on normal remaining (NR) polyclonal B cells was also used (MFI clone/MFI NR) with a new gating strategy for bcl-2 expression analysis.

Results
The mean of the conventional bcl-2 index is significantly higher in CLL patients [1.52 ± 0.53(SD)] compared to the control [0.5 ± 0.19(SD)], p<0.001 Student‘s t test. When comparing the mean of conventional bcl-2 index (clone/T cell) versus the mean of the modified bcl-2 index (clone/NR) [1.78 ±0.61 (SD)] in only CLL patients there was no significant difference. On the other hand, the rank order analysis of the conventional and modified bcl-2 index showed an r=0.7, p< 0.001 indicating that both methods give similar results. In addition to the high correlation between the conventional and the modified ratio, the modified ratio was multimodal in distribution.

Conclusions
Bcl-2 expression varies largely among the lymphocyte sub-sets. The choice of the polyclonal B cells allows better segregation of multimodal bcl-2 expression. Since bcl-2 mRNA is a validated mir15a/16 target, increased bcl-2 expression maybe a direct result of and a surrogate marker for mir15a/16 levels and/or the 13q14 status. There are three possibilities: no deletion (diploid), heterozygous deletion, or homozygous deletion. This needs to be verified by fluorescence in situ hybridization (FISH) analysis of sorted CLL B cells based on bcl-2 expression.

Disclosures:
No relevant conflicts of interest to declare.
Neuropilin-1 – Novel, Promising Target for Chronic Lymphocytic Leukemia patients.
Authors: Giannopoulos Krzysztof , Omiotek Marcin , Mlak Radosław , Tomczak Waldemar , Rolinski Jacek M. , Dmoszynska Anna , Stilgenbauer Stephan , Bullinger Lars 
Published: October 2019

Abstract
Abstract 4392
Neuropilin – 1 (NRP-1) represents a receptor for VEGF, which has been reported to be overexpressed in several malignancies. NRP-1 expression was also found on plasmacytoid dendritic cells (PDC) as well as on regulatory T cells (Tregs). Both, PDC and Tregs represent cells that are involved in tolerance mechanisms. Thus, in addition to its role in angiogenesis, NRP-1 might be involved in tumor escape mechanisms, and expression of NRP-1 on tumor cells, Tregs and PDC might point to a promising target for therapy.
To further investigate this hypothesis we assessed NRP-1 expression on leukemic cells, Tregs and PDC in 38 CLL patients. Using five parameters flow cytometric assessment we found increased expression of NRP-1 on leukemic lymphocytes of all CLL cases compared to NRP-1 expression on lymphocytes derived from healthy volunteers (1.8% vs. 0.29%, respectively). There was no significant difference between patients of different Binet stages, between CD38 positive vs. negative patients as well as between ZAP-70 positive vs. negative patients. In accordance, the expression of NRP-1 did not influence the treatment-free survival. However, we also found expression of NRP-1 on Tregs as well as PDC derived from the CLL patients. The median expression of NRP-1 on Tregs was 42.6 % (range: 10-100%). NRP-1 was expressed on almost all PDC with median expression 100% (range: 98.2 – 100%). In additional studies, we found that NRP-1 expression might be regulated by the VEGF levels in CLL. Magnetically separated CLL cells increased expression of NRP-1 after treating cultured cells with different VEGF concentrations. While VEGF levels of 0.1 – 0.5ng/ml, which are in the range of VEGF concentration observed in CLL patient samples, effectively induced expression of NRP-1, higher VEGF concentrations inhibited NRP-1 expression. Interestingly, we also observed that VEGF can also regulate the NRP-1 expression on Tregs.
In conclusion, we found NRP-1 expression on CLL cells, and for the first time demonstrated that CLL derived Tregs as well as PDC also express NRP-1. Furthermore, our data provide evidence that NRP-1 expression might be regulated by VEGF levels in CLL. Thus, NRP-1 might not only be involved in angiogenesis, but also in tolerance mechanisms. Therefore NRP-1 might represent an interesting molecule for therapy of CLL since it could target both leukemic cells as well as the main players such as Treg and PDC causing escape of tumor cells from the immunosurveillance.

Disclosures:
No relevant conflicts of interest to declare.
Reversal of Multidrug-Resistance in Human Leukemia Cell Line K562/A02 by Tyrosine Kinase Inhibitors.
Authors: Chen Bao-An , Shan Xue-Yun , Cheng Jian , Gao Feng , Ding Jia-Hua , Gao Chong , Chen Ning-Na , Pei Xiao-Ping , Xia Guo-Hua 
Published: October 2019

Abstract
Abstract 4828

Objective
This study was aimed to investigate the reversible effect of tyrosine kinase inhibitors(TKI)on Multidrug resistance cell line K562/A02.

Methods
The expression levels of mdr-1 mRNA and bcr-abl mRNA were assayed by RT-PCR. The protein levels of P-glycoprotein (P-gp) and P210 were detected by Western blot. The DNR accumulation of K562/A02 cells were analyzed by flow cytometry (FCM).

Results
Analysis of the inhibition rate showed that 0.0625μmol/L Imatinib or 5nM Nilotinib alone had no effect on the inhibition of K562/A02 cells. The fluorescence intensity of intracellular DNR of Imatinib, Nilotinib in K562/A02 cells was 7.85%, 12.02% (respectively of that in K562 cells). Imatinib or Nilotonib alone could decrease the mdr-1 mRNA and bcr-abl mRNA expression levels (Imatinib 0.65±0.02, 0.87±0.02; Nilotinib 0.48±0.04, 0.73 ±0.02) respectively, all these of which were significantly lower than the K562/A02 cells group 0.96±0.01, 1.87±0.04. The P-gp and P210 protein expression levels were also down after treated with different drugs (Imatinib 0.74±0.02, 0.68±0.01; Nilotinib 0.61±0.05, 0.60±0.01; the K562/A02 cells group 0.93±0.01, 1.25±0.03).

Conclusion
It is concluded that multidrug resistance (MDR) can be partially reversed by Imatinib or Nilotinib. The effect of Nilotinib was greater than Imatinib.

Disclosures
No relevant conflicts of interest to declare.
Azacitidine Is Effective in Patients with Intermediate-2 / High IPSS Risk Myelodysplastic Syndrome Managed in Community Based Practice: Preliminary Data From the Spanish Azacitidine Compassionate Use Registry.
Authors: Garcia Regina , González José Ramón , Bailen Alicia , Falantes Jose F , Sanchez Joaquin , Duarte Rafael F , Besalduch Juan , Lapiedra Andreu 
Published: October 2019

Abstract
Abstract 4835

Background
Myelodysplastic syndrome (MDS) is comprised of a group of heterogeneous hematological disorders. Although the decision regarding treatment of a patient with MDS is based on performance status, age, patient preference and concomitant illnesses, NCCN-recommended treatment approaches vary according to IPSS risk score. Azacitidine (AZA) is a hypomethylating agent recently approved in Europe for the treatment of MDS. AZA was available in Spain under compassionate use before its regulatory approval and marketing authorization from the Spanish Medicines Agency in May 2009.
Material and

Methods
We present the preliminary analysis of the clinical data from a longitudinal, multicenter Spanish patient registry. Data on the disease course and management of patients with MDS treated with AZA under compassionate use conditions were retrospectively collected from community-based hematology clinics. As of August 1, 2009, 65 patients with intermediate-2 / high IPSS-risk MDS diagnosed according to WHO criteria had been included.

Results
At baseline the median age was 69 years, the male/female ratio was 60/40, and the majority of patients had primary MDS (56 patients; 88%) and an ECOG performance status of 0-1 (43 patients; 67%). The most frequent initial dose of AZA applied was 75 mg/m2 (53 patients, 83%), and the most common dosing schedules were as follows: days 1-7 (82%), and days 1-5 and 8-9 (5%) in a 28-day cycle. AZA was administered mostly subcutaneously (56 patients, 89%). The mean number of cycles administered was 6 (range 2-29). The overall treatment response was 59% (International Working Group 2006 criteria): 16% complete response, 13% complete bone marrow response, 13% partial response and 18% hematological response. In addition, 23% achieved stable disease. AZA was generally well tolerated. The grade 3/4 adverse events documented in these patients, regardless of their relationship to active treatment, were neutropenia (37%), thrombocytopenia (26%), anemia (17%), febrile neutropenia (8%), rash (2%), vomiting or nausea (2%), and constitutional symptoms (2%).

Conclusion
These preliminary data do not differ from those previously obtained from clinical trials (Silverman et al 2006, Fenaux et al 2009). Our results demonstrate that in a community-based setting, patients with intermediate-2 / high-risk MDS respond to treatment with AZA. In line with previous clinical trials, we expect this could point to a better prognosis for MDS patients in Spain, with prolonged survival and a better quality of life.

Disclosures
No relevant conflicts of interest to declare.