bluuebunny/crossref_metadata_2025_split huggingface dataset:
Allogeneic Hematopoietic Stem Cell Transplantation for Treatment of Philadephia Chromosome Negative Acute Lymphoblastic Leukemia.
Authors: Qu Shiqiang , Fu Chengcheng , Depei Wu 
Published: October 2019

Abstract
Abstract 4338

Objective
To explore the optimum donor selection of allogeneic hematopoietic stem cell transplantation (allo-HSCT) applied in patients with Philadephia chromosome-negative acute lymphoblastic leukemia(Ph- ALL) and investigate its relevant prognostic factors.

Methods
A total of 48 adult patients with Ph- ALL who had admitted to our hospital and been treated by allo-HSCT from February 2002 to May 2008 were followed up until July 2008. They were divided into match related donor(MRD -HSCT) group, match unrelated donor(MUD-HSCT) and Haploidentical (Haplo-HSCT) group. Clinical characteristics of these groups were retrospectively analyzed. Survival data were analyzed by the Kaplan-Meier method and the prognostic factors were analyzed with the COX regression model.

Results
Of all the 48 cases, 5-year overall survival(OS) was 45.4±8.1%, disease free survival(DFS) was 40.7±7.9%.The 5-year OS and DFS of MRD –HSCT subgroup, MUD-HSCT subgroup and Haplo-HSCT subgroup were 50%±14.4%,53.2%±13.2%, 31.3%±13.6%(p=0.048) and 44.7%±13.3%,41.4%±13.6%,32.1±14.2%(p=0.167), respectively. Haplo-HSCT subgroup 5-year OS lower than other two subgroups, which showed statistical significance. GradeIIto‡W acute graft versus host disease(aGVHD) [p=0.001,RR=6.980] and white blood cell at diagnosis higher than 30×109 /L[p=0.028, RR=2.679]were the risk factor of OS in multiple covariate analysis model. The HSCT type was not independent risk factor of OS.

Conclusion
MUD-HSCT and MRD-HSCT have similar efficacy in adult Ph- ALL. Haplo-HSCT can be a distinct option in High-risk adult Ph- ALL patients without a MRD and MUD.

Disclosures:
No relevant conflicts of interest to declare.
Donor Stem Cell Source Does Not Impact Outcome of High Risk (HR) Acute Myeloblastic Leukaemia (AML) Patients After Reduced Intensity Conditioning Allogeneic Hematopoietic Stem Cell Transplantation (RIC-ALLO).
Authors: Furst Sabine , Castagna Luca , Prébet Thomas , Lemarie Claude , Cheikh Jean El , Faucher Catherine , Vey Norbert , Charbonnier Aude , Ladaique Patrick , Chabannon Christian , Blaise Didier 
Published: October 2019

Abstract
Abstract 4339
Allogeneic Stem Cell Transplantation (ASCT) offers a potential curative treatment approach of HR AML patients (pts). Over years, the use of umbilical cord blood (UCB) has become an attractive alternative stem cell source for those pts lacking a suitable HLA matched related or unrelated donor.
The aim of this analysis was to assess the outcome of 50 pts who received a RIC-ALLO in our centre between 2005 and 2008 with a special focus on three different donor sources: identical sibling, unrelated donor or UCB.
All pts had HR AML in complete remission (CR) at time of transplant. HR features were defined as at least one of the following criteria: CR1 with unfavourable cytogenetics, secondary AML, more than one induction chemotherapy for obtaining CR or CR2 and above. Reasons for RIC regimen were older age, unfit physical condition, comorbidities or prior autologous transplant. All pts received a Fludarabine-based RIC regimen with GVHD prophylaxis consisting in CSA alone or CSA and MMF.
The median age of all pts was 51 (range, 19-70) years. 28 pts had identical sibling donors, 7 pts had a matched 10/10 (5 pt) or mismatched 9/10 (2 pt) unrelated donors and 15 pt received a single or double UCBT. Pts characteristics were comparable between the three groups but for pt age [identical sibling group: 52 (range, 35-70) years; unrelated donor group: 61 (range, 50-66) years; UCB group: 44 (range, 19-61) years].
After a median follow-up of 886 (range, 336-1528) days, 20 pts have died (disease=6, treatment related=14) and 8 pts have experienced relapse. Four year OS and EFS for all pts were 57% and 54%, respectively with no significant difference between the 3 groups (2 year OS: 61%, 54% and 66%; 2 year EFS: 59%, 54% and 45% respectively). One year TRM was 20% for the entire group and did not significantly differ between the 3 groups.
Despite the obvious limitations of this small series, results seem to indicate that in this population, donor type does not highly influence outcome. This is quite encouraging as most of the pts lack a compatible sibling donor. This may invite to consider privileging a rapid identification of an alternative donor rather than a given donor type when a match sibling is not available. Thus concomitant search for both graft type should be undertaken in order to perform allo SCT in a larger number of pts otherwise not treated because of early progression as illustrated in the underrepresentation of alternative transplant as compared with familial transplant in this retrospective study (28 familial vs 22 alternative).

Disclosures:
No relevant conflicts of interest to declare.
Outcome of IgD Myeloma After Autologous Hematopoietic Stem Cell Transplantation.
Authors: Qureshi Sofia , Sharma Manish , Hosing Chitra , Mendoza Floralyn L , Shah Jatin , Alousi Amin , Anderlini Paolo , Kebriaei Partow , Khouri Issa F , Popat Uday , Lima Marcos de , Champlin Richard E , Giralt Sergio , Qazilbash Muzaffar H. 
Published: October 2019

Abstract
Abstract 4354

BACKGROUND
Multiple Myeloma (MM) is a clonal disorder of plasma cells characterized by monoclonal immunoglobulin (Ig) secretion. Immunoglobulin D (IgD) MM constitutes <2% of all myeloma cases and is characterized by a younger age, male predominance, frequent extra osseous disease, amyloidosis, renal insufficiency and a poor prognosis. We retrospectively analyzed the outcome of patients with IgD myeloma transplanted at our institution.

METHODS
Between August 1988 and June 2008, 15 patients with IgD MM (13 males, 2 females) received autologous hematopoietic stem cell transplantation (auto HCT) at MD Anderson Cancer Center. Twelve patients received high-dose melphalan (200 mg/m2) as preparative regimen; 3 patients received high-dose melphalan in combination with other agents.

RESULTS
At diagnosis 7/15 (47%) patients had Durie-Salmon stage III disease, 6/15 (40%) had serum creatinine ≥2 mg/dl and 6/15 (40%) had hypercalcemia. Median age at the time of auto HCT was 53 yrs (range 38–64 yrs) and median interval between diagnosis and auto HCT was 12.6 months (range 3-75 months). Prior to auto HCT 11 patients achieved a partial remission (PR), one had a very good partial remission (VGPR), 2 had minimal response (MR) and one patient had no response to induction. Median follow-up in surviving patients was 25 months. Median time to neutrophil engraftment (ANC > 500/dl) was 10 days (range 9–15 days) and for platelet engraftment (>20,000/dl) was 11 days (range 8–16 days). Non-relapse mortality at 100 days was 0%. Complete responses were seen in 6/15 (40%) patients; 3 converted from PR to CR, 2 from MR to CR and one from VGPR to CR. Only one patient progressed within 3 months of auto HCT. Kaplan-Meiers estimates of 3-year progression-free survival (PFS) and overall survival (OS) were 38% and 64%, respectively. Median time to progression was 18 months. One patient with complex cytogenetics including deletion 13q had disease progression 7 months following an auto HCT. He subsequently received an allogeneic transplant, achieved stable disease status and died 11 months later due to progressive disease. Another patient received a second auto HCT for relapse, but died 3 months later due to progressive disease.

CONCLUSIONS
Patients with IgD MM, despite a higher incidence of renal insufficiency and hypercalcemia at diagnosis, can safely receive auto HCT, with overall response rates, PFS and OS comparable to other MM subtypes.

Disclosures:
Shah: Celgene, Amgen, Novartis, Elan: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.
The Role of High Dose Chemotherapy/Autologous Stem Cell Transplantation for Salvage Treatment for Relapsed Peripheral T Cell Lymphoma.
Authors: Cho Yoojin , Kang Myoung Joo , Choi Dae Ro , Kim Eun Kyoung , Kim Shin , Lee Dae Ho , Kim Sang We , Huh Jooryung , Lee Jeong Shin , Suh Cheolwon 
Published: October 2019

Abstract
Abstract 4363

Introduction
Although the role of high dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT) in the treatment of aggressive lymphoma has been established, optimal second line treatment, including high-dose therapy with autologous stem cell support, is not well established in patients with peripheral T cell lymphoma (PTCL). The purpose of this retrospective study was to compare the outcome of salvage chemotherapy only with that of HDCT and ASCT in patients with relapsed disease after having reaching a complete response (CR).

Methods
We retrospectively investigated the outcome of salvage treatments for patients with relapsed PTCL who had reached a CR.

Results
Between January 1999 and February 2009, 39 patients (15 peripheral T cell lymphoma; 14 extranodal natural killer/T cell lymphoma; 5 anaplastic large cell lymphoma; and 6 angioimmunoblastic T-cell lymphoma) were identified to be eligible for this analysis in our institution. Among them, 25 were treated with only salvage chemotherapy and 14 were treated with HDCT/ASCT. The salvage chemotherapy regimens were ESHAP given in 52% and DHAP given in 12%. Also the conditioning chemotherapy regimens for autologous stem cell transplantation (ASCT) were ESHAP given in 50% and DHAP given in 14.2%. The median number of chemotherapy regimen was 3. The overall response rate of salvage chemotherapy was 92% with a CR rate of 50%. With median follow-up time of 20.7 months, there were no statistical differences between the two groups in terms of progression-free survival and overall survival (p=0.794, and p=0.390, respectively).

Conclusion
There were no significant differences between the two groups in terms of survival outcome. Therefore, considering the dismal outcome in relapsed PTCL patients even after treated with HDCT/ASCT, incorporation of novel therapeutics into a treatment regimen should be considered.

Disclosures:
No relevant conflicts of interest to declare.
Primary Granulocytic Sarcoma:A Allo-Transplantation Case Report and Literature Review.
Authors: Li Xiaolin , Fu Jie , Xue Yan , Yang Yang , Wang Yang , Zhang Cixian 
Published: October 2019

Abstract
Abstract 4368

Objective
To investigate the effect of allogeneic transplantation in treating primary granulocytic sarcoma.

Methods
We report the diagnosis and treatment of one patient with primary granulocytic sarcoma and review the related articles.

Results
Firstly appeared as one isolated tumor in breast, the disease was diagnosed by pathological methods with immunochemistry positive stain in MPO, CD68(KP-1) and bacteriolysis enzyme. After radical operation on sick breast, the patient was treated with four courses chemotherapy according to that of acute granulocytic leukemia,then followed by matched sibling transplantation. After 6 months follow-up, the patients is still in complete remission.

Conclusion
If having suitable donor, patient with primary granulocytic sarcoma shoud be treated with allogeneic transplantation.

Disclosures:
No relevant conflicts of interest to declare.
Spontaneous in Vitro Death of CLL Cells Can Be Prevented by Mitochondrial Stabilization Via CD160 Signaling.
Authors: Liu Feng-Ting , Jia Li , Farren Timothy , Giustiniani Jerome , Bensussan Armand , Gribben John G. , Agrawal Samir G 
Published: October 2019

Abstract
Abstract 4372
B-cell chronic lymphocytic leukemia (CLL) is an incurable disease, which is at least partly attributable to the majority of cells being in the G0/G1 phase of the cell cycle and expressing high levels of anti-apoptotic Bcl-2 family proteins. Despite their prolonged survival in vivo, CLL cells rapidly undergo spontaneous apoptosis in vitro, suggesting that survival signals in vivo have been lost in in vitro culture conditions. CD160, a glycosylphosphatidylinositol-linked surface antigen, was found to be expressed by CLL cells. In normal NK and T-cells, CD160 mediates cellular growth and activation, but its role in CLL is unclear. Using monoclonal antibodies to CD160 (CL1-R2 or BY55 - non cross blocking) led to increased expression of Bcl-2, Bcl-xL and Mcl-1 anti-apoptotic proteins and protected CLL from spontaneous apoptosis in vitro - mean cell viability increased from 66.8 to 79.4% (n = 17, p = 0.02). These CD160-mediated events were also accompanied by decreased cytochrome C release and prevention of mitochondrial membrane potential collapse, indicating stabilization of both inner and outer mitochondrial membrane integrity. PI3K/AKT signalling is a well known survival pathway in cancer cells and in normal lymphocytes CD160 has been shown to act via PI3K/AKT. Activation of CD160 in CLL led to phosphorylated AKT, while inhibition of PI3K by wortmannin completely blocked AKT phosphorylation and CD160-mediated protection from apoptosis.
In summary, the activation of CD160 protected CLL cells from spontaneous cell death in vitro via a PI3-kinase/AKT pathway. This improved survival was also associated with increased Bcl-2, Bcl-xL and Mcl-1 expression and preservation of mitochondrial function.

Disclosures:
No relevant conflicts of interest to declare.
Vascular Endothelial Growth Factor (VEGF) Acts Via Auto- and Paracrine Mechanisms as a Critical Microenvironmental Factor for the Survival of Chronic Lymphocytic Leukemia (CLL) Cells.
Authors: Gehrke Iris , Paesler Julian , Gandhirajan Rajesh Kumar , Razavi Regina , Poll-Wolbeck Simon Jonas , Filipovich Alexandra , Uhrmacher Sabrina , Erdfelder Felix , Hertweck Magdalena , Hallek Michael , Kreuzer Karl Anton 
Published: October 2019

Abstract
Abstract 4376
The major pathophysiological characteristic of chronic lymphocytic leukemia (CLL) is the accumulation of malignant, immuno-incomptetent B-cells, which is commonly known as the apoptotic block. Recently, it was speculated that vascular endothelial growth factor (VEGF) might be involved in this process. Whereas most of the available studies are solely descriptive, functional data are largely missing. The aim of this study was therefore to describe the effect and functional background of VEGF on CLL cells for the identification of potential strategies for a targeted CLL therapy. We identified an autocrine VEGF feedback loop in CLL cells, but not healthy B-cells. Recombinant human (rh) VEGF stimulation lead to increased expression of the anti-apoptotic proteins Mcl1 and XIAP, but was not sufficient to prolong survival. When CLL cells were cocultured with the bone marrow derived stromal cell line HS5, survival was significantly enhanced 28.5 ± 6.5% after 72h relative to monoculture, whereas healthy B-cells did not profit from coculture (-0.5 ± 4.7%). HS5 cells produce and secrete high amounts of VEGF themselves. When cocultured with HS5 CLL cells also showed an increased VEGF expression, indicating the existence of a paracrine VEGF feedback loop. The actual relevance of VEGF in the coculture mediated survival support was proofed by siRNA experiments. When VEGF expression and secretion was downregulated in HS5 cell by siRNA, the survival advantage CLL cells obtained from the coculture was reduced down to that in monoculture. Also the addition of a VEGF-neutralizing monoclonal antibody largely reversed the survival supporting effect of the coculture, clearly indicating the critical role of VEGF in bone marrow stromal cell-mediated CLL cell survival. We further found rhVEGF to induce upregulation and activation of STAT3 via Tyr705-phosphorylation and a subsequent expression of STAT3 targets such as Cyclin D1 and BclXL. VEGF-stimulation further induced downregulation of the tumor suppressor RB1 and E2F1, which act as proapoptotic factors. Vice versa inhibition of VEGF by using selective VEGF-R inhibitors reduced both, Tyr705 phosphorylation and expression of STAT3 target genes. We therefore, propose a dual mechanism of VEGF-mediated CLL cell survival support via upregulation of the potent oncogene STAT3 and downregulation of the tumor suppressor RB1/E2F1. Hence, VEGF might function as a potential new therapeutic target to overcome the apoptotic block in CLL cells.

Disclosures:
Hallek: BayerScheringAG: Honoraria, Research Funding.
Chromosome Study On Chronic Lymphocytic Leukemia Using CpG- Oligodeoxynucleotide as Immunostimulant Agent.
Authors: Wu Yafang , Xue Yongquan , Yao Li , Jiang Hui , Zhang Jun , Shen Juan , Pan Jinlan , Wang Yong , Bai Shuxiao , Chen Suning 
Published: October 2019

Abstract
Abstract 4383

Objective
To verify whether CpG-oligodeoxynucleotide (CpG-ODN) can raise the detection rate of the karyotypic abnormalities in chronic lymphocytic leukemia (CLL).

Methods
The bone marrow (BM) or peripheral blood (PB) cells from 57 cases of CLL were collected and cultured with CpG-ODN DSP30+interleukin-2 (IL-2), phytohemagglutinin (PHA), pokeweed(PWM) or IL-2, respectively. 5 days later cells were harvested for chromosome preparation. Karyotypic analysis was performed using R banding technique. Panel fluorescence in situ hybridization (FISH) was carried out on 19 cases of CLL with normal karyotype using following probes: Cen12, D13S25, Rb1, ATM, P53, MYB and IgH. Genomic DNA from 21 cases of them was extracted from BM or PB. The immunoglobulin variable heavy chain (IgVH) were amplified by polymerase reaction (PCR) and sequenced. CD38 and ZAP70 expressions in leukemic cells were determined by flow cytometry (FCM).

Results
The detection rate of karyotypic abnormalities in CpG-ODN+IL-2 group (43.85%) was obviously higher than PHA (15.09%), PWM (17.31%) and IL-2 (3.13%) groups (P<0.01). 52 karyotypic abnormalities were found. Among them, trisomy12 (+12) or +12 with other abnormalities were the most common, while translocations were the most frequent structural abnormalities including 3 unbalanced and 11 balanced translocations among which 7 had 14q32 rearrangements. 13 cases showed one or more abnormalities on FISH examination including trisomy12 and P53 deletion each in one case, IgH rearrangement and partial deletion each in one case, 13q14.3 deletion in 11 cases of which 5 cases also had Rb1 deletion, one case had Rb1 partial deletion. No cases with ATM or MYB deletions were found. IgVH mutation was detected in 10/21 cases by PCR and sequencing. FCM showed 10/45 cases expressed CD38, while 11/27 cases expressed ZAP70. Among 26 cases examined for CD38 and ZAP70 expressions simultaneously, 5 cases were CD38+ZAP70+, 13 cases CD38-ZAP70-, 6 cases CD38-ZAP70+, 2 cases CD38+ZAP70-, respectively. Statistics disclosed a correlation between complex karyotype and IgVH without mutation, but no association between karyotype and CD38 or ZAP70 expression.

Conclusion
CpG-ODN immunostimulation can obviously raise the detection rate of abnormal karyotypes, especially balanced and unbalance translocations in CLL. FISH is important complement to conventional karyotypic analysis, the combination of both methods can provide more comprehensive genetic information for CLL.

Disclosures:
No relevant conflicts of interest to declare.
TNF-α and MDM2 Polymorphism in Pathogenesis of Chronic Lymphocytic Leukemia.
Authors: Bakirov Bulat , Warshavsky Anton , Sgibneva Anastasiya , Karimov Denis 
Published: October 2019

Abstract
Abstract 4390

Introduction
Apoptosis dysfunction one of the main process in pathogenesis of CLL. One of the apoptosis regulators is cytokine TNF- α. In normal condition in cells expressed protein p53 and main tumor suppressor MDM2. The high expression of protein MDM2 is oncogenic factor. The gene of protein MDM2 placed on the long arm 12 chromosome (12q14.3-12q15). Our aim was studying of frequencies of polymorphic variants of genes TNA-α and MDM2.

Patients and Methods
We observed 133 patients with CLL (male-75, female-58). The median age was 49. The control group was 196 healthy donors from the same region, same ethnic group, age 47 (male-107, female-89).

Results
In patient group in polymorphic locus -308G>A gene TNFα genotype GG met often than in control group (82% and 65% accordingly, χ2=10,674; p=0,002). On the contrary genotype GA authentically often met in group of healthy individuals (33 %) whereas its frequency in group of CLL patients was 17 % (χ2=8,837; p=0,004). Frequency of allele G a polymorphic locus-308G> A gene TNF-α in group of CLL patients it is authentic more than in control group (91 % and 81 % accordingly, χ2=10,411; p=0,002). Distinctions also were observed on frequencies of allele A, in control group 19 % and 9 % and in the group of CLL patients (χ2=10,411; p=0,002). On frequencies of genotype AA of authentic distinctions it is not revealed. Thus, as a result of research it has been shown that markers of risk of CLL development are genotype GG (OR=2,468; 95 % CI 1,452-4,194) and allele G (OR=2,244; 95 % CI 1,384-3,638) of polymorphic locus-308G> A gene TNF-α. Opposite stability markers are genotype GA (OR=0,432; 95 % CI 0,252-0,741) and allele A (OR=0,446; 95 % CI 0,275-0,724). The analysis of distribution of frequencies of a polymorphic locus 309T> G gene MDM2 in patients group and group of healthy individuals has shown statistically authentic distinctions, on allele T, frequency in group of CLL patients was 54 % and in group of healthy individuals was 63 % (χ2=4,141; p=0,042; OR=0,679; 95 % CI 0,475-0,972). Also in allele G 46 % in patient group against control group - 37 % (χ2=4,141; p=0,042; OR=1,474; 95 % CI 1,03-2,108).

Conclusions
Thus, the cited data of researches testifies to the important role of genes TNF α, MDM2 in CLL development. In particular genotypes GG and allele G in a polymorphic locus-308G> A gene TNF-α and allele G in a polymorphic locus 309T> G gene MDM2 have appeared as markers of the raised risk in CLL development. On the contrary genotype GA and allele A in a polymorphic locus-308G> A gene TNF α and allele T in a polymorphic locus 309T> G gene MDM2 are the markers of the raised stability to CLL development.

Disclosures:
No relevant conflicts of interest to declare.