bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-Term Follow-up Results Over 7 Years for Survival, and Safety with Imatinib Mesylate Accompany with Allogeneic Transplantation for Chronic Myeloid Leukemia
Authors: Wang Jun , Sun Aining , Depei Wu , Qiu Huiying , Tang XiaoWen 
Published: October 2019

Abstract
Abstract 4529

Objective:
To observe the efficacy and safety of imatinib mesylate (IM) accompany with allogeneic transplantation for chronic myeloid leukemia (CML).

Methods:
During the period from January 2003 to August 2011,we retrospectively observed 95 patients with CML receiving IM for a minimum of 4 months before allogeneic hematopoietic stem cell transplantation (HSCT). Patients with advanced CML received IM from 3 month after transplantation for 12 months.

Results:
Among 95 enrolled patients (CML-CP 76, CML-AP 10, CML-BP 9), types of transplantation: sib-matched HSCT 64, unrelated-HSCT 19, haplo-HSCT 12. For the whole patients, 7 year overall survival (OS) is 80.5%, and disease free survival (DFS) is 74.5%. Complete hematologic response (CHR) is 93.6%, complete cytogenetic response (CCR) is 84.5%, major cytogenetic response (MCR) is 60.3% at 7 year. For CML-CP1, OS is 83.2% and CML-AP/BC is 33.3% (P<0.05). Compared patients of advanced CML achieving CP2 after IM and with no CP2,the former has better results of CCR or MCR, OS and PFS (P<0.05). The total treatment related mortality (TRM) is 16.8%. Cox multivariate regression analysis of prognostic factors indicates that status of CML and severe acute graft-versus-host disease (aGVHD III-‡W) retain independent predictive value. No increase in rates of serious adverse events was observed with continuous use of IM for up to 7 years.

Conclusions:
For chronic myeloid leukemia, combining with imatinib mesylate and allogeneic transplantation is a good strategy, with favorable long-term follow-up results and acceptable TRM, especially for the patients with advanced CML.

Disclosures:
No relevant conflicts of interest to declare.
Propylene Glycol-Free Melphalan Induces Higher Remission Rates in Multiple Myeloma Patients Undergoing Autologous Transplantation
Authors: Aljitawi Omar S. , Ludlow Anna , Ganguly Siddhartha , Abhyankar Sunil , Lin Tara , Pipkin J.D , McGuirk Joseph 
Published: October 2019

Abstract
Abstract 4551

Background:
In a recent phase IIa open-label, randomized, cross-over design study, we evaluated the pharmacokinetics of Propylene Glycol-Free Melphalan (PG-free Mel) HCL and Alkeran in multiple myeloma patients undergoing transplantation. In this study, we have shown through statistical tests of the geometric means of AUC that PG-free Mel was bioequivalent to Alkeran, and provided marginally higher blood drug levels.

Hypothesis:
Because this new formulation is associated with marginally higher blood drug levels and because melphalan is associated with a linear dose-response curve, we speculated that patients treated on study would have a better multiple myeloma response compared to matched controls.

Goal:
To assess day +100 multiple myeloma responses from the study patients (n=24) receiving PG-free Mel conditioning in combination with Alkeran. Responses were assessed based on International Uniform Response Criteria for Multiple Myeloma. Comparison was made to a matched cohort of patients who received conventional melphalan.

Methods:
We compared the study patient responses to matched controls (n=24) treated exclusively with Alkeran or generic melphalan conditioning within the same time frame in a case-control study design. The controls were matched to study population based on disease stage, age, and pre-transplant response.

Results:
The study population and the control cohort were well matched in terms of age, gender, disease stage, and pre-transplant response. However, the study population had more patients with high-risk cytogenetics (10 vs 3). Overall response (CR, VGPR, and PR) was higher in the study population (22 vs 19). While no patient on the study progressed within 100 days of transplant, 3 patients in the matched cohort progressed within 100 days. The median duration of follow up of surviving patients was 650 days in the study cohort and 409 days in the matched control cohort. Twenty three study patients and 22 patients in the matched control cohort were reported alive. On the other hand, 7 study patients and 8 patients in the matched cohort progressed during follow up.

Conclusion:
Compared to matched controls, PG-free Mel, as part of the melphalan conditioning regimen, resulted in higher remission rates and less disease progression at day 100 post autologous transplant for multiple myeloma.

Disclosures:
Off Label Use: Propylene glycol free melphalan for high-dose therapy and autologous transplant for multiple myeloma.
Pilot Study: Favorable Outcomes with Addition of Topotecan to Busulfan/Melphalan As High-Dose Myeloablative Therapy Followed by Autologous Hematopoietic Cell Transplantation
Authors: Rosenthal Joseph , Pawlowska Anna , Cheng Jerry , Kechichian Steven , Hitt Debbie , Suarez Mary , Tsai Ni-Chun , Palmer Joycelynne 
Published: October 2019

Abstract
Abstract 4553
High dose (HD) therapy followed by autologous hematopoietic stem cell transplantation (AHCT) has been the mainstay of treatment in patients diagnosed with advanced neuroblastoma (NBL). Busulfan and Melphalan (Bu/Mel) was demonstrated to be superior to other HD regimens and is widely considered as standard treatment. (Ladenstein, Bone Marrow Transplant. 2008 Jun;41 Suppl 2:S118-27), Topotecan (Topo) with or without cyclophosphamide has demonstrated efficacy in treatment of advanced NBL (Kushner, Cancer 116: 3054, 2010). We hypothesize that adding Topo to Bu/Mel as HD therapy followed by AHCT is well tolerated and will result in favorable outcomes.

Patients and Methods:
Patients with NBL, stage III or IV were eligible and consented to participate in the study. Seven patients were enrolled, the median age was 2.65 yrs (range 2.3 – 4.x yrs), and there were 4 males (57%). All patients were initially treated on COG protocols and in all cases a complete response was documented prior to proceeding with AHCT. Autologous hematopoietic cells were collected, following mobilization with G-CSF, after 2 (n=6) or 3 (n=1) cycles of chemotherapy. All patients were given post transplant radiation therapy to the primary tumor bed and cis-retinoic acid, 3 patients were also given monoclonal antibodies. Data on engraftment, toxicities, event free survival (EFS) and overall survival (OS) were analyzed.

Results:
The median cell dose was 6.62 × 106 CD34+/kg (5.57×106−7.33 × 107). Engraftment occurred promptly in all patients. Myeloid and platelet recovery occurred at a median of 12 (8–17 days) and 22 (17–41 days), respectively. The treatment was well tolerated with no grade 4 or higher toxicities. Grade 3 toxicities included; mucositis (n=7, 100%), electrolyte imbalance (n=3), diarrhea (n=3), autoimmune hemolysis (n=1) and epistaxis (n=1). Three patients suffered disease recurrence, 156, 821 and 899 days post AHCT. One patient is dead and two continue salvage therapy 55 and 52 months, post transplant, respectively. The 4-year OS and EFS were 87% to 57%, respectively.

Conclusion:
This novel regimen of Topo/Bu/Mel appears to be well tolerated with low TRM and promising EFS and OS. Further and larger studies are required to establish its role as HD therapy prior to AHCT in patients with advanced NBL.

Disclosures:
No relevant conflicts of interest to declare.
Hematopoietic Stem Cell Transplantation Combined with Imatinib to Treat Philadelphia Chromosome-Positive Acute Lymphocytic Leukemia: A Comparative Research
Authors: Chen Jia , Chen Feng , Depei Wu 
Published: October 2019

Abstract
Abstract 4555

Objective
To compare the effect of the hematopoietic stem cell transplantation with and without imatinib to treat adult patients sufferred from Philadelphia chromosome-positive acute lymphocytic leukemia by evaluating the survival post-transplantation and the quality of life.

Method
35 acute lymphocytic leukemia patients with Philadelphia chromosome-positive have taken hematopoietic stem cell transplantation between 2003 and 2011, in which 23 cases who were treated combined with imatinib were conducted in imatinib group, and the rest cases who haven't utilized imatinib were conducted in the control group. The incidence of relapse, incidence of graft-versus-host disease (GVHD), overall survival (OS) and disease-free survival (DFS) of the groups were compared so as to identify the advantage of combining treatment.

Results
The age, gender, cytogenetic classification, doner type, preparative regimen and counts of stem cells were comparative between the two groups. The proportion of patients who were in the first remission (CR1) in the imatinib group was higher than that in control group, however, the single factor analysis showed that it didn't affect the survival significantly. The incidences of relapse were 17.4% in the imatinib group and 16.7% in the control group (P = 0.9569), and the incidences of acute GVHD of Grade II to Grade IV were 35.3% and 41.7% (P = 0.4506), respectively. The 2-year-OS of two groups showed statistical difference of 62.6% versus 41.7% (P = 0.028), and 2-year-DFS were 53.7% and 33.3% (P = 0.054), respectively. Patients who survived more than 2 years post-transplantation would have a favorable prognosis.

Conclusion
Patients of imatinib group had a better survival, but the incidences of relapses and severe GVHD between the two groups had no significant difference. Thus, patients of Philadelphia chromosome-positive acute lymphocytic leukemia may benefit from the combination of hematopoietic stem cell transplantation and imatinib.

Disclosures:
No relevant conflicts of interest to declare.
Bortezomib-Based Induction Therapy Followed by High-Dose Chemotherapy and Autologous Stem Cell transplantation in Newly-Diagnosed Myeloma: Initial Report From a Chinese Multiple-Center Study
Authors: Hu Jiong , Shen Zhi-Xiang 
Published: October 2019

Abstract
Abstract 4557
Bortezomib-based induction therapy followed by high-dose chemotherapy and autologous stem cell transplantation (ASCT) is considered as standard treatment for patients with newly-diagnosed myeloma. Though front-line treatment of Bortezomib containing regimen is widely used in China, first-line treatment of high-dose chemotherapy with ASCT is not widely accepted for Chinese patients. There is also no prospective study in Chinese population to evaluate the efficacy, safety and feasibility of such treatment strategy. This is a prospective study in young Chinese population (18–65 year old) with newly-diagnosed myeloma (NCT00984828). All patients will receive 4 cycles of Bortezomib and Dexamethasone as frontline therapy. After that, patients will receive either a single ASCT conditioning with melphalan 200mg/m2 (mel 200) or ASCT with mel 200 + bortezomib conditioning and another 3 cycles of Bortezomib monotherapy as consolidation after ASCT. From Jan 2010, a total of 37 patients (median age 54, 31∼64) were enrolled in this study. There were 2 patients died of treatment toxicity 1 and 3 months after entering study. In the remaining 35 patients, 17 already finished ASCT and other 18 patients declined the ASCT. In 23 evaluable patients, 11 achieved CR (n=10) and VGPR (n=1), 9 with PR, 2 with SD and 1 PD. At the last follow-up at May 2012, a total of 6 patients experienced disease progression and no patients died of disease or treatment associated toxicity. As a whole group, with a median follow-up of 10 months (1∼33 months), the estimated 2-year OS and PFS were 94.3±4% and 66.2±12.3% respectively. Though further analysis was impossible with limited number of patient enrolled in the study with short follow-up, overall, the treatment was safe particularly no significant treatment associated toxicity or treatment mortality documented during and after ASCT procedure. The overall 43% CR rate was comparable to most previous reports. The early analysis of the study demonstrated that Bortezomib-Dexa followed by ASCT can be safely performed in Chinese population and further enrolled and follow-up may provide evidence of long-term efficacy of such strategy in Chinese population.

Disclosures:
No relevant conflicts of interest to declare.
CD34+ Marker As Prognostic Factor in Chronic Lymphoid Leukemia
Authors: De Salvo Cardullo Luigi , De Salvo Dalila , Salas Rodolfo J , Hassanhi Manzur , Paz Luis S , Weir Jesus E. , Salas Dalida , Fuenmayor Alba 
Published: October 2019

Abstract
Abstract 4591
From 2008 to date we marked all Chronic Lymphocytic Leukemia (CLL) with monoclonal CD34. The authors consider presence of said marker on the CLL cell membrane is a prognostic added factor to positivity for CD38 and ZAP70. CLL frequency is lower in countries with mixed races, compared with Europe and North America. In Venezuela is 5.4% (Luigi De Salvo personal communication) where I have never diagnosed a CLL case in a pure Venezuelan Indian. Similar reports are documented from Japan and China, provided racial genetics. Since 2008 to date we studied 28 patients for CLL: male 18 and female 10 with CD34-labeled. All patients presented lymphadenopathy, splenomegaly, and hypogammaglobulinemia. Flow cytometry revealed: HLA-Dr (33–100%), CD19 (44–100%), CD20 (28–95%), CD23 (63–100%), CD19 + CD5 (44–100%), CD23 + CD5 (28–100%) and CD19 + CD23 (28–100%) ZAP-70 (31–97%) and CD38 (12–75%). Of 28 patients studied, 21 individual CD34+ presented a variability of 10–99%. All had diffuse bone marrow infiltration, anemia and a white cell count range of 20.000–325,000/dl, with more than 80% lymphocytes of mature appearance. All patients presented discrete thrombocytopenia 70,000–120,000 plt/ml and responded well to standard treatment with Fludara + Rituximab. We believe presence of CD34 antigen on the cell membrane is an added risk factor for patients with CLL, producing an increased angiogenesis, and infiltration of organs and bone marrow by the leukemia cell. Lack of complete remission or negativity of Minimal Residual Disease may be CD34-linked.

Disclosures:
No relevant conflicts of interest to declare.
Silencing c-Myc Using Myc Inhibitor JQ1 and EZH2 Inhibitor DZNep Blocks Converging Survival Signals in Aggressive B-Cell Lymphomas
Authors: Zhao Xiaohong , Lwin Tint , Zhang Xinwei , Huang Andy , Wang Jian , Marquez Victor E. , Chen-Kiang Selina , Bradner James E , Dalton William S. , Sotomayor Eduardo M. , Tao Jianguo 
Published: October 2019

Abstract
Abstract 4618
c-Myc (hereafter Myc) overexpression has been recognized in aggressive B-cell lymphomas and linked to adverse prognosis. Myc activation results in widespread repression of miRNA expression and lymphoma aggressive progression. Our recent study identified a Myc-miRNAs-EZH2 feed-forward loop linking over-expression of Myc, EZH2, and miRNA repression. Here, using a novel small-molecule bromodomain inhibitor, JQ1, to silence Myc and the EZH2 inhibitor DZNep, we demonstrated that combined inhibition of Myc and EZH2 cooperatively disrupted Myc activation, resulting in restoration of miR-26a expression, which subsequently suppressed lymphoma growth and clonogenicity in aggressive lymphoma cells. Furthermore, Myc and EZH2 cooperatively regulated miR-26a expression in aggressive lymphoma cells. MiR-26a functioned as a tumor suppressor miRNA and mediated the combinatorial effect of JQ1 and DZNep. These findings represent a promising, novel approach for silencing Myc with JQ1 for combinatorial therapy of aggressive B-cell lymphomas.

Disclosures:
No relevant conflicts of interest to declare.
Tyrosine Kinase FLT3 and C-KIT Receptor Expression in Patients with Myelodysplastic Syndromes – A Preliminary Study
Authors: Cortesão Emília , Goncalves Ana Cristina , Sousa Isabel , Moucho Carlos , Rito Luís Carlos , Magalhaes Emília , Carda José Pedro , Geraldes Catarina , Sousa Patrícia , e Silva Nuno Costa , Espadana Ana , Pereira Amélia , Teixeira Adriana , Ribeiro Graça , Costa José Nascimento , Ribeiro Ana Bela Sarmento 
Published: October 2019

Abstract
Abstract 4620
Myelodysplastic syndrome (MDS) is a clonal hematopoietic stem cell disorder characterized by dyshematopoiesis and high susceptibility to acute myeloid leukemia.
Deregulated epigenetic mechanisms are likely involved in the pathogenesis of MDS. Gene silencing through aberrant CpG island methylation is the most extensively analyzed epigenetic event in human tumorigenesis and has huge diagnostic and prognostic potential. Aberrant methylation of gene promoter region is responsible for inappropriate gene silencing, and it has been associated to initiation and progression of cancer. However, in the MDS disease process, more and more gene dysfunction has been related with the pathogenesis. FLT3 and c-KIT are important members of the receptor tyrosine kinase family that are overexpress or dysexpress in many malignant hematologic diseases. However, little is known about the distribution and the role of these proteins in MDS.
The study is to investigate the role of receptor tyrosine kinase FLT3 and c-KIT expression in patients with myelodysplastic syndromes (MDS) and their clinical implication.
We have at moment examined c-kit protein (CD117) expression by flow cytometry, in CD34 bone marrow cells collected at diagnosis of 12 patients with de novo MDS and 5 non-neoplastic patients (controls). FLT3 mutations, in particular Internal Tandem Duplications (ITD) and the D835 mutation were analysed by PCR-RFLP. The median age was 72 years (22–89), gender M/F=5/7, WHO subtypes: RCMD (n=6), RA (n=3), RARS (n=1), AREB-2 (n=1), CMML (n=1) and IPSS: low (n=6), intermediate-1 (n=5) and intermediate-2 (n=1). None of the patients evolved to acute leukemia, with a median follow up of 24 months (7–74).
Our preliminary results show an increase in c-KIT expression in CD34 positive cells in MDS patients as compared with controls. However, the percentage of c-KIT protein expressing cells was also higher than in the controls in particular in CD34 negative cells. There was a correlation of the c-kIT protein expression with the CD34 antigen of the cells. Expression is correlated with the WHO MDS classification and with IPSS, being highest in RAEB-2 and INT2 MDS prognostic group. These results suggest that the elevated c-KIT expression could maintain the affected clone in MDS. Besides that we didn't find any FLT3 mutations in our population However further data and refinement of data analysis are needed to confirm our results and to predict clinical outcomes. The preliminary results suggest that c-KIT expression could be helpful to the pathogenesis and prognosis prediction of MDS patients.

Disclosures:
No relevant conflicts of interest to declare.
Towards Cell Therapy for FPD/AML with Patient-Specific IPS Cells
Authors: Connelly Jon P , Horwitz Marshall S , Liu Pu Paul 
Published: October 2019

Abstract
Abstract 4677
Induced pluripotent stem cells (iPSCs) have the potential to differentiate into any cell type. This makes them a valuable source of cells for treating genetic diseases. If the disease causing mutation can be corrected in patient-specific iPSCs and the cells differentiated to therapeutically relevant cell types and transplanted back, the symptoms of the disease may be alleviated or possibly cured. Hematopoietic diseases are an attractive target due to the ability of hematopoietic stem cells (HSCs) to reconstitute the entire hematopoietic system. However, directing the differentiation of iPSCs towards a HSC fate has proven difficult. Our lab aims to (1) Derive iPSCs from patients with a hematopoietic disease and correct the mutant gene through gene targeting. This will provide iPSCs that could be used in treating the patients. (2) Develop methods that direct the differentiation of iPSCs towards a HSC fate. This will be accomplished through novel iPSC reporter lines that we will use in small molecule and RNAi screens to identify factors that direct iPS cell differentiation towards a HSC fate.
Familial Platelet Disorder with propensity to acute myeloid leukemia (FPD/AML) is an autosomal dominant disorder caused by a mutation in the gene RUNX1 resulting in thrombocytopenia, platelet defects, and a predisposition to AML. Our first goal is to derive iPSCs from FPD/AML patients and correct the genetic defect using zinc finger nuclease mediated gene targeting. This will provide a potential source of cells for therapy. Towards this goal, we have obtained fibroblasts from four members of a FPD/AML family and derived iPSCs from two of the individuals. Currently we are correcting the RUNX1 mutation in these iPSC lines using zinc finger nuclease mediated gene targeting. We have developed a pair of zinc finger nucleases that bind and cleave RUNX1, resulting in gene targeting frequencies of 80–90% in 293 cells and iPSCs respectively.
Our second goal is to develop RUNX1 iPSC reporter lines for use in screening small molecule and RNAi libraries to find methods of directing iPSC differentiation to the HSC fate. RUNX1 is a key player in the development of adult hematopoiesis and is expressed at the earliest stages of hematopoiesis. We have targeted fluorescent proteins and a luciferase cassette into the RUNX1 locus of wild type iPSC lines using the RUNX1 zinc finger nucleases at high efficiency. We will use these RUNX1 reporter iPSC lines in screens to identify inducers of RUNX1 expression soon. We believe such inducers have the potential to direct iPSCs towards a HSC fate.

Disclosures:
No relevant conflicts of interest to declare.
Implementation of an End-of-Life Care Pathway in Cancer Patients
Authors: Karthaus Meinolf , Riesle-Keil J , Weber Ursula , Wolf Ingeburg 
Published: October 2019

Abstract
Abstract 4689

Background:
Supportive care for dying hemato-oncological patients in the hospital remains an unmet need. The Liverpool Care Pathway (LCP) has been developed in Europe for patients in the final 24–72 h of life to help physicians and nurses in the end-of-life care (ELC). We evaluated appropriately timed cessation of treatment in a Hemato-Oncology Department after integration of a modified LCP in a tertiary Munich cancer center. The End-of-life Care Pathway was modified to suit local conditions. The aim of the trial was to include over 40% of dying patients in the ELC. The effectiveness of symptom control which included termination of not necessary drugs, sufficient pain relief, control of agitation, bronchial fluid secretion, dyspnoea, nausea and emesis was compared with a control group (CG). The ELC was in accordance to local ethics. Nurses and physicians were trained. The ELC was periodically reviewed by a local multidisciplinary steering group for improvements.

Patients and Methods:
From 01/10 until 06/11 a total of 228 cancer deaths were observed. Criteria for entry onto the ELC were that the multidisciplinary team agreed the patient was dying, and was at least two of the following: bedbound; semi-comatose; only able to take sips of fluid; no longer able to take tablets. 96 pts (41 male/55 female) went on the ELC (42%), while 132 dying cancer pts were not enrolled due to a variety of reasons (e.g. lack of informed consent, rapid deterioration). The mean age was 72,6 ys (range 33 to 91 ys). The median duration of ELC use was 41,3 hours (range 0.5 to 189 h). Six patients improved after they had entered the ELC and left the ELC consecutively. Out of these four patients reentered the ELC and died, one of these six patients died without being reentered on the ELC. Symptom control (ELC/CG in %) was achieved in pain in 92/50%; agitation 89/50%, nausea 96/40%, dyspnoea 92/55% while unnecessary medication was terminated in 95/90%. All patients had current medication assessed and non-essential drugs were discontinued. Inappropriate interventions with antibiotics (85/65%), blood tests (95/75%), iv fluids (90/70%) were terminated more often when pts entered the ELC.

Conclusion:
Integration of an ELC in a hematology unit provides a better symptom control for dying patients. Inappropriate interventions could be reduced. Appropriate template design and supervision are the keys to success for end-of-life care in cancer patients.

Disclosures:
No relevant conflicts of interest to declare.