bluuebunny/crossref_metadata_2025_split huggingface dataset:
Attempts to Optimise Induction and Consolidation Chemotherapy in Patients with Acute Myeloid Leukaemia: Results of the MRC AML15 Trial.
Authors: Burnett Alan K , Hills Robert K , Milligan Donald , Hunter Ann E. , Goldstone Anthony H. , Prentice Archie , Gibson Brenda ES , Kjeldsen Lars , Yin John AL , Wheatley Keith , Russell Nigel H. 
Published: October 2019

Abstract
Abstract 484

On behalf of the NCRI AML Working Group, United Kingdom
There is a general acceptance that survival in younger patients (<60 years) with AML has improved over the last 20 years, the majority still fail treatment. While the induction rate is satisfactory at >75% relapse remains a problem. Optimisation of induction and defining the schedule and duration of post-induction chemotherapy remains important even as novel approaches such as antibody directed therapy or small molecule therapy are added. The MRC AML15 compared 3 induction chemotherapy schedules and 4 post induction options. In induction patients were randomised to two course of DA or ADE or FLAG-Ida. In each case patients were also eligible to be randomised to receive Gemtuzumab Ozogamicin (GO) or not, which has been separately reported. In consolidation patients were randomised to MRC schedule (MACE/MidAC) or two courses of High Dose Ara-C and for those randomised to Ara-C to a dose of 3g/m2 or 1.5g/m2. Finally patients could be randomised to receive, or not, a 5th course comprising Ara-C.
Between October 2002 and January 2009, 1982 patients were randomised between DA (n=994) and ADE (n=988); up to May 2007, patients could also be randomised to FLAG-Ida; the randomised comparison with ADE recruited 1266 patients (FLAG-Ida n=635, ADE n=631). For part of the trial patients could be randomised to GO or not (306 patients in the DA v ADE and 297 in the FLAG-Ida v ADE comparisons were randomised). The median age of patients in the randomised comparisons was 49 years. Overall the ORR was 85% (CR 80%, CRi 5%) and the OS at 5 years is 43%. The randomisations were balanced for age, sex, performance status, de Novo/secondary disease, cytogenetics, white cell count, and GO allocation.
With the exception of a suggestion of greater benefit on ORR with FLAG-Ida among patients given GO, overall outcomes were not affected by GO treatment. In consolidation 1445 patients were randomised between MRC (n=723) and HD Ara-C (n=722). Of the 723 Ara-C patients, 328 were randomised to 3g/m2 and 329 to 1.5g/m2: 227 of the 1619 patients who received 4 courses were randomised for a 5th course with 112 allocated 5 courses.

Conclusions:
There were no significant differences in the response rate between induction treatments. FLAG-Ida resulted in a reduced relapse rate but this was balanced by increased myelosuppression and deaths in CR resulting in no overall benefit in survival. No survival differences were seen in any of the post induction comparisons, but the MACE/MidAc arm produced more myelosuppression and required more supportive care, and led to increased death in remission.

Disclosures:
No relevant conflicts of interest to declare.
Prominent Elevation of Survivin Expression in High-Risk Myelodysplastic Syndrome.
Authors: Yoshida Akira , Tanaka Saki , Yamauchi Takahiro , Takagi Kazutaka , Kishi Shinji , Urasaki Yoshimasa , Tohyama Kaoru , Ueda Takanori 
Published: October 2019

Abstract
Abstract 4842
Survivin, a new member of the inhibitor of apoptosis protein (IAP) family, has been reported to be expressed in a variety of human malignancies. We identified a novel splice variant of survivin, designated as survivin-3B. Overexpression of survivin-3B in leukemia and colon cancer cells reduced cell death after etoposide and cisplatin treatment, suggesting that survivin-3B possesses anti-apoptotic activity. Using Taqman RT-PCR and flow cytometer, we examined the expression of wt-survivin and survivin-3B in 48 patients with MDS and 55 patients with de novo AML. We found that wt-survivin and surivivin-3B are especially overexpressed in high-risk MDS and overt AML following MDS. Expression levels of wt-survivin and survivin-3B are significantly associated with higher international prognostic index score of MDS. Flow cytometric analysis also revealed that myeloblast from high-risk MDS possesses abundant expression of wt-survivin, but erythoroblast dose not. In contrast, myeloblasts from de novo AML show quite low levels of wt-survivin expression (mean expression value of de novo AML is less than 8% compared with that of high-risk MDS and overt AML). Interestingly, lack of wt-survivin expression was found in 7 patients (2 MDS and 5 AML). Instead of wt-survivin, expression of survivin-3B can be detected in these samples, suggesting that survivin-3B may play an important role as an alternative apoptosis inhibitor and mitosis regulator. Our data suggests that high levels of wt-survivin and survivin-3B expression are distinctive molecular feature of high-risk MDS and overt AML following MDS.

Disclosures
No relevant conflicts of interest to declare.
Secondary Myelodysplastic Syndrome.(sMDS) Presentation and Evolution.
Authors: Kornblihtt Laura , Enrico Alicia , Milone Jorge , Prates Maria Virginia , Belli Carolina B , Arbelbide Jorge , Lafalce Diana , Penchasky Diana , Fantl Dorotea , Rivas Maria Marta , Cabrejo Maria , Caicedo Maria 
Published: October 2019

Abstract
Abstract 4850

Background
The Secondary Myelodysplastic Syndrome (sMDS) represents a severe complication in the treatment of cancer. They are associated to the use of alkylating agents, radiation and immunosuppressive therapy. Their prognosis is unfavorable. Conventional chemotherapy is mainly palliative whereas allogenic bone marrow transplantation allows the cure of a small percentage of cases. Aims: To characterize and to describe the clinical presentation, therapeutic conduct and evolution in sMDS. This results where compared with those of primary MDS (pMDS) in patients enrolled into the observational study of Sociedad Argentina de Hematología from January 2007 to June 2009

Methods
There were analyzed 253 patients with diagnosis of MDS. sMDS correspond to 12.2 % (31/253)of the total, mean age 71 years old (r 23-84), relation M: F of 1:2.8 (being 1:2.2 in pMDS). Previous pathologies were: solid tumors in 17 patients (54%); 6 prostate Ca, 5 breast Ca, 4 GI Ca, 1 thyroid Ca, 1 bladder Ca, 1 pharynx Ca. Hematology malignancies were found in 7 patients: 2 Non Hodgkin Lymphoma, 2 Hodgkin Lymphoma, 1 Myeloma Multiple, 1 Chronic Myelomonocyticleukemia, 1p aplastic anemia. Six patients (23%) received immunosuppressive treatment for kidney transplantation, Wegener disease and glomerulonephritis. 85% of the patients received previous chemotherapy and/or radiotherapy. Result: There were analyzed 217 karyotypes (85.7%), 25 in the sMDS group and 189 in the pMDS, abnormal karyotypes in 14/25 (56%) vs 55/189 (29%) (p=0.006), complex karyotypes (unfavorable): 6/25 (24%) vs 8/189 (7%) (P=0.002). Twenty eight patients requiered treatment 28/31 (90.3%) vs 167/222 (75.2%) (p=0.09), transfusional therapy 23/31 (77.55%) vs 93/222 (42%) (p=0.001). Hypomethylating agents were used in 22,5% in sMDS vs 21,1% in pMDS and Erythropoyetin in 45,2% vs 48,6%. With a median follow up of 136 days (r:4-650), 8/31 progressed to AML (25.8%) vs 28/222 (13%) (p=0.005). Fourteen patients (45%) were death vs 47/222 (20.6%) (p=0.005); 17/31 (54.8%) of patients were alive in the sMDS group and 153/189 (80%) in the pSMD group (p= 0.005). Summary and

Conclusions
sMDS constituted 12.2% of the total of MDS that were reported. This entity has in our experience presence of unfavorable karyotype in more than the 50% of the cases, greater transfusion request, greater evolution to acute myeloid leukemia with high mortality and greater mortality than pMDS. This results confirm the bad prognosis of sMDS.

Disclosures
No relevant conflicts of interest to declare.
Clinical and Prognostic Relevance of Magnetic Resonance Imaging of the Spine in Newly Diagnosed Multiple Myeloma Patients Receiving Autologous Stem Cell Transplantation.
Authors: Tosi Patrizia , Petrucci Alessandro , Pantani Lucia , Zamagni Elena , Tacchetti Paola , Perrone Giulia , Brioli Annamaria , Ceccolini Michela , Baccarani Michele , Cavo Michele 
Published: October 2019

Abstract
Abstract 4885
Magnetic resonance imaging (MRI) of the spine has demonstrated to be a useful tool for a correct staging of multiple myeloma (MM), as it is more sensitive than plain x-rays in detecting vertebral lesions. Furthermore, both pattern of bone marrow involvement (focal, diffuse or normal), and number of focal lesions can be detected, and this could contribute to better define the prognosis and the outcome of newly diagnosed patients. In the present study we prospectively evaluated the clinical and prognostic role of spinal MRI in 152 newly diagnosed MM patients (89M, 63F, median age = 56yrs) that subsequently received high-dose chemotherapy and autologous stem cell transplantion, either single (n=43) or double (n=109). Pattern of marrow involvement was normal in 11% of the cases, diffuse in 20% and focal in 69%, with 34% of the patients showing > 7 focal lesions. Patients with a diffuse pattern or a focal pattern with > 7 lesions showed a significantly higher bone marrow plasma cell infiltration (p=0.04) and beta2 microglobulin values (p= 0.04) as compared to patients with a focal pattern with < 7 lesions. Response rate to the assigned treatment program was similar in the three groups of patients, with > VGPR obtained in 63% of the patients with a diffuse pattern, and in 70% of those with a focal pattern. Median progression-free survival (PFS) was significantly longer in patients with < 7 focal lesions as compared to those with >7 lesions or a diffuse pattern (55 vs 46 months p=0.05). Normalization of MRI was more frequently obtained in patients with < 7 lesions (67% vs 38% in patients with > 7 lesions, p=0.005); patients achieving a normal MRI pattern showed a significantly longer PFS (67 months) as compared to patients failing to achieve a negative MRI at the end of treatment (p=0.0000). According to our data, MRI confirms its prognostic role in newly diagnosed MM receiving high-dose therapy and autologous stem-cell transplantation; a diffuse pattern of bone marrow involvement or a focal pattern with > 7 lesions are predictive of a more aggressive outcome of the disease; furthermore normalization of MRI pattern after therapy is predictive of a longer progression-free survival

Disclosures
No relevant conflicts of interest to declare.
Myeloid-Derived Suppressor Cells in Patients with Multiple Myeloma and Monoclonal Gammopathy of Undetermined Significance.
Authors: Parrinello Nunziatina , La Cava Piera , Tibullo Daniele , Giallongo Cesarina , Di Bartolo Orazio , Spina Eleonora , Cavalli Maide , Schinocca Luciana , Triolo Anna , Romano Alessandra , Chiarenza Annalisa , Palumbo Giuseppe A , Di Raimondo Francesco 
Published: October 2019

Abstract
Abstract 4890

Background
Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of cells of myeloid origin, and include immature macrophages, granulocytes, dendritic cells (DC) and other myeloid cells. In mice, are phenotypically characterized as CD11b+Gr-1+. Humans MDSC have an immature phenotype, including lineage negative (Lin-), CD14-, HLA-DR-, CD15+, CD34+, CD11b+, CD33+, and CD13+ cells. MDSC impair T-cell functions through secretion immunosuppressive cytokines, perturbation of the arginine metabolism by inducible nitric oxide synthase (iNOS), up-regulation of reactive oxygen species (ROS), therefore are considered an important tumor escape mechanism. These cells, also promote tumor-dependent angiogenesis as well as tumor metastasis, and to provide tumor resistance to antiangiogenic drugs. Their accumulation has been described in the peripheral blood of patients affected by breast, lung, renal and neck carcinoma, melanoma, chronic infections, inflammatory diseases, and traumatic stress.
We investigate MSDC in patients with multiple myeloma (MM) and monoclonal gammopathy undetermined significance (MGUS) by flow cytometry

Methods
We studied 22 patients with MM at diagnosis, 20 patients with MGUS, and 10 healthy controls (HC).

Results
we observed that patients with MGUS showed the same number of MDSC (CD11b+,CD13+,CD34+,CD14-,CD45+) in the peripheral blood compared to HC (1,90±1,03/mmc, p=0,23). On the contrary, patients affected by MM showed a significant increase of MDSC vs HC (6,80±8,79/mmc vs 1,45± 0,98/mmc, p=0,003).

Conclusion
Our results suggest that these myeloid-derived suppressor cells, through their mechanisms immunesuppressive and proangiogenesis, could be involved in the progression of MGUS towards overt MM.

Disclosures
No relevant conflicts of interest to declare.
Myeloma Treatment Side Effects and Unmet Patient Needs 2009: Results of An International Comparative Survey Conducted by Myeloma Euronet (ME), the European Network of Myeloma Patient Groups.
Authors: Waldmann Anita , Barragán Begoña , Cursaru Viorica , Heberlein Candy , Hrianka Miroslav , Richter Friedrich , Sadżuga Roman 
Published: October 2019

Abstract
Abstract 4900
Recent advances in the treatment of multiple myeloma have increased response rates and treatment outcomes and raised hopes that myeloma may soon be turned into a chronic disease. However, myeloma treatment is often associated with various side effects that can sometimes have a significant impact on the quality of life of myeloma patients and also affect the overall treatment plan. An international comparative survey of myeloma patients and patient relatives and healthcare professionals is conducted to assess perceptions of how myeloma patients are informed about potential side effects of myeloma treatment options, the impact of treatment side effects on a myeloma patient's overall well-being and on the course of myeloma treatment, the satisfaction concerning the management of treatment side effects, potential side effects that myeloma patients don't feel comfortable reporting to their doctor as well as potential reasons for not reporting them, and the satisfaction concerning access to information and support, access to novel treatments, coverage of treatment costs, overall quality of treatment and care, and psycho-social and emotional support. The comparative survey is conducted based on 2 comparable two-page questionnaires, 1 for healthcare professionals and 1 for myeloma patients and patient relatives. The survey consists of 9 multiple-choice and ranking format questions. The questionnaires were developed by ME. They were pre-tested with both professional and patient communities and are available in 6 languages: DE, EN, ES, FR, IT, PL. The survey is distributed by mail or e-mail, it can be taken online via accessing the organisation's web site, and it is conducted on paper at haematological and oncological congresses and patient information days. To date, a total of 272 healthcare professionals from 44 countries and 257 myeloma patients and patient relatives from 21 countries have responded to the survey. Data gathering will continue until mid OCT 2009 and final survey results will be presented at ASH 2009. The survey was made possible through an unrestricted grant from Ortho Biotech, Biopharmaceutical Division of Janssen-Cilag.

Disclosures
No relevant conflicts of interest to declare.
The Incidence of Corrected Hypercalcemia and Its Relationship with Prognosis for Chinese Multiply Myeloma.
Authors: Zhang Xi , Chang Chunkang , Li Xiao , Su Jiying , Wu Lingyun , Zhou Liyu , He Qi , Xu Li , Song Luxi , Pu Quan 
Published: October 2019

Abstract
Abstract 4903

Purpose
This paper is to study and analze the serum calcium level after corrected for serum albumin and its effect on prognosis in Chinese multiple myeloma (MM).

Methods
Serum calcium levels before and after corrected by serum albumin were retrospectively analyzed in 165 Chinese multiple myeloma patients. Corrected serum calcium (mmol/L)=serum calcium (mmol/L) – 0.025 x serum albumin (g/L)+1.0 (mmol/L). We also analyzed the relationship of serum calcium, serum creatinine and disease categories in Durie-Salmon (DS) staging system with patients' long-term overall survival rate.

Results
In 165 patients, the incidences of before and after corrected hypercalcemia were 8.7% and 40.6%, which were statistically significantly different (p=0.0245). Based on DS staging, the before and after corrected serum calcium levels of sixteen MM patients in I stage were 2.316±0.082 mmol/L and 2.344±0.073 mmol/L with a p value equal to 0.3236; the before and after correccted serum calcium levels of fifty MM patients in II stage were 2.314±0.17 and 2.407±0.235 mmol/L with a p value equal to 0.0251; the before and after corrected serum calcium levels of ninety-nine MM patients in II stage were 2.428±0.32 and 2.671±0.309 mmol/L with a p value equal to 0.0000. There is no significant difference in overall survival time between normal serum calcium group and elevated serum calcium group, p=0.8929. There is significant difference in overall survival time between normal serum creatinine patients and raised serum calcium patients with a p value equal to 0.0170. Patients in I stage in DS staging system have statistically significant longer overall survival time than those patients in II/III stage in DS staging system, p=0.0382.

Conclusion
The incidence of corrected hypercalcemia in Chinese MM is similar to foreign reports. Hypercalcemia has smaller or limit impact on patients' long-term overall survival compared to serum creatinine and DS staging.

Disclosures
No relevant conflicts of interest to declare.
Myeloma Treatment Compliance 2009: Results of An International Comparative Survey Conducted by Myeloma Euronet (ME), the European Network of Myeloma Patient Groups.
Authors: Waldmann Anita , Barragán Begoña , Cursaru Viorica , Heberlein Candy , Hrianka Miroslav , Richter Friedrich , Sadżuga Roman 
Published: October 2019

Abstract
Abstract 4907
Patients who follow all the instructions about a course of treatment as directed by their doctor or nurse can be described as ‘compliant’ with a treatment plan. It is well-understood that failure of patients to follow treatment plans or understand the requirements after leaving their care could result in poor treatment outcomes, compounding health problems and additional health care costs. An international comparative survey of myeloma patients and patient relatives and healthcare professionals is conducted to assess perceptions of how myeloma treatment plans are determined, the familiarity of myeloma patients with their treatment plan, the satisfaction concerning the level of treatment compliance-related information, the factors that might have a negative effect on treatment compliance, the effect of one exemplary treatment side effect (peripheral neuropathy) on treatment compliance, and overall myeloma treatment compliance. The goal of the survey is to help patient and medical communities recognise the importance of patient compliance and the issues and challenges patients face in complying with their treatment. Learnings from the survey will be used to help improve myeloma patient compliance. The comparative survey is conducted based on 2 comparable two-page questionnaires, 1 for healthcare professionals and 1 for myeloma patients and patient relatives. The survey consists of 9 multiple-choice and ranking format questions. The questionnaires were developed by ME. They were pre-tested with both professional and patient communities and are available in 6 languages: DE, EN, ES, FR, IT, TR. The survey is distributed by mail or e-mail, it can be taken online through accessing the organisation's web site, and it is conducted on paper at haematological and oncological congresses and patient information days. To date, a total of 129 healthcare professionals from 42 countries and 191 myeloma patients and patient relatives from 11 countries have responded to the survey. Data gathering will continue until mid OCT 2009 and the final survey results will be presented at ASH 2009. The survey was made possible through an unrestricted grant from Celgene International.

Disclosures
No relevant conflicts of interest to declare.
The Novel Histone Deacetylase Inhibitor RAS2410 (Resminostat) Interferes with Important Signalling Pathways and Induces Apoptosis in Multiple Myeloma Cells.
Authors: Baumann Philipp , Mandl-Weber Sonja , Meinel Felix , Jankowsky Ruediger , Oduncu Fuat S. , Schmidmaier Ralf 
Published: October 2019

Abstract
Abstract 4928
Inhibition of histone deacetylase (HDAC) is a promising target for novel, anti-myeloma agents. In this study we investigated the biologic effects of the novel HDAC inhibitor RAS2410 (also known as “4SC-201”, “resminostat”) on Multiple Myeloma (MM) cells in vitro. RAS2410 is a potent, direct inhibitor of HDACs 1, 3 and 6 (IC50 = 43-72nM) representing the HDAC classes I and II. Accordingly, RAS2410 induces hyperacetylation of histone H4 in MM cells. Low micromolar concentrations of RAS2410 abrogate cell growth and strongly induce apoptosis (IC50 = 2.5-3μM in 3 out of 4 cell lines) in MM cell lines (NCI-H929, U-266, RPMI-8226, OPM-2) as well as in primary MM cells isolated from patients. At 1μM, RAS2410 induces G0/G1 cell cycle arrest in 3 out of 4 MM cell lines associated with decreased levels of cyclin D1, cdc25a, Cdk4, pRb and p53 as well as upregulation of p21. This cell cycle arrest is reflected by an inhibition of cell proliferation. RAS2410 decreases phosphorylation of 4EBP-1 and P70S6K indicating that RAS2410 induces apoptosis by interfering with Akt pathway signalling downstream of Akt. Treatment with RAS2410 results in increased protein levels of Bim and Bax and decreased levels of Bcl-xL. Caspases 3, 8 and 9 are activated by RAS2410. Furthermore, additive and synergistic effects in terms of apoptosis induction are observed for combinations of RAS2410 with melphalan, doxorubicin and the proteasome inhibitors bortezomib and S2209. In conclusion, we have identified potent anti-myeloma activity for the novel HDACi RAS2410. This study has yielded further insight into the biological sequelae of HDAC inhibition in MM and provides the rationale for in vivo studies and clinical trials using RAS2410 to improve patient outcome in MM.

Disclosures
Jankowsky: 4SC: Employment. Schmidmaier:4SC : Research Funding.