bluuebunny/crossref_metadata_2025_split huggingface dataset:
GeneXpert Essay for BCR-ABL Compared to RT-PCR for Clinical Management of CML
Authors: Pica G. , Catania G. , Castelli F. , Repetto C , Carella A. M. , Mussap M. 
Published: October 2019

Abstract
Abstract 4416
Reverse transcriptase-polymerase chain reaction (RT-PCR) is considered the most sensitive method available for detecting low copy numbers of the BCR-ABL gene fusion. The difference between the BCR-ABL Ct (threshold cycle) and ABL Ct is expected to represent the ratio of the two populations of mRNAs and ultimately the percentage of neoplastic cells present.
An international scale (IS) has been proposed for BCR-ABL RQ-PCR measurements. To enable testing centers to gain access to the IS, the Adelaide laboratory initiated a process to develop and validate laboratory-specific conversion factors (CFs) that can be used to convert local values to IS values. Recently, Cepheid introduced its GeneXpert-based assay for the identification of the BCR-ABL gene fusion in cells from blood samples. This system comprises a walkaway self-contained instrument that combines cartridge- based microfluidic sample preparation with reverse transcriptase-polymerase chain reaction-based fluorescent signal detection and BCR-ABL and ABL Ct determination. The CF provided by Cepheid for this procedure is 0.47. We tested this BCR-ABL fusion detection system, compared with a classical RT-PCR analysis as a clinical diagnostic tool for CML patients.
We tested 19 patient peripheral blood samples by both methods. The negative control group included 3 blood samples, obtained from 3 patients with hematological disorders unrelated to BCR-ABL gene fusion: one with essential thrombocythemia, one with chronic myelomonocytic leukemia, one with T-cell-prolymphocytic leukemia. The remaining 16 clinical samples belonged to 12 patients with an established diagnosis of CML in chronic phase and to one patient with Philadelphia chromosome-positive acute lymphoblastic leukemia (p210).
GeneXpert software reported as negative 2 samples with a numerical threshold limit calculated on Ct (i.e. BCR-ABL was not detected at a detection limit of 0.00046%); the 3rd negative control was indicated as BCR-ABL invalid: this result was probably due to the high proportion of ABL detected as consequence of hyperleukocytosis (WBC 559,6 × 109/L) in T-Cell prolymphocytic leukemia patients. Therefore, the performance of GeneXpert test in this series was: Sensitivity 100%, Specificity 0,66%, Positive Predictive Value 100%, Negative Predictive Value 100%.
Among the series of 16 true positive samples GeneXpert revealed mean 8,67; mean standard deviation 27,55; median 1,48. Whereas in the same series RT-PCR results were: mean 37,09; mean standard deviation 59,33; median 3,37.
In conclusion GeneXpert essay for BCR-ABL could be an important tool for diagnose and monitor CML but require complete clinical data for the correct interpretation of results.

Disclosures:
No relevant conflicts of interest to declare.
Role of ABL Gene Mutations in Chronic Myeloid Leukemia Patients Resistant to Imatinib and Results of Treatment Shift to Second-Generation Tyrosine Kinase Inhibitors
Authors: Marce Silvia , Zamora Lurdes , Cabezon Marta , Xicoy Blanca , Boqué Concha , Dominguez Diana , Ribera Jordi , Fernandez Cristalina , Rodriguez Lluis , Portal Imma , Plensa Esther , Velez Patricia , Medina Jorge , Grau Javier , Xandri Marisol , Navarro Jose-Tomas , Fernandez de Sevilla Alberto , Ribera Josep-Maria , Feliu Evarist , Millá Fuensanta 
Published: October 2019

Abstract
Abstract 4442

Introduction:
Chronic myeloid leukemia (CML) is a model of disease in the development of targeted therapies. Tyrosine kinase inhibitors (TKIs) have transformed the approach to management of CML and have dramatically improved patients' outcome. Clinical response is obtained in the majority of patients. However, a significant proportion of patients do not achieve the optimal desirable outcome or are completely resistant to this treatment. ABL kinase domain mutations have been extensively implicated in the pathogenesis of TKI resistance. Treatment with second-generation TKIs has produced high rates of hematologic and cytogenetic response in mutated ABL patients.
The aim of this study was analyzed the presence of ABL mutations in imatinib resistant patients and determine the importance of changing to second-generation TKIs treatment as soon as failure or suboptimal response is recognized.

Patients and methods:
From 420 CML patients diagnosed in 6 centers between 2004 and 2010, we have amplified and sequenced the ABL1 domain from BCR-ABL1 amplicon of 45 imatinib resistant patients (23 patients with suboptimal response, 14 with treatment failure, 4 who lost the molecular response and 4 patients who progressed to blast phase). The obtained sequences were compared with the published ABL1 sequence, GenBank U07563, using BLAST 2 software.

Results:
We have detected mutations in 15 of 45 patients (33%), some of them with more than one mutation (Table 1). Seven of these patients were treated with second-generation TKIs as a single treatment. Three of them achieve a major molecular response (MMR), one patient is in complete cytogenetic response (CCyR) and the other two patients are in major (MCyR) and partial (PCyR) cytogenetic response. Another patient received nilotinib followed by hematological stem cell transplantation (HSCT) and is in MMR. Two patients were submitted to a HSCT and achieve MMR. Only one patient treated with nilotinib as second option has not reach a cytogenetic response one year after detection of the mutation.
Two of the patients with the T315I mutation were treated with IFN and nilotinib achieving PCyR and MCyR, respectively, and are still alive. The other T315I patient, and two patients in blast-crisis (BC) disease with the F317L mutation who received dasatinib prior to the study of ABL mutations, died before a change of treatment could have been performed.

Conclusions:

Disclosures:
No relevant conflicts of interest to declare.
Rearrangements of 12p in Acute Myeloid Leukemia (AML) Remain a Significant Adverse Prognostic Marker When Patients Are Treated with Stem Cell Transplantation
Authors: Walter Claudia Ulrike , Almhareb Fahed , Chaudhri Naeem A. , Zahrani Hazzaa Al , Chebbo Wahiba , Ibrahim Khalid , Bakr Mohammad , Mohamed Said , Rasheed Walid , Alsharif Fahad , Aljurf Mahmoud , Albitar Maher 
Published: October 2019

Abstract
Abstract 4464

Background:
Alterations of the short arm of chromosome 12, most often resulting in loss of chromosomal material, are a recurrent feature in myeloid malignancies and occur in about 5 % of cytogenetically abnormal AML. Chromosomal abnormalities of 12p in AML have been reported to be associated with a non-favorable outcome. However, it is unclear how dismal the outcome is, as AML with 12p abnormalities is variably included in the intermediate or poor prognosis groups. Moreover, the role of allogeneic hematopoietic stem cell transplantation (HSCT) on outcome of patients with 12p abnormalities is not known. We investigated whether HSCT can improve the poor survival of patients with 12p abnormalities.

Method:
Bone marrow conventional cytogenetic and FISH data from 110 adult AML patients was reviewed and patients were divided into three cytogenetic risk groups according to the European LeukemiaNet reporting system while separating the patients with 12p aberrations into one independent fourth group. We also compared outcome of the 12p group with to the intermediate group alone or after combining intermediate with favorable, since there was no significant difference between the favorable and the intermediate groups. The AML cohort included 62 (56%) patients treated in their first remission (CR1) while most non-CR1 AML patients were treated with HSCT in CR2. The median age of all patients was 25 years (range: 14–58).

Result:
Patients with 12p abnormalities were 4 (4%). Patients with 12p abnormalities had a significantly shorter overall survival (OS) (P=0.03) and event-free survival (EFS) (P=0.04). Their outcome was similar to the adverse-risk cytogenetic group, and survival was significantly shorter than in the intermediate group (P=0.02). The poor outcome was significant even when only patients treated with HSCT in first remission were considered. All four patients with 12p abnormalities were treated with HSCT in CR1.

Conclusion:
Although the number is small, this data suggests that 12p chromosomal changes in AML are significant adverse abnormalities, not different from complex cytogenetics, and treatment with HSCT does not change this dismal outcome. This also suggests that for patients with 12p abnormalities, alternative therapeutic approaches should be considered.

Disclosures:
No relevant conflicts of interest to declare.
A Clinical Study on Double-Unit Umbilical Cord Blood Transplantation in Adults with Hematologic Disease
Authors: Ma Xiao , Depei Wu , Sun Aining 
Published: October 2019

Abstract
Abstract 4486

Objective:
In this study, we explored the efficiency and toxicity of 46 cases of double-unit CBT in adults with hematologic disease.

Methods:
The tolerance; transplant related complications; survival rate and disease free survival rate were observed and analyzed. A nonmyeloablative conditioning regimen included cyclophosphamide, fludarabine and 2Gy TBI. Cyclosporine combined mycophenolate mofetil and ATG were used to prevent graft versus host disease (GVHD).

Results:
All these 46 patients tolerated the therapy well while four patients had graft failure. Severe acute GVHD was presented in 6 patients. Chronic GVHD was occurred in 18 patients. Fatal infection complications were occurred in 7 patients (including CMV idiopathic pneumonia in 2 patients) and 5 patients relapsed after transplantation. Neutrophil engraftment obtained on day +17 and platelet reconstitution occurred on day +42 on median. In the follow-up duration of 29 months on median, the expected 3-year relapse mortality was 16.7%; non-relapse mortality was 26.1%; overall survival was 57.7%, and disease free survival was 48.2%.

Conclusion:
The use of double-unit CBT after reduced intensive conditioning therapy in adults with hematologic disease is an effective and safe treatment. Fatal infection and relapse are the main reasons of failure.

Disclosures:
No relevant conflicts of interest to declare.
Total Body Irradiation (TBI) or Busulfan (Bu) Plus High Dose Melphalan After Bortezomib (Bz) Containing Regimen As Front Line Treatment of High Risk Multiple Myeloma (MM) Patients with 17p Deletion and/or t(4;14) Translocation
Authors: Arnulf Bertrand , Szalat Raphael , Karlin Lionel , Harel Stephanie , Asli Bouchra , Malphettes Marion , Soulier Jean , Fermand Jean Paul 
Published: October 2019

Abstract
Abstract 4501
Despite recent improvement of overall survival of MM due to the use of novel agents, the high risk sub group of patients, especially with 17p deletion and/or t(4;14) still have a poor prognosis. New therapeutic strategies are needed to improve this outcome. We report preliminary results of a study using TBI or intravenous Bu to reinforce the high dose Melphalan after a Bz containing regimen as induction therapy in patients with 17p- and/or t(4;14) MM.
Between 01/2009 and 08/2010, twenty three patients (7F and 16M, median age 55 years) were treated. At diagnosis, anemia and hypercalcemia and renal failure were noted in 14, 8 and 4 patients, respectively. The median percentage of bone marrow plasma cell was 30% and 10 (43%) had an IgA isotype. One patient had a light chain MM (65g/dl), a plasma cell leukemia was diagnosed in one patient and one patient presented with specific fever and biological inflammatory features. A 17p deletion and t(4;14) translocation were detected, using RQ-PCR and FISH analysis, in 7 and 17 patients, respectively with one patient harboring the two abnormalities. Patients were treated with a median of 3 cycles of the VTD (Bz/Thalidomide/dexamethasone) combination, 12 received a PAD regimen (Bz/doxorubicine/dexamethasone) and 1 had 4 cycles of VD (Bz/ dexamethasone). High dose therapy consisted in Melphalan 140 mg/m2 associated with Bu in 16 patients and TBI in 7 patients. Thirteen patients (4 with 17p- and 9 with t(4;14) had a consolidation with 4 cycles of VTD (n=11) or TD (n=2).
Grade >2 mucositis and gastrointestinal toxicity was noted in all patients treated with TBI but Bu was well tolerated. No patient died early from toxicity. One patient had a reactivation of a virus B hepatitis and one patient had a peripheral thrombocytopenia 3 months after HDT. No venous occlusion disease was observed. Overall response rate after high dose therapy (HDT) was 91% (21/23) including 9 VGPR, 6 CR+nCR and 6 PR. Consolidation treatment led to an improvement of response in 4 patients. Nine patients relapsed, including 6 within 6 months after HDT and 3 at 8,9, and 10 months, respectively. At analysis, five patients had died, all because of progressive disease, and 14 patients (10 CR and 4 VGPR) patients were still in first remission.
Although a larger number of patients and additional follow up are needed, these data suggest that intensifying high dose therapy regimen is feasible and correctly tolerated in pts with high risk MM, especially using intravenous Busulfan, and may be an interesting approach to improve the current poor prognosis of patients with 17p deletion and/or t(4;14).

Disclosures:
No relevant conflicts of interest to declare.
Promising Efficacy with the 308 Nm Excimer Laser Phototherapy in Early Stage Mycosis Fungoides
Authors: Deaver Darcie , Cauthen Ashley , Cohen George , Sokol Lubomir , Glass L. Frank 
Published: October 2019

Abstract
Abstract 4990

Background:
Mycosis fungoides is the most common type of cutaneous T-cell lymphoma. Early stage disease is effectively managed with skin directed therapies such as UV light and topical steroids. Excimer laser (EL) delivers monochromatic, UVB light at a wavelength of 308 nm via hand held device that covers an area of 2 × 2 cm. It generates a short-pulse radiation that is concentrated on an affected area of skin, thereby allowing a delivery of higher dose on precisely targeted tissue. In contrast to other phototherapy techniques such as narrow band UV light, the EL is ideally suited for patients with small number of patch lesions. Although EL was successfully utilized in the management of psoriasis and vitiligo, there is not extensive experience with this modality in patients with CTCL.

Objectives:
To assess safety and efficacy of EL therapy in patients with early stage MF who failed ≥1 skin directed therapy.

Design and Methods:
This is a retrospective analysis of seven consecutive patients with stage 1 MF treated with EL phototherapy between January 2011 and August 2011 in a single institution. Seven patients with histologically confirmed common type MF, and one patient with folliculotropic MF received 308 nm EL therapy after failure of at least one prior skin directed therapy. The median age was 48 years (range 24–77 yrs). Four (57%) were male, 3 (43%) were female, six (86%) were Caucasian, and 1(14%) were African American. Biopsies and photos were obtained at diagnosis and after the completion of 24 treatments.

Results:
Treatment was initiated at a dose of 200 millijoules (mJ) and was increased by 10–15% each subsequent treatment. The max dose of treatment ranged from 240 mJ to 850 mJ. The total number of administered treatments was 24 delivered over period of 3 months. The median number of treated lesions was 2 (range 1–5). The surface area of treated lesions was <10%. Six patients achieved clinical improvement in appearance of lesions and intensity of pruritis; 2 (29%) achieved clinical remission as confirmed with photos and post-treatment biopsies. One (14%) patient developed first degree burn and 1 (14%) patient developed pruritis. These resolved by the second treatment with EL. There were no treatment-related serious adverse events observed.

Conclusion:
Our results suggest that EL is effective and well tolerated skin-directed treatment modality for selected patients with early stage MF. However, longer follow-up will be required to assess durability of responses. Advantages of this approach include shorter treatment duration and lower risk of carcinogenesis in the non-affected areas of skin. Prospective study with a larger cohort of patients is necessary to further assess efficacy and safety of this approach.

Disclosures:
No relevant conflicts of interest to declare.
Prognostic Significance of Cytogenetic Abnormalities, Serum P53 Protein Concentration, Staging, Patient Factors in Chinese Patients with Non–Hodgkin Lymphomaprognostic Significance of Cytogenetic Abnormalities, Serum P53 Protein Concentration, Staging, Patient Factors in Chinese Patients with Non–Hodgkin Lymphoma
Authors: Zhou Min , Cen Ling , Yang Jianhe , Li Jianyong 
Published: October 2019

Abstract
Abstract 4993

Objective:
To investigate prognostic significance of cytogenetics abnormalities, staging, patient factors, serum p53 protein concentration with Non–Hodgkin lymphoma (NHL). Methods: 43 patients with NHL were identified form August 2003 to December 2010. The clinical characteristics of these cases were performed by morphological, immunohistochemical, cytogenetic analyses and quantitative detection of human serum p53 protein were performed. Results: After conventional chemotherapy, a higher proportion of complete/ partial remission (CR/PR) rates and a prolonged overall survival (OS) in patients with early-stage(I–II) lymphoma, normal karyotype and lower level of Serum p53 protein compared with patients with advanced-stage (III–IV) lymphoma, cytogenetic abnormalities and higher p53 protein level (≥0.35U/ml) in serum, respectively. Bone marrow infiltration is also a predictor of poor response and OS. No statistical difference was noted with respect to the rate of disease remission between male versus female(<70 years versus ≥70 years), B-cell lymphoma versus T-cell lymphoma subgroups. Conclusions: Staging is an effective way of assessing disease extent; Cytogenetic examination provided useful information on diagnosis, staging and prognostic estimation; Serum p53 protein level may be a potential prognostic marker in patients with NHL.

Disclosures:
No relevant conflicts of interest to declare.
Obesity Is Poor Prognostic Factor in Lower Risk Myelodysplastic Syndrome
Authors: Mishra Asmita , Rollison Dana E , Al Ali Najla H , Corrales-Yepez Maria , Epling-Burnette Pearlie K , Lancet Jeffrey E. , List Alan F. , Komrokji Rami S. 
Published: October 2019

Abstract
Abstract 5018

Background:
Obesity was associated with a more than 2-fold greater risk of myelodysplastic syndrome (MDS) in a recent epidemiological study (Ma et al, Am J Epidemiol. 2009 June 15; 169(12): 1492–1499). The impact of obesity on outcome of disease in patients with an established diagnosis of MDS has not been studied. We examined the prognostic value of obesity in a large cohort of lower risk MDS patients treated at the Moffitt Cancer Center (MCC).

Methods:
Data were collected retrospectively from the Moffitt Cancer Center (MCC) MDS database and individual charts reviewed. The primary objective was to evaluate the impact of obesity on overall survival (OS) in lower risk patients with MDS. Patients with low or intermediate-1 (int-1) risk disease by International Prognostic Scoring System (IPSS) were included. Obesity was defined as a body mass index (BMI) ≥ 30 (Standard definition) measured at time of referral to MDS program at MCC. Patients were divided into two groups according to BMI ≥ 30 or BMI < 30. All analyses were conducted using SPSS version 19.0. Chi square and independent t-test were used to compare baseline characteristics between the 2 groups for categorical and continuous variables, respectively. The Kaplan–Meier method was used to estimate median overall survival. Log rank test was used to compare Kaplan–Meier survival estimates between two groups. Cox regression was used for multivariable analysis.

Results:
Between January 2001 and December 2009, 479 low/int-1 IPSS risk MDS patients were included. Among those, 132 (27.6%) had BMI ≥ 30 and 325 (67.8%) had BMI <30; BMI was missing in 22 patients (4.6%). The baseline characteristics between the two groups were comparable. No difference was noted in mean age, WHO subtype, karyotype, MD Anderson risk model group, red blood cell transfusion dependency (RBC-TD), or serum ferritin (Table-1).
The median OS was 59 mo (95%CI 48–70) in patients with BMI <30 compared to 44 (95%CI 38–50) in patients with BMI ≥ 30. (p=0.03). There was no difference in rate of AML transformation according to BMI, 12.9% and 15.7% respectively for BMI ≥ 30 and BMI <30. (P=0.3). In Cox regression analysis obesity predicted inferior OS (Hazard ratio (HR) 1.7 (95%CI 1.15–2.4) (P=0.007) after adjustment for age, MD Anderson risk group, serum ferritin, RBC-TD, use of hypomethylating agents and tobacco use.

Conclusion:
Our data suggest that obesity is an independent adverse prognostic factor for OS in patients with lower risk MDS. Obesity may be associated with other comorbidities and metabolic dearrangements that contribute to the pathogenesis of the underlying disease.

Disclosures:
No relevant conflicts of interest to declare.
Overall Survival by Prognosis Score in High-Risk Myelodysplastic Syndromes (MDS) Patients Receiving Decitabine Treatment: Results From Clinical Experience
Authors: Iastrebner Marcelo , Jang Jun Ho , Kim Kihyun , Jung Chul W. , Nucifora Elsa , Sackmann Federico , Orlando Sergio , Klein Graciela , Garcia Juan , Belli Carolina , Quiroga Luis , Santini Fernando , Bernard Haydee i , Salvatierra Lino , Taborda Gustavo , Bengió Raquel 
Published: October 2019

Abstract
Abstract 5024
Background The DNA-targeted hypomethylating agent, decitabine, has made a real impact on response rate in Myelodysplastic Syndromes (MDS) patients, and may improve overall survival in high-risk patients. Aim: To describe overall survival by prognosis score in decitabine-treated MDS patients. Methods: From May 2007 to January 2011, MDS patients who received decitabine were followed at centers in Argentina and South Korea. Patients ≥18 years of age with de novo MDS (all WHO Subtypes and CMML type-1 and type-2) were included, provided they had received ≥4 cycles of decitabine (recommended dose, 20 mg/m2 IV over 1 hour × 5 days every 4 weeks) and had stable disease or better by IWG 2006 criteria. Median life expectancy was determined according different categories of the MD Anderson and International Prognostic Scoring Systems (MDAPSS and IPSS). Decitabine treatment was effective when the patient outlived the median life expectancy. Results: Sixty-one patients received ≥4 cycles of decitabine and had stable disease or better. Median age was 61 years and 69% were male. All patients had de novo MDS with ECOG ≤2. Median time from MDS diagnosis was 24 months. Baseline WHO classification was: RA (0%); RARS (2%); RCMD (18%); RCMDRS (3%); RAEB-1 (13%); RAEB-2 (30%); MDS/MPD (2%); AML/MDS (5%); CMML type-1 (21%); and CMML type-2 (6%). Forty one percent had comorbidities. Patients received a median of 8 cycles of decitabine (range, 4–18). Forty four percent died during the study and 31% progressed to AML. Median overall survival was higher than life expectancy among patients with high-risk MDS by MDAPSS (Kantarjian H. et al. Cancer 2008; 113: 1351) and by IPSS (Greenberg P. et al. Blood 1997; 89: 2079). Survival exceeded life expectancy for 90%, 100%, and 86% of patients with MDAPSS 7–8, MDAPSS ≥9, and IPSS Int-2 + High, respectively. Conclusion: High-risk MDS patients who received ≥4 cycles of decitabine and had stable disease or better showed improvement in survival compared with predicted life expectancy published in literature.Median OS, MonthsPredictedActual*p-ValueMDAPSS (N=61)0–454395–625697–81431> 96230.014IPSS (N=58)Int-14237Int-2 + High14 to 5290.001*Kaplan-Meier and log-rank Test (Mantel-Cox).

Disclosures:
No relevant conflicts of interest to declare.