bluuebunny/crossref_metadata_2025_split huggingface dataset:
PB1665 TREATMENT OF FAVORABLE RISK YOUNG PATIENTS WITH ACUTE LYMPHOBLASTIC LEUKEMIA (ALL) USING A LOW‐DENSE/ LOW‐INTENSE CHEMOTHERAPY PROTOCOL
Authors: Salamoon M. , balti M. , ghanem K. , kenj M. 
Published: June 2019

Background:ALL is a disease affecting the lifespan from neonates to elderly, however, overall survival reaches 90% using pediatric protocols. In older patients, survival is still very poor reaching only 45% which can be attributed to several reasons including heterogeneity of biology, physiologic status of patients as well as therapeutic approach. Another factor justifying the poor outcome is the low rate of enrollment in clinical trials of this population aged between 15‐39 years as defined by the National Cancer Institute (NCI).Aims:the study evaluates the response rate, progression free survival (PFS) and overall survival at % years (OS) as well as the safety profile.Methods:this is a multicenter study performed in part at Al Bairouni university cancer center, Al Mwasat charity and Ospedale Italiano in Damascus, Syria between 2008 and 2013 where we recruited 224 patients having a favorable risk ALL confirmed by Bone Marrow aspiration (morphologic study, Flocytometeric study and Karyotype) was performed in all patients. Induction with (Dxorubicin 45 mg/m2+ Cyclophosphamide 75 mg/m2+ Vincristin 1.4 mg/m2) every weeks X 4 weeks and prednisolone 1 mg/kg for 4 weeks. Complete responders consolidated with 1st block: Cyclophosphamide 75 mg/m2+ Cytarabine 30 mg/m2 BID/SC for 5 days+ 6‐Mercaptopurine 75 mg/m2 every day repeated every 14 days 4 times followed by a 2nd block: Methotrexate 3 gram/m2+ Kidrolase 10000IU repeated every 14 days for 4 times. Maintenance with cyclophosphamide 750 mg/m2+ Vincristin 1.4 mg/m2+ oral Methotrexate 15 mg + 6‐Mercaptopurine daily, repeated every month for 24 times. Intralthecal prophylaxis with Methotrexate as performed 2 times in the induction, with every consoloidation and every 3 month during maintenance.Results:complete remission in the first induction was seen in 185 patients (82.5%) with other 32 joined them after an extra induction round (96.8%). Only 8 patients progressed in the consolidation period versus 10 in the maintenance with a PFS of 88.9% at 5 years and 202 patients still surviving after 5 years with an overall survival rate of (90.17%). We have lost 4 patients in the induction and 2 in the consolidation due to unusual toxicity profile of Methotrexate, however, other toxicities were manageable. Response was more prominent in younger population (those younger than 22) (p value 0.003) and late in those with Philadelphia positive disease (p value 0.02).Summary/Conclusion:ALL is still a lethal disease especially in those who do not respond well to induction protocols. Progress was made during the last decade in both understanding the biology and employment of new treatment approach especially in pediatric population, however, results are still poor in elderly patients. Our study shows good results compared with published data which could be adopted in the light of other trials conducted to test our results.
PB1675 ASSESSMENT OF SERUM IL‐15 IN ADULT ACUTE LEUKEMIA PATIENTS (EGYPTIAN SAMPLE)
Authors: Moussa M.M. , Sheeba M. , Elmohsen E. Abd , Elshazly M. , Hussein N.E. 
Published: June 2019

Background:Interleukin 15 (IL‐15), a proinflammatory cytokine, regulates the functions of the immune system and controls the differentiation of hematopoietic cells. However, it may also promote the development of leukemia through its role in enhancing the survival, proliferation and differentiation of leukemic precursors.Aims:To assess expression of IL‐15 level in adult Egyptian acute leukemia patients, its correlation with disease free survival, overall survival and relapse rate, as well as its possible correlation with other prognostic parameters.Methods:Serum IL‐15 level was measured using enzyme‐linked immunosorbent assay in 30 newly diagnosed acute lymphoblastic leukemia (ALL) patients, 30 newly diagnosed acute myeloid leukemia (AML) patients and 30 age and sex‐matched healthy control subjects. The patients were recruited from clinical hematology department at Ain shams university hospital over the period from April 2017 to October 2018.Results:In ALL patients: The serum IL‐15 level was higher in ALL patients compared to control subjects (P = 0.015). The serum IL‐15 level was higher in ALL patients with non high risk cytogenetics compared to those with high risk cytogenetics (P = 0.047). Patients with ALL with high serum IL 15 level achieved 1stcomplete response (CR) less than those with low or average serum IL 15 level (P = 0.038). Patients with ALL with high serum IL 15 level achieved minimal residual disease (MRD) negativity less than those with low or average serum IL 15 level (P = 0.006). Patients with ALL with high serum IL 15 level had shorter survival compared to those with low or average serum IL 15 level (P = 0.005). The optimal cut‐off value for serum IL‐15 in predicting patient survival in patients with ALL was 200 ng/L.In AML patients: The serum IL‐15 level was higher in AML patients compared to control subjects (P =  0.010). The serum IL‐15 level was higher in AML patients with high risk features compared to those with non high risk features (P = 0.048). Patients with AML with high serum IL 15 level achieved 1stcomplete response (CR) less than those with average serum IL 15 level (P = 0.015). Patients with AML with high serum IL 15 level achieved minimal residual disease (MRD) negativity less than those with average serum IL 15 level (P = 0.002). Patients with AML with high serum IL 15 level had shorter survival compared to those with low or average serum IL 15 level (P < 0.001). The optimal cut‐off value for serum IL‐15 in predicting patient survival in patients with AML was 190 ng/L. Serum IL15 level has negative correlation with the date of death in patients with AML (P =  0.001).Summary/Conclusion:Interleukin 15 (IL‐15) is a useful poor prognostic marker in patients with newly diagnosed acute leukemia, also it can be used as a predictor for complete remission (CR), minimal residual disease (MRD) and survival.
PB1680 SURVIVAL OF ADULT PATIENTS WITH ACUTE LYMPHOBLASTIC LEUKEMIA (PH NEG) WHO DEVELOP HYPERGLYCEMIA DURING THE INDUCTION OF REMISSION IN AN INTENSIVE CHEMOTHERAPY PROTOCOL IN MEXICO
Authors: Alvarado M. , Rojas F. , Alvarez J. L. , Ortiz M. , Mena V. , de la Peña A. , Espitia M.E. , Perez J. M. 
Published: June 2019

Background:During the induction phase of the treatment exist several factors, besides glycemia control, that predisposed to severe infections like decreased immunity, aplasia of the epithelia, disease activity and chemotoxicity.13 But the effect of hyperglycemia during induction to remission have impact the leukemia‐free survival (LFS) results.Aims:The purpose of this study is to determine the incidence of hyperglycemia in therapeutic programs that includedexamethasone during the induction, and compare leukemia free survival (LFS) and disease‐free survival (DFS) in patients older than 15 yearsMethods:We performed a unicentric, longitudinal, case control study in ALL patients older than 15 years old admitted to the adult hematology Service of the CMN “20 de Noviembre” during the period from 2000 to 2014 treatment with the chemotherapy. Exclusion criteria: history of myelodysplastic syndrome, previous chemotherapy and / or radiotherapy, HIV infection or any condition that precluded their inclusion in chemotherapy (CT) protocols. Patients who abandoned the treatment, who violated the chemotherapy protocol or went to BMT due to high risk disease, were eliminated. Both therapeutic programs (LAL‐6 and LAL‐10) included 4 days of IV dexamethasone (pre‐induction phase) before the start of CT.Results:We included 159 patients, 77 women and 82 men; 77 patients presented hyperglycemia during induction phase. The mean follow‐up was 19 months (2 to 61). Hyperglycemia incidence was 51.5%.The LAL‐6 protocol was received by 56 patients (53% of the group without hyperglycemia and 17% in the hyperglycemia group). The LAL‐10 protocol was used in 102 patients (47% and 83% respectably). The highest elevations occur immediately after concluding the use of dexamethasone, with hyperglycemia in 91 patients and without in 68. This phenomenon maintained until the end of induction and the levels of glucose start to decrease in the following phases (p = 0.0001).In patients with hyperglycemia at the end of the induction, the average age was 44 years (SD 13) and in those who did not have it was 31 years (SD 12), p = 0. 0001.Summary/Conclusion:In the multivariate analysis, the factors that predict the appearance of hyperglycemia, in our experience, were age, female sex, the existence of diabetes and the basal glucose level (> 135 mg / dL). O
PB1699 A SCREENING OF ANTINEOPLASTIC DRUGS FOR ACUTE MYELOID LEUKEMIA REVEALS THAT FLUDARABINE AND CYTARABINE HAVE WEAK CAPACITY AS INDUCERS OF IMMUNOGENIC CELL DEATH
Authors: Ocadlikova D. , Lecciso M. , Redavid A. , Cavo M. , Curti A. 
Published: June 2019

Background:Although antineoplastic drugs used as induction chemotherapy for patients with acute myeloid leukemia (AML) result in high rate of complete remission, disease relapse occurs in the majority of cases, unless stem cell transplant is not performed. Development of new therapies is, then, a major medical need. Among them, strategies harnessing the immune system against leukemia are under active investigation. It is known that the cancer cell death induced by some antineoplastics drugs, such as anthracyclines, is highly immunogenic and results in the maturation of dendritic cells (DCs) and in the efficient cross‐priming of anti‐tumor T cells. This process, named immunogenic cell death (ICD), is characterized by Calreticulin (CRT) and Heat Shock Proteins 70 and 90 (HSP70/90) translocation to cell membrane and release of HMGB1 protein from nucleus.Aims:In this study, we were interested in in vitro comparison of five among the most widely used drugs for AML as ICD inducers.Methods:HL‐60 AML cell lines were treated with Daunorubicin (DNR), Cytarabine (Ara‐C), Etoposide (VP‐16), Fludarabine (Fluda) and Bortezomib. After apoptosis detection by flow cytometry, traslocation of CRT, HSPs70/90 and HMGB1 release from nucleus were evaluated using flow cytometry and immunofluorescence. Successively, the treated cells were used for loading into healthy donor‐derived DCs which were used to induce T cell proliferation as evaluated by flow cytometry using CFSE.Results:All five tested drugs induced a comparable levels of apoptosis. While Bortezomib and VP16 as well as DNR, which is a well‐known ICD inducer, were capable to induce CRT and HSP70/90 traslocation and HMGB1 release from nucleus, Fluda and Ara‐C have low, if any, capacity to induce ICD‐related events. Importantly, only DNR, Bortezomib and VP16 treatment, but not Ara‐C and Fluda, induced DC maturation, thus confirming that ICD‐related events correlate with immunogenic changes in DCs. At the functional level, VP16 was comparable to DNR at eliciting T‐cell proliferation via DCs, whereas Bortezomib, despite its capacity of inducing DC maturation via ICD, had low effect on T‐cell proliferation. Again, Ara‐C and Fluda had no effect on T‐cell proliferation.Summary/Conclusion:Our results indicate a novel and poorly‐investigated feature of antineoplastic drugs, commonly used for the treatment of AML, which is based on their different immunogenic potential. Under this viewpoint, Fluda and Ara‐C have weak, if any, capacity as inducers of immunogenic cell death, whereas VP16 and DNR are very effective. Further experiments, addressing the synergistic effects of these different drugs, may help to combine their conventional cytotoxic activity with their immunogenic capacity, thus providing the platform for a novel approach to anti‐leukemia chemotherapy.
PB1713 NEW METHODS FOR ASSESSING THE GENOTOXICITY OF CHEMOTHERAPY DRUGS IN ACUTE MYELOID LEUKEMIA
Authors: Zhogolev D. , Polyakov A. , Kolubaeva S. , Alexander Z. , Noskov Y. 
Published: June 2019

Background:This abstract presents the experience of cultivating the peripheral blast cells of a patient with resistant acute myeloid leukemia (AML) and testing 2 methods for assessing the effects of chemotherapy drugs on them.Aims:Suitability examination of cell sorting (CS) and micronucleus test (MT) for assessing the genotoxicity of chemotherapy drugs.Methods:Blast cells were obtained by taking blood from a patient with multi‐resistant AML. On sampling days, the percentage of blasts in the patient's peripheral blood ranged from 50% to 75%. In total, 3 in vitro experiments were conducted.In experiment №1, 520650 CD34+ cells were sorted into 2 tubes, which were incubated for 4 days (37 °C, 5% CO2) in 5 ml of complete nutrient medium (CM): 80% RPMI‐1640, 10% fetal calf serum, 10% of the patient's original serum, 10 μl of phytohaemagglutinin and 100 U/ml penicillin.After the first day, decitabine was added to one of the samples at a concentration of 1160 ng/ml. To assess the genotoxicity of the drug at the end of cultivation, we determined the number of cells that retained viability by evaluating the results of labeling free DNA.In experiments №2 and №3, 0.5 ml of blood was cultured with 5 ml of CM. After 24 hours, various concentrations of decitabine (290 ng/ml, 580 ng/ml, 1160 ng/ml) were added to the samples of experiment №2. Daunorubicin (3400 ng/ml) was added to the samples of experiment №3, as well as its combination with interferon alpha‐2a in the calculation of 3600 IU/ml. Next, samples were cultured for 48 hours. To assess the genotoxicity in these experiments MT was used.Results:The results of experiment №1 are presented in Figure 1, №2 in table 1, №3 in table 2.Summary/Conclusion:1. CS allows selection of the required number of cells with the required phenotype and assess their viability after cultivation with high accuracy. In the sample with the addition of decitabine, living blast cells turned out to be almost 2 times less than in the control sample.imageimage2. MT can be used to assess the genotoxicity of chemotherapy drugs for peripheral blood blast cells. From the results of experiment №2, it follows that the concentration of the drug has a direct correlation with the level of its genotoxicity on blast cells. In experiment №3, the combination of daunorubicin with interferon showed much stronger genotoxic effects on blast cells compared to daunorubicin without interferon.
PB1727 OUTCOME OF CORE BINDING FACTOR ACUTE MYELOID LEUKEMIA IN ADULT PATIENTS
Authors: El Gammal M. , Mahmoud A. , Samra M. , Elnagar A. , El Shakankiry N. 
Published: June 2019

Background:Core binding factor acute myeloid leukemia (CBF AML) encodes two recurrent cytogentic abnormalities, t(8;21) and inv (16) and carries an overall good prognosis, yet some cases relapse.
Aims:is to define unfavorable group of CBF AML by analysis of (C‐KIT and FLT3‐ITD) and to correlate with outcome of therapy.Methods:Prospective study started at Jan 2015 till June 2017, and included 70 patients CBF AML diagnosed and managed at medical oncology department of National Cancer Institute (NCI), Cairo University. All patients received standard of care protocol at NCI (“3+7”induction followed by 3‐4 courses of high dose cytarabine consolidation. The study was approved by the Institutional Review Board (IRB), of NCI, Egypt.Results:the median age was 31 years (18‐60, with a male/female ratio of 4/3. 42(60%) patients had t(8;21) and 28 patients had inversion 16(40%). C‐KIT mutations (exon 8 and exon 17) were detected in 10/52 tested patients and FLT3‐ITD was detected in 3/70 patients. While patients with Inv.16 had more lymphadenopathy and splenomegaly, median initial leucocytic count and exclusive gum hyperplasia, HCV‐Ab positivity (8/42) was exclusively present in patients with t(8;21). Clinically, lymphadenopathy, pallor and dyspnea were associated with worse overall survival (OS)(<0.05). BM cellularity at day 28 of induction had a significant impact on survival (P = 0.002). Median OS was 19.5 month while median disease free survival (DFS) was not reached for the whole group. Patients with Inv.16 had non‐significant better DFS than patients with t(8;21)(P = 0.07). Neither C‐ KIT D816 V mutation nor FLT3‐ITD mutation had significant impact on OS or DFS, but when taken together (either C‐KIT or FLT3‐ITD mutant) had negative impact on DFS (P = 0.04).Summary/Conclusion:C‐KIT or FLT3‐ITD mutation had negative effect on DFS but not OS. HCV‐Ab positivity may be associated with t(8;21)AML, while Inv.16 is associated with more extramedullary diseaseimage
PB1743 LIPOSOMAL ANNAMYCIN ‐ A NEW GENERATION ANTHRACYCLINE THAT OVERCOMES MDR AND HAS NO CARDIAC TOXICITY FOR THE TREATMENT OF R/R AML
Authors: Shepard R. 
Published: June 2019

Background:Anthracyclines remain the backbone for induction therapy in the treatment of AML. Unfortunately, most patients will relapse with refractory disease and quickly succumb to their AML. One of the major reasons if not the major reason for developing resistance is the development of MDR. Annamycin was developed and has been shown both preclinically and clinically to overcome MDR and have no cardiac toxicity. Furthermore, it is formulated in a nanomolecular bi‐lamellar liposomal delivery mechanism that targets the leukemic cells in the bone marrow and spares cardiac and other normal cells. Therefore, a new phase I/II clinical trial has been started in both the US and Europe using L‐Annamycin for the treatment of all patients with R/R AML agnostic of mutational status.Aims:The aim of the phase I component is to determine the RP2D of L‐Annamycin for the treatment of R/R AML. The phase II component is designed to demonstrate efficacy leading to a phase II registration study for accelerated approval in both the US and EU. PK determinations are being performed for all patients.Methods:The phase I component is a standard modified Fibonacci 3+3 design to determine the RP2D. An additional 21 patients will be enrolled as an early determinant of efficacy at the RP2D. The sample size for this is based upon an expected response rate of 15%. Utilizing the optimized Simon two stage design, the assumption is that alpha = 0.1 and beta = 0.2. If less than 1 CR is observed in the first 14 subjects, the study will be stopped for futility. To be declared a success, at least 4 subjects of the 21 needs to demonstrate a CR. A DMC will monitor all data and decide if the study should continue and if any changes to the protocol are needed.Results:The study is ongoing in both Europe and the US. The first cohort has completed in the US. Even at the very low starting dose, one of the three patients had a near CR with just MRD after just one three‐day course of L‐Annamycin. The first cohort in Europe has enrolled two patients and updated results will be presented at the EHA Congress.Summary/Conclusion:Anthracyclines remain the backbone of induction therapy in AML but most patients will relapse and die from their refractory disease. Resistance develops because of MDR. L‐Annamycin overcomes this and has little to no cardiac toxicity even with up to eight cycles. This study will is designed to demonstrate its efficacy in all patients with R/R AML including the majority with no targetable mutations.image
PB1753 CHIDAMIDE MAY BE EFFECTIVE FOR RELAPSED/REFRACTORY ACUTE MYELOID LEUKEMIA, ESPECIALLY FOR AML/ETO POSITIVE PATIENTS
Authors: Yao W. , Tong J. , Liu H. , Sun Z. 
Published: June 2019

Background:Epigenetic changes are encountered in acute myeloid leukemia (AML) and are thought to contribute to leukemogenesis. Decreased histone acetylation was frequently found in AML, especially in high‐risk cytogenetics, higher age, secondary or relapsed/refractory AML. HDAC inhibitors have been found to be effective in AML. But the data was limited in China.Aims:This retrospective study evaluated the clinical outcomes of chidamide combined with FLAG regimen for relapsed/refractory AML in our single center.Methods:From May 2018 to December 2018, 12 patients with relapsed/refractory AML including 6 AML/ETO positive received induction chemotherapy of “chidamide +FLAG” regimen (chidamide 30 mg/d twice a week for two weeks, fludarabine 30 mg/m2/ d for 5 days, Ara‐C 2 g/m2 /d for 5 days, G‐CSF 5‐10ug/kg/d continuedly until neutrophil recoverd).Results:A total of 7 patients achieved a complete remission (CR) after induction chemotherapy (CR rate 58.3%). In 6 AML/ETO positive patients, 5 patients achieved molecular remission (CR rate 83.3%). At the end of the follow‐up period, 8 patients underwent hematopoietic stem cell transplantation and 7 patients survived in CR.Summary/Conclusion:Chidamide might be suitable drugs in relapsed/refractory AML therapy, especially in AML/ETO positive patients.
PB1754 THE PERIPHERAL CD4+CD8+ T‐CELL LEVEL OF ACUTE LEUKEMIA PATIENTS AFTER HAPLO‐HSCT IS HIGHER THAN THAT OF THESE PATIENTS AFTER HLA‐IDENTICAL‐HSCT
Authors: Li Y. , Dai J. , Huang X. 
Published: June 2019

Background:Nowadays, we generally think that the immune responses after the HLA‐haploidentical hematopoietic stem cell transplantation (haplo‐HSCT) of acute leukemia (AL) patients mainly results from the cross reactivate by donor‐derived memory T‐cells. However, the role of thymus on immune reconstitution after haplo‐HSCT is not clearly understood yet.Aims:Regarding the development of CD4‐CD8− (double negative, DN) and CD4+CD8+ (double positive, DP) T‐cell is associated with the function of thymus, we investigate the levels of DN and DP T‐cell in AL patients who have received the haplo‐HSCT or HLA‐identical hematopoietic stem cell transplantation (identical‐HSCT).Methods:In the 1st to the 12th months after hematopoietic stem cell transplantation (HSCT), the DN T‐cell and DP T‐cell levels in the peripheral blood of 77 AL patients are evaluated by flow cytometry. And 51 of these patients received haplo‐HSCT, while 26 of them received identical‐HSCT. The repeated measures one‐way ANOVA is used for statistic analysis.Results:The DP T‐cell level of AL patients after haplo‐HSCT is significantly higher than those patients after identical‐HSCT (F = 12.02, p = 0.00). however, The DN T‐cell level in these two groups of patients do not show a significantly difference (F = 0.87, p = 0.36). Furthermore, when we only look into the haplo‐HSCT group, we found that the DP T‐cell level of patients donated by the parents (n = 31) is significantly higher than that of the patients donated by the children, (n = 7, F = 6.37, p = 0.03) as well as that of the patients donated by the sister/brother(n = 13, F = 6.64, p = 0.02).Summary/Conclusion:From the data of our center, in AL patients after haplo‐HSCT show a high DP T‐cell level than these patients after identical‐HSCT, and this indicates that thymus as the human central immune organ, has a possibility to play a role in immune reconstitution after haplo‐HSCT. But the clinical significance of DP T‐cell on predicting thymus function and immune reconstitution need to be further explored with more patient data. Here, we would like to share our finding on the peripheral DP T‐cell level after haplo‐HSCT, in order to inspire further exploration with other hematologists to clarify the mechanism involve in it.