bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hemangioblastic Activity of Infant Leukemia with t(4;11).
Authors: Hu Zhongbo , Li Xiaomiao , Slayton William B. 
Published: October 2019

Abstract
Background: Infant leukemia patients with t(4;11) have an extremely high risk for treatment failure. Hemangioblasts are cells that were initially described in the embryonic yolk sac, where they make both blood and blood vessels when these two systems are forming. It was demonstrated that hemangioblasts are present in the adult bone marrow and CML patients. Recently, subgroups of infant ALL patients with t(4;11) were found to have gene expression profiles similar to hemangioblasts by microarray. However, whether infant leukemia cells behave like hemangioblasts and produce their own blood vessels remains unknown.
Objective: We sought to determine whether infant leukemia cells with t(4;11) are derived from malignant hemangioblasts and can produce their own blood vessels.
Design/Methods: Three childhood leukemia cell lines with t(4;11): MV4-11, SEM-K2 and RS4-11, were used to analyze the expression pattern of key angiogenic receptors by flow cytometry and angiogenesis related proteins by protein array in comparison with benign endothelial cells. These cell lines were also cultured in vitro using Matrilgel, an in vitro angiogenesis assay system, in order to test their ability to produce vascular tubes. These cell lines were injected into the immune deficient NOD/SCID mice after sublethal irradiation to establish leukemia in vivo. Some of primary cells from MLL patients were obtained and subcutaneously injected into NOD/SCID mice mixed with BD Matrigel to observe their vessel development in vivo together with these three cell lines. The bone marrow, liver, spleen and tumor tissues together with Matrigel were collected to look for the evidence of t(4;11) in endothelial cells by immunohistochemical staining and fluorescent in situ hybridization (FISH).
Results: The leukemia cell lines expressed many angiogenetic cytokines, such as VEGF, VEGF-D, RANTES, PIGF, PDGF-BB, MCP-1, IGF-1, ENA-78, and angiogenin, at the same levels as HUVEC cells, a human umbilical vessel endothelial cell line. Different cell lines expressed some angiogenesis-related receptors, such as CD31, Tie-2, PDGFRalpha, CD141, CD146, and KDR. None of the cell lines formed tubes in Matrigel. When these three cell lines generated leukemia in NOD/SCID mice, the microvessel density level increased in the tumor areas. However, immunostaining for human and murine endothelial markers demonstrated that all the vessels came from the mouse, not from the human leukemia cells.
Conclusions: We conclude that infant leukemia cell lines with t(4;11) have proangiogenesic activity. However, these cells do not function as hemangioblasts, as they do not produce blood vessels in culture or in vivo in NOD/SCID mice. We plan to look further by examing bone marrow biopsies from patients with t(4;11) leukemia to determine whether the translocation is present in their blood vessels.
Intensification of Hyper-CVAD with L-Asparaginase, Vincristine, and Dexamethasone ("Augmented Hyper-CVAD") Has Activity in Adult Patients with Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL).
Authors: Faderl Stefan , Thomas Deborah A. , Ravandi Farhad , Garcia-Manero Guillermo , Beran Miloslav , Rytting Michael , Koller Charles A. , Verstovsek Srdan , Borthakur Gautam , Andreeff Michael , Kornblau Steve , O’Brien Susan , Vu Khanh , Kwari Monica , Bretz Jennie , Kantarjian Hagop M. 
Published: October 2019

Abstract
Few treatment options exist for adults patients (pts) with relapsed/refractory ALL and prognosis for these pts remains poor. The hyper-CVAD program (fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone) has been established as an active induction regimen with a 91% CR rate and 5-yr. survival of 39% (Kantarjian et al. JCO 18:547, 2000). Following this lead, we designed an “augmented” hyper-CVAD (AHCVAD) combination intensifying the doses of vincristine, L-asparaginase, and dexamethasone during induction and consolidation. In this phase II study, pts received up to 8 courses of HCVAD alternating with methotrexate and high-dose cytarabine. With each course, pts received L-asparaginase 20,000 units i.v. and vincristine 2 mg i.v. at days 1, 8, and 15 each, and dexamethasone 80 mg i.v./p.o. on days 1–4 and 15–18. From June 2003 to July 2007, 55 pts with relapsed/refractory ALL have been enrolled. Median age was 34 yrs (range 14–70). Forty-one pts (75%) had pre-B ALL (2 pts with isolated CNS disease and one with an isolated testicular mass), 12 (22%) T cell ALL (2 with isolated extramedullary disease), 1 (2%) pt mature B ALL, and 1 (2%) biphenotypic leukemia. Karyotype was diploid in 25 (45%) pts and abnormal in 27 (49%) pts (1 Ph+ ALL). Median number of prior regimens was 1 (1–6). Median remission duration to the initial induction regimen was 11.5 mos (1–68). Seven (13%) pts were primary refractory. Forty-nine pts are evaluable for response (1 too early, 5 off study for toxicity or pt choice). Twenty-two (45%) pts achieved CR, 3 (6%) PR, and 4 (8%) hematologic improvement (HI). Median remission duration following AHCVAD was 4.75 mos (range, 0.2–45.5+). Twelve (24%, 8 in CR, 1 in PR, 1 with HI) pts proceeded to receive a stem cell transplant. Eight (15%) died while on study from infectious complications. Uncomplicated neutropenic fever was common. Three pts (5%) were intolerant to L-asparaginase and had to be taken off study early. Intensification of hyper-CVAD with asparaginase, vincristine, and dexamethasone is active in ALL salvage producing a CR rate of 45%. Further improvements should include:
identification of salvage pts with maximum chance of response; combination with new drugs and attempts to prolong remission duration for these pts.
Induction of Oxidative Stress and Glutathione Depletion by ABT-737, a Novel Small Molecule Inhibitor of Bcl-2, Contributes to Cytotoxicity in Leukemia Cells.
Authors: Chandra Joya , Howard Adrienne , Jensen Kathleen , Meyn Ray 
Published: October 2019

Abstract
The Bcl-2 family of proteins regulate the process of cell death. Bcl-2 and Bcl-xL are potent anti-apoptotic members that are overexpressed in a number of malignancies, providing a means to evade cell death, which has been described as a characteristic hallmark of cancer. Several lines of evidence suggest that Bcl-2 and Bcl-xL possess anti-oxidant properties. Overexpression of Bcl-2 is protective against menadione and hydrogen peroxide induced cell death and causes an increase in intracellular levels of glutathione (GSH), the most abundant antioxidant defense. In the present study, we utilized a novel small molecule to test effects of Bcl-2 inhibition on intracellular redox status. ABT-737 is a first generation inhibitor of Bcl-2, Bcl-xL and Bcl-w and and acts as a mimic of the BH3-only antagonists of these family members. Exposure of acute lymphocytic leukemia (ALL) cells to ABT-737 caused a dose dependent increase in intracellular levels reactive oxygen species (ROS), namely superoxide and hydrogen peroxide. This dose dependent increase in intracellular oxidants was significantly less pronounced in cells treated with the less active enantiomer of ABT-737. A greater than 50% decrease in intracellular GSH levels was seen with similar doses of ABT-737 and the combination of buthionine sulfoximine, an agent that depletes GSH levels further, with ABT-737, caused synergistic cell death. These data were verified using cells transfected with a tetracycline repressable Bcl-2 expression plasmid. Taken together, our data identifies a novel sequelae for Bcl-2 inhibition: the induction of oxidative stress. Combination therapies utilizing ABT-737 or its analogs may be devised based on the observed effects on the redox environment.
Imatinib Plus Vincristin & Prednisolone Induces Complete Remission and Prolonged Survival in Elderly Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia Patients.
Authors: Mukhopadhyay Ashis , Mukhopadhyay Soma , Gupta Pinaki Ranjan , Roy Ujjal Kanti , Sinha Ajoy 
Published: October 2019

Abstract
Introduction: Acute lymphoblastic Leukemia (ALL) in elderly patients (50yrs or older) carries a poor prognosis. In survival studies using in variety of therapeutic regimens. This may be because of relatively high frequency of the Philadelphia chromosome (Ph). With the advent of dose intensive chemotherapy regimen such as hyper CVAD (Fractionated Cyclophosphamide, Vincristin, Doxorubicin, Dexamethasone) overall survival has not improved. The aim of our study was to see the effectiveness of Imatinib plus Vincristin & Prednisolone in Philadelphia Chromosome positive in elderly acute lymphoblastic leukemia patients.
Material & Methods: During period from January 2006 December 2006 we selected 10 consecutive elderly (more than 50yrs) Ph+ ALL patients in the haemato-oncology department Netaji Subhash Chandra Bose Cancer Research Institute. There were 4 males & 6 females. The median age of the patient was 64years (range 51 to 77yrs). All patients were started with Imatinib mesylate (Natco pharma) 400mg daily. Prednisolone was given 40mg /m2 over 6weeks & followed by 2weeks tapering dose. Vincristin was given 2mg/m2 weekly for 6weeks. All patients were evaluated by bone marrow and molecular testing done every 3monthly for 1year then 6monthly.
Result: All patients (100%) obtained complete haematological & partial molecular response at 3month. Three patient (30%) achieved complete molecular response at 9month. With median follow-up of 8months (range 6–15months) the disease free survival and overall survival were 80% & 90% respectively. Most of the induction treatment was done as OPD basis, no hospitalization required. The therapy was tolerated well.
Conclusion: We concluded that Imatinib plus Vincristin & Prednisolone is a feasible, highly active protocol for elderly Philadelphia Chromosome positive acute lymphoblastic leukemia patients. It is well tolerated & associated with good quality of life.
Histone Deacetylase Inhibitors as Adjuvants for the Differentiation of Dendritic Cell from Leukemic Blasts.
Authors: Moldenhauer Anja , Seeger Karl , Schmidt Kerstin , Kiesewetter Holger , Salama Abdulgabar 
Published: October 2019

Abstract
Purpose. Recurrent cytogenetic abnormalities in leukemic blasts make these cells an attractive source of dendritic cells (DC) for leukemia-specific immune therapies. The purpose of this study was the evaluation of different histone deacetylase inhibitors in their potential to enhance the immunogenicity of leukemic DCs.
Methods. Leukemic blasts from 96 patients with acute lymphoblastic leukemia were cultured in two different cytokine combinations and either SAHA, valproic acid, isobutyramide or trichostatin A. Immune phenotype, T-cell allostimulatory capacities and cytotoxic responses were determined in DC generated after culture for one and two weeks.
Results. 71 of 96 blasts developed a typical DC morphology with 55 showing an upregulation of CD83, HLA-DR and costimulatory molecules like CD80 and CD86. The allostimulatory potential of the leukemic DCs was not influenced by the addition of HdI. DCs generated with cytokines and SAHA or valproic acid from TEL/AML1-positive blasts of patients with a t(12;21) translocation induced blast-specific cytotoxic T-cell responses in HLA-A matched T cells. The DC differentiability of TEL/AML1-negative blasts was not diminished by the use of HdI.
Conclusion. Histone deacetylase inhibitors could be used for the development of a dendritic cell-based anti-leukemia vaccine.
Safety of Lumbar Puncture (LP) and Instillation of Intrathecal (IT) Chemotherapy during Thrombocytopenia in Adults with Acute Lymphocytic Leukemia (ALL).
Authors: Atallah Ehab , O’Brien Susan , Kaled Susan , Lynn Alice , Cortes Jorge , Kantarjian Hagop , Thomas Deborah A. 
Published: October 2019

Abstract
Background: The platelet (PLT) count at which LPs can safely be performed in adults has varied in practice. A few pediatric studies have suggested a threshold level of 10 K/μL above which prophylactic PLT transfusion is not required; however, this has not been systematically studied in adults with ALL. We therefore investigated the incidence of traumatic LPs (TLP >10 RBCs/μL), the incidence of complications, and the relationship to thrombocytopenia.
Methods: Adults with ALL undergoing frontline therapy with hyper-CVAD (fractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone alternating with methotrexate and cytarabine) or variations incorporating rituximab and/or imatinib were reviewed. Patients (pts) were stratified to receive standard intrathecal treatment (IT) with methotrexate alternating with cytarabine based on CNS risk assessment (proliferative index ≥ 14% or serum lactate dehydrogenase ≥ 1400) [Cortes et al, Blood 86:2091, 1995]. Low risk pts received 6 IT, high or indeterminate risk 8 IT, and BLL 16 IT. Pts with PLT count ≤ 30 K/μL received PLT transfusions immediately prior to LP. Procedures were performed by trained practitioners.
Results: Outcome of 1998 LPs (282 pts) performed at our institution was reviewed. Median age was 42 years (range, 15–84). PLT count was ≤ 30 K/μL in 292 LPs (15%), 31–50 K/μL in 157 (8%), 51–80 K/μL in 211 (11%) and > 80 K/μL in 1338 (67%). Criteria for TLP was met in 910 (45%) of the LPs. The incidence of TLP was higher in patients with PLT count ≤ 50 K/μL (52% versus 44%, p=0.004). Four pts developed subdural hematomas. Of those, 3 had a history of CNS trauma, with only 1 considered possibly related to the LP. The latter occurred with PLT count of 28 K/μL prior to transfusion. Three pts developed diskitis or epidural abscesses after 3, 6 and 9 LPs, respectively, and were treated successfully with antibiotics.
Conclusions: Although the incidence of TLP appears to be higher with a lower PLT, it appears safe to perform LPs in thrombocytopenic pts with a threshold of 30 K/μL for prophylactic PLT transfusion as per our standard practice. However, this study does not address whether a lower threshold for PLT count (e.g., 20 K/μL) would yield similar findings.
Arsenic Trioxide Induce the Upregulation of β1-Subunit of Proteasome in NB4 Cell.
Authors: Wang Huaiyu , Zhang Mei , He Pengcheng , Chen Ying , Chen Limei , Lu Xiaohong 
Published: October 2019

Abstract
Arsenic trioxide has proven efficacy in inducing molecular remission in patients with acute promyelocytic leukemia (APL). The degradation of PML-RARα fusion protein induced by arsenic trioxide is related to its clinical efficacy in APL. The ubiquitin (Ub)/ proteasome pathway may involved in the degradation, but the mechanism in detail is unclear. In our previous study, we found that PSMB6 gene which encoded the β1-subunit of 26s proteasome was up-regulated after the treatment of arsenic trioxide (0.5 mmol/L). In current study, by western-blot analysis, we investigated the expression of β1-subunit of 26s proteasome after As2O3 exposure. We found that β1-subunit of 26s proteasome was upregulated after 24h treatment of As2O3(0.5 mmol/L). But the expression of β1-subunit of 26s proteasome return to baseline after 48h treatment. These findings are consistent with the results of the degradation of PML-RARα fusion protein. It is well known that the differentiation and apoptosis of NB4 cells are associated with the degradation of PML-RARα fusion protein and the reconstitution of the nuclear bodys (NBs). These results indicate that increase of β1-subunit of 26s may be associated with the degradation of fusion protein and the NB reorganization and play roles in the differentiation and apoptosis of NB4 cells. This pathway employs a complex enzymatic system to degrade proteins and whether other subunits are involved in the process is still unclear.
Gemtuzumab Ozagamicin Is Well Tolerated as Post-Consolidation Therapy in Childhood AML.
Authors: Hasle Henrik , Abrahamsson Jonas , Clausen Niels , Forestier Erik , Gustafsson Göran , Heldrup Jesper , Hovi Liisa , Jahnukainen Kirsi , Jonmundsson Gudmundur , Palle Josefine , Zeller Bernward 
Published: October 2019

Abstract
The NOPHO-AML 2004 protocol includes a post-consolidation randomization to Gemtuzumab ozagamicin, (GO, Mylotarg) or no further therapy. Randomization is offered to all standard-risk patients and to high-risk patients without a donor for SCT. GO is administered as a 2-hour infusion of 5 mg/m2 at least four weeks after the last consolidation including high-dose cytarabine and etoposide (HA2E). GO is repeated following a scheduled interval of three weeks. By August 2007 a total of 45 patients have been randomized (39 with standard-risk and 6 with high-risk AML). An additional nine patients were eligible but not randomized due to clinical decision (n=2), parental refusal (n=6), or administrative error (n=1). Twenty-three were randomized to receive GO. Detailed toxicity data were available from 21 of these patients. The median age was 3 years (six patients less than 2 years of age) at the time of GO. The median interval from HA2E to first GO was 32 days (range 27 – 43). The median interval from first to second GO was 22 days (range 20 – 28). All randomized patients received the second GO except one who relapsed shortly after the first infusion. No major events were reported in relation to the infusion. ALAT showed a slight elevation from a median baseline of 64 U/L to a median peak of 82 U/L and bilirubin increased from a median baseline of 5 μmol/L to a median peak of 8 μmol/L; highest value 25 μmol/L. No patients showed signs of VOD. No significant decrease in hemoglobin was observed whereas all patients became severely leukopenic (median nadir WBC 0.6) and neutropenic (median nadir ANC 0.1). Recovery to ANC > 0.5 lasted a median of 14 days (range 0 – 21). Fever needing antibiotic treatment occurred following 8 of 40 GO courses. None of the infectious episodes were life-threatening. Only a modest decline in platelet count was noted, median nadir 77 (range 10 – 239). Platelet transfusion was given following 5 of 40 GO courses. In conclusion GO infusion was well tolerated without clinical liver toxicity. Severe neutropenia was common but antibiotics were necessary following only 20% of the courses. Thrombocytopenia was modest.
Evaluation of the Expression of MDM2 & CD44v6 in Hodgkin’s Lymphoma.
Authors: El-Sebaaie Amr Farag , Youssef Samya Ahmed , Hassan Osama Abed El-Fatah , Aggina Hala Adel , Zafer Nehal Saad , El-Slam Mahmoud Slah Abed 
Published: October 2019

Abstract
Owing to the advances made in the fields of immunology and molecular biology, identification of biological factors with potential factors with potential prognostic signficance in HL were tried aiming to prevent primary resistance or relapse with as efficient first-line of treatment as possible . biological markers as cell cycle molecules (MDM) and adhesion molecules (CD44V6) were studied in current research on 100 cases of already diagnosed HL of different subtypes using specific monclonal antibodies and Envision detection kit as a staining system. The 100 cases studied comprised 70 males and 30 females, in a ratio of 7:3. The cases were retrived from files of pathology department, El-Maddi Hospital, cairo, Egypt from 1990–2000. The age ranged between 11–68 years with mean age in males of 40.8+/− 13.39 years in males and 35.8 +/− 18.9 in females. Cases were reclassified according to WHO classfication, 2002. Follow up period of 5 years was obtained from files of all patients including 2-years free disease and 5 years overall survival. In 53% of cases studied (53/100) a variable proprtion of H&RS cells expressed MDM2 that was strictly confined to the nuclei, particularly the nucleoplasm, while 30% (30/100)of the studied cases expressed CD44V6 as membranous staining with a variable proprtion In H&RS cells. A significant staistical correlation between expression of MDM2& CD44v6 with both age groups (P<0.05 & P<0.001) and subtypes of HL (P>0.05 & P>0.001) respectively were found. An inverse signficant stastical correlation between MDM2 expression and both 2 years free and 5-years free survival (P> 0.001 & P<0.001) was detcted. also a same relation was seen and both prognostic parameters (P>0.001 & P< 0.001) respectively. A strong signficant correlation between MDM2 and CD44V6 immunoreasctivites was expressed (P< 0.001). Our findings suggest that combined use of MDM2 and CD44v6 could be powerful prognostic factor in both presdiction of relapse and overall survival.
High Prevalence of Chronic Health Conditions in Survivors of Hodgkin Lymphoma Treated during Adulthood.
Authors: Matasar Matthew J. , Butos John N. , Riedel Elyn R. , Ford Jennifer S. , Weinstock David M. , Oeffinger Kevin C. , Straus David J. 
Published: October 2019

Abstract
Background: An increased risk of morbidity, including second primary malignancies and cardiovascular disease, has been reported in survivors of Hodgkin lymphoma (HL) diagnosed during adulthood. However, in contrast to our understanding of the late effects of treatment of children with HL, the global burden of chronic morbidity among long-term survivors of adult-onset HL is poorly characterized.
Methods: We conducted a survey-based cohort study of patients treated as adults with protocol-based first-line therapy for HL at our center from 1975 to 2000. The protocols included 6 combined modality trials (CMT) of chemotherapy (CT) + radiation therapy (RT), with the exception of a single CT-only arm in 1 trial. Chronic health conditions were assigned severity scores based on a modification of the Common Terminology Criteria for Adverse Events, version 3 (grades 1 through 4, ranging from mild to life-threatening or disabling).
Results: Of 707 patients for whom follow-up was available, 517 were alive. Median survival was 29 years. Survey data were available from 169 patients, with a median time from last treatment to interview date of 21 years. Of responders, median age at interview was 48 years (range, 25–88) and median age at treatment was 29 years (range, 16–66). Fifty percent were women, and 96% were white, non-Hispanic. Self-reported chronic health conditions were very common in our cohort: 94% of respondents reported any chronic health condition, and 60% described chronic health conditions that were grades 3 or 4 in severity (Table 1). Frequently reported conditions included cardiovascular, musculoskeletal, endocrine, and psychiatric disorders. Sixty percent of patients reported grade ≥1 cardiovascular dysfunction (20% ≥grade 3), 40% grade ≥1 musculoskeletal (7% ≥grade 3), 71% ≥grade 1 endocrine (17% ≥grade 3), and 23% ≥grade 1 psychiatric (21% ≥grade 3). Second primary malignancies were reported by 23%, and infectious conditions by 34%. Additional data collection on surviving and deceased patients is ongoing.
Conclusions: These results document the high prevalence of chronic illness among survivors of HL treated as adults. Evidence-based guidelines built upon such data are needed to aid clinicians in the management of the late morbidities associated with HL treatment.
Table 1. Chronic health conditions among adult-onset Hodgkin lymphoma survivors, according to severity score. Health Condition Frequency (%) Conditions by grade No condition 10 (6%) Grade 1 17 (10%) Grade 2 41 (24%) Grade 3 67 (40%) Grade 4 34 (20%) Any condition Grades 1–4 159 (94%) Grade 3 or 4 101 (60%) Multiple health conditions ≥Grade 1 ≥2 conditions 142 (84%) ≥3 conditions 120 (71%) ≥Grade 2 ≥2 conditions 111 (66%) ≥3 conditions 72 (43%) ≥Grade 3 ≥2 conditions 50 (30%) ≥3 conditions 19 (11%)