bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase I Study of Gemcitabine, Fludarabine and Mitoxantrone for Relapsed or Refractory Leukemia.
Authors: Misra Debashish , Moore Joseph O. , Gockerman Jon P. , Diehl Louis , de Castro Carlos , Yang Yiping , Gasparetto Cristina , Abernathy Amy , Horwitz Mitchell , Long Gwynn D. , Chute John , Peterson Bercedis , Chao Nelson J. , Rizzieri David A. 
Published: October 2019

Abstract
Purpose: To estimate the maximum tolerated duration (MTD) of gemcitabine given as a continuous infusion in combination with fludarabine and mitoxantrone for patients with relapsed or refractory leukemia.
Patients and Methods: Patients received gemcitabine at 10mg/m2/min (day 1) with fludarabine at 25mg/m2/day for 5 days (days 1–5) and mitoxantrone at 10mg/m2/day for 3 days (days 1–3). The duration of gemcitabine infusion was escalated using the modified continuous assessment method (mCRM) at 3 hour increments (3, 6, 9, 12, and 15 hours). This three-drug regimen was build upon our previous studies with fludarabine, mitoxantrone and continuous infusion gemcitabine (Blood2003;102:250b Abstract). The MTD was estimated as the duration of gemcitabine infusion in combination with fludarabine and mitoxantrone at which 33% of the patients would experience a dose limiting toxicity (DLT). DLT was defined as either neutropenia for more than 28 days with less than 5% blasts in the marrow, a non-hematologic grade 4 toxicity lasting ≥ 3 days, or a non-hematologic grade 3 toxicity lasting ≥ 7 days.
Results: Ten patients with relapsed or refractory leukemia have been treated so far since Aug 2004 and fully evaluated. The median age was 55 years (range 30 – 67). The median number of prior regimens was 3 (range 1 – 5) and the median range of prior cycles was 4 (range 1 – 6). As expected, hematologic toxicity, mucositis and nausea were common but did not meet criteria for DLT in any patient. One patient had parainfluenza lung infection with alveolar hemorrhage and this was the only DLT on the study. 2/10 patients achieved CR. Both patients are alive, 20 weeks and 52 weeks later, respectively but have received further therapy in the form of chemotherapy or allogeneic stem cell transplantation.
Toxicity by Duration of Gemcitabine Infusion Duration of Infusion (hrs) # of Patients with DLT/Total Probability of Toxicity at this Dose Probability that Dose is MTD 3 0/1 0.001 0.0 6 0/2 0.009 0.005 9 0/3 0.1 0.22 12 1/4 0.36 0.59 15 0/0 0.6 0.18
Conclusion: Only one patient on this study had a DLT. This combination therapy is myelotoxic and has some anti-leukemia activity with 2/10 patients achieving CR. The duration of gemcitabine infusion as part of the above three drug regimen will be studied further on this ongoing study to more accurately estimate the MTD and determine if phase II trials are warranted.
Phenolhexyl Isothiocyanate, a New Histone Deacetylase Inhibitor, Can Prevent Tumor Formation and Inhibit Leukemia Cell Growth In Vivo.
Authors: Lu Lulu , Ma Xudong , Becklemisheva A. , Chaio J.W. , Liu Delong 
Published: October 2019

Abstract
We have demonstrated that phenolhexyl isothiocyanate (PHI) induces growth arrest and apoptosis in leukemia cells HL-60 through inhibition of the activity of histone deacetylases (HDAC), the enhancement of histone acetylation and activation of p21. In this study, we examined the effects of PHI on the growth of HL-60 leukemic xenograft in immunodeficient mice. The PHI was given to the mice by gavage. The maximum tolerated dose by the mice was determined following standard design. To determine the in vivo effect of PHI on leukemia growth, a sub-MTD dose was given to the control and the treatment groups with 17 mice in each group after injection of 1.0 x 10e6 HL-60 cells per mouse. There was a significant reduction in the incidence of tumor formation (94.1% control group vs 58.5% PHI group, p=0.004). In addition, there was also a significant difference in the tumor size between the two groups. Determined at autopsy, the mean weight of control tumors was 0.8 g vs. the tumors of the experimental group 0.35g, revealing a significant reduction of 44.4% (P<0.03). There were no detectable toxicity as evaluated by body and organ weight, and necropsy examination. The histology of the tumor showed increased apoptotic cell death. Apoptosis in the tumors was further confirmed by the cleavage of poly ADP-ribose polymerase (PARP), the target of proteolysis of caspases that execute apoptosis with Western blot analyses. The results suggest that PHI can prevent tumor formation and inhibit leukemia cell growth in vivo without significant toxicity that is routinely associated with conventional chemotherapeutic agents.
FLAG-(IDA)-Mylotarg in the Therapy of Relapsed and Refractory Acute Myeloid Leukemia.
Authors: Fabbiano Francesco , Mondello Francesca , Magrin Silvana , Felice Rosaria , Marino Carla , Turri Diamante , Mirto Salvatore 
Published: October 2019

Abstract
Patients with relapsed and refractory AML have a bad prognosis. In this setting it is often difficult to obtain a complete remission. In the last few years fludarabine and high dose Citarabine with or without Idarubicine and G-CSF have been frequently used (FLAG and FLAG-IDA schedules). The immunotoxin gemtuzumab ozogamicin (Mylotarg)(GO) Wyeth is a humanized IgG4 monoclonal antibody directed against the CD33 epitope, which is chemically linked to calicheamicin, a highly potent antitumor antibiotic. As a single agent it has been shown to be an effective agent in the treatment of relapsed AML with a tolerable toxicity profile. Recently the United Kingdom Medical Research Council (MRC) published the preliminary results of AML15 trial, which was designed to evaluate the effect of adding GO to each course of intensive induction or consolidation chemotherapy in patients younger than 60 years as first-line treatment. These results are encouraging. We are using this association in the treatment of relapsed and refractory adult AML. Until now 10 patients have been enrolled in this trial and we show our preliminary results.
Patients and methods. 3 patients were resistant to induction; 3 patients were in the first relapse and 1 in the third after conventional chemotherapy, 1 was relapsed after autologous transplant and 2 were relapsed after allogeneic transplantation. The demography and characteristics are shown in the table. 8 Pts were treated with Fludarabine 30 mg/sqm dd 1–5, Citarabine 2,0 gr/sqm dd 1–5, Idarubicine 10 mg/sqm dd 3–5, Mylotarg 3 mg/sqm d −1, G-CSF 375 mg dd 1–6. 2 patients with the same schedule without Idarubicine.
Results: 6 patients obtained Complete Remission, 2 died after therapy and 2 were resistant to this schedule.Out of the 6 patients in CR 4 are in continuous complete remission at 3, 3, 8 and 11 months Three of these underwent allogeneic BMT with no significant toxicity and are actually in CR.. Two relapsed at 3 and 7 months. In our experience the toxicity of FLAG-(IDA)-GO schedule is acceptable and the results are promising in refractory and relapsed AML.
pts age years disease status treat.response further therapies outcome 1 46 resistant CR BMT CR +11 M 2 52 resistant resistant -- died 3 69 1 th relapse CR -- relapse 7 M 4 65 3th relapse died -- 5 57 relapse after auBMT died -- 6 58 relapse after BMT resistant -- died 7 28 relapse after BMT CR 2nd BMT CR +6 M 8 42 1th relapse CR BMT CR +3 M 9 74 1th relapse CR -- CR +4 M 10 64 resistant CR __ relapse 3 M
High Rates of Epstein Barr Virus Expression in Hodgkin’s Lymphoma in Lebanese Children.
Authors: Abboud Miguel R. , Muwakkit Samar , Kattar Mireille , Khoury Ruby , Zaatari Ghazi , Razzouk Bassem 
Published: October 2019

Abstract
Introduction: Hodgkin’s disease (HD) accounts for around 6% of all cancers in Lebanese children ≤ 15 years of age. HD shows wide geographic variation in its association with EBV virus. The prognostic significance of Latent EBV infection in HD is still controversial
Purpose: To examine EBV (LMP-1) positivity in pediatric patients treated for HL at the American University of Beirut-Medical Center and the Children’s Cancer Center of Lebanon and its association with age, sex, histologic subtype and treatment outcome.
Methods: The charts of all pediatric patients treated for Hodgkin’s Lymphoma at the American University of Beirut Medical Center between 1980 and 1996, and at the Children’s Cancer Center of Lebanon from 2002 to 2005 were reviewed. Their paraffin blocks were studied for Epstein-Barr virus association by latent membrane protein-1 (LMP-1) immunohistochemistry.
Results: The charts of 34 patients with HD were reviewed. The median age was 7.5 years (range: 2–16 yrs); only 4 patients were above 13 years of age. The M: F ratio was 4.6:1, and the mean follow-up was 4.5 yrs (range 4 months −12y). 6 had stage I, 10 had stage II, 15 had stage III (5 patients IIIA and 10 patients IIIB disease), and 3 had stage IVA disease. 53% had advanced stage disease. 16 patients (47%) had mixed cellularity histologic subtype, 15 patients (44%) had nodular sclerosis subtype, and 3 patients had the lymphocyte predominance subtype. All nine patients who were tested for EBV- IgG were positive. Twenty-three patients were studied for the LMP-1 and 17 (74%) tested positive. These 17 patients make up 89% of the children under 13 years of age who were tested. LMP-1 positivity was associated with young age (≤13 yrs 100%), MC subtype (14 patients; 82.4%) and male sex (16 patients; 94%). Four patients with stage IIIB relapsed. Their treatment consisted of 6–9 cycles of COPP or COPP alternating with ABVD. Three of the relapsed patients were LMP-1 positive and had the MC subtype. Two patients had siblings who had HD; one of them who later relapsed was positive for LMP-1, had the MC subtype, and both he and his brother had immune deficiency and lymphoproliferative disorder.
Conclusions: Our findings show a high prevalance of EBV expression in HD in Lebanese children. These rates are higher than those reported from other neighboring countries and much higher than those of North American and European countries. This may be related to earlier in life infection with EBV. LMP-1 positivity in Lebanese children was associated with younger age, male sex and mixed cellularity subtype. The impact of LMP-1 on treatment outcome remains to be determined.
Pericardial Involvement in Newly Diagnosed Children and Adolescents with Pediatric Hodgkin’s Disease at a Single Children’s Cancer Hospital.
Authors: Bashir Hamid , Metzger Monika , Krasin Matt , Kaste Sue , Howard Scott , Hudson Melissa M. 
Published: October 2019

Abstract
Background: Because most cases are clinically silent, incidence, clinical course and outcome of pericardial involvement in Hodgkin disease are unknown.
Methods: Records of all 274 newly diagnosed Hodgkin disease patients treated at our institution between 1991 and 2004 were reviewed. Cases were selected on the basis of pericardial involvement with focal thickening or nodularity at the time of presentation identified by CT and/or pericardial effusion on echocardiogram. Variables noted, in addition to basic demographic data, were stage, histologic subtype, clinical presentation, treatment, serial EKG, echocardiography and CT findings, and resolution versus progression of disease. Statistical analysis was performed using SAS version 9.1.
Results: The incidence of pericardial involvement in our cohort was 5% (13 of 274 patients). Patient characteristics (age, sex, and race), stage of disease and presence of B-symptoms were equally distributed among affected and unaffected individuals. All 13 cases were nodular sclerosing histology (p=0.02) and 9 (67%) had a bulky mediastinal mass (p=0.002). Of the 13 patients, five had extension into the pericardium by CT, two of which also had pericardial effusion (one large and one massive). Eight patients had only pericardial effusions (trace to large) without other CT findings. Two patients required pericardiocentesis for symptomatic effusions and one underwent pericardial drainage procedure for impending tamponade. Two of the 13 patients relapsed but were successfully salvaged and all remain alive and free of disease at a median follow up of 8.7 years (range, 1.1–11.9 years) and 6.3 years (range 0.4–12.7 years) for patients without pericardial involvement.
Conclusions: In our experience, secondary pericardial involvement due to lymphoma is largely asymptomatic unless accompanied by significant effusion. Most of these resolve with treatment of underlying malignancy but require watchful observation for hemodynamic complications. Once treated for symptomatic effusion, there is no difference in mortality amongst various groups.
Figure Figure
Quality of Life (QoL) Impairment and International Prognostic Index (IPI) in New Aggressive Non-Hodgkin’s Lymphoma (ANHL) Patients.
Authors: Novik Andrei A. , Ionova Tatiana I. , Kishtovich Anton V. , Myasnikov Alexander A. , Chagorova Tatiana V. , Kopp Mikhail V. , Osipova Nina E. , Lebedeva Julia K. , Malakchova Natalia N. , Pankova Anastasia V. , Fedorenko Denis A. , Gorodokin Gary I. 
Published: October 2019

Abstract
The population of new ANHL patients is heterogeneous in terms of their biological parameters and the IPI scoring system is widely used to make the disease prognosis. Recently heterogeneity of ANHL patients in terms of their QoL has been shown. There are four groups of patients with the following grades of QoL impairment: none, mild, significant, and critical impairment. We aimed to study the distribution of new ANHL patients according to the grades of QoL impairment and to identify the relationship between the QoL impairment groups and the IPI groups.
73 new aggressive NHL lymphoma patients (Stage IIB-IV, mean age 55.2 SD=17.6, males/females – 39/34) were involved in this study. QoL assessment was conducted before treatment using SF-36. The method of integral profiles was used to calculate the integral QoL index (IQLI). Patients were stratified using IQLI. Gamma correlation between ranges of QoL impairment groups and IPI groups was used.
The following distribution of ANHL patients was demonstrated on the basis of different grades of QoL impairment: 9% - no impairment (IQLI - 0.6); 12% - mild impairment (0.3); 24% - significant impairment (0.13); 55% - critical impairment (0.02). The distribution of patients in these groups who were classified as high-intermediate or high risk according to the IPI was 28%, 67%, 83%, and 90%, respectively. High correlation between ranges of QoL impairment groups and IPI groups was observed: Gamma correlation – 0.6 (p<0.05).
In conclusion, aggressive NHL patients are heterogeneous in terms of their QoL. The majority of patients exhibit significant or critical QoL impairment. The higher the grade of QoL impairment, the higher the risk according to the IPI. Stratification of aggressive NHL patients based on IQLI along with the traditional IPI stratification could contribute to the improvement of the prognostic model for this heterogeneous group of lymphoid malignancies.
Primary Pancreatic Anaplastic Large Cell Lymphoma, ALK-: A Care Report.
Authors: Savopoulos Lecturer Christos G. , Tsesmeli Niki E. , Kaiafa Georgia D. , Zantidis Anestis Th. , Bobos Matheos T. , Hatzitolios Apostolos I. , Papadopoulos Athanasios , Kostopoulos Ioannis S. 
Published: October 2019

Abstract
INTRODUCTION: Primary pancreatic lymphomas constitute less than 0.5% of pancreatic malignancies and less than 2% of extranodal lymphomas. Primary pancreatic anaplastic large cell lymphomas (PPALCL) are extremely rare.
AIMS-METHODS: To present an extremely rare case of PPALCL
RESULTS: An 80-year-old man, who was under evaluation of a fever of unknown origin in a Private Health Center, was admitted to our Clinic for further investigation. He noted anorexia, weight loss and fatigue. On physical examination, he had a leg edema. His blood tests were unremarkable except for normochrome normocyte anaemia (Ht 31%, Hb 9,9 g/dl) and a great elevation of ESR (110 mm), LDH (1880 U/L)and β2-microglobulin (4,19 mg/L). In CT and MRI scan, available from patient’s file, a soft tissue mass located in the pancreas, especially the uncinate process and a slow signal flow of inferior vena cava, due to mass compression, had been observed. He had undergone a normal gastrointestinal endoscopy at that time whereas a new endoscopy, after his admission to us, revealed an ulcerated mass-like deformity of the duodenal bulb with a friable surface. Explorative laparotomy confirmed a diffuse spread of an unresectable malignant mass of the pancreas extending to the adjacent organs. Biopsy specimen was taken from the adhesion of pancreatic surface and gastric serosa, because of the brittle consistency and and necrotic surface of the mass. The duodenal and surgical biopsy results identified an ALCL of T-cell lineage, ALK negative. Bone marrow biopsy showed no evidence of lymphoma involvement. Chemotherapy treatment was not initiated because he died in Intensive Care Unit two days after the explorative laparotomy, due to hemodynamic instability.
CONCLUSIONS: Our case supports that primary pancreatic lymphoma should be a high diagnostic possibility in a patient with a pancreatic mass accompanied by elevated LDH and β2-microglobulin. Biopsy specimens’ results, from the mass or the adjacent infiltrated organs, confirm the diagnosis, identify the lymphoma and lead to an appropriate and timeable treatment.
Resveratrol Induces Cell Cycle Arrest in the OCI-LY18 B-Cell Lymphoma.
Authors: Faber Anthony C. , Chiles Thomas C. 
Published: October 2019

Abstract
Resveratrol is a polyphenolic compound with well-documented anti-tumor properties. Despite reports of its efficacy in chronic B lymphocytic leukemia, little is known regarding the antiproliferative and/or proapoptotic effects of resveratrol in other B-cell malignancies. Diffuse large B cell lymphoma (DLBCL) has recently been subdivided into three major categories or subtypes, each with apparently distinct etiologies, gene expression profiles, and responses to conventional chemotherapy. These three DLBCLs comprise germinal center B cell (GC), activated B cell (ABC), and primary mediastinal DLBCL. Herein, we report that treatment of the OCI-LY18 B-cell lymphoma with resveratrol induced cell cycle arrest and apoptosis in a dose-dependant manner. Preliminary analyses suggest that OCI-LY18 exhibits a surface immunophenotype indicative of a GC DLBCL. The molecular mechanisms underlying cell cycle arrest by resveratrol were also investigated. We report herein that resveratrol induced the expression of p27 concomitant with inhibition of cdk2 and a decreased phosphorylation of the retinoblastoma protein (pRb). Resveratrol also induced the up-regulation of p53. In addition, resveratrol treatment resulted in the phosphorylation of p53 on Ser15/37, modifications that corresponded to the upregulation of p53. These data suggest that resveratrol induces growth arrest in OCI-LY18 via a mechanism that involves upregulation of p27 and p53. These results suggest that resveratrol might be beneficial as a novel treatment of GC DLBCL.
Good but Variable Humoral Response to Trivalent Influenza Vaccination in Patients with Non-Hodgkin’s Lymphoma - Two Seasons Experience.
Authors: Centkowski Piotr , Brydak Lidia , Machala Magdalena , Kalinka Ewa , Blasinska-Morawiec Maria , Wegrzyn Joanna , Skotnicki Aleksander , Federowicz Irena , Walewski Jan , Wolowiec Dariusz , Sawczuk-Chabin Joanna , Bilinski Przemyslaw , Warzocha Krzysztof 
Published: October 2019

Abstract
We assessed humoral response to influenza vaccination (vacc) in two consecutive seasons 2003/2004 and 2004/2005 in 123 NHL patients. In season 03/04 50 patients (29 previously treated with chemotherapy - group A03/04 and 21 not treated - group B03/04) and 73 patients in season 04/05: 34 treated - A04/05, 39 not treated - B04/05 were vaccinated with trivalent subunit influenza vaccine. Antibody responses to influenza hemagglutinin (HI) and neuraminidase (NI) were determined in sera collected before vacc, after 1 month and after 6 months. One month after vacc geometric mean antibody titers (GMTs) of antiHI antibodies significantly increased (p<0.05) and mean fold increases (MFIs) ranged from 10.4 to 24.3 in A03/04, 10.9–11.7 in A04/05, 6.5–31.6 in B03/04 and 14.8–21 in B04/05, than fell after 6 months to 3.6–7.8 in A03/04, 3.7–4.4 in A04/05, 1.7–11.2 in B03/04 and 7.8–8.5 in B04/05. Prevacc protection rate, i.e. the number of subjects with the protective HI antibody titers >1:40, ranged from 3.4 to 10.3% in A03/04, 2.9-8.8% in A04/05, 0–4.6% in B03/04 and 0–5.1% in B04/05. After 1 month protection rates ranged from 78.1 to 87.5% in A03/04, 61.8–70.6% in A04/05, 73.3–93.3% in B03/04 and 66.7–74.4% in B04/05 and decreased after 6 months to 24.1–37.9% in A03/04, 32.4–35.3% in A04/05, 19–47.6% in B03/04 and 17.9–35.9% in B04/05. Response rates, i.e. the number of subjects with at least a 4-fold increase of antiHI antibody titers after vacc, ranged from 58.6–75.9% in A03/04, 50–67.6% in A04/05, 57.1–81% in B03/04 and 61.5–71.8% in B04/05. Six months after vacc it decreased to 17.2–34.5% in A03/04, 20.6–29.4% in A04/05, 19–38.1% in B03/04 and 15.4–33.3% in B04/05. In all patients’ groups, post-vacc antiNI GMTs were significantly higher (p<0.05) than pre-vacc. MFIs of antiNI antibodies 1 month after vacc ranged from 11 to 17.5 in A03/04, 4.1–9.4 in A04/05, 5.1–9.9 in B03/04 and 6.3–9.9 in B04/05, then fell to 2.9–6.9 in A03/04, 1.3–5.1 in A04/05, 3.4–4.9 in B03/04 and 2.8–3.6 in B04/05. In season 03/04 only hemagglutinin H1 antibody titers were significantly higher in CTR than in patients in contrast of season 04/05 when in patients the titers of H1, H3 and N1, N2, NB were significantly lower. We conclude that the response to influenza vaccine is similar in patients previously treated and not-treated with chemoterapy. It is highly immunogenic in NHL patients, but the level of specific antibodies is variable and may depend on immunogenecity of vaccine for actual season. After 6 months the antibody titers rapidly decline, thus the NHL patients may need the second dose of vaccine to maintain good protective level.
Apoptosis Regulating Proteins bax and p53 in Mantle Cell Lymphoma.
Authors: Schrader Carsten , Klapper Wolfram , Janssen Dirk , Riis Paul , Meusers Peter , Brittinger Guenter , Siebmann Jens U. , Kneba Michael , Parwaresch Reza 
Published: October 2019

Abstract
In malignant tumors beside cell proliferation also cell death plays role for cell survival. Apoptosis regulating genes can be divided into two groups: death antagonists and death agonists such as bax. The ratio of death agonists and antagonists determines if a cell goes into apoptosis. We investigated in a large collective the immunohistochemical expression of the apoptotic marker p53 and bax in relation to the clinical course. Biopsies were stained immunohistochemically with monoclonal antibodies against bax and p53 and the expression was subdivided in three groups: negative, weak positive and strong positive. The expression profiles were analyzed with the overall survival data according to Kaplan and Meier. Patients with mantle cell lymphoma that had negative p53 expression had a median overall survival time of 38.1 months compared to 22.3 months for patients with a weak and 11.3 months for a strong p53 expression (0<0.0001). The bax expression was in the majority of cases positive. Only one case showed a negative staining. Patients with weak and strong bax expression showed no differences in clinical outcome (median overall survival time: 23 vs 33 months, p=0.6051). The immunohistochemical detection of p53 in mantle cell lymphoma is a good predictor for the clinical outcome.