bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fixed-Dose Single Administration of Pegfilgrastim vs Daily Filgrastim in Patients with PTLD Undergoing a Sequential Therapy of Rituximab and CHOP Chemotherapy.
Authors: Trappe Ralf , Matthias Papp-Vary , Oertel Stephan , Hanno Riess 
Published: October 2019

Abstract
Infectious complications are frequent events in patients with post-transplant lymphoproliferative disorders (PTLD) undergoing CHOP-based cytotoxic chemotherapy and previous studies had demonstrated the need for growth factors to conduct chemotherapy in these patients. To evaluate whether a single subcutaneous injection of pegfilgastrim (6mg) is as safe and effective as daily filgastrim (5 μg/kg/day), 84 cycles of CHOP-21 chemotherapy in patients with PTLD have been analyzed. Patients were treated with four weekly doses of 375mg/m2 of rituximab as a single therapeutic agent at days 1, 8, 15 and 22. CHOP chemotherapy had been administered at days 50, 72, 94 and 116 and was supported by GCSF. In case of disease progression during administration of rituximab or during the 4-week interval between antibody therapy and CHOP administration the patients directly entered chemotherapy. In total, 7 patients undergoing 23 cycles of CHOP chemotherapy received a single subcutaneous injection of 6mg pegfilgastrim on day 3 after application of CHOP and were compared retrospectively with 20 patients receiving 5 μg/kg/day of filgastrim starting from day 3 after application of CHOP. In the pegfilgastrim group 5 patients were renal transplant recipients, one was a liver transplant recipient and one was a heart transplant recipient. In the filgastrim group 10 patients were renal transplant recipients, 6 were liver transplant recipients, four were heart transplant recipients. 1 patient was a combined heart/lung transplant recipient, one was a combined kidney/pancreas transplant recipient and one patient was after bone marrow transplantation. 4/7 patients of the pegfilgastrim group had stage III or stage IV disease, while 14/20 patients in the filgastrim group had stage III or stage IV disease. Age ranged from 20 to 76 years with a median age of 57 years in the pegfilgastrim and from 16 to 80 years with a median age of 55 years in the filgastrim group. The incidence of grade III/IV infections in the pegfilgastrim and filgastrim groups were 2 in 23 applied cycles of chemotherapy and 7 in 61 cycles of applied chemotherapy, respectively. The incidence of grade III/IV leucopenia in the pegfilgastrim and filgastrim groups were 15 in 23 cycles in the pegfilgastrim group and 29 in 61 cycles in the filgastrim group. The results of the two groups were not significantly different for incidence of grade III/IV infections and grade III/IV leucopenia. A single injection of pegfilgastrim administered at day 3 post CHOP-based chemotherapy showes a comparable efficacy and safety profile to daily injections of filgastrim in patients with PTLD.
A New BACOPP Schedule Is Feasible and Effective in Elderly Hodgkin’s Lymphoma Patients - Interim Results of a Multicenter Phase-II Trial of the German Hodgkin Study Group (GHSG).
Authors: Nogova Lucia , Sieniawski Michal , Nisters-Backes Hildrud , Jennissen Veronika , Diehl Volker , Engert Andreas , Josting Andreas 
Published: October 2019

Abstract
Introduction:
The outcome of Hodgkin’s lymphoma (HL) patients (pts) increased over the last decades. However, treatment results in HL pts > 60 years are poor, particularly in patients with advanced stage disease. Large prospective studies are still lacking in this group. Based on the results for adult HL pts, we adapted the BEACOPP schedule for elderly HL pts with an increased dose of doxorubicin while omitting etoposide.
Methods:
From December 2003 to Mai 2005, 52 HL pts with a median age of 66 (range 61 – 75 years) and newly diagnosed HL in unfavourable clinical stage (CS) I, II and CS III, IV were prospectively recruited to receive 6 to 8 cycles of bleomycin (10 mg/m2), doxorubicin (50 mg/m2), cyclophosphamide (650 mg/m2), vincristine (1.4 mg/m2), procarbazine (100 mg/m2), and prednisone (40 mg/m2) (BACOPP) followed by local radiotherapy to residual lymphoma. Epoetin beta (30.000 IE once weekly) was administered to avoid therapy induced anaemia.
Results:
Up to day, 29 pts (14 males and 15 females) were evaluable for feasibility and response of treatment. Overall response rate after chemotherapy was 83% (38% CR and 45% PR). So far 2 pts (7%) developed progressive disease during chemotherapy. The treatment was generally well tolerated with WHO grade 4 toxicities: 31% leukopenia, 14% thrombopenia and 0% anaemia. Till now one patient died several weeks after treatment under sepsis.
Conclusion:
The first interim analysis of this new BACOPP schedule showed that this regimen is feasible in elderly HL pts. Full analysis of updated results will be presented.
Fludarabine, Mitoxantrone and Dexametasone in the Treatment of Relapsed and Refractory Low-Grade Non-Hodgkin Lymphoma.
Authors: Sawczuk-Chabin Joanna , Kalinka Ewa , Centkowski Piotr , Budziszewska Katarzyna , Ceglarek Bernadeta , Najda Jacek , Blasinska-Morawiec Maria , Sulek Kazimierz , Holowiecki Jerzy , Konopka Lech , Warzocha Krzysztof ,   for Polish Lymphoma Research Group
Published: October 2019

Abstract
The purpose of the study was to evaluate response, duration of response, and toxicity of fludarabine (F), mitoxantrone (M), and dexamethason (D) (FMD) in patients (pts) with relapsed or refractory low-grade non-Hodgkin lymphoma (LGNHL). 26 pts with advanced relapsed/refractory LGNHL exposed to previous chemotherapy (CHT) received 3–6 monthly cycles of FMD. The median age was 60 years (range 34–73), included 13 male (50%) and 13 female (50 %). The regimen consisted of F (25 mg/m2 i.v., day 1–3), M (10 mg/m2 i.v., day 1) and D (20 mg p.o., day 1–5). Parameters analyzed included response, toxicity and infection rates, number of previous CHT lines, performance status (ECOG), Ann Arbor scale, LDH, International Prognostic Index score, freedom from progression (FFP) and overall survival (OS). In total 78 cycles of FMD was administered. This induced 25% complete and 37,5% partial response, with a total response rate of 62,5%. After 14 months of the median follow-up of the pts remaining alive, median FFP was 11 months and median OS has not been achieved yet. Out of 78 administered cycles 16 (20%) were associated with toxicity, including 8 (10%) severe infections despite prophylaxis and 6 (8%) grade III/IV neutropenias. In addition, one case of grade III/IV thrombocytopenia and acute noninflammatory renal dysfunction were observed. Toxicity rate was not correlated with the number of previous CHT lines or ECOG, but IPI >2 was significant factor predictive for FMD-related toxicity (p=.037). Shorter OS was observed for the pts with ECOG>1 (p=.049), IPI>2 (p=.005) and FMD-related toxicity (p=.036). FMD is an active regimen for relapsed and refractory LGNHL. Toxicity rate is substantial and seems to predict survival.
A Phase II Trial of FM (Oral Fludarabine and Mitoxantrone) Chemotherapy Followed by Yttrium 90 (90Y) Ibritumomab Tiuxetan (Zevalin) for Previously Untreated Follicular Lymphoma (FL) Patients.
Authors: Zinzani Pier Luigi , Tani Monica , Stefoni Vittorio , Alinari Lapo , Marchi Enrica , Fina Mariapaola , Baccarani Michele 
Published: October 2019

Abstract
Follicular lymphoma (FL) has been considered as low-grade malignant B-cell lymphoma usually characterized by an indolent course with a continuous pattern of relapse and a median survival of 10 years. The therapeutic approach to FL is particularly controversial. One of the effective strategies is the combination of fludarabine-containing regimens (particularly, Fludarabine and Mitoxantrone) with anti-CD20 monoclonal antibody. Single-agent radioimmunotherapy activity, in particular Yttrium 90 (90Y) Ibritumomab Tiuxetan (Zevalin), has been demonstrated in heavily pretreated FL patients. The results of these studies support a further evaluation of 90Y Ibritumomab Tiuxetan in combination with chemotherapy earlier in the time course of FL. Recently, some phase II trials showed that the sequential combination of conventional chemotherapy (CHOP) and 90Y Ibritumomab Tiuxetan has useful activity in the treatment of FL patients, with no unexpected toxicities observed. We conducted a prospective, single-arm, open-label, non-randomized, multicenter, phase II to evaluate the efficacy and safety of 90Y Ibritumomab Tiuxetan of a novel new approach combining induction chemotherapy with oral Fludarabine and Mitoxantrone (FM) followed by consolidation with 90Y Ibritumomab Tiuxetan for patients with previously untreated elderly FL. Patient eligibility was represented by: patients age 18 years or older with biopsy-proven, untreated, bidimensionally measurable stage II, stage III, or stage IV FL expressing the CD20 antigen; performance status of 0 to 2, a pretreatment granulocyte cell count of 1500/μL or greater, and a platelet count of 100.000/μL or greater. All patients were notified of the investigational nature of this study and signed a written informed consent approved in accordance with institutional guidelines, including the Declaration of Helsinki. The study was approved by the institutional review board. Patients were treated with standard FM chemotherapy (in this case, Fludarabine was administered orally at the dose 40 mg/m2/day for 3 consecutive days) every 21 days for 6 cycles. Patients were restaged 4 to 8 weeks after completion of the sixth cycle of FM chemotherapy. Patients achieving at least a partial response after 6 cycles of FM chemotherapy were eligible for consolidation with 90Y Ibritumomab Tiuxetan provided the granulocyte count was greater than 1500/μL, the platelet count exceeded 100.000/μL, and the bone marrow examination at the completion of CHOP chemotherapy demonstrated no more than 25% involvement with lymphoma. All patients were to receive a single dose of 90Y Ibritumomab Tiuxetan 14.8 MBq/kg (0.4 mCi/kg) up to a maximum dose of 1184 MBq (32 mCi). A total of 60 patients have to be enrolled and preliminary results of this trial will be presented.
Long Term Follow up of the Patients with Non-Hodgkin’s Lymphoma Treated with Rituximab in Combination with CHOP Regimen.
Authors: Li Jun-Min 
Published: October 2019

Abstract
Objectives: We performed this prospective study with single arm to evaluate the long term efficacy and safety of rituximab in combination with CHOP regimen in B cell non-Hodgkin’s Lymphoma (NHL) patient.
Methods: All patients received 4~8 cycles of CHOP plus rituximab. For each cycle, Rituximab (375 mg/m2 per dose) was given on day 1 and CHOP regimen on day 3. CHOP regimen consisted of cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, and vincristine 1.4 mg/m2 (maximum dose, 2.0 mg/d) given intravenously on day 3, and oral prednisone 60 mg given from day 3 to 7.
Results: 102 patients were enrolled in this trial, 65 of them are males and 37 are females, with the median age of 47.5 (range 16–76). The main subtypes were diffuse large B cell lymphoma (DLBCL, 82/102), follicular lymphoma (FL, 9/102), mucosa associated lymphoma (MALT, 3/102), marginal zone lymphoma (MZL, 3/102), lymphoplasmacytic lymphoma (LPL, 2/102) and mantle cell lymphoma (MCL, 3/102). The overall response (OR) rate was 91.2% and complete response (CR) rate was 71.6%. The OR and CR of DLBCL were 90.2% and 70.7%, respectively; and the OR and CR of indolent lymphoma (MALT, FL, and LPL) were 100.0% and 82.4%, respectively. The patients with lower (0,1) and higher (≥2) IPI score achieved CR rate and OR rate of 87.88% and 59.18%, and 100.00% and 83.67%, respectively. International prognosis index (IPI) score showed significant impact on both CR and OR rate (P=0.006 and 0.019, respectively). The patients with and without bulky disease achieved CR rate and OR rate of 50.00% and 74.29%, and 83.33% and 91.43%, respectively, and there was no statistical significance (P=0.100 and 0.332, respectively). The patients were followed after achieving objective response (CR+PR) for 2–64 months (median 20 months). Estimated 5 year progress free survival (PFS) rate and estimated 5 year overall survival (OS) rate was 60.33%±6.94% and 75.88%±6.94%, respectively. In DLBCL patients, PFS and OS rate was reached at 56.45%±8.26% and 74.12%±7.48%, respectively. 4 year PFS rate and OS rate of the patients with indolent lymphoma was 86.15%±9.11% and 100%, respectively. IPI score showed significant survival impact on OS and PFS in DLBCL patients, respectively (P=0.0339 and 0.0122, respectively); however, the bulky disease showed impact on PFS but not on OS (P=0.0472 and 0.106, respectively).
Conclusions: The results suggested that the rituximab in combination with chemotherapy regimen in most B cell NHL patient was effective and safe.
Assessing the Predictive Value of Plasma FLT3-L Levels for Hematologic Toxicity after Yttrium-90 Ibritumomab Tiuxetan ([90Y]-Zevalin) Given as Consolidation in Patients with Advanced B-Cell Follicular NHL Responding to First Line Therapy.
Authors: Morschhauser F. , Radford J. , van Hoof A. , Kuss I. , Chlistalla A. , Hagenbeek A. 
Published: October 2019

Abstract
Background: [90Y]-Zevalin is a radiolabeled monoclonal antibody approved for the treatment of relapsed or refractory low-grade follicular or transformed B-cell NHL. Myelosuppression following [90Y]-Zevalin is reversible with nadir counts at 7 to 9 wks after administration of Zevalin and grade 4 thrombocytopenia, neutropenia, and anemia occurring in 10%, 30%, and 3% of patients (pts), respectively. Currently, baseline platelet counts and the degree of bone marrow involvement are the most reliable predictors of hematologic toxicity. Recently, plasma FLT3-L levels have been shown to reflect more accurately bone marrow radiosensitivity to iodine I-131 radioimmunotherapy than peripheral blood counts in patients with solid tumors. The purpose of this analysis was to determine if plasma FLT3-L cytokine levels would help to predict the magnitude of hematologic toxicity after [90Y]-Zevalin treatment.
Methods/Results: In this prospective, multicenter, phase III clinical trial, [90Y]-Zevalin was studied as consolidation therapy (14.8 MBq/kg [0.4 mCi/kg; maximum 32 mCi]) versus no further treatment in 414 patients with advanced follicular-NHL responding to first-line induction therapy with single-agent chlorambucil, CVP, CHOP/CHOP-like regimens, or regimens containing fludarabine or rituximab. Pts were required to have an absolute neutrophil count (ANC) of at least 1500/μL and a platelet count of >150,000/μL. Hematologic toxicity was determined by collecting hematologic data (platelets, ANC, and hemoglobin [Hb]) before therapy and weekly thereafter for 14 wks. Plasma FLT3-L cytokine levels were evaluated in 71 of 208 patients before treatment with [90Y]-Zevalin. FLT3-L levels (pg/mL) were determined by immunoassay with a reference range from 48.3 to 173.8pg/mL. The mean FLT3-L level of all pts was 140.8 (range 49.5 to 300.4). The incidences of grade 3/4 thrombocytopenia, neutropenia, and anemia were 46.5%/8.5%, 40.8%/33.8%, and 8.5%/4.2%, respectively. Severe hematologic events were transient. The FLT3-L levels were not correlated with the nadir of platelets, ANC and Hb per patient during week 1 to 14. The correlation coefficent between FLT3-L and platelets, ANC and Hb was 0.10, −0.25 and −0.18, respectively for all pts. These results do not indicate a relationship between baseline FLT3-L and any of the 3 hematologic parameters.
Conclusions: Baseline FLT3-L levels did not identify pts who are likely to develop a grade 3/4 myelosuppression following [90Y]-Zevalin consolidation therapy. Overall, the incidence and severity of cytopenias were transient, reversible, and comparable to those obtained with [90Y]-Zevalin in relapsed/refractory follicular NHL.
Pomolic Acid-Induced Apoptosis in Cells from Chronic Myeloid Leukemic Patients Is Not Affected by the MDR Phenotype and Status of Disease.
Authors: Vasconcelos Flavia C. , Gattas Cerli R. , Fernandes Janaina , Rumjanek Vivian M.D. , Maia Raquel C. 
Published: October 2019

Abstract
Pomolic acid (PA), isolated from Chrysobalanus icaco, is a pentaciclic triterpene highly effective in inhibiting the growth and promotes cell death in the human chronic myeloid leukemia (CML) K562 cell line. In addition, PA is also very effective in blocking the proliferation of K562-Lucena-1, a vincristine-resistant derivative of K562 that displays multidrug resistance (MDR) phenotype. Due to antiproliferative and antiapoptotic effect of PA on positive and negative MDR leukemic cells, and considering that some patients with CML exhibit resistance to imatinib, the aim of this work was to investigate if PA could have an effective role in induce apoptosis in cells from CML patients. Fourteen peripheral blood samples from CML patients in various stages (three in blastic phase and eleven in chronic phase being one juvenile patient) including previously clinically imatinib resistant patients were studied. Informed consent was obtained according to institutional guidelines. Cells from patients were plated in 96 well tissue culture plates for 24h and then treated with two different concentrations of PA: 12.5 μg/ml and 25 μg/ml. Drug-induced apoptosis was evaluated by annexin V/propidium iodide assessed by fluorescence-activated cell-sorting (FACS). Functional MDR phenotype was performed by measuring the fluorescent dye rhodamine-123 efflux in the presence or absence of the MDR blocker cyclosporin A. These experiments were analysed by FACS. Functional activity of MDR was observed in 9 out of 14 samples and it was independent of CML stage. Using 12.5 μg/ml and 25μg/ml concentrations, the apoptotic effect of PA ranged from 10.5 to 53.1 (median: 31.5) and 14.7 to 65.9 (median: 42.2), respectively. These results were also independent of CML stage being even effective in blastic phase and in juvenile CML, which have a clinically aggressive course. Our data demonstrate that PA is a potent anti-leukemic agent not only for MDR positive CML patients but also especially for the blastic phase in the setting of imatinib resistance.
Increased Expression of the Nitric Oxide Synthase (iNOS) in the Bone Marrow of Myelodysplasia (MDS) Patients.
Authors: Shami Paul J. , Elenitoba-Johnson Kojo S.J. 
Published: October 2019

Abstract
MDS constitutes a set of heterogeneous hematopoietic stem cell diseases that are manifested by cytopenias in spite of a cellular bone marrow. MDS carries an increased risk of acute myeloid leukemia (AML). Data suggest that overproduction of inflammatory cytokines in the marrow plays a role in the cytopenias of MDS. Nitric oxide (NO) has important functions in the immune system. Inflammatory cytokines trigger the expression of the inducible nitric oxide synthase (iNOS) and NO production. NO inhibits bone marrow progenitor cell growth and induces DNA mutations. Consequently, NO could play a role in the pathophysiology of MDS. We have evaluated iNOS expression in the bone marrow of MDS patients. Archival bone marrow biopsy samples from 10 MDS patients were compared to 10 normal bone marrow biopsies. The distribution by cases according to the FAB classification was 4 RA, 2 RARS, 3 RAEB, and 1 RAEB-T (Table). Immunohistochemical studies for human iNOS expression were performed using a polyclonal rabbit antibody. A sample was considered positive for iNOS expression when 10% or more cells were positive. Using this criterion, 7/10 MDS samples expressed iNOS while none of the normal bone marrows did (Table). iNOS expression was found exclusively in the myeloid lineage cells. Overexpression of iNOS in the bone marrow of MDS patients could lead to local overproduction of NO and therefore contribute to the ineffective hematopoiesis and cytopenias seen in early MDS. Chronic exposure to high levels of NO could enhance the risk of evolution to AML. iNOS could therefore constitute a new therapeutic target for MDS.
iNOS expression in MDS and normal bone marrows Diagnosis (FAB) Number of samples Number iNOS positive RA 4 3 RARS 2 1 RAEB 3 2 RAEB-T 1 1 Total MDS 10 7 Normal bone marrow 10 0
Selective Inhibition of I kappaB Kinase Sensitizes Mantle Cell Lymphoma B Cells to TRAIL by Decreasing c-FLIP Level.
Authors: Roué Gaël , Pérez-Galán Patricia , López-Guerra Mónica , Villamor Neus , Campo Elias , Colomer Dolors 
Published: October 2019

Abstract
Mantle cell lymphoma (MCL) is an aggressive B lymphoid neoplasm with a mature B-cell phenotype and genetically characterized by the t(11;14)(q13;q32) leading to cyclin D1 overexpression with the consequent deregulation of cell cycle at the G1-S checkpoint. MCL cells also present a constitutive activation of the NF-kappaB pathway which leads to the overexpression of several anti-apoptotic regulators. We have analyzed sensitivity to the extrinsic apoptotic signal triggered by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) on six human MCL cell lines and primary cells from 10 MCL patients, which differ in their p53-dependent pathway status, growth characteristics and sensitivity to cytotoxic drugs. TRAIL has been shown to exert in vivo a selective anti-tumor activity with minimal toxicity on normal cells. We observed that TRAIL was able to trigger apoptosis in a majority of MCL cell lines and primary MCL tumor cells, while sparing normal peripheral B cells. TRAIL-induced cell death was characterized by a time- and dose-dependent loss of membrane potential, Bax and Bak activation, caspase activation and phophatidylserine exposure. MCL sensitivity to TRAIL was irrespective of TRAIL-R1 and TRAIL-R2 receptor levels, Bcl-2 family members or caspase regulators expression, but was closely linked to the activity of the NF-kappaB p50 factor and to the expression of c-FLIP, a NF-kappaB-regulated factor. C-FLIP accumulated into the TRAIL-dependent complex in resistant cells and its transient knockdown overcame MCL resistance to TRAIL. In parallel, NF-kappaB inhibitors differentially modulated TRAIL cytotoxicity. Indeed, sub-toxic doses of bortezomib increased TRAIL cytotoxic effects by up-regulating TRAIL-R2 receptor expression, but also led to the intracellular accumulation of c-FLIP, impeding full synergistic interaction in cells with highest c-FLIP basal level. In contrast, the IkappaB kinase (IKK) inhibitor BMS-354451 allowed to consistent reduction of NF-kappaB activity, decreased total and DISC-associated c-FLIP levels, and sensitized all MCL cells to TRAIL cytotoxic effects. These results indicate that pharmacological enhancement of MCL cells sensitivity to TRAIL does not depend on TRAIL receptors level but is rather regulated by NF-kappaB-regulated c-FLIP expression. Considering that both TRAIL and BMS-345541 have already demonstrated selective cytotoxicity against malignant cells, combining TRAIL, with pharmacological inhibitors of IkappaB kinase signaling may represent an attractive model for the design of a new and rational combination therapy for MCL.