bluuebunny/crossref_metadata_2025_split huggingface dataset:
First Line Treatment with the R-VAD+C Regimen Followed by ASCT for Patients under 65 with a Mantle Cell Lymphoma (MCL). From the GOELAMS Group.
Authors: Gressin Remy , Maugendre Sylvie Caulet , Damaj Ghandi , Milpied Noel-Jean , Senecal Delphine , Berger Mathilde Hunault , Yamani Abdrrazak El , Maisonneuve Herve , Tournilhac Olivier , Celigny Philippe Solal , Quitet Philippe , Feugier Pierre , Choufy Cachera , Fontan Jean , Barbe Martine Escoffre , Cornillon Jerome , Lemevel Annie , Martin Claude , Moreau Philippe , Colombat Philippe 
Published: April 2020

Abstract
This protocol followed the first GOELAMS protocol (also presented at ASH 2006) for MCL pts testing the addition of Rituximab with the VAD+C regimen followed by ASCT. Thirty nine pts were included in this phase II prospective study opened between January 2003 and December 2005.
Inclusion criteria: MCL by the WHO (common or blastoïd variants), under 65 years with PS under 3, who never received chemotherapy.
Treatment: the first step consist of 4 courses of R-VAD+C regimen (J1, Rituximab 375 mg/sqm; J1 to J4, Vincristin 0,4 mg/D, Adriblastin 9 mg/D and Dexamethasone 40 mg/D; J20 to J29 Chlorambucil 12 mg/D) every 35 days. Evaluation after 4 cycles with the Cheson criterias. Responders (at least 50%) have been collected after a 4 g/sqm cyclophosphamide stimulation and an in vivo purge with rituximab (375). Then, the second step consisted on one R-VAD+C and one VAD+C regimens followed by the transplantation prepared by the myeloablative regimen including Alkeran 140 mg/sqm and 8 grays/4 fr TBI.
Results: 38/39 pts are evaluable. 34 biopsies were reviewed and consisted of 26 common forms and 8 blastoïd variants. 4 other diagnosis were possible only on blood (n=3) or bone marrow (n=1) analysis.
Treatment: 28/38 (74%) have had a response to the first 4 R-VAD+C, 6 progressed (16%) and 4 (10%) have had only a minor response under 50%. 17/38pts (44,5%) were in CR or CRu after 4 R-VAD+C courses and 11 (29%) in PR&gt;50%. Among the 23 pts evaluated after the transplantation, 20 were in CR, two progressed and one have a PR&gt;50%.
Survival: With a median follow-up of 19 months, OS and PFS at 2 years are 80% and 50 % respectively. The PFS is significantly affected by the Goelams Index for MCL described recently from a cohort of patients studied in our previous protocol (see abstract ASH 2006).
Conclusion The R-VAD+C regimen followed by PBSCT is a good sequence for the treatment in first line of MCL patients, especially for those with a good prognosis profile defined by the new Goelams prognostic index which would worth being tested on a larger cohort.
Rituximab Maintenenance Therapy in CD20+ B-Cell Non-Hodgkin-Lymphoma - Results of a Multicenter Prospective Randomised Phase II Study.
Authors: Witzens-Harig Mathias , Hensel Manfred , Schmier Johann W. , Neben Kai , Benner Axel , Dreger Peter , Kuhn Christian , Schmidt-Wolf Ingo , Krämer Alwin , Ho Anthony D. 
Published: April 2020

Abstract
Clinical and pharmacokinetic data suggest that the effect of rituximab could be improved by prolonged exposure to the drug. To test for this hypothesis we performed a prospective randomized trial of rituximab maintenance therapy in patients with CD20+ B-cell Non-Hodgkins-Lymphoma. After completion of standard treatment patients were randomized to either observation or maintenance therapy with rituximab (375 mg/m2) every 3 months for 2 years. Patients after first line therapy as well as relapse patients were included in the study. Patients with aggressive lymphoma were enrolled if they had achieved a complete response (CR) after initial treatment. Patients with aggressive lymphoma with residual tumor mass were examined with positrone emission tomography (PET) and qualified for randomization if PET showed no signs of tumor activity. Patients with indolent lymphoma qualified for the study if at least a partial response (PR) was achieved. So far 162 patients (pts) with CD20+ B-cell Non-Hodgkins-Lymphoma were enrolled in this trial. Histological subtypes included diffuse large cell lymphoma (69 pts), follicular lymphoma (41 pts), mantle cell lymphoma (18 pts), primary mediastinal lymphoma (15 pts), marginal zone lymphoma (9 pts), Burkitt’s lymphoma (3 pts), immunocytoma (2 pts), primary intestinal lymphoma (1 pt), hairy cell leukemia (1 pt), chronic lymphocytic leukemia (1 pt) and unclassified B-cell lymphoma (2 pts). No severe adverse events were observed during rituximab maintenance therapy. We conclude that rituximab maintenance therapy is feasable, safe and well tolerated in patients with CD20+ B-cell Non-Hodgkins-Lymphoma. Results including event free survival and overall survival for the observation group and for the maintenance therapy group will be presented.
Rituximab-CHOP Versus CHOP Alone in Patients with Diffuse Large B Cell Lymphoma.
Authors: Cetiner Mustafa , Salepci Taflan , Atesoglu Elif Birtas , Gumus Mahmut , Guven Aslihan , Undar Levent , Tuglular Tulin Firatli , Bayik Mahmut 
Published: April 2020

Abstract
Recently, the cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) regimen plus rituximab (R-CHOP) have been used widely to treat patients with newly diagnosed diffuse large B cell lymphoma (DLBCL) and it has also been reported to improve the outcome of DLBCL.
We represent a retrospective analysis of newly diagnosed DLBCL patients between the years of 2003–2005 to evaluate the impact of R-CHOP therapy on response rates.
Patients with DLBCL between 20–80 years of age (median: 46.0 and mean 56.2 ± 14.92) received 6 cycles of R-CHOP (n=28). For comparison, DLBCL patients between 15–76 years of age (median: 60.5 and mean 47.3 ± 16.6) who received 6 courses of CHOP therapy (n=30) were used as the control group. All patients received classical CHOP (cyclophosphamide 750 mg/m m2, doxorubicin 50 mg/m2, vincristine 1.4 mg/m m2 on day 1 and prednisone 40 mg/m m2 for 5 days) every 4 weeks. In R-CHOP group, rituximab 375 mg/m m2 was administered one day before CHOP chemotherapy.
The median follow-up for R-CHOP and CHOP groups were 15.66 ± 5.90 (7–29) and 21.79 ± 9.20 (8–46) months, respectively. The International Prognostic Index (IPI) scores were not significantly different between these groups (median IPI of R-CHOP: 2.0 and mean IPI 2.01.27 ± 1.16 versus median IPI of CHOP: 1.0 and mean IPI 1.88 ± 1.26).
Complete response (CR) and complete undetermined response (CuR) rate for R-CHOP was 92% (26 of 28 patients) which was statistically significantly higher than CHOP (24 of 30 patients, 80%) (p=0.004). Partial response (PR) rates for R-CHOP and CHOP groups were 7% (2 of 28 patients) and 10% (3 of 30 patients), respectively. While there were no unresponsive patients in the R-CHOP group, refractory disease rate was 10% (3 of 30 patients) in the CHOP group. Relapse rates during the follow up period were 13% (4 of 30 patients) for CHOP and 4% (1 of 28 patients) for R-CHOP group (p&lt;.0001). No long-term toxicity appeared to be associated with the addition of rituximab to the CHOP combination.
These results also confirmed the benefit of the addition of rituximab to standard CHOP chemotherapy in DLBCL even in young patients with low IPI scores.
Safety of Intrathecal Rituximab as Prophylaxis or Treatment in CD20+ Acute Lymphoblastic and Aggressive Lymphoma: Report from a Mexican Pilot Study.
Authors: Villela Luis , Caballero-Caballero Rocio , Piedras-Ross Josefa , Garcia-Herrera Hetor , Mejia Dolores , Escoboza Jose R. Borbolla 
Published: April 2020

Abstract
CNS infiltration of neoplastic B-cell lymphocytes both in acute leukemia as well as in lymphoma, carry very bad prognosis. There are no universal guidelines for the prophylaxis of such CNS relapse in these patients. Current prophylactic regimes have early and late side effects, sometimes with severe toxicities. Although rituximab has improved treatment results in lymphoproliferative diseases, it cannot reach the CNS when administered systemically (Feugier, Ann Oncol 2004, Rubenstein, Blood 2004). Schulz (Haematologica 2004) used this drug in the treatment of relapse of primary brain lymphomas with positive results using a dose of 10 to 40mg, and estimated 25mg to be a good standardized dose.
After approval from our ethics committee and obtaining the informed consent signature, patients received 25 mg of intrathecal rituximab (IT-R) according to the standard intrathecal regimen, plus the standard systemic chemotherapy protocol in our department. Side effects were evaluated according to the NIC toxicity scale.
Nine patients have been enrolled in the protocol so far: 8 were male and 1 female, median of age was 49 years (range 14–72). A total of 57 IT-R were administered to our patients (median: 6, range 3–15). They had the following diagnosis: Two with large diffuse B cell lymphoma (LDBCL); two with mantle cell lymphoma (one of them blastic type), three with acute lymphoblastic leukemia; one with Burkitt’s lymphoma (BL) and one with anaplastic lymphoma. Two patents had initial CNS infiltration; the blastic type Mantle Cell Lymphoma (patient 2) and the anaplastic Lymphoma (patient 9); these patients received IT-R three times per week, plus two extra doses after complete remission in CNS. Median follow-up was 9 months (range: 3–15 months). All patients had risk factors that warranted prophylaxis (see table). Toxicity included headache in 35% of administrations (Grade I/II), temporal paresthesias in 24.5% of administrations (lasting a median of 5 minutes, range 2–15), neuropathic pain and vomit in 12.3% of administrations (grade I/II), fever and chills in 7% of administrations (Grade I/II). All side effects were temporary and no patient has shown neurological or other late toxicities. The patient with mantle cell lymphoma infiltrated to CNS achieved complete remission after 5 doses of IT-R which continues after autologous stem cell transplantation.
The use of rituximab as IT-R is safe and effective. We are starting a phase II study using IT rituximab as prophylaxis and treatment, in a larger group of patients.
Efficacy of Rituximab in Hairy Cell Leukemia.
Authors: Kokoris Styliani I. , Angelopoulou Maria K. , Galani Zacharoula I. , Anargyrou Konstantinos , Sachanas Sotirios , Vassilakopoulos Theodoros P. , Siakantaris Marina P. , Kontopidou Flora N. , Dimitriadou Evangelia M. , Dimopoulou Maria N. , Tsaftaridis Panayiotis , Plata Eleni , Kalpadakis Christina , Kyrtsonis Marie-Christine , Panayiotidis Panayiotis , Pangalis Gerassimos A. 
Published: April 2020

Abstract
BACKGROUND: Hairy Cell Leukemia (HCL) is a rare B-chronic lymphoproliferative disorder (BCLD) with an indolent course. First-line treatment modalities include 2-chlorodeoxyadenosine (2-CDA), 2-deoxycoformycin (2-DCF) and interferon-alpha. The efficacy of anti-CD20-Rituximab (R) in other BCLDs, as well as strong CD20 expression by HCL cells, indicate that R could be an alternative treatment of HCL.
AIMS: The experience of a single Hematology Unit in the treatment of relapsed HCL with R.
PATIENTS AND METHODS: We retrospectively analyzed all HCL patients (pts) who received R as salvage therapy in 1st or subsequent relapse.
RESULTS: 13 patients treated with R were located among 110 patients diagnosed with HCL between 1980 and 2005. 11 were males and their median age before R treatment was 46 years (range: 42–88). 5 pts had splenomegaly with a median spleen size of 7cm below left costal margin (range:5–20cm). 3 pts has an absolute neutrophil count&lt;1.5×109/L, 4 a hemoglobin &lt;10g/dL and 5pts a platelet count&lt;100×109/L. All patients displayed a typical immunophenotype from blood and/or bone marrow (CD20 strongly +, CD19+, CD22+, FMC-7+, CD11c+, CD25+, CD103+). Four of them were CD23+ and two CD10+. 8 pts received Rituximab at 1st relapse. Among them, one had received 2-DCF as first-line treatment, one 2-CDA and 6 interferon-alpha as induction and maintenance. 3 pts had received more than one prior treatments. Two pts received R at diagnosis, due to older age. The median time from diagnosis to R initiation was 61 months (range: 4–275). R was administered at 375mg/m2 weekly for 6 cycles. Overall response rate was 67%, with 4 pts showing a negative immunophenotype. One pt discontinued treatment after the first cycle due to the development of thrombocytopenia that was attributed to the drug. 7/8 responders showed a complete restoration of their cytopenias. No other complications were recorded, except of mild infusion-related symptoms. Among the responding pts, none has relapsed so far with a median follow-up of 14 months (range: 4–40+). Among partial responders, one achieved a complete response including a negative bone marrow and immunophenotype after R retreatment.
CONCLUSIONS: R is a highly effective and tolerable treatment for HCL in relapse with a response rate of 67%. Retreatment or maintenance with R may be important, since ongoing responses are seen.
Rituxan-HCVAD in Mantle Cell Lymphoma: To Transplant or Not To Transplant: The University of Pennsylvania Experience.
Authors: Nasta Sunita Dwivedy , Xavier Marin F. , Andreadis Charalambos , Tsai Donald E. , Porter David , Luger Selina , Schuster Stephen J. 
Published: April 2020

Abstract
Mantle cell lymphoma is a difficult disease entity with no standard therapy. The best reported results for treatment of de novo patients has been from the MD Anderson Cancer Center with long term remission rates reported of 77%, using the HCVAD regimen in combination with autologous stem cell transplantation. (Khouri, ASH 1998) In later reports, the addition of Rituximab to the HCVAD regimen appears to obviate the need for additional consolidative auto-PBSCT. (Romaguera, ASH 2005) In a retrospective analysis of patients treated at the University of Pennsylvania between 1999 and 2006, we seek to compare patients receiving the R-HCVAD regimen without transplant to those who received auto-PBSCT in the same time period. Patients were stratified by their transplant status. Survival data, disease status, and secondary malignancy information were assessed. Twenty-five patients were identified, with an age range of 41–76 years at diagnosis. All but one patient had advanced disease at diagnosis (stage III or IV) There were 18 men and 7 women. 17 patients received R-HCVAD alone, and 8 patients went on to Cyclophosphamide/TBI autologous stem cell transplant. Survival in the patients treated with R-HCVAD alone was 82.3% with a median follow-up of 3 years, with all deaths due to progressive disease. Of surviving patients in this group, 1 out of 14 has had additional therapy but remains in second complete remission. Survival of patients post-transplant was 75%, with one death due to disease and one death due to secondary malignancy (lung cancer). One additional case of secondary MDS was also reported in the transplant group. In summary, our series reveals that the R-HCVAD therapy can provide excellent long-term remission rates with no additional survival advantage gained from autologous transplant. An increased risk for secondary malignancies was observed in patients undergoing autologous PBSCT. Further prospective studies of consolidative therapy are warranted in this population.
The Anticancer Effect of Cytochrome P450 2E1 Gene Which Was Mediated by Recombination Adenovirus in Mesenchymal Stem Cells.
Authors: Wang Jishi , Hu Xiaoyan , Liu Xinmei , Yang Yuan , Wu Yingya , Fang Qin 
Published: April 2020

Abstract
Dacarbazine (DTIC) can inhibit purine nucleotide synthesis after activated by P4502E1(CYP2E1) in liver and can be used for the treatment of malignant melanoma and Hodgkins lymphoma.
Objective: To explore the anticancer effect of the combination of CYP2E1 and DTIC.
Methods:
A full length cDNA fragment encoding the human CYP2E1 was cloned and was transfected into bone marrow mesenchymal stem cells (BMSCs) through recombinant adenovirus vector. The recombinant adenovirus vectors pAd5CMV-CYP2E1 and pAd5CMV-EGFP were constructed and transfected into the packing cell lines HEK293 cells by liposome encapsulation method. The expression of CYP2E1 gene was detected by Real-time PCR and Western Blot and contrasted to the cells which were transfected into the recombinant adenovirus including EGFP. In vitro, gene transfected BMSCs were co-cultured with DTIC, and then the supernatant was added into the medium of human malignant melanoma M14 cells. Fluorescence microscopy, DNA Ladder, flowcytometry, electrophoresis were employed to tests the apoptosis, and MTT method was applied to detecting the IC50. In the animal experiment, the CYP2E1 gene tranfected BMSCs were injected in combination with DTIC directly into the malignant melanomas on nude mice or through caudal vein, and the injected BMSCs transfected pAd5CMV-EGFP and DTIC in the same manner into nude control mice. The inhibiting effect of new planted tumors of experimental group was monitored through Immuno-histochemistry analysis and the shape and size of tumors were measured. CYP2E1-EGFP gene tranfected BMSCs were injected into nude mice through caudal vein and tracked by fluorescence.
Results:
CYP2E1 gene(1482bp) was cloned successfully and it was conformed by DNA sequencing; Endonuclease and PCR analyses showed that recombinant adenovirus vector had been constructed and high titer recombinant adenovirosome(1×1012pfu/ml) had been packaged successfully. BMSCs had been isolated and flowcytometry showed their phenotype were CD44(+),CD105(+), CD34(−)and CD45(−). The mRNA and protein quantities of the group of CYP2E1 gene tranfected BMSCs were significantly higher than the control group (P&lt;0.05, n=24). In vitro, immunity fluorescence microscope, DNA Ladder, and flowcytometry all showed the supernatant of co-culture of CYP2E1 gene tranfected BMSCs and DTIC) significantly decreased the mortality of M14 cells compared with pAd5CMV-EGFP-BMSCs control group (P &lt; 0. 05, n=24). In vivo, the sizes of the tumor in the nude mice treated with transfected BMSCs and DTIC were significantly smaller than control case and changed along with concentration. (P&lt; 0.05, n=20). No new tumor was found in the nude mouse inoculated with M14 cells after the injection of CYP2E1 transfected BMSCs and DTIC.
Conclusion: Recombination adenovirus vector was able to express CYP2E1 in BMSCs. Gene CYP2E1 transfected BMSCs and DTIC showed anticancer activity both in vitro and vivo.
Evaluation of Novel Cell Cycle Inhibitors in Mantle Cell Lymphoma.
Authors: Park In-Woo , Reddy M.V. Ramana , Reddy E. Premkumar , Groopman Jerome E. 
Published: April 2020

Abstract
Signature abnormalities in the cell cycle and apoptotic pathway have been identified in mantle cell lymphoma (MCL), affording the opportunity to develop targeted therapies. Here, we report on a novel class of kinase inhibitors, styryl sulfones, that differ from prior cell cycle inhibitors in that they are not related to purines or pyrimidines. We observed that two closely related compounds, ON013100 and ON01370, altered the growth and cell cycle status of MCL lines and potently inhibited the expression of several important molecules, including CDK4, p53, MDM2, cyclin D, and cyclin B. Using both TUNEL and PARP assays, we found that these compounds caused apoptosis in MCL cells. In addition, using molecular analyses, we observed the modulation of caspase-3 activity but not the expression of Bcl family molecules in these cells. Next, we investigated the cytotoxicity of the MCL lines upon treatment with styryl sulfone compounds in combination with other currently used chemotherapeutic agents, such as doxorubicin (DOX) or vincristine (VCR). We found that the combination of DOX plus styryl sulfone or VCR plus styryl sulfone increased cytotoxicity by one log scale, compared with the single styryl sulfone compound. Thus styryl sulfones alone, or in combination with chemotherapeutic agents, present attractive opportunities for new drug development in MCL.
Abnormalities in Lipoprotein Metabolism Provide Insight into Novel Therapeutic Approaches for Waldenstrom’s Macroglobulinemia (WM).
Authors: Patterson Christopher J. , Moreau Anne Sophie , Leleu Xavier , Soumerai Jacob , Hunter Zachary , Hatjiharissi Evdoxia , Xu Lian , Treon Steven 
Published: April 2020

Abstract
WM is an incurable B-cell disorder characterized by the presence of lymphoplasmacytic cells in the bone marrow and an IgM monoclonal protein. The presence of hypocholesterolemia has often been observed in WM patients, though the incidence and significance has not been investigated. As part of these studies, we evaluated lipoprotein levels in 110 patients with WM. The median age for this cohort was 62, and median number of prior therapies was 1. Twenty-one (19.1%) patients were on a lipid-lowering agent (lovastatin, simvastatin, pravastatin). We observed decreased total cholesterol (&lt;160 mg/dL), LDL (&lt;100 mg/dL) and VLDL (&lt;40 mg/dL) levels in 41 (37.3%), 68 (61.8%) and 90 (81.8%) patients, respectively. Among the 41 patients with a cholesterol level of &lt;160 mg/dL, only 7 patients were on a lipid lowering agent. Importantly, median serum IgM levels which serve as a surrogate marker for WM disease burden were higher among patients with hypocholesterolemia (3440 vs. 1587 mg/dL; p=0.0004). Moreover, significantly lower levels of serum IgM (885 vs. 1960 mg/dL; p=0.004) were observed among patients on a lipid-lowering agent. Given these results, which suggested a possible disease dependency on cholesterol metabolism, as well as possible anti-tumor effect of statins, we explored the impact of two statins (lovastatin, simvastatin) on the growth and survival of BCWM.1 WM cells. The studies demonstrated that both lovastatin and simvastatin inhibited proliferation (by MTT assay), and induced apoptosis (by Annexin-PI assay) in a dose dependent manner (0.5–50 um) at concentrations that overlapped pharmacologically achievable levels. Taken together, these studies suggest that lipoprotein metabolism may be essential for WM growth and survival, and that statin agents may represent clinically useful agents for the treatment of WM.