bluuebunny/crossref_metadata_2025_split huggingface dataset:
Survival Benefit of Post Induction Consolidation Therapy in MCL (Mantle Cell Lymphoma): a Polish Lymphoma Research Group (PLRG) Retrospective Multicenter Analysis
Authors: Jurczak Wojciech , Giza Agnieszka , Krochmalczyk Dorota , Zimowska-Curylo Dagmara , Sobocinski Marcin , Stella-Holowiecka Beata , Holowiecka-Goral Aleksandra , Boguradzki Piotr , Kisiel Elzbieta , Mazur Grzegorz , Wrobel Tomasz , Knopinska-Posluszny Wanda , Warzocha Ewa Kalinka - , Skotnicki Aleksander B. 
Published: April 2020

Abstract
Background: In MCL, early intensification and consolidation of the first line therapy by ASCT is the treatment of choice. Elderly age and co-existing co-morbidities makes it however feasible for less than a third of patients.
Methods: All MCL cases consulted in 8 PLRG centers within the last 5 years (n=140) were included in a retrospective analysis. Only 23% (n=32) were consolidated with ASCT, further 28% (n=40) by radioimmunotherapy (Ibritumomab), while in 49% (n=68) neither consolidation was performed. Rituximab was used in 36/72 patients subjected to consolidation and 25/68 treated without consolidation. There were no statistically significant differences in IPI, CS (clinical stage), frequency of extranodal manifestations and B symptoms between analyzed subgroups (Table 1) although patients subjected to ASCT were younger (median age 54 vs 62) and tend to have higher LDH (556 IU vs 473), while those who were not consolidated more frequently had a large tumor burden (defined as a mass &gt; 7 cm, 24 vs 15%).
Results: There was a clear impact of consolidation on Overall and Progression Free Survival (OS,PFS): at 5 years OS 65 vs 20 % (p= 0.0003 in Gehan Wilcoxon test); and PFS 40 vs 0 % (p= 0.0003 in Gehan Wilcoxon test). Rituximab used in the first line therapy further increased it’s efficiency in terms of PFS, prolonging median time to progression from 15 to 26 months, however the OS benefit was seen only in consolidated patients (at 5 years 75% OS in those with Rituximab including induction followed by consolidation).
Conclusion: With all limitations of retrospective analysis, it strongly supports the necessity of post induction therapy in MCL patients. The role of ASCT is established in younger patients, radioimmunotherapy may prove to be a feasible approach for the elderly and unfit ones.
N IPI Age LDH WHO CS (IV) Extra-nodal B sympt. X (&gt;7 cm) Radioimmunotherapy 40 2,49 61,7 542 1,43 83% 78% 63% 12% ASCT 32 2,62 54 556 1,24 80% 84% 68% 17% No Consolidation 68 2,98 62,8 473 1,74 85% 83% 68% 24% All cases 140 2,76 60,13 497 1,55 81% 81% 67% 20%
Treatment of Good Prognosis CD20+ Large-Cell Lymphomas in Patients Aged 65 to 80, with 3 Cycles of R-CHOP14 Followed by An Injection of 90Y Ibritumomab Tiuxetan
Authors: Frederic Peyrade , Gérard Lepeu , Provencio Mariano , Lauris Gastaud , Xavier Fontana , Jean-Marc Broglia , Patricia Carrier , Emmanuel Chamorey , Christophe Hebert , Thyss Antoine 
Published: April 2020

Abstract
Background : Treatment of newly diagnosed DLBCL in patients aged 65 to 80 is based on 6 to 8 cycles of R-CHOP at 14 to 21 day intervals. Recent data suggest that for patients with an IPI of 0 or 1, a shorter treatment may be considered. Furthermore, early negative PET-CT results after chemotherapy are an important favourable prognostic factor.
Patients and methods : We propose carrying out two cycles of R-CHOP 14 in patients aged 65 to 80 with newly diagnosed DLBCL and an IPI of 0 or 1. PET-CT will be performed on D28. If the results are normal, an R-CHOP cycle followed by an injection of ibritumomab tiuxetan 90Y will be administered. The anticipated total treatment period is 51 days. Ten patients were included from June 2007 to June 2008 (7 women and 3 men), the age-adjusted IPI was 0 and 1 in 6 and 4 cases, respectively. None of the patients had bone marrow involvement and the PS was 0 or 1 in every case.
Results : CT and PET-CT showed complete remission in 9 out of 10 patients, who therefore received the full protocol. The average age was 72 (range, 68–77). The average duration of treatment for these patients was 54 days. As regards to safety, hospitalisation or the prescription of antibiotics was not necessary in any case. No serious adverse event was reported. Mean platelet and leukocyte nadirs were 23,000/mm3 and 1,180/mm3, respectively. Two transfusions of red cell concentrates and one of platelet concentrate were necessary in one patient. To date, all patients are in complete remission.
Conclusion : The treatment regimen of 3 cycles of R-CHOP14 followed by an injection of 90Y ibritumomab tiuxetan appears to be tolerated by patients aged 65 to 80 with newly diagnosed DLBCL. Longer follow-up and the inclusion of more patients are necessary to confirm these preliminary data.
Therapeutic Compliance and Efficacy of Dose-Dense R-CHOP-14 Immunochemotherapy Plus Pegfilgrastim for First-Line Treatment of Low Risk Diffuse Large B-Cell Lymphoma Patients: Preliminary Results of An Open-Label Clinical Trial in Spain
Authors: Gonzalez-Barca Eva , Canales Miguel , Salar Antonio , Ferrer Secundino , Bargay Joan , Grande S. , Gardella Santiago , Vidal María Jesús , Oriol Albert , López A. , García J. , Bello Jl , Tomás Fj , Briones Javier , Caballero Dolores 
Published: April 2020

Abstract
Diffuse large B-cell lymphoma (DLBCL) is the most prevalent form of non-Hodgkin lymphoma. Three-weekly R-CHOP has become the standard treatment for DLBCL. Dose-dense immunochemotherapy could improve the efficacy of treatment; however these regimens are worse tolerated due to mielotoxicity. We are conducting a prospective, open-label, single arm clinical trial of treatment with dose-dense R-CHOP supported by pegfilgrastim in patients with DLBCL older than 65 with IPI 0–5 or younger than 65 with IPI 0–2. The aim of this sub-analysis was to evaluate the efficacy and treatment compliance in patients with low risk DLBCL (IPI 0–2). Patients received R-CHOP administered every 14 days followed by pegfilgrastim (6 mg per cycle) on day 2. Patients with tumor masses &gt; 10 cm were allowed to receive radiotherapy with 30 Gy, and those at risk of central nervous system infiltration receive prophylactic lyposomal cytarabine. Fifty-eight patients with IPI 0–2 were included in this analysis, median age was 58 years old (range 18–82), 22 (38%) patients were older than 65 yr, and 32 (53%) were male. Characteristics of the patients at diagnosis were as follows: stage III–IV: 29 (50%), bulky disease: 13 (22%), extra nodal involvement: 34 (59%), ³2 extranodal sites: 6 (10%), B symptoms: 10 (17%), ECOG 0–1: 55 (95%), elevated LDH 21 (36%), elevated b2microglobulin: 15 (26%), IPI 0–1 28 (48%). Fifty-four patients completed 6 cycles of treatment and 4 patients were dropped out, 1 due to progression and 3 due to exitus: 1 respiratory insufficiency, 1 bilateral pneumonia and 1 septic shock. Overall, 335 chemotherapy cycles were administered and 23 (6.9%) were delayed due to: neutropenia (3), febrile neutropenia (4), hepatotoxicity (1), fever or infection without neutropenia (11) and other adverse events (4). Doses of myelotoxic drugs were reduced in 8 (2.4%) cycles (3 patients). Most cycles (91.9%) were administered as scheduled. Serious adverse events were reported in 23 (39.7%) patients. Among them, febrile neutropenia episodes were observed in 10 patients (17.3%). Out of 54 evaluated patients for efficacy after 130-days follow-up, 45 (83%) achieved complete remission, 5 (9%) partial remission, 3 (5.5%) stable disease and 1 (1.8%) progressed. In an intention-to-treat analysis among the 58 patients, 46 (79.3%) patients achieved CR, 6 (10.3%) PR and 2 (3.4%) were not evaluable. High remission rates suggest that dose-dense immunochemotherapy with pegfilgrastim support is an efficacious treatment for DLBCL in low risk patients. The regimen is well tolerated, treatment compliance is high and most of cycles were administered as scheduled.
Pegfilgrastim Use and Risk of Bleomycin Induced Pulmonary Toxicity in Hodgkin Lymphoma
Authors: Janakiram Murali , O’Brien Timothy E. 
Published: April 2020

Abstract
Background Filgrastim may increase the risk of bleomycin induced pulmonary toxicity (BPT) in Hodgkin lymphoma patients, particularly those &gt;age 40 [Martin WG, J Clin Onc, 2005; 23(30): 7614]. It is not clear if pegylated filgrastim, with a longer 1/2 life and delayed onset of action, also increases this risk.
Methods: 38 cases of Hodgkin lymphoma treated with a bleomycin containing regimen were included in this analysis. 29 of these pts (Group A) also received pegfilgrastim and 9 pts (Group B) did not receive any growth factor support. All of the patients who received pegfilgrastim had it administered the day after chemotherapy and in all cases it was given to maintain dose intensity and prevent treatment delays. BPT was defined by the presence of pulmonary symptoms, interstitial infiltrates on chest x ray or computed tomography and the absence of infection.
Results: Grp A: 60% male, 40% female, mean age 39 (19 to 73), stage-I 2/29, II -14/29, III -5/29, IV-8/29; subtype- NS 20, MC 5, LP 3, LD 1. 27/29 received full dose ABVD (which included 10 units/m2 of bleomycin q 2weeks); one received ABD and one received full dose ABVD then had bleomycin held after 3 cycles. Mean number of cycles= 6 (4–8), median duration of treatment =160 days (71 to 231 days). Average ANC during treatment: 6590/mm3 (790 to 17273). Total # of bleomycin treatments: 274. Total # pegfilgrastim treatments: 203. Only 1/29 pts (age 44) developed BPT. There were no serious infections. Response to chemo: 22/29 CR, 5/29 PR, data not available in 2/29. At a median follow up of 18 months (range 4 to 48) 2/29 had relapsed. Grp B: 9 patients; mean age 39 (22 to 51), stage- II: 5/9; III: 4/9; subtype- NS 7, LP 2. All patients received full dose ABVD; ave # cycles= 6 (range 4–8), median duration of treatment= 145 days (30–220 days); average ANC during treatment: 2721/mm3 (2101 to 3535/mm3). Total # bleomycin treatments= 80. 1/9 pts (age 42) developed BPT. Response to chemo: 7/9 CR; 1 PR, 1 w/o response data. At a median follow up of 39 months (range 4–71), 2/9 relapsed.
Conclusions: In this small series, pegfilgrastim use with ABVD chemotherapy did not lead to a high risk of BPT in Hodgkin lymphoma, with only 1/29 patients (which included 203 treatments with both pegfilgrastim and bleomycin) developing BPT, as compared with 1/9 patients treated with ABVD and no pegfilgrastim. Both of the patients who developed BPT were &gt;age 40. Larger studies will need to be performed to confirm our findings.
Result of Paediatric Non Hodgkin’s Lymphoma with Intensified Short Duration Chemotherapy : A Result from Eastern India
Authors: Mukhopadhyay Ashis , Adde Melissa , Magrath Ian , Mukhopadhyay Soma 
Published: April 2020

Abstract
Background: The Non-Hodgkin’s Lymphomas (NHL) in childhood are usually high grade and diffuse histology. They require intensified short duration chemotherapy in contrast to adult NHL. The aim of our study was to observe the result of aggressive short duration chemotherapy in paediatric NHL.
Materials & Methods: We included consecutive 160 paediatric NHL patients in paediatric haemato-oncology department of Netaji Subhash Chandra Bose Cancer Research Institute during period from June 1996 to December 2007. The inclusion criteria were patients less than 25 yrs of age with a diagnosis of NHL and Patients are clinically staged according to the St. Jude’s (Murphy’s) classification. Patients with &gt; 25% blasts in the bone marrow were treated as leukemia and excluded from the study. Each patient received 3 cycles A and 3 cycles B of MCP842 protocol of INCTR. Response was assessed at the completion of 2cycles of chemotherapy (1 each of A and B).
Result: A total of 160 previously untreated patients were entered in this study. The age range was 1 to 25 yrs (median 13.5). Fourty Eight (48) patients had Lymphoblastic Lymphoma (LL), 64 patients (40%) had Burkitt Lymphoma, 40 (25%) diffuse Large B Cell Lymphoma (DLCL) and 8 (5%) had Anaplastic Large Cell. The abdomen was the most common site (56%) of involvement followed by the mediastinum (15.62%). One hundred and Thirty four (134)(83.75%) patients achieved complete response after 2 cycles of therapy, 14 patients (8.75%) achieved partial response and 6 (3.75%) had no response, 6 (3.75%) were not evaluable. With median follow up of 4 & 1/2 yaers (range 7 months – 10 years) a total of 38 (23.75%)patients (19 LL, 13 Burkitt Lymphoma, 5 DLCL and 1 ALCL) have died. The causes of death were progressive disease in 26 (16.25%), infection in 6 (3.75%), tumour lysis in 4 (2.5%), hepatitis in 1 (0.63%), and unknown 1 (0.63%). One hundred and twenty two (122) patients (76.25%) are alive and in complete remission. The patients tolerated chemotherapy well. Grade IV febrile Neutropenia was seen in 34 patients (21.25%).
Conclusion: Result of MCP 842 was promising and we will continue the protocol in future.
Rituximab + IEV/MINE Second Line Approach in Relapsed/Refractory Non Hodgkin Lymphoma (NHL): Efficacy and Safety
Authors: Bongarzoni Velia , Anaclerico Barbara , Borza Paola Anticoli , Cedrone Michele , Chierichini Anna , Fenu Susanna , Ronci Benedetto , Vittori Mariangela , Cantonetti Maria , Petti Maria Concetta , Annino Luciana 
Published: April 2020

Abstract
Background. Relapsed/refractory high grade NHL is a very aggressive pathology characterised by a poor prognosis. High dose therapy followed by peripheral blood stem cell (PBSC) rescue is to date the gold standard therapy. The results of high dose therapy are influenced by remission status after II line therapy as patients who undergo transplantation in complete response have better progression free survival with respect to those in partial response. While Rituximab+chemotherapy has become the approach of choice in 1st line-therapy, this type of schedule has not yet been largely applied in 2nd line therapy. In the aim of testing the efficacy of 2nd line-combined immuno-chemotherapy we designed a protocol including Rituximab + IEV/MINE.
Methods. The planned treatment consists of 3 cycles of IEV or MINE (&gt;65 y patients), plus Rituximab (375 mg/sqm) given on day +1 and on day +14 every cycle. G-CSF was administered from day 7 to ANC recovery and was continued until the CD 34+ collection after the third cycle. From April 2002 to July 2008 30 consecutive patients – 19 males and 11 females, median age 57 y (range 21–73 y) with refractory (12) and relapsed (18) Diffuse Large B Cell Lymphoma (DLBCL) entered the study. According to IPI score 20/30 patients were intermediatehigh risk; 21/30 had extranodal disease.
Results. 27 patients completed treatment and are evaluable; 3 pts are not evaluable because of lethal infection after Ist cicle (2pts) and lost to follow up (1pt). 21/27 (78%) were responders: 12 (44%) achieved CR, 9 (33%) PR, while 6 progressive disease (PD) were withdrawn. Hematological toxicity including WHO grade III or IV neutropenia, anemia and thrombocytopenia was recorded in 19, 8 and 14 pts, respectively. Target CD 34 harvest was reached in 19/27 (70%) pts with CD 34+ median value 7,03 × 106/Kg. Among the responders 4 pts failed CD 34 harvest. 17/27 (63%) patients underwent transplantion, 11 autologous stem cell transplantation (ASCT) and 6 (&gt;60 y) reduced intensity allogeneic-SCT. Of transplanted patients 4 (2 in CR post Mini Allo-SCT, 2 in relapse post ASCT) died 6, 2,10 and 10 months after transplantation, respectively. The remaining 13 (4 mini-alloSCT and 9 ASCT) are alive in CR which is lasting for 23 months median time (11–73). As of July 2008 15/27 (55%) patients are alive: 14 CR and 1 PR. Median follow up post R-IEV/MINE is 28 months (range 12–77), PFS was 38% and median OS is 32 months (range 7–90).
Conclusions. Our experience, if limited to a small series of patients, shows that the addition of Rituximab to second line chemotherapy:
increases response rate even in adverse IPI score cases, allows to obtain a good CD 34 harvest, represents an effective in vivo purging agent.
Antiproliferative Effects of Lenalidomide in Combination with Chemotherapeutic Agents in Lymphoma Cell Lines
Authors: Gandhi Anita K , Kang Jian , Capone Lori , Zhang Ling-Hua , Bartlett Blake , Pietronegro Dennis , Ervin-Haynes Annette , Schafer Peter H 
Published: April 2020

Abstract
Introduction: Lenalidomide (Revlimid®) is approved for the treatment of patients with myelodysplastic syndromes with a del(5q), and in combination with dexamethasone for previously treated multiple myeloma. It is currently being evaluated in lymphomas, as monotherapy or combination therapy. This study aims to identify beneficial combinations of lenalidomide with established or potential chemotherapeutic agents for lymphoma therapy.
Methods: Lenalidomide-sensitive lymphoma cell lines were selected for in vitro tumor cell proliferation studies. These included mantle cell lymphoma (MCL) lines Rec-1 and Jeko- 1, diffuse large-B-cell lymphoma (DLBCL) cell line Farage, the follicular lymphoma (FL) cell line DOHH2, and the chromosome 5-deleted Burkitt’s lymphoma cell line Namalwa CSN.70. Lenalidomide was tested with other therapeutic agents on cells incubated 72 hours and assayed for proliferation using 3H-thymidine incorporation. Twenty-one different therapeutic agents were tested in combination with lenalidomide, at concentrations ranging from 1 pM to 100 μM, depending upon the sensitivity of the cells to the particular agent.
Results: In MCL cells, lenalidomide was at least partially additive with mitoxantrone, rituximab, temsirolimus, bortezomib and azacytidine, and up to partially additive with doxorubicin. Results were similar in Rec-1 and Jeko-1 MCL cells. Lenalidomide was fully additive in the DLBCL cells with gemcitabine, melphalan, dexamethasone, carboplatin, and oxaliplatin, partially additive with cisplatin, mitoxantrone, vincristine, azacytidine, doxorubicin, carmustine, rituximab, etoposide and prednisolone, and non-additive with cytarabine. Synergy with lenalidomide was observed in the FL cells with rituximab, while partially additive with bendamustine and fludarabine, and non-additive with vincristine. In the Burkitt’s lymphoma cells, lenalidomide was synergistic with dexamethasone, rapamycin, and UCN-01. It was partially additive with prednisone and etoposide, and non-additive with other agents tested.
Conclusion: Among the tested lymphoma cell lines, lenalidomide combined synergistically with rituximab, dexamethasone, rapamycin, and UCN-01, and additively with mitoxantrone, temsirolimus, bortezomib, azacitidine, gemcitabine, melphalan, dexamethasone, carboplatin, and oxaliplatin. Thus, these results demonstrate a beneficial antineoplastic pharmacological interaction between lenalidomide and several therapeutic agents including monoclonal antibodies, corticosteroids, mTOR inhibitors, kinase inhibitors, proteasome inhibitors, DNA methyltransferase inhibitors, nucleoside analogs, alkylating agents, and topoisiomerase inhibitors in the treatment of lymphoma.
Pharmacodynamic Effects of Administration of Maytansine Conjugated Anti-CD22 Monoclonal Antibodies to Cynomolgus Monkeys
Authors: Fuh Franklin , Fuji Reina , Poon Kirsten A , Li Dongwei , David Clarissa , Nguyen Quyen , Howell Kathy , Beyer Joseph , Fielder Paul , Manning William , Berry Karen , Ramakrishnan Vanitha , Polson Andrew G. , Ebens Allen , Prabhu Saileta , Williams Marna 
Published: April 2020

Abstract
CD22 is a B cell-specific glycoprotein expressed on the cell surface of all mature B cells. A candidate therapeutic anti-CD22 antibody, 10F4v3, was conjugated to the anti-mitotic agent maytansine (10F4v3-DM1). DM1 disrupts cellular mitosis through inhibition of tubulin polymerization when internalized into cells. The anti-CD22 DM1 conjugate was shown to have significant potency in preclinical efficacy models of NHL. In order to further characterize this antibody-drug conjugate in preclinical studies, we first evaluated the binding characteristics of the 10F4v3 to peripheral blood B cells from various geographical sources of cynomolgus monkeys. 10F4v3 bound to peripheral blood B cells from all cynomolgus monkeys of Indonesian and Mauritian origins, but displayed only limited binding to cynomolgus monkeys of Chinese and Cambodian origins.
Therefore, further pre-clinical evaluation of 10F4v3-DM1 was conducted in Indonesian cynomolgus monkeys to examine the safety, pharmacokinetic, and pharmacodynamic effects in monkeys dosed at 10, 20, and 30 mg/kg (2000, 4000, and 6000 mg/m2 DM1). Pharmacodynamic assessments of peripheral blood and lymphoid tissues included examination of B cells, B cell subsets, CD4+ T cells, CD8+ T cells, and CD3−CD20− (NK) cells. B cell subsets included CD20+, CD20+CD21+, CD20+CD21−, CD20+CD21+CD27+, CD20+CD21+CD27−, and CD20+CD21high lymphocytes which are phenotypically similar to human B cells, mature B cells, germinal center B cells, memory B cells, naïve B cells, and marginal zone B cells, respectively.
B cells and B cell subsets were substantially depleted in peripheral blood at all doses, with no apparent dose-dependent effects. In lymphoid tissue, B cells were also depleted, with substantial depletion of CD20+CD21− and CD20+CD21high B cell subsets in spleen and bone marrow.
Based on the nonclinical data, 10F4v3-DM1 exhibits an encouraging pharmacodynamic profile that supports clinical development for the potential treatment of non-Hodgkin’s lymphoma.
Treatment of Posttransplant Lymphoproliferative Disorder Presenting as Protracted Infectious Mononucleosis with Rituximab
Authors: Chiang Alan Kwok Shing 
Published: April 2020

Abstract
Two young children who received living related-donor orthotopic liver transplantation for congenital biliary atresia developed persistent and progressive symptoms of fever, hepatosplenomegaly, upper airway obstruction, swollen eyes and face, malaise and cervical lymphadenopathy consistent with infectious mononucleosis within one year post-transplantation. Significant anemia, elevated liver transaminases and hypergammaglobulinaemia were observed. Serological assays did not detect any antibodies to Epstein-Barr virus (EBV) pre-transplantation indicating seronegative status. Both patients showed recent seroconversion to EBV (viral capsid antigen IgM and IgG positive but EBV nuclear antigen negative) at the peak of the clinical symptoms. The diagnosis of primary EBV-driven posttransplant lymphoproliferative disorder (PTLD) was established. Lowering or withdrawal of tacrolimus for a period of 2–3 weeks did not lead to any discernible clinical improvement. Both children were treated with four weekly doses of rituximab of 375 mg/m2/dose. They developed infusion reaction of fever, vomiting and unstable blood pressure within half hour of first dose of rituximab requiring stoppage of the drug administration. Subsequent doses were tolerated much better without adverse events. Clinical improvement was gradually observed over the next few weeks with resolution of fever, upper airway obstruction, decreasing liver transaminases and improvement of general condition. Complete resolution of infectious mononucleosis and normalization of hematological and biochemical parameters was achieved over a period of 6 months. No recurrence of PTLD was observed up to one year after treatment with rituximab.