| 1. |
- Bosly, Andre, et al.
(författare)
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A Randomized Study of Interferon alpha-2b Versus No Treatment as Consolidation After High Dose Therapy and Autologous Stem Cell Transplantation for Patients With Relapsed Lymphoma
- 2013
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Ingår i: The Oncologist. - : Oxford University Press (OUP). - 1083-7159 .- 1549-490X. ; 18:11, s. 1189-1189
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background. Patients with lymphoma who have experienced a first relapse or progression and have disease deemed sensitive to salvage chemotherapy nevertheless have a high likelihood of having a second relapse. To decrease the likelihood of a second relapse after high-dose therapy (HDT) and autologous stem cell transplantation (ASCT), interferon (IFN) alpha-2b was given in a prospective randomized international trial. Methods. In this trial, 221 patients with varying histologic diagnoses (8 small lymphocytic, 37 follicular, 9 mantle, 90 diffuse large B-cell, 20 peripheral T-cell, 3 high-grade B-cell non-Hodgkin lymphoma, and 54 Hodgkin lymphoma) were randomly assigned to receive no further treatment (armA: 117 patients) or IFN alpha-2b, 3 MU three times weekly, for 18 months (arm B: 104 patients). Results. In arm B, 21 patients (20%) did not receive IFN alpha-2b because of early progression or absence of hematologic recovery, 29 patients (28%) completed the 18 months of treatment, and 54 patients (52%) interrupted treatment because of progression (23%) or toxicity (29%). Event-free survival and overall survival were not different between the two arms on an intent-to-treat analysis and also if analysis was restricted to patients who were a live and had not experienced disease progression three months after transplantation. The study was not sufficiently powered to evaluate effects in histologic subtypes. Conclusion. In this trial, post-autograft IFN alpha-2b did not improve outcomes in a heterogeneous group of patients with lymphoma.
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| 2. |
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| 3. |
- Cuccuini, Wendy, et al.
(författare)
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MYC+ diffuse large B-cell lymphoma is not salvaged by classical R-ICE or R-DHAP followed by BEAM plus autologous stem cell transplantation
- 2012
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 119:20, s. 4619-4624
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Tidskriftsartikel (refereegranskat)abstract
- Approximately 5-10% of diffuse large B-cell lymphomas (DLBCL) harbor a 8q24/MYC rearrangement (MYC+). We determined the prognostic significance of MYC rearrangement in patients with relapsed/refractory DLBCL prospectively treated by R-ICE or R-DHAP followed by highdose therapy and autologous stem cell transplantation. Twenty-eight (17%) of the 161 patients analyzed presented a MYC+ rearrangement, targeted as either simple hit (25%) or complex hits (n = 75%) including MYC/BCL2, MYC/BCL6, and MYC/BCL2/BCL6. Results were statistically highly concordant in matched primary and relapsed biopsies (n = 45). Compared to the MYC+ DLBCL patients, the MYC+ DLBCL patients presented with a more elevated lactico-deshydrogenase level (P = .0006) and a more advanced age adjusted international prognostic index (P = .0039). The 4-year PFS and OS were significantly lower in the MYC+ DLBCL patients than those in the MYC- DLBCL patients, with rates of 18% vs 42% (P = .0322), and of 29% vs 62% (P = .0113), respectively. Type of treatment, R-DHAP or R-ICE, had no impact on survivals, with 4-year PFS rates of 17% vs 19% and 4-year OS rates of 26% vs 31%. In conclusion, MYC rearrangement is an early event in DLBCL. MYC+ DLBCL patients have a significant inferior prognosis than MYC- DLBCL patients. Their outcome was not influenced by the proposed salvage therapy.
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| 4. |
- Erny, Christian, et al.
(författare)
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Metrology of high-order harmonics for free-electron laser seeding
- 2011
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Ingår i: New Journal of Physics. - : IOP Publishing. - 1367-2630. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- We examine the characteristics of high-order harmonics generated with 800 nm, 25 mJ, 160 fs laser pulses in an Ar gas cell with the objective of seeding a free electron laser. We measure the energy per pulse and per harmonic, the energy jitter, the divergence and the position stability of the harmonic beam. We perform ab initio numerical simulations based on integration of the time-dependent Schrodinger equation and of the wave equation within the slowly varying envelope approximation. The results reproduce the experimental measurements to better than a factor of two. The interaction of a frequency comb of harmonic fields with an electron bunch in an undulator is examined with a simple model consisting of calculating the energy modulation owing to the seed-electron interaction. The model indicates that the undulator acts as a spectral filter selecting a given harmonic.
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| 5. |
- Finke, Aaron D., et al.
(författare)
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The 6,6-Dicyanopentafulvene Core : A Template for the Design of Electron-Acceptor Compounds
- 2015
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Ingår i: Chemistry - A European Journal. - : Wiley. - 0947-6539 .- 1521-3765. ; 21:22, s. 8168-8176
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Tidskriftsartikel (refereegranskat)abstract
- The electron-accepting ability of 6,6-dicyanopentafulvenes (DCFs) can be varied extensively through substitution on the five-membered ring. The reduction potentials for a set of 2,3,4,5-tetraphenyl-substituted DCFs, with varying substituents at the para-position of the phenyl rings, strongly correlate with their Hammett sigma(p)-parameters. By combining cyclic voltammetry with DFT calculations ((U)B3LYP/6-311+G(d)), using the conductor-like polarizable continuum model (CPCM) for implicit solvation, the absolute reduction potentials of a set of twenty DCFs were reproduced with a mean absolute deviation of 0.10eV and a maximum deviation of 0.19eV. Our experimentally investigated DCFs have reduction potentials within 3.67-4.41eV, however, the computations reveal that DCFs with experimental reduction potentials as high as 5.3eV could be achieved, higher than that of F-4-TCNQ (5.02eV). Thus, the DCF core is a template that allows variation in the reduction potentials by about 1.6eV.
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| 6. |
- Gisselbrecht, Christian, et al.
(författare)
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Rituximab Maintenance Therapy After Autologous Stem-Cell Transplantation in Patients With Relapsed CD20(+) Diffuse Large B-Cell Lymphoma : Final Analysis of the Collaborative Trial in Relapsed Aggressive Lymphoma
- 2012
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Ingår i: Journal of Clinical Oncology. - 0732-183X .- 1527-7755. ; 30:36, s. 4462-4469
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Tidskriftsartikel (refereegranskat)abstract
- Purpose The standard treatment for relapsed diffuse large B-cell lymphoma (DLBCL) is salvage chemotherapy followed by high-dose therapy and autologous stem-cell transplantation (ASCT). The impact of maintenance rituximab after ASCT is not known. Patients and Methods In total, 477 patients with CD20(+) DLBCL who were in their first relapse or refractory to initial therapy were randomly assigned to one of two salvage regimens. After three cycles of salvage chemotherapy, the responding patients received high-dose chemotherapy followed by ASCT. Then, 242 patients were randomly assigned to either rituximab every 2 months for 1 year or observation. Results After ASCT, 122 patients received rituximab, and 120 patients were observed only. The median follow-up time was 44 months. The 4-year event-free survival (EFS) rates after ASCT were 52% and 53% for the rituximab and observation groups, respectively (P=.7). Treatment with rituximab was associated with a 15% attributable risk of serious adverse events after day 100, with more deaths (six deaths v three deaths in the observation arm). Several factors affected EFS after ASCT (P<.05), including relapsed disease within 12 months (EFS: 46% v 56% for relapsed disease after 12 months), secondary age-adjusted International Prognostic Index (saaIPI) more than 1 (EFS: 37% v 61% for saaIPI < 1), and prior treatment with rituximab (EFS: 47% v 59% for no prior rituximab). A significant difference in EFS between women (63%) and men (46%) was also observed in the rituximab group. In the Cox model for maintenance, the saaIPI was a significant prognostic factor (P<.001), as was male sex (P=.01). Conclusion In relapsed DLBCL, we observed no difference between the control group and the rituximab maintenance group and do not recommend rituximab after ASCT.
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| 7. |
- Gisselbrecht, Christian, et al.
(författare)
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Salvage Regimens With Autologous Transplantation for Relapsed Large B-Cell Lymphoma in the Rituximab Era
- 2010
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Ingår i: Journal of Clinical Oncology. - 0732-183X .- 1527-7755. ; 28:27, s. 4184-4190
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Salvage chemotherapy followed by high-dose therapy and autologous stem-cell transplantation (ASCT) is the standard treatment for relapsed diffuse large B-cell lymphoma (DLBCL). Salvage regimens have never been compared; their efficacy in the rituximab era is unknown. Patients and Methods Patients with CD20(+) DLBCL in first relapse or who were refractory after first-line therapy were randomly assigned to either rituximab, ifosfamide, etoposide, and carboplatin (R-ICE) or rituximab, dexamethasone, high-dose cytarabine, and cisplatin (R-DHAP). Responding patients received high-dose chemotherapy and ASCT. Results The median age of the 396 patients enrolled (R-ICE, n = 202; R-DHAP, n = 194) was 55 years. Similar response rates were observed after three cycles of R-ICE (63.5%; 95% CI, 56% to 70%) and R-DHAP (62.8%; 95 CI, 55% to 69%). Factors affecting response rates (P < .001) were refractory disease/relapse less than versus more than 12 months after diagnosis (46% v 88%, respectively), International Prognostic Index (IPI) of more than 1 versus 0 to 1 (52% v 71%, respectively), and prior rituximab treatment versus no prior rituximab (51% v 83%, respectively). There was no significant difference between R-ICE and R-DHAP for 3-year event-free survival (EFS) or overall survival. Three-year EFS was affected by prior rituximab treatment versus no rituximab (21% v 47%, respectively), relapse less than versus more than 12 months after diagnosis (20% v 45%, respectively), and IPI of 2 to 3 versus 0 to 1 (18% v 40%, respectively). In the Cox model, these parameters were significant (P < .001). Conclusion In patients who experience relapse more than 12 months after diagnosis, prior rituximab treatment does not affect EFS. Patients with early relapses after rituximab-containing first-line therapy have a poor prognosis, with no difference between the effects of R-ICE and R-DHAP.
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| 8. |
- Hess, Georg, et al.
(författare)
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Phase III Study to Evaluate Temsirolimus Compared With Investigator's Choice Therapy for the Treatment of Relapsed or Refractory Mantle Cell Lymphoma
- 2009
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Ingår i: Journal of Clinical Oncology. - 0732-183X .- 1527-7755. ; 27:23, s. 3822-3829
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Temsirolimus, a specific inhibitor of the mammalian target of rapamycin kinase, has shown clinical activity in mantle cell lymphoma (MCL). We evaluated two dose regimens of temsirolimus in comparison with investigator's choice single-agent therapy in relapsed or refractory disease. Patients and Methods In this multicenter, open-label, phase III study, 162 patients with relapsed or refractory MCL were randomly assigned (1: 1: 1) to receive one of two temsirolimus regimens: 175 mg weekly for 3 weeks followed by either 75 mg (175/75-mg) or 25 mg (175/25-mg) weekly, or investigator's choice therapy from prospectively approved options. The primary end point was progression-free survival (PFS) by independent assessment. Results Median PFS was 4.8, 3.4, and 1.9 months for the temsirolimus 175/75-mg, 175/25-mg, and investigator's choice groups, respectively. Patients treated with temsirolimus 175/75-mg had significantly longer PFS than those treated with investigator's choice therapy (P = .0009; hazard ratio = 0.44); those treated with temsirolimus 175/25-mg showed a trend toward longer PFS (P = .0618; hazard ratio = 0.65). Objective response rate was significantly higher in the 175/75-mg group (22%) compared with the investigator's choice group (2%; P = .0019). Median overall survival for the temsirolimus 175/75-mg group and the investigator's choice group was 12.8 months and 9.7 months, respectively (P = .3519). The most frequent grade 3 or 4 adverse events in the temsirolimus groups were thrombocytopenia, anemia, neutropenia, and asthenia. Conclusion Temsirolimus 175 mg weekly for 3 weeks followed by 75 mg weekly significantly improved PFS and objective response rate compared with investigator's choice therapy in patients with relapsed or refractory MCL.
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| 9. |
- Maloney, David, et al.
(författare)
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Diversity in antibody-based approaches to non-Hodgkin lymphoma
- 2010
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Ingår i: Leukemia & Lymphoma. - : Informa UK Limited. - 1042-8194 .- 1029-2403. ; 51, s. 20-27
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Konferensbidrag (refereegranskat)abstract
- Non-Hodgkin lymphoma (NHL) remains one of the most common cancers in the US, with survival dependent on the type and stage of disease. B-cell lymphomas account for similar to 85% of all cases of NHL, and are commonly treated with chemotherapy, or monoclonal antibodies (mAbs) that t arget CD20 antigens on the surface of malignant tumors. The use of mAbs, either as single agents or in combination with chemotherapy, has made a huge impact on NHL survival rates. Rituximab remains the most commonly used and established mAb, and is used in a wide range of NHLs, but does not produce an effective therapeutic response in all patients. Novel therapeutics with enhanced binding affinity or alternative antigen targets are currently in development and in some cases have demonstrated improved efficacy over currently available treatments. Radioimmunotherapy has been included in transplant conditioning regimens to improve long-term disease control while limiting toxicity. These regimens have been safe, effective, and feasible, and are therefore promising for patients who cannot tolerate high-dose chemotherapy and/or total body irradiation.
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| 10. |
- Oghbaie, Shabnam, et al.
(författare)
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Dissociation of cyclopropane in double ionization continuum
- 2017
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Ingår i: Physical chemistry chemical physics : PCCP. - 1463-9084. ; 19:30, s. 19631-19639
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Tidskriftsartikel (refereegranskat)abstract
- Dissociative double photoionization of cyclopropane is studied in the inner-valence region using tunable synchrotron radiation. With the aid of ab initio quantum chemical calculations the energies of dication states and their favoured fragmentation pathways are determined. These are compared to the experimental appearance energies of two-body fragmentation processes and to the kinetic energy released upon dissociation. Photon energy dependent state-selective dissociation in the 25–35 eV range is found. Calculations of dissociation pathways suggest that cyclopropane ring-deformation is selectively triggered at certain photon energies. The calculations suggest that initial ring deformation essentially determines the population of different dication states that function as gateways for particular dissociation channels. The measurements show that stepwise ionization processes populate dissociative 3e′−2 states via ring-opening and Jahn–Teller active states at photon energies below the double-ionization threshold. For energies above the double-ionization threshold the kinematics indicate that double ionization takes place predominantly within the Franck–Condon region populating 3e′−1 1e′′−1 states.
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