PD-1 Blockade with Nivolumab as a New Immunotherapy for Classical Hodgkin’s Lymphoma

During the last two decades individualization of programmed treatment combined with intensified chemotherapy has proven to be effective treatment for the majority of classical Hodgkin’s lymphoma (cHL) patients. However, in 10–30 % of cases relapses and resistance to therapy still occur. Further intensification of therapy induces toxicity that leads to decrease in overall survival and quality of life. The standard second-line treatment with high-dose chemotherapy (HDCT) and autologous hematopoietic stem cell transplantation (auto-HSCT) allows for the achievement of long-term 5-year progression-free survival only in 50–60 % of patients with relapsed disease and not more than 40–45 % of patients with refractory disease. Approximately 50 % of patients relapse after HDCT and auto-HSCT. The median overall survival of relapsed patients does not exceed 2 years. Allogeneic HSCT improves treatment results to some extent, but is not an optimal strategy in all patients. A search for new treatment options has been made to improve effectiveness of relapsed and refractory cHL treatment and to reduce toxicity of highly effective programs. А new CD30-targeted conjugate brentuximab vedotin was developed to use anti-CD30 monoclonal antibodies against a specific marker of tumor Reed-Sternberg cells allowing for the transfer of the highly effective antitumor compound of monomethyl auristatin E directly to tumor cells. This drug showed high effectiveness, although failed to provide a complete solution to the problem. The development of anti-PD1 antibody nivolumab opened up new opportunities for cHL treatment. This paper reviews literature information on pharmacological data and antitumor mechanisms of the drug as well as the results of significant international randomised studies

Epstein-Barr Virus in Patients with Classical Hodgkin’s Lymphoma

Background. A close relationship between Epstein-Barr virus (EBV) and classical Hodgkin’s lymphoma (cHL) has been established in approximately 1/3 patients. EBV-positive lymphomas are characterized by increased level of EBV specific antibodies emerging long before tumor symptoms, аs well as a high plasma EBV DNA concentration. These viral markers normally correlate with clinical manifestations and the outcome of treatment performed. In patients with EBV-negative lymphomas, however, there has been no attempt to assess the clinical significance of either humoral response to EBV or EBV DNA concentration in plasma. Aim. To evaluate diagnostic and prognostic significance of EBV markers in patients with EBV-negative lymphomas. Methods. The clinical trial included 13 cHL-patients admitted at the Department of chemotherapy of hemoblastoses of NN Blokhin National Medical Cancer Research Center. The male to female ratio was 1:1.3, the median age was 26.4 years. Leukocyte and lymphocyte counts were evaluated in all the patients before, during, and after treatment as well as throughout the follow-up period. The same indicators were analysed in the control group which contained 40 healthy persons (with the median age of 41.1 years, male to female ratio 1.5:1). The study was based on serologic test for EBV antibodies and quantitative analysis of the viral DNA copy number in plasma. Results. The obtained data show a low immunie response to EBV and its diminishment after several polychemotherapy treatment cycles, correlating with decreased leukocyte and lymphocyte levels. As opposed to levels of virus-specific antibodies which do not reflect the efficacy of anticancer therapy, plasma EBV DNA concentration in 2 patients decreased to 0 after remission had been achieved. Conclusion. Although the number of observations is limited, one could suggest that viral load values in plasma of patients with EBV-negative lymphomas can prove to be a useful marker of anticancer therapeutic effect. Additional studies of these markers are required

First-Line Therapy for Patients with Advanced Hodgkin’s Lymphoma: Efficacy and Toxicity of Intensive ЕАСОРР-14 Program (NN Blokhin National Medical Cancer Research Center Data)

Aim. To assess the efficacy and toxicity of intensive 6 courses EACOPP-14 treatment with or without radiotherapy (RT) for advanced stages of Hodgkin’s lymphoma (HL). Materials & Methods. From November 2009 to February 2015, 95 patients with advanced stages of HL (IIX–IIE, III–IV) aged between 17 and 50 years (median 29 years) were selected for the participation in the protocol ЛХМосква1-3. The study population consisted of 46.3 % men and 53.7 % women. The results of the treatment were assessed in 91 patients who have received more than 2 courses of EACOPP-14. The follow up period was at least 3 months after the receiving the therapy. Consolidation RT with a total dose of 30 Gy for residual tumor lesions and/or initially large tumors was performed after the chemotherapy. Results. Complete remission was achieved in 82 (90.1 %) patients, partial remission in 2 (2.2 %), and the progression was observed in 7 (7.7 %) patients. The overall 4-year survival rate was 90.8 %, the progression-free survival was 88.2 %. The toxicity of the ЕАСОРР-14 program was slightly lower than that of 8 courses of ВЕАСОРРesc, and was comparable to the toxicity of other modifications of intensified ВЕАСОРР scheme. Hematological toxicity grade 3 and 4 was most commonly observed: leukopenia was observed after 64.9 % of courses, anemia — after 24 % of courses, thrombocytopenia — after 3.8 % of courses. The rate of infections did not singificantly differ and accounted for 24 %. The most frequent non-infectious complications were mucositis (21.1 %) and polyneuropathy (11.7 %). Complications resulted in the change of treatment in only 3 (3.01 %) of patients. The exclusion of bleomycine from the ЕАСОРР-14 program reduced the frequency of RT complications. Grade 3 pulmonitis developed in 4.5 % of cases, while radiation-induce pulmonary fibrosis verified by CT developed in 15.2 % of cases. The ЕАСОРР-14 6 courses program showed its high efficacy both with and without RT, high tolerance and the possibility of full administration for the majority of patients with the various stages of HL. Conclusion. Current research showed the efficacy of treatment without RT for patients with advanced stages of HL with negative PET results and small (< 2.5 cm) residual tumors after intensive ЕАСОРР-14 program. This approach allowed to avoid a number of late treatment complications

Relevance of Positron-Emission Therapy for Optimization of Treatment of Advanced Hodgkin’s Lymphoma Using Intensive ЕАСОРР-14 Program

Aim. To evaluate the relevance of the positron-emission therapy (PET) for optimization of the therapy of advanced Hodgkin’s lymphoma (HL) using the intensive EACOPP-14 program. Materials & Methods. 91 patients with advanced HL (IIX–IIE, III–IV) received the treatment according to the “ЛХМосква1-3” protocol over the period from November 2009 to February 2015, and then the treatment was analyzed. The median age was 29 years (range: 17–50); there were 42 men (46.3 %) and 49 (53.7 %) women. The treatment included 6 cycles of polychemotherapy according to the regimen ЕА(50)СОРР-14 ± radiation therapy. The radiation therapy was performed in 66 patients (72.5 %) after the completion of the chemotherapy. The cumulative focal dose was 30 Gy onto the areas of residual lesions and/or initially large tumor masses. Results. PET performed during the initial HL diagnosing permited to identify new areas of neoplastic lesions without changes in staging and treatment scheme, as well as specify areas and field size of planned radiation consolidation. The paper confirms the prognostic value of the intermediate PET in patients with advanced HL during the intensive first-line chemotherapy. The intensive therapy at the beginning of the treatment program is associated with higher chances for survival for patients with extremely unfavorable prognosis. After completion of the drug therapy, negative PET findings had a higher prognostic value, than the positive ones. The analysis of the relevance of residual tumor dimensions in the PET negative group demonstrated that the relapses were more common, if the residual tumor was more than 4.5 cm (according to CT findings). Conclusion. This study confirmed that it reasonable to discuss the discontinuation of the radiation therapy in patients with advanced HL, negative PET findings and small (< 2.5 cm) residual tumor after the intensive ЕАСОРР-14 program. This tactics permits avoiding a number of delayed complications

Search for New Physics in e mu X Data at D0 Using Sleuth: A Quasi-Model-Independent Search Strategy for New Physics

We present a quasi-model-independent search for the physics responsible for electroweak symmetry breaking. We define final states to be studied, and construct a rule that identifies a set of relevant variables for any particular final state. A new algorithm ("Sleuth") searches for regions of excess in those variables and quantifies the significance of any detected excess. After demonstrating the sensitivity of the method, we apply it to the semi-inclusive channel e mu X collected in 108 pb^-1 of ppbar collisions at sqrt(s) = 1.8 TeV at the D0 experiment during 1992-1996 at the Fermilab Tevatron. We find no evidence of new high p_T physics in this sample.Comment: 23 pages, 12 figures. Submitted to Physical Review

Ratio of the Isolated Photon Cross Sections at \sqrt{s} = 630 and 1800 GeV

The inclusive cross section for production of isolated photons has been measured in \pbarp collisions at $\sqrt{s} = 630$ GeV with the \D0 detector at the Fermilab Tevatron Collider. The photons span a transverse energy ($E_T$) range from 7-49 GeV and have pseudorapidity $|\eta| < 2.5$. This measurement is combined with to previous \D0 result at $\sqrt{s} = 1800$ GeV to form a ratio of the cross sections. Comparison of next-to-leading order QCD with the measured cross section at 630 GeV and ratio of cross sections show satisfactory agreement in most of the $E_T$ range.Comment: 7 pages. Published in Phys. Rev. Lett. 87, 251805, (2001

Measurement of the Forward-Backward Asymmetry in the B -> K(*) mu+ mu- Decay and First Observation of the Bs -> phi mu+ mu- Decay

We reconstruct the rare decays $B^+ \to K^+\mu^+\mu^-$, $B^0 \to K^{*}(892)^0\mu^+\mu^-$, and $B^0_s \to \phi(1020)\mu^+\mu^-$ in a data sample corresponding to $4.4 {\rm fb^{-1}}$ collected in $p\bar{p}$ collisions at $\sqrt{s}=1.96 {\rm TeV}$ by the CDF II detector at the Fermilab Tevatron Collider. Using $121 \pm 16$ $B^+ \to K^+\mu^+\mu^-$ and $101 \pm 12$ $B^0 \to K^{*0}\mu^+\mu^-$ decays we report the branching ratios. In addition, we report the measurement of the differential branching ratio and the muon forward-backward asymmetry in the $B^+$ and $B^0$ decay modes, and the $K^{*0}$ longitudinal polarization in the $B^0$ decay mode with respect to the squared dimuon mass. These are consistent with the theoretical prediction from the standard model, and most recent determinations from other experiments and of comparable accuracy. We also report the first observation of the $B^0_s \to \phi\mu^+\mu^- decay and measure its branching ratio${\mathcal{B}}(B^0_s \to \phi\mu^+\mu^-) = [1.44 \pm 0.33 \pm 0.46] \times 10^{-6}$using$27 \pm 6$signal events. This is currently the most rare$B^0_s$ decay observed.Comment: 7 pages, 2 figures, 3 tables. Submitted to Phys. Rev. Let

Measurements of the properties of Lambda_c(2595), Lambda_c(2625), Sigma_c(2455), and Sigma_c(2520) baryons

We report measurements of the resonance properties of Lambda_c(2595)+ and Lambda_c(2625)+ baryons in their decays to Lambda_c+ pi+ pi- as well as Sigma_c(2455)++,0 and Sigma_c(2520)++,0 baryons in their decays to Lambda_c+ pi+/- final states. These measurements are performed using data corresponding to 5.2/fb of integrated luminosity from ppbar collisions at sqrt(s) = 1.96 TeV, collected with the CDF II detector at the Fermilab Tevatron. Exploiting the largest available charmed baryon sample, we measure masses and decay widths with uncertainties comparable to the world averages for Sigma_c states, and significantly smaller uncertainties than the world averages for excited Lambda_c+ states.Comment: added one reference and one table, changed order of figures, 17 pages, 15 figure

Search for a New Heavy Gauge Boson Wprime with Electron + missing ET Event Signature in ppbar collisions at sqrt(s)=1.96 TeV

We present a search for a new heavy charged vector boson $W^\prime$ decaying to an electron-neutrino pair in $p\bar{p}$ collisions at a center-of-mass energy of 1.96\unit{TeV}. The data were collected with the CDF II detector and correspond to an integrated luminosity of 5.3\unit{fb}^{-1}. No significant excess above the standard model expectation is observed and we set upper limits on $\sigma\cdot{\cal B}(W^\prime\to e\nu)$. Assuming standard model couplings to fermions and the neutrino from the $W^\prime$ boson decay to be light, we exclude a $W^\prime$ boson with mass less than 1.12\unit{TeV/}c^2 at the 95\unit{%} confidence level.Comment: 7 pages, 2 figures Submitted to PR

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO