The Risk of Therapy-Related Myelodysplasia/Acute Myeloid Leukemia in Hodgkin Lymphoma has Substantially Decreased in the ABVD Era Abolishing Mechlorethamine and Procarbazine and Limiting Volumes and Doses of Radiotherapy

Patients with Hodgkin lymphoma treated with DNA-breaking alkylating agents such as mechlorethamine and procarbazine in the MOPP regimen and with topoisomerase II inhibitors, such as etoposide did show a long-term risk of developing therapy-related myelodysplasia and acute myelogenous leukaemia (MDS/AML). With the introduction of the ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) regimen, this risk has substantially been reduced. In this review, different experiences are discussed to determine whether and how modifications of treatment in different cohorts of patients have reduced the overall risk of secondary MDS/AML. These data are drawn from large cohorts of patients treated over time with different therapies with an adequate follow-up

methotrexate renal clearance by low dose dopamine in severe nephrotoxicity

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therapy related late adverse events in hodgkin s lymphoma

Hodgkin's lymphoma (HL) is one of the most curable hematologic diseases with an overall response rate over 80%. However, despite this therapeutic efficacy, HL survivors show a higher morbidity and mortality than other people of the same age because of long-term therapy-related events. In the last decades, many efforts have been made to reduce these effects through the reduction of chemotherapy dose, the use of less toxic chemotherapeutic agents, and the introduction of new radiation techniques. In this paper, we will describe the main long-term effects related to chemotherapy and radiotherapy for HL, the efforts to reduce toxicity made in the last years, and the clinical aspects which have to be taken into consideration in the followup of these patients

Hodgkin's lymphoma: post- autologous transplantation consolidation therapy

A first-line chemotherapy program based on the ABVD regimen is currently considered the golden standard by most hematologists, being able to achieve a cure without any need of subsequent therapies in >70% of patients with advanced-stage Hodgkin's lymphoma (HL). To increase this percentage, efforts in recent decades focused on the development of new therapeutic strategies. A first major effort was the introduction of the BEACOPP chemotherapy regimen, which is able to increase the response rate and to reduce the need of salvage therapies. However, this result did not demonstrate an advantage in terms of overall survival compared to ABVD, mainly due to an excess of non lymphoma-related events in the follow-up phase. Here we describe three clinical cases of young HL patients who had relapsed/refractory disease after the induction chemotherapy. These three clinical cases provide practical and real world evidence in favor of the use of BV in monotherapy as consolidation treatment after autologous stem cells transplantation in patients with relapsed/refractory HL

Bendamustine in combination with gemcitabine and vinorelbine is an effective regimen as induction chemotherapy before autologous stem-cell transplantation for relapsed or refractory Hodgkin lymphoma: Final results of a multicenter phase II study

Purpose: This multicenter, open-label, phase II study evaluated the combination of bendamustine, gemcitabine, and vinorelbine (BeGEV) as induction therapy before autologous stem-cell transplantation (ASCT) in patients with relapsed or refractory Hodgkin lymphoma (HL). Patients and Methods: Patients with HL who were refractory to or had relapsed after one previous chemotherapy line were eligible. The primary end point was complete response (CR) rate after four cycles of therapy. Secondary end points were: overall response rate, stem-cell mobilization activity, and toxicity. Progression-free and overall survival were also evaluated. Results: In total, 59 patients were enrolled. After four cycles of therapy, 43 patients (73%) achieved CR, and six (10%) achieved partial response, for an overall response rate of 83%. The most common grade 3 to 4 nonhematologic toxicities included febrile neutropenia (n = 7) and infection (n = 4). Regarding hematologic toxicities, grade 3 to 4 thrombocytopenia and neutropenia were each experienced by eight patients (13.5%). CD34+ cells were successfully harvested in 55 of 57 evaluable patients, and 43 of 49 responding patients underwent ASCT. With a median follow-up of 29 months, the 2-year progression-free and overall survival rates for the total population were 62.2% and 77.6%, respectively. The same figures for patients undergoing autograft were 80.8% and 89.3%, respectively. Conclusion: This phase II study demonstrates that BeGEV is an effective salvage regimen able to induce CR in a high proportion of patients with relapsed or refractory HL before ASCT. These data provide a strong rationale for further development of the BeGEV regimen

Utility of baseline 18FDG-PET/CT functional parameters in defining prognosis of primary mediastinal (thymic) large B-cell lymphoma

The International Extranodal Lymphoma Study Group (IELSG) 26 study was designed to evaluate the role of (18)F-fluorodeoxyglucose (18FDG) positron emission tomography/computed tomography (PET/CT) in the management of primary mediastinal (thymic) large B-cell lymphoma (PMBCL). We examined the prognostic impact of functional PET parameters at diagnosis. Metabolic activity defined by the maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) was measured on baseline 18FDG PET/CT following a standard protocol in a prospectively enrolled cohort of 103 PMBCL patients. All received combination chemoimmunotherapy with doxorubicin- and rituximab-based regimens; 93 had consolidation radiotherapy. Cutoff values were determined using the receiver-operating characteristic curve. At a median follow-up of 36 months, progression-free survival (PFS) and overall survival (OS) were 87% and 94%, respectively. In univariate analysis, elevated MTV and TLG were significantly associated with worse PFS and OS. Only TLG retained statistical significance for both OS (P = .001) and PFS (P < .001) in multivariate analysis. At 5 years, OS was 100% for patients with low TLG vs 80% for those with high TLG (P = .0001), whereas PFS was 99% vs 64%, respectively (P < .0001). TLG on baseline PET appeared to be a powerful predictor of PMBCL outcomes and warrants further validation as a biomarker. The IELSG 26 study was registered at www.clinicaltrials.gov as #NCT00944567

Italian real life experience with ibrutinib: Results of a large observational study on 77 relapsed/refractory mantle cell lymphoma

Although sometimes presenting as an indolent lymphoma, mantle cell lymphoma (MCL) is an aggressive disease, hardly curable with standard chemo-immunotherapy. Current approaches have greatly improved patients' outcomes, nevertheless the disease is still characterized by high relapse rates. Before approval by EMA, Italian patients with relapsed/refractory MCL were granted ibrutinib early access through a Named Patient Program (NPP). An observational, retrospective, multicenter study was conducted. Seventyseven heavily pretreated patients were enrolled. At the end of therapy there were 14 complete responses and 14 partial responses, leading to an overall response rate of 36.4%. At 40 months overall survival was 37.8% and progression free survival was 30%; disease free survival was 78.6% at 4 years: 11/14 patients are in continuous complete response with a median of 36 months of follow up. Hematological toxicities were manageable, and main extra-hematological toxicities were diarrhea (9.4%) and lung infections (9.0%). Overall, 4 (5.2%) atrial fibrillations and 3 (3.9%) hemorrhagic syndromes occurred. In conclusions, thrombocytopenia, diarrhea and lung infections are the relevant adverse events to be clinically focused on; regarding effectiveness, ibrutinib is confirmed to be a valid option for refractory/relapsed MCL also in a clinical setting mimicking the real world

Quantum numbers of the X(3872)X(3872) state and orbital angular momentum in its ρ0Jψ\rho^0 J\psi decay

Angular correlations in $B^+\to X(3872) K^+$ decays, with $X(3872)\to \rho^0 J/\psi$, $\rho^0\to\pi^+\pi^-$ and $J/\psi \to\mu^+\mu^-$, are used to measure orbital angular momentum contributions and to determine the $J^{PC}$ value of the $X(3872)$ meson. The data correspond to an integrated luminosity of 3.0 fb$^{-1}$ of proton-proton collisions collected with the LHCb detector. This determination, for the first time performed without assuming a value for the orbital angular momentum, confirms the quantum numbers to be $J^{PC}=1^{++}$. The $X(3872)$ is found to decay predominantly through S wave and an upper limit of $4\%$ at $95\%$ C.L. is set on the fraction of D wave.Comment: 16 pages, 4 figure

Les droits disciplinaires des fonctions publiques : « unification », « harmonisation » ou « distanciation ». A propos de la loi du 26 avril 2016 relative à la déontologie et aux droits et obligations des fonctionnaires

The production of tt‾ , W+bb‾ and W+cc‾ is studied in the forward region of proton–proton collisions collected at a centre-of-mass energy of 8 TeV by the LHCb experiment, corresponding to an integrated luminosity of 1.98±0.02 fb−1 . The W bosons are reconstructed in the decays W→ℓν , where ℓ denotes muon or electron, while the b and c quarks are reconstructed as jets. All measured cross-sections are in agreement with next-to-leading-order Standard Model predictions.The production of $t\overline{t}$, $W+b\overline{b}$ and $W+c\overline{c}$ is studied in the forward region of proton-proton collisions collected at a centre-of-mass energy of 8 TeV by the LHCb experiment, corresponding to an integrated luminosity of 1.98 $\pm$ 0.02 \mbox{fb}^{-1}. The $W$ bosons are reconstructed in the decays $W\rightarrow\ell\nu$, where $\ell$ denotes muon or electron, while the $b$ and $c$ quarks are reconstructed as jets. All measured cross-sections are in agreement with next-to-leading-order Standard Model predictions

Multidifferential study of identified charged hadron distributions in ZZ-tagged jets in proton-proton collisions at s=\sqrt{s}=13 TeV

Jet fragmentation functions are measured for the first time in proton-proton collisions for charged pions, kaons, and protons within jets recoiling against a $Z$ boson. The charged-hadron distributions are studied longitudinally and transversely to the jet direction for jets with transverse momentum 20 $< p_{\textrm{T}} < 100$ GeV and in the pseudorapidity range $2.5 < \eta < 4$. The data sample was collected with the LHCb experiment at a center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 1.64 fb$^{-1}$. Triple differential distributions as a function of the hadron longitudinal momentum fraction, hadron transverse momentum, and jet transverse momentum are also measured for the first time. This helps constrain transverse-momentum-dependent fragmentation functions. Differences in the shapes and magnitudes of the measured distributions for the different hadron species provide insights into the hadronization process for jets predominantly initiated by light quarks.Comment: All figures and tables, along with machine-readable versions and any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-013.html (LHCb public pages