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A letter to the editor is presented regarding the incidence of Pneumocystis jirovecii pneumonia (PCP) in patients receiving dose-dense therapy with rituximab, cyclophosphamide, non-pegylated liposomal doxorubicin, vincristine, and prednisolone.

Summary: Mantle cell lymphoma is a rare and incurable lymphoproliferative disorder. In the MCL01 trial, patients were treated with the R‐HCVAD regimen [rituximab plus HyperCVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone; R‐CVAD) alternating with high‐dose methotrexate and cytarabine (AM)] for four cycles followed by autologous stem cell transplantation (ASCT) for those who reached only a partial response. After a median follow‐up of 10·5 years, we reported 10‐year progression‐free and overall survival rates of 35% and 61% respectively, with a 10‐years cumulative incidence rate of second malignancies of 10·6%. Mature results of the MCL01 trial confirmed the efficacy of HyperCVAD‐AM as a frontline regimen for younger patients (≤65 years). [ABSTRACT FROM AUTHOR]

The article discusses a study on the predictive value of the chronic lymphocytic leukemia-international prognostic index (CLL-IPI), determined at the time of first treatment, for progression-free survival (PFS) in CLL patients who underwent different frontline chemo-immunotherapy treatment regimens. Topics include the treatment regimens undergone by the patients, capability of the CLL-IPI score to predict PFS, and prognostic power of CLL-IPI when evaluated at the time of first-line therapy.

Single-agent bortezomib (B) has shown activity in heavily pretreated patients with relapsed/refractory indolent lymphoma. On the basis of these findings, we performed a phase II study of B combined with rituximab (R) in patients with relapsed follicular lymphoma (FL). Forty-five patients with fairly good prognostic profiles were enrolled from 2007 to 2011 and received a total of 6 cycles of the B+R combination. The endpoints were the overall response rate (ORR), progression-free survival (PFS), duration of remission (DoR), overall survival (OS), and toxicity evaluation. When considering all the enrolled patients the ORR was 64%. At 5 years, the estimated PFS, DoR, and OS were 34, 49, and 70%, respectively. After excluding the 7 R-naïve patients, the ORR was 58%, with a PFS of 19 months. The most common grade >2 toxicities were thrombocytopenia (18%), peripheral neuropathy (13%), and neutropenia (2%). Our study shows the feasibility, long-term efficacy, and excellent tolerability of the B+R combination. We are aware that our study has specific limitations, such as the small sample size consisting of patients with a relatively good prognostic profile. However, because FL patients will be treated with subsequent chemotherapy regimens, a well-tolerated and effective chemotherapy-free therapy could be considered an additional tool for long-term disease control. [ABSTRACT FROM AUTHOR]

Recently, encouraging results in terms of safety and efficacy have been obtained using bendamustine–rituximab (BR) in untreated chronic lymphocytic leukaemia (CLL) patients enrolled in a phase II study. Here, we report a retrospective international multicenter study of CLL patients treated with BR as front-line therapy. The cohort included 279 patients with progressive CLL from 33 centers (29 Italian, 3 Israeli and 1 German) who received at least 1 cycle of BR as first-line treatment during the 2008–2014 period. The primary objective of this study was to evaluate the efficacy and safety of BR administered as front-line therapy, outside of controlled clinical trials. Median age was 70 years (range, 43–86 years); 62.4% were males and 35.8% had Binet stage C. Forty-two patients (15.2%) were unfit (cumulative illness rating scale [CIRS] score ≥7), and 140 (50.2%) had creatinine clearance ≤70 ml/min. Fluorescent in situ hybridisation analysis, available for 192 cases, showed that 21 (10.9%) had del11q and 18 (9.4%) del17p. The overall response rate (ORR) was 86.4%, with a complete remission rate of 28%. Patients with del17p had an ORR of 66.7%. After median follow-up of 24 months, the 2-year progression-free survival (PFS) was 69.9%; CIRS ≥7, immunoglobulin heavy-chain variable-region ( IGHV ) unmutated status, del17p and BR dose intensity <80% were independently associated with shorter PFS. Grade III or IV neutropenia, thrombocytopenia, and anaemia were observed in 25.9%, 15.4%, and 15.1% of patients, respectively. Twenty-four patients (8.6%) had severe infections. BR is also an effective and safe regimen for untreated CLL patients, outside of controlled clinical trials. [ABSTRACT FROM AUTHOR]

Critical measurements for understanding accretion and the dust/gas ratio in the solar nebula, where planets were forming 4.5 billion years ago, are being obtained by the GIADA (Grain Impact Analyser and Dust Accumulator) experiment on the European Space Agency's Rosetta spacecraft orbiting comet 67P/Churyumov-Gerasimenko. Between 3.6 and 3.4 astronomical units inbound, GIADA and OSIRIS (Optical, Spectroscopic, and Infrared Remote Imaging System) detected 35 outflowing grains of mass 10-10 to 10-7 kilograms, and 48 grains of mass 10-5 to 10-2 kilograms, respectively. Combined with gas data from the MIRO (Microwave Instrument for the Rosetta Orbiter) and ROSINA (Rosetta Orbiter Spectrometer for Ion and Neutral Analysis) instruments, we find a dust/ gas mass ratio of 4 ® 2 averaged over the sunlit nucleus surface. A cloud of larger grains also encircles the nucleus in bound orbits from the previous perihelion.The largest orbiting clumps are meter-sized, confirming the dust/gas ratio of 3 inferred at perihelion from models of dust comae and trails. [ABSTRACT FROM AUTHOR]

The article discusses research of the nucleus structure and activity of comet 67P/Churyumov-Gerasimenko based on images form the Optical, Spectroscopic, and Infrared Remote Imaging System (OSIRIS) onboard the European Space Agency's (ESA's) Rosetta spacecraft. Topics include the shape of comet 67P, it rotational motion and bulk properties, such as density, and the geomorphological differences in structures and textures of various regions, such as Seth.

The article discusses research of comet 67P/Churyumov-Gerasimenko using images acquired by the OSIRIS (Optical, Spectroscopic and Infrared Remote Imaging System) imaging system onboard the European Space Agency's (ESA's) Rosetta spacecraft. Topics include regional structural and textual differences in various regions, such as the Ma’at, Ash, and Seth regions, and the importance of airfall, surface dust transport, mass wasting, and insolation weathering for cometary surface evolution.

Abstract: In 45, ≤60 years old patients with CLL and an adverse biologic profile, a front-line treatment with Fludarabine and Campath (Alemtuzumab®) was given. The overall response rate was 75.5%, the complete response rate (CR) 24.4% with the lowest CR rates, 16.7% and 8.3%, in 11q and 17p deleted cases. The 3-year progression-free survival (PFS) and overall survival were 42.5% and 79.9%, respectively. PFS was significantly influenced by CLL duration, beta2-microglobulin, and improved by post-remissional stem cell transplantation. Front-line fludarabine and alemtuzumab showed a manageable safety profile and evidence of a benefit in a small series of CLL patients with adverse biologic features. [Copyright &y& Elsevier]

Summary This study investigated the clinical activity and toxicity of R-HCVAD-AM [rituximab plus HyperCVAD (R-HCVAD) alternating with high-dose cytarabine and methotrexate (AM)] in patients with newly diagnosed Mantle Cell Lymphoma (MCL). Patients aged ≤70 years with confirmed MCL received four alternating cycles each of R-HCVAD and AM. Patients who obtained a partial response proceeded to autologous stem cell transplant. Sixty-three patients were enrolled and 60 were fully eligible. Median age was 57 years (22-66); 60%, 33% and 7% were classified at low (L)-, intermediate (I)- or high (H)-risk, respectively, according to the MCL International Prognostic Index (MIPI). Only 22 patients (37%) completed the four cycles and three patients died during therapy. Overall response and complete response rates were 83% and 72% respectively. After a median follow-up of 46 months (range 1-72) the estimated 5-year overall survival (OS) and progression-free survival rates were 73% [95% confidence interval (CI) 59-83%], and 61% (95%CI 45-73%) respectively. MIPI maintained the prognostic value with an estimated 5-year OS of 89%, 80% and 24% for L, I, and H groups respectively ( P < 0·001). This multicentre study confirms that R-HCVAD-AM is an active regimen for the initial treatment of patients with MCL, but is associated with significant toxicity. [ABSTRACT FROM AUTHOR]

The article discusses the survival rate of the patients with folicular lymphoma under new treatment options. It says that patients were treated with bleomycin, epidoxorubicin, cyclophosphamide, vincristine, and prednisone (BACOP) plus fludarabine, mitoxantrone, and dexamethasone (FND). Under the treatment, the complete remission rate for BACOP/FND was 62% ad its failure-free survival (FFS) and overall survival (OS) rates were 53% and 77% respectively.

Abstract: Space probes entering planetary atmospheres are used for in situ study of their physical structures. During the entry phase aerodynamic forces exerted on the probe depend on atmospheric density. As a consequence accelerations measured by on-board sensors can be used to derive probe trajectory as well as atmospheric density, pressure and temperature profiles. In this work acceleration data acquired by the Huygens Atmospheric Structure Instrument (HASI) have been used to reconstruct the probe trajectory and the Titan''s atmospheric structure from down to of altitude. An accurate six degree of freedom model of Huygens during the entry phase has been developed and a new reconstruction technique based on Kalman filtering is presented. This technique estimates simultaneously the probe trajectory, the attitude profile consistent with measured data and the atmospheric density, pressure and temperature. [Copyright &y& Elsevier]

Abstract: During the first phase of Huygens arrival into Titan''s atmosphere the probe is subjected to gravitational and aerodynamic forces in aerodynamic hypersonic regime. Atmospheric drag exerts a strong deceleration on the capsule measured by Huygens atmospheric structure instrument (HASI) servo accelerometer. A 6 DOF (Degree of Freedom) model of the Huygens probe entry dynamics has been developed and used for data analysis. The accelerometer data are analysed and the model allows the retrieval of dynamics information of Huygens probe from 1545km altitude down to end of the entry phase. Probe''s initial conditions (velocity and position) were refined to match the measured deceleration profile resulting in a different altitude at interface epoch with respect to those of the Cassini Navigation Team. Velocity and position of probe at interface epoch are compatible with those used by Descent Trajectory Working Group (DTWG). Measurements acquired before atmosphere detection are used to estimate probe''s angular rate, bound attitude and characterise the angle of attack profile which results to be lower than during the whole entry. Probe''s spin calculated (6.98RPM) is slightly different with respect to DTWG of 7.28RPM but considering a 2% error in the Inertia matrix these results are inside the error band. [Copyright &y& Elsevier]

The article provides information on a study which evaluated the impact of evolving therapy including the introduction of rituximab on follicular lymphoma patients. The study made use of data from the consecutive Gruppo Italiano Studio Linfomi (GISL) trials between 1988 and 2004 which enrolled 438 advanced-stage follicular lymphoma patients. Patients enrolled in the trial received anthracycline- and/or fludarabine-based regimens. From the said trial, the overall survival (OS), failure-free survival (FFS) and survival after recurrence (SAR) were analyzed.

The IELSG38 trial was conducted to investigate the effects of subcutaneous (SC) rituximab on the complete remission (CR) rate and the benefits of SC rituximab maintenance in patients with extranodal marginal zone lymphoma (MZL) who received front-line treatment with chlorambucil plus rituximab. Study treatment was an induction phase with oral chlorambucil 6 mg/m2/day on weeks 1-6, 9-10, 13-14, 17-18, and 21-22, and intravenous rituximab 375 mg/m2 on day 1 of weeks 1-4, and 1,400 mg SC on weeks 9, 13, 17, and 21. Then, a maintenance phase followed with rituximab administered at 1,400 mg SC every two months for two years. Of the 112 patients enrolled, 109 were evaluated for efficacy. The CR rates increased from 52% at the end of the induction phase to 70% upon completion of the maintenance phase. With a median follow-up of 5.8 years, the 5-year event-free, progression-free, and overall survival rates were 87% (95% CI: 78-92), 84% (95% CI: 75-89), and 93% (95% CI: 86-96), respectively. The most common grade ≥3 toxicities were neutropenia (33%) and lymphocytopenia (16%). Six patients experienced treatment-related serious adverse events, including fever of unknown origin, sepsis, pneumonia, respiratory failure, severe cerebellar ataxia, and fatal acute myeloid leukemia. The trial showed that SC rituximab did not improve the CR rate at the conclusion of the induction phase, which was the main endpoint. Nevertheless, SC rituximab maintenance might have facilitated long-term disease control, potentially contributing to enhanced event-free and progression-free survival.

Doxorubicin is the most effective single agent in the treatment of non-Hodgkin's lymphoma (NHL). Its use is limited because of the cardiac toxicity primarily in elderly patients (pts) and in pts with history of cardiac disease. Liposomal doxorubicin has been proven to reduce cardiotoxicity. The aim of this retrospective study was the use of nonpeghylated liposomal doxorubicin (NPLD) in term of efficacy, response rate and incidence of cardiac events. We retrospectively collected the experience of 33 Hematological Italian Centers in using NPLD. Nine hundred and forty-six consecutive pts treated with R-COMP (doxorubicin was substituted with NPLD, Myocet) were collected. Median age was 74 years, the reasons for use of NPLD were: age (466 pts), cardiac disease (298 pts), uncontrolled hypertension (126 pts), other reasons (56 pts). According to clinicians' evaluation, 49.9% of pts would not have used standard doxorubicin for different situations (age, cardiomyopathy, previous use of doxorubicin, and uncontrolled hypertension). Overall 687 pts (72.6%) obtained a complete remission (CR). About 5% (n = 51) of subjects developed major cardiotoxic events including heart failure (N = 31), ischemic heart disease (N = 16), acute heart attack (N = 3), and acute pulmonary oedema (N = 1). After a median follow-up of 32 months, 651 pts were alive and the overall survival (OS) was 72%. After a median observation period of 23 months disease free survival (DFS) was 58%. Either in univariate or in multivariate analysis OS and DFS were not significantly affected by age or cardiac disease. Our findings strongly support that including R-COMP is effective and safe when the population is at high risk of cardiac events and negatively selected. Moreover, the use of this NPLD permitted that about half of our population had the opportunity to receive the best available treatment., (© 2020 The Authors. Hematological Oncology published by John Wiley & Sons Ltd.)

The incidence of COVID-19, a severe acute respiratory syndrome caused by SARS-CoV-2, is rapidly growing worldwide. In this pandemic period, the chance of incidental pulmonary findings suggestive of COVID-19 at F-FDG PET/CT in asymptomatic oncological patients is not negligible. To suspect COVID-19 is more demanding whether its presentation is atypical. We describe the incidental PET/CT detection of an F-FDG-avid isolated centrilobular pulmonary consolidation in an asymptomatic lymphoma patient, which later resulted in an unexpected and atypical COVID-19 presentation. The nuclear medicine physicians should be prepared to suspect COVID-19 even in asymptomatic patients presenting with a "far-from-COVID-19" finding at PET/CT.