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Micro-Abstract In this limited retrospective analysis, we report on 52 “high risk” AL amyloidosis patients treated with first line bortezomib based chemotherapy. Achieving a hematological complete response (CR+VGPR) at day 30 confirmed its prognostic value. Nevertheless, patients who reached a suboptimal response (PR) at day 30 have a reasonable chances of survival, and do not necessarily need a change in therapeutic strategy even in the face of permissive clinical conditions. On the other hand, an early identification of NR patients should prompt a shift in therapy trying to improve the well-known dismal prognosis of these patients. We have also shown that even “high-risk” AL amyloidosis patients can be managed safely and effectively in a hematology ward. Purpose To assess the feasibility and the results of Bortezomib-based treatment of “high-risk” AL-amyloidosis patients in a hematology ward. Methods We report on 52 high-risk amyloidosis patients treated with first-line bortezomib-based chemotherapy. Results At day 30 from the beginning of the therapy, 23 patients (44%) achieved a hematological response (complete response plus very good partial response); 14 patients (27%) achieved a partial response; 15 patients (29%) were non-responders. After a median follow-up of 28.5 months, the survival rates were 18/23 (78%) for responders; 9/14 (64%) for partial responders and 3/15 (20%) for non-responders with a median overall survival of 43, 24 and 11 months, respectively (log-rank test: p Conclusions These results show that high-risk AL-amyloidosis patients can be managed safely and effectively in a hematology ward. A partial hematologic response may herald a later better response, organ response, and can allow a subsequent second-line therapy and a good survival.

Simple Summary Both BR, and R-BAC are suitable induction therapies in elderly patients with mantle cell lymphoma (MCL). However, the two regimens have not been compared before. We retrospectively analysed the outcome and the safety features of elderly patients with newly diagnosed MCL, treated with BR or R-BAC between 2008 and 2019 at eight institutions. We used propensity scores to reduce selection bias, thus analysing 156 patients (53 BR, 103 R-BAC). Patients treated with R-BAC achieved higher CR rate than BR (91% vs. 60%, p < 0.0001). The 2-year PFS was 87 ± 3% and 64 ± 7% for R-BAC and BR, respectively (p = 0.001). Median overall survival (OS) was 121 months for R-BAC and 78 months for BR (p = 0.08). R-BAC was associated with significantly more pronounced grade 3–4 thrombocytopenia than BR (50% vs. 17%). This study indicates that R-BAC is associated with significantly prolonged 2-year PFS than BR in elderly patients with MCL. Abstract Background: Rituximab plus bendamustine (BR), and rituximab, bendamustine, and cytarabine (R-BAC) are well-known induction therapies in elderly patients with mantle cell lymphoma (MCL), according to clinical guidelines. However, a direct comparison between the two regimens has never been performed. Methods: In this multicentre retrospective study, we compared the outcome of patients with newly diagnosed MCL, treated with BR or R-BAC. Primary endpoint was 2-year progression-free survival (PFS). Inclusion bias was assessed using a propensity score stratified by gender, age, MCL morphology, and MIPI score. Results: After adjusting by propensity score, we identified 156 patients (53 BR, 103 R-BAC) with median age of 72 (53–90). Median follow-up was 46 months (range 12–133). R-BAC was administered in a 2-day schedule or with attenuated dose in 51% of patients. Patients treated with R-BAC achieved CR in 91% of cases, as compared with 60% for BR (p < 0.0001). The 2-year PFS was 87 ± 3% and 64 ± 7% for R-BAC and BR, respectively (p = 0.001). In terms of toxicity, R-BAC was associated with significantly more pronounced grade 3–4 thrombocytopenia than BR (50% vs. 17%). Conclusions: This study indicates that R-BAC, even when administered with judiciously attenuated doses, is associated with significantly prolonged 2-year PFS than BR in elderly patients with previously untreated MCL.

POEMS syndrome is a disease due to underlying plasma cells (PC) dyscrasia. Because of its rarity, there are no established upfront or second-line therapies. Treatment is borrowed from other PC diso...

This paper shows the main results of a multidisciplinary study performed along the southeastern sector of the Agri Valley in Basilicata (Southern Italy), where Cenozoic units, crucial for constraining the progressive evolution of the Southern Apennine thrust and fold belt and, more in general, the geodynamic evolution of the Mediterranean area are widely exposed. In particular, we aimed at understanding the stratigraphic and tectonic setting of deep-sea, thrust-top Cenozoic units exposed immediately to north of Montemurro, between Costa Molina and Monte dell’Agresto. In the previous works different units, showing similar sedimentological characteristics but uncertain age attribution, have been reported in the study area. In our study, we focussed on the Albidona Formation, pertaining to the Liguride realm, which shows most significant uncertainties regarding the age and the stratigraphic setting. The study was based on a detailed field survey which led to a new geological map of the area. This was supported by new stratigraphic, biostratigraphic and structural analyses. Biostratigraphic analysis provided an age not older than the upper Ypresian and not younger than the early Priabonian. Recognition of marker stratigraphic horizons strongly helped in the understanding of the stratigraphy of the area. The study allowed a complete revision of the stratigraphy of the outcropping Cenozoic units, the recognition of until now unknown tectonic structures and the correlation between surface and subsurface geology.

Daratumumab demonstrated activity in the treatment of AL amyloidosis in two recently concluded phase II clinical trials in relapsed and refractory patients. Its role in upfront therapy is under evaluation in a phase III study. In this report we evaluated the safety and efficacy of 28-day cycles of daratumumab (single agent or combined with bortezomib or lenalidomide) in 72 previously treated patients with multiple myeloma and AL amyloidosis. Fifty (69%) were refractory to the last line of therapy. After eight infusions of daratumumab, 59 patients (82%) achieved a hematologic response, with 12 (16%) complete responses (CRs) and 30 (42%) very good partial responses (VGPRs). After 16 infusions, the quality of response improved with 22 patients (30%) achieving CR and 21 (29%) attaining VGPR. Cardiac response was observed in 11 of 37 evaluable patients (29%) and renal response in 23 of 38 patients (60%). Daratumumab is highly effective in heavily pretreated patients with relapsed/refractory AL amyloidosis and high bone marrow plasma cell burden. Renal responses, which are usually rare in this setting, were frequently observed.

Hairy cell leukemia variant (HCLv) is a chronic lymphoproliferative disorder classified as a provisional entity in the 2016 WHO Classification of Lymphoid Tumors. HCLv is characterized by unfavorable prognosis, low complete remission rates and limited disease control following classical hairy cell leukemia-based regimens. In this study, we report 3 cases of elderly patients with treatment-naive, TP53 un-mutated HCLv, who were effectively treated with four cycles of bendamustine plus rituximab. The regimen was completed in all the patients with acceptable toxicity. All patients achieved a complete clinical response with no evidence of residual disease at bone marrow biopsy and flow-cytometry examination. After a median follow-up of 19 months, the 3 subjects are still in complete remission. In this work, bendamustine plus rituximab proved to be an effective and feasible first-line treatment strategy for elderly patients with TP53 un-mutated HCLv.

Dysfunctions of the immune system, both as hyperactivity or defect, may lead to the development of different diseases. Malignant transformation of cells involved in the immune regulation, such as i...

INTRODUCTION: Daratumumab has been recently introduced in the treatment of patients with multiple myeloma (MM). Two phase II trials of this drug in relapsed/refractory AL amyloidosis were recently completed, but final reports have not been published so far. One randomized phase III trial in treatment-naïve patients with this diseases has recently completed enrollment and the results are eagerly awaited. However, several retrospective series showed encouraging response rates with daratumumab alone or in combination with bortezomib or immune modulatory drugs in AL amyloidosis. After this drug was marketed for MM in Italy, it became routinely accessible also to patients with myeloma-associated AL amyloidosis (MM-AL). We evaluated the efficacy of daratumumab in a consecutive series of patients with MM-AL in three centers of the Italian Amyloidosis Study Group. METHODS: Consecutive patients with a diagnosis of MM-AL treated with daratumumab were included in the study. Patients received daratumumab 16 mg/Kg body weight e.v. once a week for the first two months and then every other week for the next four months and subsequently every 28 days. The standard DVd (daratumumab, bortezomib and dexamethasone) and DRd (daratumumab, lenalidomide and dexamethasone) regimens were also used in subsets of patients. Hematologic and organ responses were assessed according to the International Society of Amyloidosis (ISA) criteria. RESULTS: Seventy-two patients were included in the study (61 in Pavia, 10 in Padua and 1 in Turin), Table. Median age was 61 years (range: 37-79 years) and 45 (63%) patients were males. The heart and the kidney were involved in 49 patients each (68%). Median bone marrow plasma cell infiltrate was 18% (range: 11-50%). Median time from diagnosis to treatment initiation was 32 months (range: 3-185 months). Fifty (69%) patients were refractory to the line of therapy immediately preceding daratumumab. Median number of prior treatments was 2 (range: 1-9) and daratumumab was used as second line option in 20 (28%) cases. Forty-seven (65%) patients received daratumumab as single agent. The remaining patients received DVd 14 (19%) and DRd in 11 (15%) cases. After 8 infusions 59 (82%) patients achieved a hematologic response (HR): complete response (CR) in 12 (16%), very good partial response (VGPR) in 30 (42%) and partial response (PR) in 17 (24%). Cardiac response was observed in 9 of 37 evaluable patients (24%) and renal response in 21 of 38 patients (55%). Among patients in VGPR, 4 did not qualify for CR due to the persistence of an abnormal free light chain (FLC) ratio (FLCR) despite normalization of involved FLC (iFLC) due to lower than normal levels of uninvolved FLC, while serum and urine immunofixation were negative. After 16 infusions there was only a modest improvement of overall HR rate (60 patients, 83%), but quality of response improved: with CR in 22 patients (30%), VGPR in 21 (29%), and PR in 17 (24%). Of the 4 patients in iFLC-response after 8 infusions, 2 qualified for CR with normalization of FLCR after 16 infusions. In the other 2 patients FLCR did not normalize and we found persistence of the amyloid light chain at high-resolution immunofixation of serum and/or urine. No difference in HR was seen between patients treated with daratumumab single agent and those who received daratumumab combinations (after 16 infusions 81% vs. 88%, P=0.470). After 16 infusions, cardiac response was observed in 11 of 37 evaluable patients (29%) and renal response in 23 of 38 patients (60%). After a median follow-up of living patients after daratumumab initiation of 12 months, 5 subjects died due to disease progression and projected survival at 1 year was 95%. CONCLUSION: Daratumumab is effective in heavily pretreated patients with MM associated AL amyloidosis. Quality of response improved over time with 60% of patients achieving CR or VGPR after 16 infusions. Suppression of uninvolved FLC may result in delayed normalization of FLC ratio in some patients. Disclosures Milani: Pfizef: Honoraria; Janssen: Honoraria. Larocca:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria. Oliva:Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees. Petrucci:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Palladini:Celgene: Other: Travel grant; Janssen-Cilag: Honoraria; Sebia: Honoraria; Janssen-Cilag: Other: Travel grant.

F 2 gas mixtures offer ideal properties to be employed as chamber cleaning gas: low dissociation energy and high reactivity, which leads to superior efficiency and ease of abatement. In this work, a new F 2 gas mixture was used with a combination ratio of 10% Ar, 20% F 2 and 70% N 2 in order to obtain a maximum of 20% fluorine in inert gases. This novel Ar/N 2 /F 2 gas mixture has been evaluated as a candidate to replace conventional cleaning gases, like NF 3 , C 2 F 6 and CF 4 in an industrial AMAT P5000 CVD chamber tool. Standard equipment has been used, showing complete compatibility with the new gas. The tested Ar/N 2 /F 2 mixture shows improvements in both parameters, cleaning at a faster rate (up to more 27%), even requiring a lower amount of gas (minus 96% versus NF 3 ). The higher etching rate and the lower gas consumption assure a sensible CoO (Cost of Ownership) advantage to any potential user. The superior etch rate performance of the Ar/N 2 /F 2 gas mixture was combined with excellent etch non uniformities values, of °3% (1sigma) on SiO 2 and of °8% (1sigma) on Si 3 N 4 , respectively. Also amorphous Silicon (a-Si) was etched completely and uniformly. The particle performance data showing in average just 14 particle adders (0.25µm), indicating that no significant particle contamination was induced by the process and Ar/N 2 /F 2 can be used as a highly clean and efficient etching gas as well as an ideal drop-in replacement for the conventional cleaning gases.

Vinylformiat wurde in Substanz, Aceton, Chloroform bzw. Dimethylformamid bei Temperaturen zwischen +60 und −20°C radikalisch polymerisiert. Aus der Temperaturabhangigkeit des Verhaltnisses Xi/Xs an isotaktischen und syndiotaktischen Diaden wurde die Differenz der Aktivierungsenthalpien (ΔHi≠ − ΔHs≠) bzw. -entropien (ΔSi≠ − ΔSs≠) fur die Polymerisation in den einzelnen Losungsmitteln berechnet. Zwischen (ΔHi≠ − ΔHs≠) und (ΔSi≠ − ΔSs≠) besteht ein Kompensationseffekt. Aus der Kompensationstemperatur T0 = 344°K der Stereokontrolle wird geschlossen, das die Stereokontrolle mindestens teilweise durch Wasserstoffbruckenbindungen im ubergangszustand bedingt ist. Vinylformate has been polymerized by free radicals in bulk, acetone, chloroform, and dimethylformamide at temperatures between +60 and −20°C. The differences (ΔHi≠ − ΔHs≠) of the activation enthalpies and (ΔSi≠ − ΔSs≠) of activation entropies were calculated from the temperature dependence of the ratio Xi/Xs of the mole fractions of isotactic and syndiotactic dyads, resp., formed in the different solvents. A compensation effect exists between (ΔHi≠ − ΔHs≠) and (ΔSi≠ − ΔSs≠) resp. The compensation temperature for the stereocontrol was determined as T0 = 344°K. This numerical value points towards a stereocontrol by hydrogen bonds during the transition state.