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Recent advances in machine learning research, combined with the reduced sequencing costs enabled by modern next-generation sequencing, paved the way to the implementation of precision medicine through routine multi-omics molecular profiling of tumours. Thus, there is an emerging need of reliable models exploiting such data to retrieve clinically useful information. Here, we introduce an original consensus clustering approach, overcoming the intrinsic instability of common clustering methods based on molecular data. This approach is applied to the case of non-small cell lung cancer (NSCLC), integrating data of an ongoing clinical study (PROMOLE) with those made available by The Cancer Genome Atlas, to define a molecular-based stratification of the patients beyond, but still preserving, histological subtyping. The resulting subgroups are biologically characterized by well-defined mutational and gene-expression profiles and are significantly related to disease-free survival (DFS). Interestingly, it was observed that (1) cluster B, characterized by a short DFS, is enriched in KEAP1 and SKP2 mutations, that makes it an ideal candidate for further studies with inhibitors, and (2) over- and under-representation of inflammation and immune systems pathways in squamous-cell carcinomas subgroups could be potentially exploited to stratify patients treated with immunotherapy.

Background Pathophysiological features of coronavirus disease 2019-associated acute respiratory distress syndrome (COVID-19 ARDS) were indicated to be somewhat different from those described in nonCOVID-19 ARDS, because of relatively preserved compliance of the respiratory system despite marked hypoxemia. We aim ascertaining whether respiratory system static compliance (Crs), driving pressure (DP), and tidal volume normalized for ideal body weight (VT/kg IBW) at the 1st day of controlled mechanical ventilation are associated with intensive care unit (ICU) mortality in COVID-19 ARDS. Methods Observational multicenter cohort study. All consecutive COVID-19 adult patients admitted to 25 ICUs belonging to the COVID-19 VENETO ICU network (February 28th–April 28th, 2020), who received controlled mechanical ventilation, were screened. Only patients fulfilling ARDS criteria and with complete records of Crs, DP and VT/kg IBW within the 1st day of controlled mechanical ventilation were included. Crs, DP and VT/kg IBW were collected in sedated, paralyzed and supine patients. Results A total of 704 COVID-19 patients were screened and 241 enrolled. Seventy-one patients (29%) died in ICU. The logistic regression analysis showed that: (1) Crs was not linearly associated with ICU mortality (p value for nonlinearity = 0.01), with a greater risk of death for values 2O; (2) the association between DP and ICU mortality was linear (p value for nonlinearity = 0.68), and increasing DP from 10 to 14 cmH2O caused significant higher odds of in-ICU death (OR 1.45, 95% CI 1.06–1.99); (3) VT/kg IBW was not associated with a significant increase of the risk of death (OR 0.92, 95% CI 0.55–1.52). Multivariable analysis confirmed these findings. Conclusions Crs 2O was associated with ICU mortality, while DP was linearly associated with mortality. DP should be kept as low as possible, even in the case of relatively preserved Crs, irrespective of VT/kg IBW, to reduce the risk of death.

IntroductionThe efficacy of non-invasive ventilation (NIV) in acute respiratory failure secondary to SARS-CoV-2 infection remains controversial. Current literature mainly examined efficacy, safety and potential predictors of NIV failure provided out of the Intensive Care Unit (ICU). On the contrary, the outcomes of ICU patients, intubated after NIV failure, remain to be explored. The aims of the present study are: 1) investigating in-hospital mortality in coronavirus disease 2019 (COVID-19) ICU patients receiving endotracheal intubation after NIV failure and 2) assessing whether the length of NIV application affects patient survival. MethodsThis observational multicenter study included all consecutive COVID-19 adult patients, admitted into the twenty-five ICUs of the COVID-19 VENETO ICU network (February-April 2020), who underwent endotracheal intubation after NIV failure. ResultsAmong the 704 patients admitted to ICU during the study period, 280 (40%) presented the inclusion criteria and were enrolled. The median age was 69 [60-76] years; 219 patients (78%) were male. In-hospital mortality was 43%. Only the length of NIV application before ICU admission (OR 2.03 (95% CI 1.06 - 4.98), p = 0.03) and age (OR 1.18 (95% CI 1.04 - 1.33), p < 0.01) were identified as independent risk factors of in-hospital mortality; whilst the length of NIV after ICU admission did not affect patient outcome. ConclusionsIn-hospital mortality of ICU patients intubated after NIV failure was 43%. Days on NIV before ICU admission and age were assessed to be potential risk factors of greater in-hospital mortality.

We present a case of a patient with a three-month history of peripheral blood cytopenia without a confirmed diagnosis of myelodysplastic syndrome, who developed a favourable-risk acute myeloid leukemia (AML), according to the European Leukemia Net (ELN) criteria. The patient achieved a complete remission with incomplete platelet recovery (CRi) after induction. The patient achieved the morphological CR after the first consolidation and completed the first-line treatment with a syngeneic stem cell transplantation (SCT). A disease relapse occurred after one year of CR (blast cell count in the bone marrow 15%), and the patient was offered a haplo-SCT, which he refused due to personal reasons. In this paper, we discuss the interplay between clinical and biological risk factors in non-high-risk AML patients and speculate that some old clinical risk factors (e.g., age of the patient, achievement of CR after induction, and previous history of myelodysplastic syndrome) may still impact on the treatment decision algorithm of some of these patients.

Lo scopo del seguente articolo è studiare gli effetti dell’automazione sul sistema lavorativo e sul layout dell’impianto, analizzando l’impatto economico ed ergonomico delle linee semi-automatiche per il disosso del prosciutto fresco.

Young patients (aged 1860 years) with good-prognosis diffuse large B-cell lymphoma (DLBCL) [0 and 1 risk factor according to age-adjusted international prognostic index (aa-IPI)] are distinguished from patients with poor-prognosis. Six cycles of cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) in combination with rituximab achieved best results in young patients with low-risk DLBCL. We retrospectively analyzed the data of 82 patients (1860 years) with untreated aa-IPI 01 DLBCL, from six Italian institutions, who underwent, between January 2002 and January 2007, rituximab-cyclophosphamide, doxorubicin, vincristine, methotrexate, bleomicin and prednisone (R-MACOP-B) therapy followed, in patients with bulky presentation, by 3036 Gy involved-field radiation therapy (34 patients). An overall response rate was noted in 77 out of 82 (94) patients (75 patients had a complete response (91), 2 patients had a partial response). With a median follow-up of 46 months, 7-year progression-free and overall survival were estimated to be 91 and 94, respectively. R-MACOP-B regimen followed by involved-field radiation on bulky presentation is safe and very effective in the treatment of young patients with low-risk DLBCL. © 2009 Informa Healthcare USA, Inc.

AIM: To evaluate the prevalence of celiac disease in a group of Brazilian individuals over 60 years of age and compare it with the previously known prevalence in a pediatric group living in the same geographical area. METHODS: The research protocol was approved by the Ethics Committee of the University of Brasilia School of Medicine, Brasilia, Brazil. Blood samples from 946 individuals (295 male and 651 female) aged 60 years or older were collected between May 2010 and July 2011. The study subjects’ mean and median ages were 68.1 and 67 years, respectively, ranging from 60 to 92 years. That age distribution closely corresponded to the age distribution of the Brazilian population according to the Brazilian 2010 census. The participants were consecutive and unselected outpatients undergoing blood tests at the University of Brasilia Hospital’s Clinical Pathology Laboratory. All sera were tested for immunoglobulin A anti-transglutaminase antibodies (IgA-tTG) by enzyme- linked immunosorbent assay, and those that were positive were further tested for immunoglobulin A anti-endomysium antibodies (IgA-EMA). Human leukocyte antigen (HLA) genotyping was performed for all individuals who exhibited positive serologic results for IgA-tTG and/or IgA-EMA. RESULTS: Out of the 946 studied patients, only one previously diagnosed case of biopsy-proven celiac disease was detected. For the remaining subjects, nine serum samples tested positive for IgA-tTG antibodies; however, none of them tested positive for IgA-EMA antibodies. The HLA genotyping of those nine subjects revealed that one was carrying DQA1*0501 and two were carrying DQB1*0201 alleles. These data showed that, among those 946 elderly individuals, the prevalence of celiac disease (CD) was 0.1% (95%CI: 0.00-0.59). The prevalence of CD for the elderly group was compared with that observed for the group of 2034 children younger than 15 years (age range, 1-14 years; mean age, 8 years) who took part in our previous CD prevalence screening study. All the children came from the same geographical region and shared a similar ethnic and low-income background. As in the elderly group in the current study, the younger group was made up of consecutive outpatients who underwent blood evaluation at the University of Brasilia Hospital’s Clinical Laboratory. The prevalence of biopsy-proven CD among those children was 0.54% (95%CI: 0.27-0.57). The comparative analysis between the two groups resulted in the following values: odds ratio = 0.19 (95%CI: 0.01-1.45) Fisher test P = 0.06. CONCLUSION: The prevalence of CD among the children of our previous study was 5.4 times higher than that found in the present elderly group.

Previous studies have shown similar effects of rabeprazole and omeprazole, when used at the same dose in the treatment of reflux oesophagitis. However, such studies have been conducted as superiority studies but interpreted as equivalence ones.To properly assess the comparative efficacy of rabeprazole and omeprazole in inducing complete endoscopic healing and symptom relief in patients with reflux oesophagitis.Patients (n=560) with Savary-Miller grade I-III reflux oesophagitis were randomised in a double-blind, double-dummy fashion to rabeprazole or omeprazole 20 mg once daily for 4-8 weeks. Then, patients endoscopically healed and symptomatically relieved were openly maintained with rabeprazole 10 mg or 2x10 mg once daily (in the event of clinical and/or endoscopic relapse) for a maximum of 48 weeks.After 4-8 weeks of treatment, healing (primary end-point) was observed in 228/233 (97.9%) patients in the rabeprazole group and in 231/237 (97.5%) in the omeprazole one (equivalence effect demonstrated by p0.0001 at Blackwelder test and an upper confidence limit at 97.5% of 0.023). However, rabeprazole was faster in inducing heartburn relief than omeprazole (2.8+/-0.2 versus 4.7+/-0.5 days of therapy to reach the first day with satisfactory heartburn relief, p=0.0045 at log-rank test). In the maintenance phase, 15.2% of patients had an endoscopic and/or clinical relapse.Rabeprazole is equivalent to omeprazole in healing reflux oesophagitis, but shows a faster activity on reflux symptoms in the early treatment phase.

A case of systemic amyloidosis of the digestive tract is described here, with particular attention to the endoscopic ultrasonography aspects, characterized by a wide-spread thickening of the stomach and rectum walls, with loss of the normal layer structure of the mucosa and submucosa. Endoscopic ultrasonography, especially in pseudotumoral forms, may contribute to the differential diagnosis from neoplastic lesions, in which the wall thickening appears to be localized and accompanied by parietal infiltration.

Ploidy was studied with flow and image cytometry in 51 polyps removed endoscopically from 44 patients. Evaluation was carried out on frozen material in 34 cases and on material fixed in formalin and embedded in paraffin in the remaining 17. Data analysis showed a statistically significant correlation between polyp size and aneuploidy frequency (P0.05). No statistically significant correlation was found between aneuploidy frequency and histological type. The linear correlation study did, however, show a correlation tendency between histological type and aneuploidy (R = 0.42211).

L’esperienza degli AA. sull’argomento assomma a 3150 epatopatie croniche diffuse non neoplastiche; qui essi riferiscono di 1250 pazienti in cui sono state eseguite contemporaneamente laparoscopia ed epatobiopsia cieca o mirata, cosi suddivisi: 759 cirrosi, 407 epatiti croniche, 80 altre epatopatie croniche non neoplastiche. La diagnosi di epatite cronica, e specialmente dei diversi tipi, deve essere formulata sulla base del reperto istologico. La laparoscopia, anche se spesso fornisce elementi presuntivi, solo di rado permette di rilevare aspetti patognomonici: infatti esiste una notevole varieta di quadri laparoscopici, che vanno dal semplice aumento di volume del fegato fino alla iperplasia nodulare appiattita con cicatrici e fibrosi diffusa. D’altra parte la biopsia esamina una zona limitata di fegato; la laparoscopia invece consente l’osservazione di gran parte della superficie dell’organo e il rilievo di una cirrosi eventualmente sfuggita alla biopsia. Per quanto riguarda la cirrosi, la laparoscopia mostra quasi sempre quadri piu o meno tipici; la biopsia, secondo l’esperienza degli AA., consente la diagnosi in poco piu nella meta dei casi. Per queste ragioni in linea generale la diagnostica di queste malattie deve giovarsi sia della laparoscopia che della biopsia, specialmente quando i dati clinici e di laboratorio non sono espliciti.

This study assesses the usefulness of ultrasound in the diagnosis of portal hypertension due to hepatic cirrhosis. Seventy-nine patients with portal hypertension and 45 control subjects underwent ultrasonography. Two factors were measured: (a) the caliber of the portal vein and (b) the caliber variation of the splenic and superior mesenteric veins during respiration. A lack of normal caliber variation (an increase during inspiration and a decrease during expiration) in these vessels is put forward as an ultrasonographic sign of portal hypertension, and the pathophysiological and clinical significance of this finding are discussed. The sensitivity of ultrasound in detecting portal hypertension, based on the measurement of caliber variation, was 79.7%, and the specificity was 100%. In contrast, the sensitivity of the method, assessed on the basis of portal dilatation, was only 41.8%.

Letters to the Editor

Nowadays, the evaluation of elderly patients' eligibility for allogeneic stem cell transplantation (allo-SCT) is crucial. We evaluated the feasibility and efficacy of a multidimensional geriatric assessment, the Fondazione Italiana Linfomi (FIL) score, on a cohort of 228 patients older than 60 years submitted to allo-SCT in Italy and France from 2008 to 2018. Based on FIL score, available in 215 patients, 125 (58%) patients were classified as “fit” and 90 as “unfit/frail.” The hematopoietic cell transplantation-specific comorbidity index (HCT-CI) was measured in 222 patients (97%); 71 (32%) patients had HCT-CI 0, 75 (34%) patients scored 1–2, and 76 (34%) ≥3. A total of 121 (53%) patients died after a median follow-up of 36 months. FIL score was found to highly predict survival, due to an excess of NRM in unfit/frail group, and confirmed its independent prognostic role on OS (HR: 0.37; 95% CI: 0.25–0.55; p

Ruxolitinib (RUX), the first JAK1/JAK2 inhibitor approved for myelofibrosis (MF) therapy, has recently been associated with the occurrence of second primary malignancies (SPMs), mainly lymphomas and non-melanoma skin cancers (NMSCs). We analyzed the incidence, risk factors and outcome of SPMs in 700 MF patients treated with RUX in a real-world context. Median follow-up from starting RUX was 2·9years. Overall, 80 (11·4%) patients developed 87 SPMs after RUX start. NMSCs were the most common SPMs (50·6% of the cases). Multivariate analysis demonstrated that male sex [hazard ratio (HR): 2·37, 95% confidence interval (95%CI): 1·22–4·60, P=0·01] and thrombocytosis>400×109/l at RUX start (HR:1·98, 95%CI: 1·10–4·60, P=0·02) were associated with increased risk for SPMs. Risk factors for NMSC alone were male sex (HR: 3·14, 95%CI: 1·24–7·92, P=0·02) and duration of hydroxycarbamide and RUX therapy>5years (HR: 3·20, 95%CI: 1·17–8·75, P=0·02 and HR: 2·93, 95%CI: 1·39–6·17, P=0·005 respectively). In SPMs excluding NMSCs, male sex (HR: 2·41, 95%CI: 1·11–5·25, P=0·03), platelet>400×109/l (HR: 3·30, 95%CI: 1·67–6·50, P=0·001) and previous arterial thromboses (HR: 3·47, 95%CI: 1·48–8·14, P=0·004) were shown to be associated with higher risk of SPMs. While it is reassuring that no aggressive lymphoma was documented, active skin surveillance is recommended in all patients and particularly after prolonged hydroxycaramide therapy; oncological screening should be triggered by thrombocytosis and arterial thrombosis, particularly in males.

CMV represents one of the most serious life-threatening complications of allogeneic stem cell transplantaion (allo-SCT). Pre-emptive treatment is highly effective, but toxicity and repetitive reactivation of CMV represent a major challenge in the clinical practice. The use of anti-CMV specific immunoglobulins (Megalotect) is controversial. We retrospectively collected data on 92 patients submitted to allo-SCT for hematological malignancies, in whom Megalotect was used either for prophylaxis (n=14) or with pre-emptive therapy (n=78). All the patients were considered at high-risk of developing CMV reactivation and CMV disease. The treatment was well tolerated, with no reported infusion reactions, nor other adverse events. None of the 14 cases treated with Megalotect as prophylaxis developed CMV reactivation. 51/78 (65%) patients who received Megalotect during pre-emptive treatment achieved complete clearance of CMV viremia, and 14/51 patients (29%) developed a breakthroug CMV infection. 7/78 patients (9%) developed CMV disease. The projected 1-year OS, 1-year TRM and 1-year RR is 74%, 15% and 19%, respectively. No differences were observed in terms of OS, TRM and RR by comparing patients who achieved a complete response after treatment versus those who did not.. These retrospective data suggest that Megalotect is safe and well tolerated. When used as prophylaxis, no CMV reactivation was recorded. We have no conclusive data regarding its efficacy in reducing the cumulative dose of anti-CMV specific drugs in the pre-emptive setting. Further prospective trials are warrented to identify the best setting of patients who can benefit from Megalotect alone or in addition to anti-CMV specific drugs.

Background A prospective, single-arm, open-label, multicenter, nonrandomised phase II trial to evaluate efficacy and safety of short fludarabine, mitoxantrone, and rituximab (FMR) induction followed by radioimmunotherapy, in untreated, intermediate/high-risk follicular non-Hodgkin’s lymphoma (NHL) patients. Patients and methods Fifty-five patients were treated using a sequential treatment schedule of four induction cycles of FMR chemoimmunotherapy, and a subsequent consolidating single administration of 90Y-ibritumomab tiuxetan (90Y-IT), 8–14 weeks later. Patients were eligible for radioimmunotherapy if at least in partial response (PR) after induction, with normal platelet and granulocyte counts and a bone marrow infiltration ≤25%. Primary study end points were response rate and hematologic toxic effects; secondary end points were overall survival (OS) and progression-free survival (PFS). Results All the 55 patients received four induction cycles with an overall response rate of 96% (38 complete responses [CR] and 15 PR). Fifty-one patients (38 in CR and 13 in PR) received 90Y-IT. By the end of the treatment, 49/55 patients achieved a CR. With a median follow-up of 21 months, the estimated 3-year PFS was 81% and the 3-year OS 100%. Conclusions This study has established feasibility, tolerability, and efficacy of a regimen composed by short FMR induction with 90Y-IT consolidation in untreated intermediate/high-risk follicular NHL patients.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of aggressive non-Hodgkin lymphoma and despite recent chemotherapeutic advances up to half of all patients relapse. Here we report the results from a phase 2, single-arm, single-center trial evaluating the safety and efficacy of lenalidomide plus rituximab in elderly patients with relapsed or refractory DLBCL. PATIENTS AND METHODS: Between March and June 2009, elderly patients (65 years of age or older) with relapsed/refractory DLBCL who had been heavily pretreated were recruited. Oral lenalidomide (20 mg/d for 21 days of each 28-day cycle) was initiated for four cycles and rituximab (375 mg/m(2)) was administered on day 1 and day 21 of each 28-day cycle for four cycles. After this induction phase, patients achieving a complete response (CR), partial response (PR), or stable disease (SD) were given lenalidomide maintenance therapy at the same schedule for another 8 months. RESULTS: A total of 23 patients with a median of three prior treatments (range, 2 to 8) were included. The overall response rate (CR + PR) at the end of the induction phase was 35% (n = 8). Ten patients (7 CR, 1 PR, and 2 SD patients) were eligible for lenalidomide maintenance and 8 of these patients achieved a CR. Adverse events were manageable and the most common included neutropenia and thrombocytopenia. CONCLUSION: Oral lenalidomide in combination with rituximab is active in elderly patients with relapsed/refractory DLBCL with a high percentage of patients achieving a continuous CR after lenalidomide maintenance.

Purpose: This study aimed to evaluate the efficacy and safety of the treatment with 90Y-ibritumomab tiuxetan following a short-course of rituximab with cyclophosphamide-adriamycin-vincristine-prednisone (R-CHOP) in high-risk elderly patients with previously untreated diffuse large B-cell lymphoma (DLBCL). Experimental Design: From December 2006 to October 2008, 55 high-risk elderly (age ≥60 years) untreated DLBCL patients were treated in seven Italian institutions with a short-course of chemotherapy consisting of four cycles of R-CHOP21 followed by 90Y-ibritumomab tiuxetan 6 to 10 weeks later. Results: Of the 55 patients, 48 underwent radioimmunotherapy. The overall response rate to the entire treatment regimen was 80%, including 73% complete remissions and 7% partial remissions. Eight (50%) of the 16 patients who achieved less than a complete response with CHOP improved their remission status after 90Y-ibritumomab tiuxetan administration. With a median follow-up of 18 months, the 2-year progression-free survival was estimated to be 85%, with a 2-year overall survival of 86%. 90Y-ibritumomab tiuxetan toxicity consisted of grade 3 to 4 hematologic toxicity in 28 of 48 patients, mainly neutropenia (23 patients) and thrombocytopenia (15 patients). Red cells and/or platelets transfusions were given to three patients. Conclusion: This study evaluated the feasibility, efficacy, and safety of a short-course R-CHOP21 regimen followed by 90Y-ibritumomab tiuxetan in high-risk elderly DLBCL patients. Clin Cancer Res; 16(15); 3998–4004. ©2010 AACR.

Background Peripheral T-cell lymphoma unspecified (PTCLU) and mycosis fungoides (MF) often show resistance to conventional chemotherapy. Gemcitabine should be considered a suitable option. We report the long-term update of 39 pretreated T-cell lymphoma patients treated with gemcitabine. Patients and methods From May 1997 to September 2007, 39 pretreated MF and PTCLU patients received gemcitabine. Inclusion criteria were as follows: histologic diagnosis of MF or PTCLU; relapsed/refractory disease; age ≥18 years; and World Health Organization performance status of two or less. Nineteen patients had MF and 20 PTCLU. All patients with MF had a T3–T4, N0, and M0 disease and patients with PTCLU had stage III–IV disease. Gemcitabine was given on days 1, 8, and 15 on a 28-day schedule (1200 mg/m2/day) for a total of three to six cycles. Results Overall response rate was 51% (20 of 39 patients); complete response (CR) and partial response (PR) rates were 23% (9 of 39 patients) and 28% (11 of 39 patients), respectively. Patients with MF had a CR rate of 16% and a PR rate of 32% compared with a CR rate of 30% and a PR rate of 25% of PTCLU patients. Among the CR patients, 7 of 9 are in continuous complete response with a variable disease-free interval (15–120 months). Conclusion In our experience, gemcitabine proved to be effective in pretreated MF and PTCLU patients, even in the long term.

BACKGROUND. Limited data exist about the role of second-line chemotherapy response assessed by positron emission tomography (PET) as a prognostic factor in patients with aggressive non-Hodgkin Lymphoma (NHL) who undergo autologous stem cell transplantation (ASCT). The objective of this analysis was to investigate the main determinants of prognosis in patients with aggressive B-cell NHL who undergo ASCT, focusing on the impact of pretransplantation PET, secondary age-adjusted International Prognostic Index (sAA-IPI) score, histology, and previous response to first-line chemotherapy. METHODS. Seventy-five patients with diffuse, large B-cell lymphoma or grade 3 follicular lymphoma who were treated at the author' institution with second-line chemotherapy (combined ifosfamide, etoposide, and epirubicin [IEV]) followed by ASCT between September 2002 and September 2006 were included. All patients were evaluated by PET after 1 to 3 courses of IEV chemotherapy before ASCT, and all patients received a conditioning regimen of combined carmustine, etoposide, cytosine arabinoside, and melphalan. The prognostic impact of pretransplantation PET, sAA-IPI score, histology, and previous response to first-line chemotherapy was evaluated by univariate and multivariate analyses. RESULTS. Seventy-two of 75 patients underwent ASCT. In a univariate analysis for progression-free survival (PFS) and overall survival (OS), a significant association was observed with pretransplantation PET (PFS, P < .00001; OS, P < .01) and previous first-line response (PFS, P = .02; OS, P = .04). In the multivariate framework, pretransplantation PET was identified as the only independent prognostic factor (PFS, P < .001; OS, P = .01). CONCLUSIONS. The current data indicated that pretransplantation PET is the main prognostic predictor in patients with aggressive B-cell NHL who are scheduled for ASCT. Cancer 2008. © 2008 American Cancer Society.

Indolent non-follicular lymphomas (inFLs) are generally regarded as incurable, apart from extranodal mucosa-associated lymphatic tissue lymphomas, which can be partially cured by surgery, local radiotherapy, or antibiotic treatment. The aim of the present study was to test the degree of effectiveness and the safety of the regimen containing fludarabine, mitoxantrone, and rituximab (FMR) in inFL patients considering all the different entities belonging to this group. An observational retrospective study was conducted on 143 inFL patients providing that their first chemoimmunotherapy performed was FMR regimen and diagnosis from September 2000 to March 2011. There were 32 small lymphocytic lymphomas and 111 marginal zone lymphomas. At the end of treatment, overall response rate was 96.5% with 88% of complete responses (CR) and 8.5% of partial responses. With a median follow-up of 48 months, 10 out of 125 (8%) CR patients had disease relapse, yielding an estimated 9-year disease-free survival (DFS) of 74.9% and an estimated 10-year overall survival of 92.8%. The estimated 9-year progression free survival was 70.5%. The 10 relapsed patients showed lymphoma recurrence within 52 months: after this time, the DFS curve presented a plateau configuration. Only two (1.4%) patients developed a secondary hematological neoplasia. This study showed promising findings for the use of a fludarabine-based regimen in combination with rituximab in the front-line treatment of symptomatic inFL with a noteworthy high percentage of CR associated to an interesting long-term DFS and favorable acute and long-term safety profile. Copyright © 2014 John Wiley & Sons, Ltd.

LETTER TO THE EDITOR

Hairy cell leukemia (HCL) patients could have an excellent prognosis with adequate treatment. Treatments are not generally curative but are extremely effective in inducing long-lasting clinical remissions. An observational retrospective study was conducted on a single-center registry of 144 patients with a median follow-up of 11.5 years, focusing on long-lasting continuous first complete remissions (CR) wondering if patients can be cured only with front-line approach. CR for more than 5 years after first-line therapy were found in 22.2 \% cases. The median duration of response was 9.8 years, while for relapsed patients, the first response had a median duration of 2.4 years. Three different subsets of long-lasting first CR were identified: 15 patients are between 5 and 10 years with a median duration of CR of 6.5 years; 7 patients are between 10 and 15 years with a median duration of CR of 12.3 years; and 10 patients present a follow-up superior to 15 years with a median duration of CR of 20.0 years. There is a need for continuous study in this field to better define the optimal therapeutic regimen and, in particular, the biological issues since at least 20-25 \% of HCL patients can be cured with only one treatment.

Not available.

Current treatments for non-Hodgkin lymphomas are not optimally effective. Among new agents, bortezomib seems to play a pivotal role in the regulation of several cell pathways involved in the development of lymphomas. After results were obtained with clinical trials, we aimed to observe treatment with bortezomib in everyday clinical practice. We performed a multicenter retrospective analysis to assess the efficacy of bortezomib in heavily pretreated (median number of previous therapies 4, range 2-6) lymphoma patients in an off-label setting. Bortezomib therapy was scheduled for 4-6 cycles (1.3 mg/m2 biweekly). Data from 50 patients were collected: 22% had a complete remission, 26% obtained a partial response and the remaining 52% was non-responder. According to histotype, we observed an overall response rate (ORR) of 51.6% in mantle cell lymphomas, an ORR of 60% among follicular lymphoma patients, and an ORR of 50% in the indolent nonfollicular lymphomas. None of diffuse large B-cell lymphoma patients obtained a response. Extra-hematological toxicity was really mild, and peripheral neuropathy occurred in only 5 patients; hematological toxicity was grades 3-4 thrombocytopenia in nine patients and grades 3-4 neutropenia in only three patients. In conclusion, treatment with bortezomib as single agent resulted safe and effective in a subset of heavily pretreated lymphoma patients with usually poor outcome. New future hypotheses of investigation are indicated. Copyright © 2012 John Wiley & Sons, Ltd.