Texture analysis of 18F-FDG PET/CT and CECT: Prediction of refractoriness of Hodgkin lymphoma with mediastinal bulk involvement.

To recognize patients at high risk of refractory disease, the identification of novel prognostic parameters improving stratification of newly diagnosed Hodgkin Lymphoma (HL) is still needed. This study investigates the potential value of metabolic and texture features, extracted from baseline 18F-FDG Positron Emission Tomography/Computed Tomography (PET) and Contrast-Enhanced Computed Tomography scan (CECT), together with clinical data, in predicting first-line therapy refractoriness (R) of classical HL (cHL) with mediastinal bulk involvement. We reviewed 69 cHL patients who underwent staging PET and CECT. Lesion segmentation and texture parameter extraction were performed using the freeware software LIFEx 6.3. The prognostic significance of clinical and imaging features was evaluated in relation to the development of refractory disease. Receiver operating characteristic curve, Cox proportional hazard regression and Kaplan-Meier analyses were performed to examine the potential independent predictors and to evaluate their prognostic value. Among clinical characteristics, only stage according to the German Hodgkin Group (GHSG) classification system significantly differed between R and not-R. Among CECT variables, only parameters derived from second order matrices (gray-level co-occurrence matrix (GLCM) and gray-level run length matrix (GLRLM) demonstrated significant prognostic power. Among PET variables, SUVmean, several variables derived from first (histograms, shape), and second order analyses (GLCM, GLRLM, NGLDM) exhibited significant predictive power. Such variables obtained accuracies greater than 70% at receiver operating characteristic analysis and their PFS curves resulted statistically significant in predicting refractoriness. At multivariate analysis, only HISTO_EntropyPET extracted from PET (HISTO_EntropyPET ) and GHSG stage resulted as significant independent predictors. Their combination identified 4 patient groups with significantly different PFS curves, with worst prognosis in patients with higher HISTO_EntropyPET values, regardless of the stage. Imaging radiomics may provide a reference for prognostic evaluation of patients with mediastinal bulky cHL. The best prognostic value in the prediction of R versus not-R disease was reached by combining HISTO_EntropyPET with GHSG stage.

Biological features and outcome of diffuse large B-cell lymphoma associated with hepatitis C virus in elderly patients: Results of the prospective 'Elderly Project' by the Fondazione Italiana Linfomi.

Up to 10%-15% of diffuse large B-cell lymphoma (DLBCL) are related to hepatitis C virus (HCV) infection, in particular in elderly patients. The Fondazione Italiana Linfomi has recently published a multicentre prospective observational study, the 'Elderly Project', on the outcome of DLBCL in patients aged ≥65 years, evaluated using a simplified comprehensive geriatric assessment. The aim of this study was to compare biological and clinical features of HCV positive (HCV+) with HCV negative (HCV-) cases. A total of 89 HCV+ patients were identified out of 1095 evaluated for HCV serology (8.1%). The HCV+ patients were older, less fit, and had frequent extranodal involvement. The cell-of-origin determination by Nanostring showed that HCV+ cases less frequently had an activated B-cell profile compared to HCV- patients (18% vs. 43%). In all, 86% of HCV+ patients received rituximab-cyclophosphamide, doxorubicin, vincristine (Oncovin) and prednisone (R-CHOP)-like immunochemotherapy. Grade 3-4 liver toxicity occurred in 3% of cases. Among centrally reviewed cases confirmed as DLBCL, the 3-year overall survival of HCV+ patients was very similar to HCV- (63% vs. 61%, p = 0.926). In all, 20 HCV+ patients were treated with direct-acting antiviral agents (DAAs), with good tolerance and sustained virological response in all cases. The 3-year progression-free survival for this subgroup was excellent (77%), suggesting DAAs' possible role in reducing the risk of relapse by eliminating the viral trigger.

Diffuse large B-cell lymphoma in octogenarians aged 85 and older can benefit from treatment with curative intent: a report on 129 patients prospectively registered in the Elderly Project of the Fondazione Italiana Linfomi (FIL).

Octogenarian patients with diffuse large B-cell lymphoma are managed mainly with palliation, but recent improvement in their overall condition makes potentially curative treatment a possibility. Studies have shown that half of selected octogenarians may be cured using reduced-dose anthracycline chemoimmunotherapy. However, patients aged >85 (late octogenarians [LO]) were underrepresented, and selection criteria were poorly defined. We analyzed the clinical characteristics and outcomes of LO enrolled in the FIL Elderly Project in terms of the treatment received (palliative vs. curative) and of their simplified geriatric assessment (sGA), then compared them with early octogenarians (EO) aged 80- 84 and with those aged 65-79 classified as UNFIT or FRAIL according to sGA enrolled in the same study. Of the 1,163 patients, 370 were >80 and 129 LO. Clinical characteristics were similar between LO and EO, but LO more frequently received palliation (50% vs. 23%; P=0.001) and had worse 2-year overall survival (OS) (48% vs. 63%; P=0.001) and 2-year progression-free survival (PFS) (43% vs. 56%; P=0.01). Patients receiving anthracycline did better than patients receiving palliation (P<0.001), without any difference between full or reduced doses. Rituximab within palliation improved outcome (2-yr OS with or without rituximab 42% vs. 22%; P=0.008). Elderly Prognostic Index (EPI) performed better than sGA in identifying different risk categories, and high-risk EPI retained an independent unfavorable effect on OS and PFS, together with treatment without anthracycline. In conclusion, late octogenarians can benefit from a curative approach with reduced-dose anthracycline and from rituximab within palliation. EPI may help in patient selection more than sGA can.

The elderly prognostic index predicts early mortality in older patients with diffuse large B-cell lymphoma. An ad hoc analysis of the elderly project by the Fondazione Italiana Linfomi.

The Elderly Prognostic Index (EPI) is based on the integration of a simplified geriatric assessment, hemoglobin levels and International Prognostic Index and has been validated to predict overall survival in older patients with diffuse large B-cell lymphoma (DLBCL). In this study, we evaluated the ability of EPI to predict the risk of early mortality. This study included all patients registered in the Elderly Project for whom treatment details and a minimum follow-up of 3 months were available. Three main treatment groups were identified based on the anthracycline amount administered: cases receiving >70% of the theoretical anthracyclines dose (Full Dose [FD] group), ≤70% (Reduced Dose [RD]) and palliative therapy (PT; no anthracyclines). The primary endpoint was early mortality rate, defined as death for any cause occurring within 90 days from diagnosis. We identified 1150 patients with a median age of 76 years (range 65-94). Overall, 69 early deaths were observed, accounting for 19% of all reported deaths. The cumulative rate of early mortality at 90 days was 6.0%. Comparing early with delayed deaths, we observed a lower frequency of deaths due to lymphoma progression (42% vs. 75%; p < 0.001) and a higher frequency due to toxicity and infections (22% vs. 4%, p < 0.001, and 22% vs. 3%, p < 0.001, respectively) for early events. A multivariable logistic analysis on 931 patients (excluding PT) confirmed an independent association of high-risk EPI (odds ratio [OR] 3.60; 95% confidence interval [CI] 1.15-11.2) and bulky disease (OR 2.08; 95% CI 1.09-3.97) with the risk of early mortality. The cumulative incidence of early mortality for older patients with DLBCL is not negligible and is mainly associated with non-lymphoma related events. For patients receiving anthracyclines, high-risk EPI and bulky disease are associated with a higher probability of early mortality.

Ibrutinib in relapsed/refractory patients with Waldenström macroglobulinemia: a real-life, retrospective study on behalf of the "RTL" (regional Tuscan lymphoma network).

Ibrutinib represents the first approved treatment for patients with Waldenström macroglobulinemia (WM). There are very few published experiences outside of a clinical trial. In this study, we investigated treatment response, survival, and safety in a real life setting. We retrospectively analyzed 49 consecutive R/R WM patients, managed in 8 Tuscan onco-hematological centers, that received ibrutinib after its approval, at a maximum dose of 420 mg once per day, until disease progression or unacceptable toxicity. Median age was 65 years (range 32-86), and the median number of previous regimens was 2 (range 1-5). Overall and major response rate were 91.8% and 87.7%, respectively. At best response, median IgM level declined from 3,094 to 831 mg/dl, and Hb level increased from 10.4 to 12.7 g/dl. In an intention-to-treat analysis, 36/49 patients (73.5%) were still receiving treatment, while 13/49 (26.5%) had discontinued therapy. Six out of 49 cases (12.2%) relapsed after an initial response, and 13/49 (26.5%) had a dose reduction. Estimated 2-year PFS, DOR, and OS were 76.7%, 88.7%, and 84.1%, respectively. After a median follow-up of 18.3 months, 43/49 patients (87.8%) were alive. The most frequent AE included atrial fibrillation or flutter (6/49 cases, 12.2%), bleeding (6/49 cases, 12.2%), arthralgia/myalgia (5/49 cases, 10.2%). Ibrutinib is a suitable treatment option for R/R WM patients and also suggested by ESMO, NCCN, and other societies. PFS and OS were durable, and DOR was sustained for responsive patients. Treatment toxicity is not negligible, but manageable in most cases without treatment discontinuation.

Burkitt lymphoma with a granulomatous reaction: an M1/Th1-polarised microenvironment is associated with controlled growth and spontaneous regression.

AIMS: Burkitt lymphoma (BL) is an aggressive B-cell lymphoma that, in some instances, may show a granulomatous reaction associated with a favourable prognosis and occasional spontaneous regression. In the present study, we aimed to define the tumour microenvironment (TME) in four such cases, two of which regressed spontaneously. METHODS AND RESULTS: All cases showed aggregates of tumour cells with the typical morphology, molecular cytogenetics and immunophenotype of BL surrounded by a florid epithelioid granulomatous reaction. All four cases were Epstein-Barr virus (EBV)-positive with type I latency. Investigation of the TME showed similar features in all four cases. The analysis revealed a proinflammatory response triggered by Th1 lymphocytes and M1 polarised macrophages encircling the neoplastic cells with a peculiar topographic distribution. CONCLUSIONS: Our data provide an in-vivo picture of the role that specific immune cell subsets might play during the early phase of BL, which may be capable of maintaining the tumour in a self-limited state or inducing its regression. These novel results may provide insights into new potential therapeutic avenues in EBV-positive BL patients in the era of cellular immunotherapy.

Obinutuzumab does not improve complete methabolic response but does not compromise mobilization or engraftment of autologous peripheral blood stem cells in diffuse large B cell lymphoma: Results from a fondazione italiana linfomi prospective phase II study (the GIOTTO study).

Salvage immunochemotherapy and transplant consolidation is the standard treatment for relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL). We tested a combination of Obinutuzumab and DHAP for treating R/R DLBCL. The primary end point was the rate of complete metabolic response (CMR). Secondary end points were stem cell mobilization, stem cell engraftment, overall survival, and feasibility. In this prospective, phase-2, single-arm trial (EudraCT 2014-004014-17) patients received the standard three doses of Obinutuzumab for the first cycle, and then one dose. Patients with CMR were consolidated with an autologous stem cell transplantation (ASCT). An interim analysis was provided after the first 29 patients to confirm the initial null hypothesis that at least 10/29 patients would achieve CMR. Among the 29 patients evaluated for the first stage only six patients (6/29, 21%) achieved CMR, thus, study enrollment was stopped. Nine patients exhibited extra-hematologic toxicities ≥ grade 3. Among the 19 patients that started stem cell mobilization, one failed (5%) and 18 achieved mobilization (95%). Of these 18 patients, nine were reinfused. Mobilization was observed in 16 patients (89%) after one or two apheresis rounds. The mean number of CD34 + cells mobilized was 5.8 × 106 /Kg (median: 5.5, IQR: 5-6.75). The mean number of reinfused CD34 + cells in the nine patients was 4.1 × 106 /Kg (median: 4.1, IQR: 3.5-5). Obinutuzumab combined with DHAP did not compromise stem cell mobilization or engraftment after ASCT in patients with DLBCL. However, Obinutuzumab + DHAP provided a lower CMR rate than expected.

Pixantrone in patients with relapsed/refractory diffuse large B-cell lymphoma: A real-life, retrospective, multicenter trial on behalf of the "RTL" (Regional Tuscan Lymphoma network).

INTRODUCTION: Pixantrone is a novel aza-anthracenedione with antineoplastic activity, currently approved for multiply relapsed/refractory diffuse large B-cell lymphoma (DLBCL), even if real-life data are limited. METHODS: We investigated pixantrone efficacy and safety in clinical practice, as 3rd or 4th line therapy. We retrospectively analyzed a cohort of 37 R/R DLBCL patients managed in 8 Tuscan onco-hematological centers. Pixantrone, 50 mg/m2 , was administered on days 1, 8, 15 of a 28 days cycle for up to 6 cycles. Response to therapy was evaluated according to the Lugano 2014 classification. RESULTS: Pixantrone was administered as 3rd or 4th line in 24/37 (64.9%) and 13/37 (35.1%) cases. Overall response rate and CR rate were 43.2% and 32.4%. After a median follow-up of 6 months, 17/37 patients (46%) were alive, the main cause of death was progressive disease (14/37 cases, 37.9%). Median PFS was 3 months, median DOR was 17.9 months, and median OS was 9.7 months. A significant proportion of patients achieved a long-lasting response >12 months (8/37 cases). IPI>2 showed a trend toward inferior PFS. CONCLUSION: In this real-life setting, pixantrone demonstrated appreciable efficacy in a population with poor prognosis; in a small proportion of cases, it can be associated with long-term remission.

A brief rituximab, bendamustine, mitoxantrone (R-BM) induction followed by rituximab consolidation in elderly patients with advanced follicular lymphoma: a phase II study by the Fondazione Italiana Linfomi (FIL).

Treatment for follicular lymphoma (FL) in the elderly is not well standardized. A phase II, multicentre, single arm trial was conducted in this setting with a brief chemoimmunotherapy regimen. Treatment consisted in four monthly courses of rituximab, bendamustine and mitoxantrone (R-BM) followed by 4 weekly rituximab as consolidation; rituximab maintenance was not applied because the drug was not licensed at the time of enrolment. The primary endpoint was the complete remission rate (CR). Seventy-six treatment-naive FL patients (aged 65-80 and a "FIT" score, according to the Comprehensive Geriatric Assessment) were enrolled. CR was documented in 59/76 patients (78%), partial remission in 12 (16%) and stable/progressive disease in five (6%) with an overall response rate in 71/76 (94%). Median follow-up was 44 months with 3-year progression-free-survival (PFS) and overall-survival of 67% and 92% respectively. Nine deaths occurred, three of progressive disease. The regimen was well tolerated and the most frequent severe toxicity was neutropenia (18% of the cycles). Bcl-2/IGH rearrangement was found in 40/75 (53%) of evaluated patients. R-BM was highly effective in clearing polymerase chain reaction-detectable disease: 29/31 (96%) evaluated patients converted to bcl-2/IGH negativity at the end of treatment. A brief R-BM regimen plus rituximab consolidation is effective and safe in "FIT" elderly, treatment-naïve, FL patients, inducing high CR and molecular remission rates with prolonged PFS.

Treatment and prognosis of primary pulmonary lymphoma: A long-term follow-up study.

Primary pulmonary lymphoma (PPL) is a rare disease with not well-defined optimal treatment. Outcomes and follow-up are variable in published data. OBJECTIVES: To define the outcome and optimal treatment strategies in PPL. METHODS: We reviewed the medical records of 49 patients with PPL treated in three Italian Hematological Institutions between 2002 and 2018. RESULTS: Thirty-eight (77.5%) cases were indolent PPL, and 11 (22.5%) cases were aggressive PPL. The majority of patients were asymptomatic at diagnosis, early stages (stages IE-IIE), normal serum LDH, no bone marrow involvement, and low or low-intermediate risks of IPI. Local therapy ± immunotherapy or immuno-chemotherapy was possible in 18/49 (37%) patients. Twenty-eight (57%) patients were treated with immuno-chemotherapy after biopsy. Waiting and watching were reported in 3 (6%) patients. Overall, the CR and ORR were 83.7% and 95.9%. With a median follow-up of 62.5 months (range 0.8-199 months), the estimated 5- and 10-year OS rates were 85% and 72.3% for all patients, 89.2% and 80.3% for indolent PPL, and 70.7% and 47.1% for aggressive PPL. Aggressive PPL tended to have a high risk of progression in the first months (P = .056). No advantages were found for indolent PPL who received immuno-chemotherapy or more conservative approaches. CONCLUSION: Our studies confirm the epidemiological and favorable survival of patients with PPL, suggesting a very conservative approach, particularly in indolent subtypes.

Clinical characteristics of interim-PET negative patients with a positive end PET from the prospective HD08-01 FIL study.

FDG-positron emission tomography (PET) performed early during therapy in advanced Hodgkin lymphoma patients has been confirmed as being important for progression-free survival. A group of patients with a negative interim-PET (i-PET) showed a positive end induction PET (e-PET). The aim of this study was to evaluate the clinical characteristics of patients with a positive e-PET as a secondary end point of the HD0801 study. A total of 519 patients with advanced-stage de novo Hodgkin lymphoma received initial treatment and underwent an i-PET. Patients with negative results continued the standard treatment. i-PET negative patients were then evaluated for response with an e-PET and those patients found to have a positive one were also then given a salvage therapy. Among 409 i-PET negative, 16 interrupted the therapy, 393 patients were evaluated with an e-PET, and 39 were positive. Sixteen out of 39 underwent a diagnostic biopsy and 15 were confirmed as HD. Seventeen out of 39 e-PET were reviewed according to the Deauville Score and, in sixteen, it was confirmed positive (10 DS 5, 6 DS 4). With the exception of high LDH value at diagnosis (p = 0.01; HR 95% CI 1.18-4.89), no clinical characteristics were significantly different in comparison with e-PET negative patients. Positive e-PET after a negative i-PET has a worse outcome when compared with i-PET positive patients salvaged with therapy intensification. It was not possible to identify clinical characteristics associated with a positive e-PET.

The classic prognostic factors in advanced Hodgkin's lymphoma patients are losing their meaning at the time of Pet-guided treatments.

The International Prognostic Score (IPS) is the most commonly used risk stratification tool for patients with advanced Hodgkin lymphoma (HL). It incorporates seven clinical parameters independently associated with a poorer outcome: male sex, age, stage IV, hemoglobin level, white blood cell and lymphocyte counts, and albumin level. Since the development of the IPS, there have been significant advances in therapy and supportive care. Recent studies suggest that the IPS is less discriminating due to improved outcomes with ABVD therapy. The aim of the present study was to asses if classic prognostic factors maintain their prognostic meaning at the time of response-adapted treatment based on interim PET scans. We evaluated the prognostic significance of IPS in the 520 advanced stage HL patients enrolled in the PET-guided, HD0801 trial in which PET2-positive patients underwent a more intense treatment with an early stem-cell transplantation after 2 cycles of ABVD. We observed that in these patients, the IPS completely loses its prognostic value together with all the single parameters that contribute to the IPS. Furthermore, neutrophils, monocytes, lymphocytes, and the ratio among them also no longer had any predictive value. We believe that the substantial improvement in survival outcomes in PET2-positive patients treated with early autologous transplantation could explain the complete disappearance of the residual prognostic significance of the IPS.

Primary pulmonary lymphoma: imaging findings in 30 cases.

PURPOSE: To present our experience of cases of primary pulmonary lymphoma (PPL) found between January 2002 and July 2018, focusing on the radiological features and the differential diagnosis in order to contribute to the difficult role of the radiologist in the disease identification and to help the clinicians to reach the diagnosis. MATERIALS AND METHODS: CT scans of 30 patients (14 men and 16 women, aged 58-86, mean age 72 years) with PPL were retrospectively reviewed. All patients had a histopathological confirmation of the disease: MALT lymphoma (23 patients, 76.6%); diffuse large B-cell lymphoma-DLBCL (seven patients, 23.4%). All the staging CT scans were evaluated by three experienced radiologists dedicated to thoracic disease in order to radiologically define the predominant pattern of presentation. RESULTS: The following parenchymal patterns were observed: 11 patients with single/multiple nodules, five with masses/mass-like consolidations, 14 with consolidations with air bronchogram, 16 with ground-glass opacity, ten with angiogram sign, 22 with perilymphatic and/or peribronchovascular spread, 15 with associated lymphadenopathies, and 13 with pleural/chest wall involvement. The main characteristics of PPLs were the presence of consolidations and ground-glass opacities, with perilymphatic and/or bronchovascular spread. CONCLUSION: All the characteristics of the work should alert the radiologist to consider lymphoma among the possible differential diagnoses, always correlating the results of the CT examination with appropriate clinical laboratory evaluations.

Italian real-life experience with brentuximab vedotin: results of a large observational study of 40 cases of relapsed/refractory systemic anaplastic large cell lymphoma.

Between November 2012 and July 2014, in accordance with national law 648/96, brentuximab vedotin was available in Italy for patients with relapsed systemic anaplastic large cell lymphoma outside a clinical trial context. A large Italian observational retrospective study was conducted on the use of brentuximab vedotin in everyday clinical practice to check whether clinical trial results are confirmed in a real-life context. The primary endpoint of this study was best response; secondary endpoints were the overall response rate at the end of the treatment, duration of response, survival and safety profile. A total of 40 heavily pretreated patients were enrolled. Best response was observed after a median of four cycles in 77.5%: globally, 47.5% patients obtained a complete response, 64.2% in the elderly subset. The overall response rate was 62.5%. At the latest follow up, 15/18 patients are still in complete remission (3 with consolidation). The progression-free survival rate at 24 months was 39.1% and the disease-free survival rate at the same time was 54% (median not reached). All the long-term responders were aged <30 years at first infusion. The treatment was well tolerated even in this real-life context and no deaths were linked to drug toxicity. Brentuximab vedotin induces clinical responses quite rapidly, i.e. within the first four cycles of treatment in most responders, thus enabling timely use of transplantation. For patients ineligible for transplant or for those in whom a transplant procedure failed, brentuximab vedotin may represent a feasible effective therapeutic option in everyday clinical practice.

Prognostic roles of absolute monocyte and absolute lymphocyte counts in patients with advanced-stage follicular lymphoma in the rituximab era: an analysis from the FOLL05 trial of the Fondazione Italiana Linfomi.

Recently, in an attempt to improve the discrimination power of the international prognostic index (IPI), patients with diffuse large B-cell lymphoma were evaluated to determine the prognostic roles of peripheral blood absolute monocyte count (AMC) and absolute lymphocyte count (ALC). Here, we analysed data of 428 patients with follicular lymphoma (FL) enrolled in a prospective, randomized trial (FOLL05 study) conducted by Fondazione Italiana Linfomi, to assess the impact of AMC and ALC on progression-free survival (PFS). All patients had been treated with one of three treatment combinations: (i) rituximab (R) plus cyclophosphamide, vincristine and prednisone; (ii) R plus cyclophosphamide, doxorubicin, vincristine and prednisone or (iii) R plus mitoxantrone and fludarabine. We showed that only AMC was a powerful predictor of PFS, and possibly overall survival, in patients with FL treated with combination chemotherapy regimens that contained R. The AMC can be used alone as a novel, simple factor that can predict survival outcome in patients with FL, independent of the immunochemotherapy regimen. It may therefore be widely used by clinicians, due to its simplicity and broad applicability. Additionally, it can be combined with other factors that determine the IPI or FLIPI, to increase the discriminating ability of these indices.

The prognostic value of positron emission tomography performed after two courses (INTERIM-PET) of standard therapy on treatment outcome in early stage Hodgkin lymphoma: A multicentric study by the fondazione italiana linfomi (FIL).

This retrospective study included 246 patients with a new diagnosis of Hodgkin Lymphoma (HL) with a localized-stage (IA-IIA), consecutively admitted from January 2002 to December 2008, by twelve Italian hematological centers on behalf of Fondazione Italiana Linfomi (FIL). Patients were staged at baseline and after two cycles of chemotherapy with PET. All patients were treated with four cycles of ABVD followed by involved-field radiotherapy. No treatment change, based on PET-2 results was allowed. Endpoint of the study was the predictive role of PET-2 on 2-y failure-free survival (FFS). PET-2 was positive in 36 patients (15%) and negative in 210. After a mean follow-up of 46 (3-105) months 19/36 PET-2 positive patients progressed or relapsed and 17 achieved and maintained a CCR. The positive and negative predictive value of a PET2 was 53% and 95%, respectively. The sensibility, specificity and accuracy of PET2 were 65.5%, 92% and 89%, respectively. PET-2 positive scans were centrally reviewed according to the recently defined Deauville Criteria. Upon review the PPV and NPV was 73% and 96% overall. Factors with prognostic significance for progression in univariate analysis were a positive PET-2 (P = 0.000) and the presence of bulky disease (P < 0.01). In a multivariate analysis the only factor that affected negatively FFS was a positive PET-2 (P = 0.000). This study confirms that interim-PET could be considered a prognostic test also in early stage HL, but is unlikely to be a factor that will justify the change of therapeutical approach.

The use of anthracycline at first-line compared to alkylating agents or nucleoside analogs improves the outcome of salvage treatments after relapse in follicular lymphoma The REFOLL study by the Fondazione Italiana Linfomi.

Follicular lymphoma (FL) patients experience multiple remissions and relapses and commonly receive multiple treatment lines. A crucial question is whether anthracyclines should be used at first-line or whether they would be better "reserved" for relapse and whether FL outcome can be optimized by definite sequences of treatments. Randomized trials can be hardly designed to address this question. In this retrospective multi-institutional study, time-to-next-treatment after first relapse was analyzed in 510 patients who had received either alkylating agents- or anthracycline- or nucleoside analogs-based chemotherapy with/without rituximab at first-line and different second-line therapies. After a median of 42 months, median time-to-next-treatment after relapse was 41 months (CI95%:34-47 months). After adjustment for covariates, first-line anthracycline-based chemotherapy with/without rituximab was associated with better time-to-next-treatment after any salvage than alkylating agents-based chemotherapy with/without rituximab or nucleoside analogs-based chemotherapy with/without rituximab (HR:0.74, P = 0.027). The addition of rituximab to first-line chemotherapy had no significant impact (HR:1.22, P = 0.140). Autologs stem cell transplantation performed better than any other salvage treatment (HR:0.53, P < 0.001). First-line anthracycline-based chemotherapy significantly improved time-to-next-treatment even in patients receiving salvage autologs stem cell transplantation (P = 0.041). This study supports the concept that in FL previous treatments significantly impact on the outcome of subsequent therapies. The outcome of second-line treatments, either with salvage chemoimmunotherapy or with autologs stem cell transplantation, was better when an anthracycline-containing regimen was used at first-line.

Interim 18-FDG-PET/CT failed to predict the outcome in diffuse large B-cell lymphoma patients treated at the diagnosis with rituximab-CHOP.

Role of interim-PET (I-PET) in diffuse large B-cell Lymphoma (DLBCL) is controversial. To determine predictive value of I-PET on progression-free survival (PFS), we enrolled 88 first-line DLBCL patients treated with 6-8 R-CHOP courses regardless of I-PET. PET/CT were performed at diagnosis, after 2 to 4 courses and at the end of therapy with central reviewing according to visual dichotomous criteria. Results are as follows: I-PET, 72% negative, 28% positive; final-PET (F-PET), 88% negative, 12% positive; clinical complete response 90%. Concordance between clinical response and F-PET negativity was 97% because of 2 false positive. With a median follow-up of 26.2 months, 2-year overall survival and PFS were 91% and 77%, respectively. Two-year PFS for I-PET and F-PET negative versus positive were as follows: I-PET 85% versus 72% (P = .0475); F-PET 83% versus 64% (P < .001). Because of a small number of events, 2 independent bivariate Cox models were tested for PFS. In model 1, F-PET contradicted I-PET (hazard ratio [HR] = 5.03, P = .015 vs 1.27, P = 691); in model 2, F-PET (HR = 4.54) and International propnostic Index score (HR = 5.36, P = .001) remained independent prognostic factors. In conclusion, positive I-PET is not predictive of a worse outcome in DLBCL; larger prospective studies and harmonization of I-PET reading criteria are needed.