Stem cell collection and hematological recovery in the Fondazione Italiana Linfomi (FIL) MCL0208 clinical trial.

In the frontline high-dose phase 3 FIL-MCL0208 trial (NCT02354313), 8% of enrolled mantle cell lymphoma (MCL) patients could not be randomised to receive lenalidomide (LEN) maintenance vs observation after autologous stem cell transplantation (ASCT) due to inadequate hematological recovery and 52% of those who started LEN, needed a dose reduction due to toxicity. We therefore focused on the role played by CD34 + hematopoietic stem cells (PBSC) harvesting and reinfusion on toxicity and outcome. Overall, 90% (n = 245) of enrolled patients who underwent the first leukapheresis collected ≥ 4 × 10 PBSC/kg, 2.

Punctual and kinetic MRD analysis from the Fondazione Italiana Linfomi MCL0208 phase 3 trial in mantle cell lymphoma.

Minimal residual disease (MRD) analysis is a known predictive tool in mantle cell lymphoma (MCL). We describe MRD results from the Fondazione Italiana Linfomi phase 3 MCL0208 prospective clinical trial assessing lenalidomide (LEN) maintenance vs observation after autologous stem cell transplantation (ASCT) in the first prospective comprehensive analysis of different techniques, molecular markers, and tissues (peripheral blood [PB] and bone marrow [BM]), taken at well-defined time points. Among the 300 patients enrolled, a molecular marker was identified in 250 (83%), allowing us to analyze 234 patients and 4351 analytical findings from 10 time points.

A Clinical Prognostic Model Based on Machine Learning from the Fondazione Italiana Linfomi (FIL) MCL0208 Phase III Trial.

Background: Multicenter clinical trials are producing growing amounts of clinical data. Machine Learning (ML) might facilitate the discovery of novel tools for prognostication and disease-stratification. Taking advantage of a systematic collection of multiple variables, we developed a model derived from data collected on 300 patients with mantle cell lymphoma (MCL) from the Fondazione Italiana Linfomi-MCL0208 phase III trial (NCT02354313).

Application of the Euro Clonality next-generation sequencing-based marker screening approach to detect immunoglobulin heavy chain rearrangements in mantle cell lymphoma patients: first data from the Fondazione Italiana Linfomi MCL0208 trial.

Minimal residual disease (MRD) determined by classic polymerase chain reaction (PCR) methods is a powerful outcome predictor in mantle cell lymphoma (MCL). Nevertheless, some technical pitfalls can reduce the rate of of molecular markers. Therefore, we applied the EuroClonality-NGS IGH (next-generation sequencing immunoglobulin heavy chain) method (previously published in acute lymphoblastic leukaemia) to 20 MCL patients enrolled in an Italian phase III trial sponsored by Fondazione Italiana Linfomi.

Targeted locus amplification to detect molecular markers in mantle cell and follicular lymphoma.

Minimal residual disease (MRD) monitoring by PCR methods is a strong and standardized predictor of clinical outcome in mantle cell lymphoma (MCL) and follicular lymphoma (FL). However, about 20% of MCL and 40% of FL patients lack a reliable molecular marker, being thus not eligible for MRD studies. Recently, targeted locus amplification (TLA), a next-generation sequencing (NGS) method based on the physical proximity of DNA sequences for target selection, identified novel gene rearrangements in leukemia.

Lenalidomide maintenance after autologous haematopoietic stem-cell transplantation in mantle cell lymphoma: results of a Fondazione Italiana Linfomi (FIL) multicentre, randomised, phase 3 trial.

Background: Fit patients with mantle cell lymphoma aged 18-65 years are usually given cytarabine and rituximab-based induction regimens followed by autologous haematopoetic stem-cell transplantation (HSCT). We investigated whether post-autologous HSCT maintenance with lenalidomide improves progression-free survival in this population.

Methods: This open-label, randomised, multicentre, phase 3 trial was done at 49 haematology and oncology units in Italy and Portugal.

Updated risk-oriented strategy for acute lymphoblastic leukemia in adult patients 18-65 years: NILG ALL 10/07.

An updated strategy combining pediatric-based chemotherapy with risk-oriented allogeneic hematopoietic cell transplantation (HCT) was evaluated in Philadelphia chromosome-negative acute lymphoblastic leukemia (Ph- ALL) and compared with a published control series. Following induction-consolidation chemotherapy, responsive patients were assigned to receive maintenance chemotherapy or undergo early HCT according to the risk stratification criteria and minimal residual disease (MRD) status. Of the 203 study patients (median age 41 years, range 17-67), 140/161 with Ph- ALL achieved complete remission (86.

Immunoglobulin kappa deleting element rearrangements are candidate targets for minimal residual disease evaluation in mantle cell lymphoma.

Minimal residual disease (MRD) assessment is of high clinical relevance in patients with mantle cell lymphoma (MCL). In mature B-cell malignancies, the presence of somatic hypermutations (SHM) in Variable-Diversity-Joining Heavy chain (VDJH) rearrangements leads to frequent mismatches between primers, probes, and the target, thus impairing tumor cells quantification. Alternative targets, such as immunoglobulin kappa-deleting-element (IGK-Kde) rearrangements, might be suitable for MRD detection.

Mantle cell lymphoma.

MCL is a well-characterized generally aggressive lymphoma with a poor prognosis. However, patients with a more indolent disease have been reported in whom the initiation of therapy can be delayed without any consequence for the survival. In 2017 the World Health Organization updated the classification of MCL describing two main subtypes with specific molecular characteristics and clinical features, classical and indolent leukaemic nonnodal MCL.

Droplet Digital PCR Quantification of Mantle Cell Lymphoma Follow-up Samples From Four Prospective Trials of the European MCL Network.

Minimal residual disease (MRD) has been increasingly investigated in mantle cell lymphoma (MCL), including for individual therapeutic stratification and pre-emptive treatment in clinical trials. Although patient/allele specific real-time quantitative polymerase chain reaction (qPCR) of IGH or BCL1-IGH clonal markers is the gold-standard method, its reliance on a standard curve for relative quantification limits quantification of low-level positivity within the 1E-4 to 1E-5 range; over half of positive MRD samples after treatment fall below the quantitative range (BQR) of the standard curve. Droplet digital PCR (ddPCR), in contrast, allows absolute quantification, including for samples with no baseline determination of tumor infiltration by multicolor flow cytometry (MFC), avoiding the need for a reference standard curve.

Applying Data Warehousing to a Phase III Clinical Trial From the Fondazione Italiana Linfomi Ensures Superior Data Quality and Improved Assessment of Clinical Outcomes.

Purpose: Data collection in clinical trials is becoming complex, with a huge number of variables that need to be recorded, verified, and analyzed to effectively measure clinical outcomes. In this study, we used data warehouse (DW) concepts to achieve this goal. A DW was developed to accommodate data from a large clinical trial, including all the characteristics collected.

Clofarabine and Treosulfan as Conditioning for Matched Related and Unrelated Hematopoietic Stem Cell Transplantation: Results from the Clo3o Phase II Trial.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) can be curative for patients with hematologic malignancies. The ideal conditioning regimen before allo-HSCT has not been established. We conducted a Phase II study to evaluate the tolerability and efficacy of clofarabine and treosulfan as conditioning regimen before allo-HSCT.

mutations and disruptions are poor prognostic biomarkers in mantle cell lymphoma receiving high-dose therapy: a FIL study.

In recent years, the outcome of mantle cell lymphoma (MCL) has improved, especially in younger patients, receiving cytarabine-containing chemoimmunotherapy and autologous stem cell transplantation. Nevertheless, a proportion of MCL patients still experience early failure. To identify biomarkers anticipating failure of intensive chemotherapy in MCL, we performed target resequencing and DNA profiling of purified tumor samples collected from patients enrolled in the prospective (high-dose chemoimmunotherapy followed by autologous transplantation and randomized lenalidomide maintenance).

Randomized trial comparing standard vs sequential high-dose chemotherapy for inducing early CR in adult AML.

Here we evaluated whether sequential high-dose chemotherapy (sHD) increased the early complete remission (CR) rate in acute myelogenous leukemia (AML) compared with standard-intensity idarubicin-cytarabine-etoposide (ICE) chemotherapy. This study enrolled 574 patients (age, 16-73 years; median, 52 years) who were randomly assigned to ICE (n = 286 evaluable) or sHD (2 weekly 3-day blocks with cytarabine 2 g/m twice a day for 2 days plus idarubicin; n = 286 evaluable). Responsive patients were risk-stratified for a second randomization.

A B-cell receptor-related gene signature predicts survival in mantle cell lymphoma: results from the Fondazione Italiana Linfomi MCL-0208 trial.

Mantle cell lymphoma patients have variable clinical courses, ranging from indolent cases that do not require immediate treatment to aggressive, rapidly progressing diseases. Thus, diagnostic tools capable of stratifying patients according to their risk of relapse and death are needed. This study included 83 samples from the Fondazione Italiana Linfomi MCL-0208 clinical trial.

Treatment for patients with relapsed/refractory mantle cell lymphoma: European-based recommendations.

Patients with mantle cell lymphoma (MCL) usually respond to initial combination chemotherapy, but the disease inevitably relapses and often follows an aggressive course. Here, clinical study results published since 2008 for patients with relapsed/refractory MCL were reviewed to compare available evidence for treatment guidance. Most trials identified were non-randomized, phase II studies performed at a limited number of sites, and many evaluated MCL as one of multiple non-Hodgkin lymphoma subtypes.

Khorana score and histotype predicts incidence of early venous thromboembolism in non-Hodgkin lymphomas. A pooled-data analysis of 12 clinical trials of Fondazione Italiana Linfomi (FIL).

Current data suggests that the risk of venous thromboembolism (VTE) in patients with non-Hodgkin lymphoma (NHL) is comparable to that observed in patients with solid tumours, although more robust confirmatory analyses are required. With that in mind, we investigated the occurrence of VTE in a pooled analysis of 12 "Fondazione Italiana Linfomi" (FIL) prospective clinical studies. Specifically, we wished to assess the cumulative incidence of VTE in NHL patients, evaluate the predictive value of the Khorana Score (KS), and identify other potential risk factors for VTEs.

Lymphoblastic lymphoma.

Lymphoblastic lymphoma (LBL) is a neoplasm of immature B cells committed to the B-(B-LBL) or T-cell lineage (T-LBL) that accounts for approximately 2% of all lymphomas. Although histological features are usually sufficient to distinguish lymphoblastic from mature B- or T-cell neoplasms, of greater importance for diagnosis is the characterization of immunophenotype by flow cytometry. LBL occurs more commonly in children than in adults, mostly in males.

Randomized Trial Comparing R-CHOP Versus High-Dose Sequential Chemotherapy in High-Risk Patients With Diffuse Large B-Cell Lymphomas.

Purpose The benefit of high-dose chemotherapy with autologous stem-cell transplantation (ASCT) as first-line treatment in patients with diffuse large B-cell lymphomas is still a matter of debate. To address this point, we designed a randomized phase III trial to compare rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP)-14 (eight cycles) with rituximab plus high-dose sequential chemotherapy (R-HDS) with ASCT. Patients and Methods From June 2005 to June 2011, 246 high-risk patients with a high-intermediate (56%) or high (44%) International Prognostic Index score were randomly assigned to the R-CHOP or R-HDS arm, and 235 were analyzed by intent to treat.

PO-03 - Khorana score and histotype predict the incidence of early venous thromboembolism (VTE) in Non Hodgkin Lymphoma (NHL). A pooled data analysis of twelve clinical trials of Fondazione Italiana Linfomi (FIL).

Background: Recent studies show that the risk of VTE in NHL pts is similar to that observed in high risk solid tumors (i.e. pancreatic, ovarian cancer).

Bortezomib, Thalidomide and Lenalidomide: Have They Really Changed the Outcome of Multiple Myeloma?

Treatment of multiple myeloma (MM) has significantly improved, although the disease remains incurable. Prospective clinical trials evaluating the impact on outcome of new drugs such as proteasome inhibitors or immunomodulating agents are limited since they are not able to reflect the clinical routine and available retrospective data are not detailed enough to directly evaluate the value of new drugs. To address these information gaps, we performed a retrospective real-life analysis.

Lymphoblastic lymphoma: an updated review on biology, diagnosis, and treatment.

Lymphoblastic lymphoma is a rare aggressive neoplasm of T-/B-precursors resembling acute lymphoblastic leukemia, with no or limited bone marrow involvement (<25%), that develops more frequently in children and young adults and is typically characterized by a grossly enlarged mediastinum, and whose diagnostic hallmark is the expression of a T-/B-precursor cell immunophenotype, the T-cell subset accounting for 90% of all cases. The adoption of pediatric-derived, intensive lymphoblastic leukemia-like protocols led to significantly improved results, with survival rates of about 70% and 90% in adults and children, respectively. Adequate central nervous system prophylaxis and mediastinal irradiation contributed to the therapeutic success; however, the role of radiation therapy is debated due to toxicity concerns and the excellent results obtained with radiation-free programs especially in pediatric patients.