Prolonged survival in the absence of disease-recurrence in advanced-stage follicular lymphoma following chemo-immunotherapy: 13-year update of the prospective, multicenter randomized GITMO-IIL trial

Aprospective trial conducted in the period 2000-2005 showed no survival advantage for high-dose chemotherapy with rituximab and autograft (RHDS) versus conventional chemotherapy with rituximab (CHOP-R) as firstline therapy in 134 high-risk follicular lymphoma patients aged <60 years. The study has been updated at the 13-year median follow up. As of February 2017, 88 (66%) patients were alive, with overall survival of 66.4% at 13 years, without a significant difference between R-HDS (64.5%) and CHOP-R (68.5%). To date, 46 patients have died, mainly because of disease progression (47.8% of all deaths), secondary malignancies (3 solid tumor, 9 myelodysplasia/acute leukemia; 26.1% of all deaths), and other toxicities (21.7% of all deaths). Complete remission was documented in 98 (73.1%) patients and associated with overall survival, with 13- year estimates of 77.0% and 36.8% for complete remission versus no-complete remission, respectively. Molecular remission was documented in 39 (65%) out of 60 evaluable patients and associated with improved survival. In multivariate analysis, complete remission achievement had the strongest effect on survival (P<0.001), along with younger age (P=0.002) and female sex (P=0.013). Overall, 50 patients (37.3%) survived with no disease recurrence (18 CHOP-R, 32 R-HDS). This follow up is the longest reported on follicular lymphoma treated upfront with rituximab-chemotherapy and demonstrates an unprecedented improvement in survival compared to the pre-rituximab era, regardless of the use of intensified or conventional treatment. Complete remission was the most important factor for prolonged survival and a high proportion of patients had prolonged survival in their first remission, raising the issue of curability in follicular lymphoma

Risk assessment in diffuse large cell lymphoma at first relapse. A study by the Italian Intergroup for Lymphomas.

BACKGROUND AND OBJECTIVES: Our aim was to identify risk factors in adults with diffuse large cell lymphoma at first relapse. DESIGN AND METHODS: We studied 474 patients observed at 45 centers in Italy. Median time from diagnosis to relapse was 395 days, median age at relapse was 55 years and median follow-up from relapse was 3.3 years. Salvage therapy consisted of polychemotherapy in 79% of patients, monochemotherapy and/or radiotherapy and/or surgery alone in 16%, and palliative therapy in 5%. Salvage treatment was intensified with high-dose chemotherapy + stem cell transplant in 20% of patients. OS and PFS were compared by sex, International Prognostic Index at diagnosis, histology, B/T phenotype, initial treatment, salvage therapy, and features at relapse: time from diagnosis, LDH, stage, performance status and bone marrow involvement. Cox models, adjusted for salvage therapy, were performed with factors related to overall survival (OS) and progression-free survival (PFS). RESULTS: Overall response (complete + partial) was 63%, OS at 3 years 35% and PFS at 3 years 26%. Relapse within 12 months from diagnosis, elevated serum lactic dehydrogenase (LDH), advanced stage and poor performance status were independent adverse factors for OS and PFS. The cumulative number of adverse factors is proposed as prognostic index for DLCL at first relapse since it identifies risk groups (p<0.0001) and has been validated (p=0.01). Moreover, it predicts OS and PFS in the selected group of patients with a responsive relapse (p<0.0001). INTERPRETATION AND CONCLUSION: Delay from initial diagnosis, LDH, stage and performance status at relapse should be balanced in comparative studies of salvage therapy of adults with DLCL. Patients with more than 2 adverse factors are one third of all cases and deserve more effective salvage treatments

G-CSF Prevents the Progression of Structural Disintegration of White Matter Tracts in Amyotrophic Lateral Sclerosis: A Pilot Trial

Background: The hematopoietic protein Granulocyte-colony stimulating factor (G-CSF) has neuroprotective and regenerative properties. The G-CSF receptor is expressed by motoneurons, and G-CSF protects cultured motoneuronal cells from apoptosis. It therefore appears as an attractive and feasible drug candidate for the treatment of amyotrophic lateral sclerosis (ALS). The current pilot study was performed to determine whether treatment with G-CSF in ALS patients is feasible.Methods: Ten patients with definite ALS were entered into a double-blind, placebo-controlled, randomized trial. Patients received either 10 mu g/kg BW G-CSF or placebo subcutaneously for the first 10 days and from day 20 to 25 of the study. Clinical outcome was assessed by changes in the ALS functional rating scale (ALSFRS), a comprehensive neuropsychological test battery, and by examining hand activities of daily living over the course of the study (100 days). The total number of adverse events (AE) and treatment-related AEs, discontinuation due to treatment-related AEs, laboratory parameters including leukocyte, erythrocyte, and platelet count, as well as vital signs were examined as safety endpoints. Furthermore, we explored potential effects of G-CSF on structural cerebral abnormalities on the basis of voxel-wise statistics of Diffusion Tensor Imaging (DTI), brain volumetry, and voxel-based morphometry.Results: Treatment was well-tolerated. No significant differences were found between groups in clinical tests and brain volumetry from baseline to day 100. However, DTI analysis revealed significant reductions of fractional anisotropy (FA) encompassing diffuse areas of the brain when patients were compared to controls. On longitudinal analysis, the placebo group showed significant greater and more widespread decline in FA than the ALS patients treated with G-CSF.Conclusions: Subcutaneous G-CSF treatment in ALS patients appears as feasible approach. Although exploratory analysis of clinical data showed no significant effect, DTI measurements suggest that the widespread and progressive microstructural neural damage in ALS can be modulated by G-CSF treatment. These findings may carry significant implications for further clinical trials on ALS using growth factors

Treatment options in skeletal localizations of hairy cell leukemia: A systematic review on the role of radiation therapy

Skeletal localizations are a rare complication in hairy cell leukaemia patients, with an extimated incidence of 3%. These lesions, mainly osteolytic, can occur at various sites and are almost always symptomatic. Localized radiation therapy (RT) has been extensively used as effective palliative treatment in such cases, with different total doses and fractionation schedules. In this article, a systematic review of all reported cases with osseous complications is presented, to underline the role of RT and to define the most appropriate approach in this subset of patients. © 2007 Wiley-Liss, Inc

Whole-body magnetic resonance imaging (WB-MRI) in lymphoma: State of the art

The improvements in magnetic resonance imaging (MRI) technology and the concern related to the increased cancer risk in patients with lymphoma, also due to radiation exposure associated with imaging examinations, have led to the introduction of whole-body MRI (WB-MRI) as a radiation-free alternative to standard imaging procedures. WB-MRI seems a less histology-dependent functional imaging test than 18F-fluorodeoxyglucose-positron emission tomography/CT (18F-FDG-PET/CT). In patients with FDG-avid lymphomas, such as diffuse large B-cell lymphoma (DLBCL) and Hodgkin lymphoma (HL), 18F-FDG-PET/CT remains the imaging reference standard for staging, with WB-MRI potentially being a complementary modality that could replace CT, especially in young patients. On the other hand, WB-MRI is a valuable imaging procedure for lymphoma surveillance and in lymphomas with variable/low FDG avidity and nonfollicular indolent lymphomas. The aim of this paper is to discuss the current state of the art of WB-MRI in lymphoma by evaluating its diagnostic performance in different lymphoma subtypes: Hodgkin, aggressive, and indolent lymphomas

HHV8-negative effusion-based large B cell lymphoma arising in chronic myeloid leukemia patients under dasatinib treatment : A report of two cases

Simple Summary: Tyrosine kinase inhibitors (TKIs) are the treatment of choice for BCR-ABL1- positive chronic myeloid leukemia (CML). Dasatinib is a second generation TKI frequently associated with pleural effusion in up to 33% of patients. Here, we describe two cases of HHV8-negative large B cell effusion-based lymphoma (EBL) confined to the pleura, incidentally, diagnosed in patients presenting with dasatinib-related pleural effusion. One patient is alive and is in remission at 17 months from diagnosis, while unfortunately the other patient died of progressive disease and novel coronavirus disease 2019 (COVID-19)-related pneumonia 16 months from diagnosis. These cases of large B cell EBL in patients receiving dasatinib raise concern about a possible association and we strongly recommend cytological investigation in patients with persistent/relapsing pleural effusion under dasatinib to improve the knowledge about this entity. Tyrosine kinase inhibitors (TKIs) are the treatment of choice for BCR-ABL1-positive chronic myeloid leukemia (CML). Although TKIs have substantially improved prognosis of CML patients, their use is not free of adverse effects. Dasatinib is a second generation TKI frequently associated with pleural effusion in up to 33% of patients. This results in symptoms as dyspnea, cough and chest pain that may require therapy discontinuation. In the present report, we describe two exceptional cases of HHV8-negative large B-cell effusion-based lymphoma (EBL) confined to the pleura, incidentally, diagnosed in patients presenting with dasatinib-related pleural effusion. One patient (case 1) is alive and is in remission at 17 months from large B-cell EBL diagnosis while unfortunately the other patient (case 2) died of progressive disease and COVID-19 pneumonia 16 months from large B-cell EBL diagnosis. These cases raise concern about a possible association between large B-cell EBL and dasatinib, and the different clinical outcome of the two cases poses a challenge in treatment decision. For this reason, we strongly recommend cytological investigation in patients with persistent/relapsing pleural effusion under dasatinib, primarily to validate its possible association with lymphoma development and to improve the knowledge about this entity

Peripheral t‐cell lymphoma, not otherwise specified : Clinical manifestations, diagnosis, and future treatment

Peripheral T‐cell lymphoma, not otherwise specified (PTCL_NOS) corresponds to about one fourth of mature T‐cell tumors, which overall represent 10–12% of all lymphoid malignancies. This category comprises all T‐cell neoplasms, which do not correspond to any of the distinct entities listed in the WHO (World Health Organization) Classification of Tumours of Haematopoietic and Lymphoid Tissues. In spite of the extreme variability of morphologic features and phenotypic profiles, gene expression profiling (GEP) studies have shown a signature that is distinct from that of all remaining PTCLs. GEP has also allowed the identification of subtypes provided with prognostic relevance. Conversely to GEP, next‐generation sequencing (NGS) has so far been applied to a limited number of cases, providing some hints to better understand the pathobiology of PTCL_NOS. Although several pieces of information have emerged from pathological studies, PTCL_NOS still remains a tumor with a dismal prognosis. The usage of CHOEP (cyclophosphamide, doxorubicin, vincristine, prednisone, etoposide) followed by autologous stem cell transplantation may represent the best option, by curing about 50% of the patients whom such an approach can be applied to. Many new drugs have been proposed without achieving the expected results. Thus, the optimal treatment of PTCL_NOS remains unidentified

Prognostic impact of baseline immunologic profile in aggressive b-cell non-hodgkin's lymphomas

Host immune homeostasis as an independent prognostic indicator has been inadequately evaluated in aggressive non-Hodgkin's lymphomas (NHL). The present study addresses the prognostic significance in aggressive NHLs of the immunologic profile evaluated by pretreatment serum levels of immunoglobulins (Ig) and lymphocyte-monocyte ratio (LMR). In this series of 90 patients with aggressive lymphoma, the median level for IgG was 1,024mg/dl (range 436-2236), and for LMR was 2.2 (range 0.2-13.8). CR rate was higher with IgG levels ≥1,024mg/dL (91% vs 77% p=0.059). LMR ≤ 2.2 was associated with lower 1-year PFS (73% vs. 92%, p 0.016). Patients with good/very good R-IPI showed a reduced PFS if IgG or LMR was low, while patients with poor R-IPI did better if LMR or IgG levels were high. We combined both parameters with the R-IPI and produced a four-risk prognostic score showing one-year PFS of 95% (95% CI 68%-99%), 100% (95% CI 100%-100%), 73% (95% CI 52%-86%), and 59% (95% CI 31%-79%), in patients with zero, one, two and three risk factors, respectively. The results indicate for the first time the value of baseline serum Ig levels in the prognostic assessment of aggressive lymphoma

Minced Umbilical Cord Fragments as a Source of Cells for Orthopaedic Tissue Engineering: An In Vitro Study

A promising approach for musculoskeletal repair and regeneration is mesenchymal-stem-cell- (MSC-)based tissue engineering. The aim of the study was to apply a simple protocol based on mincing the umbilical cord (UC), without removing any blood vessels or using any enzymatic digestion, to rapidly obtain an adequate number of multipotent UC-MSCs. We obtained, at passage 1 (P1), a mean value of 4, 2 × 106 cells (SD 0,4) from each UC. At immunophenotypic characterization, cells were positive for CD73, CD90, CD105, CD44, CD29, and HLA-I and negative for CD34 and HLA-class II, with a subpopulation negative for both HLA-I and HLA-II. Newborn origin and multilineage potential toward bone, fat, cartilage, and muscle was demonstrated. Telomere length was similar to that of bone-marrow (BM) MSCs from young donors. The results suggest that simply collecting UC-MSCs at P1 from minced umbilical cord fragments allows to achieve a valuable population of cells suitable for orthopaedic tissue engineering