Pseudotemporal ordering of spatial lymphoid tissue microenvironment profiles trails Unclassified DLBCL at the periphery of the follicle.

We have established a pseudotemporal ordering for the transcriptional signatures of distinct microregions within reactive lymphoid tissues, namely germinal center dark zones (DZ), germinal center light zones (LZ), and peri-follicular areas (Peri). By utilizing this pseudotime trajectory derived from the functional microenvironments of DZ, LZ, and Peri, we have ordered the transcriptomes of Diffuse Large B-cell Lymphoma cases. The apex of the resulting pseudotemporal trajectory, which is characterized by enrichment of molecular programs fronted by TNFR signaling and inhibitory immune checkpoint overexpression, intercepts a discrete peri-follicular biology.

Long-term overall survival and toxicities of ABVD vs BEACOPP in advanced Hodgkin lymphoma: A pooled analysis of four randomized trials.

Purpose: We explored the potential overall survival (OS) benefit of bleomycin, etoposide, doxorubicin (Adriamycin), cyclophosphamide, vincristine (Oncovin), procarbazine, and prednisone (BEACOPP) over doxorubicin (Adriamycin), bleomycin, vinblastine, and dacarbazine (ABVD) in a pooled analysis of four randomized trials.

Patients And Methods: Primary objective was to evaluate the OS impact of BEACOPP using individual patient data. Secondary objectives were progression-free survival (PFS), secondary cancers, and use of autologous stem cell transplantation (ASCT).

Brentuximab vedotin in association with bendamustine in refractory or multiple relapsed Hodgkin lymphoma. A retrospective real-world study.

Objective And Methods: In order to assess the efficacy of brentuximab vedotin (Bv) in combination with bendamustine (B) in multiple relapsed or refractory (RR) classic Hodgkin lymphoma (cHL), medical records of 47 patients treated with BvB in second relapse or beyond were reviewed.

Results: The median number of previous treatments was 2 (1-4). Bv was given at 1.

Efficacy of bendamustine and rituximab in splenic marginal zone lymphoma: results from the phase II BRISMA/IELSG36 study.

Splenectomy in addition to immunotherapy with rituximab can provide quick and sometimes durable disease control in patients with splenic marginal zone lymphoma (SMZL). However, systemic chemotherapy is ultimately required in many cases. The BRISMA (Bendamustine-rituximab as first-line treatment of splenic marginal zone lymphoma)/IELSG (International Extranodal Lymphoma Study Group)36 trial is an open-label, single arm phase II study designed by the IELSG in cooperation with the Fondazione Italiana Linfomi and the lymphoma Study Association according to Simon's two-stage method.

Paroxysmal nocturnal hemoglobinuria: When delay in diagnosis and long therapy occurs.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare clonal disorder characterized by hemolytic anemia, bone marrow failure and thrombosis, caused by a somatic mutation in PIG-A gene that results in the absence of CD55 and CD59, two important complement regulatory proteins. In this paper, a case of PNH is retrospectively examined looking for clinical and laboratory features, and the entire course of the disease from the onset of the symptoms is described, together with an adequate follow- up over a 7-years treatment period. In this case, the not specificity and the limited clinical relevance of the symptoms led to a delay in diagnosis.

Absolute Monocyte Count and Lymphocyte-Monocyte Ratio Predict Outcome in Nodular Sclerosis Hodgkin Lymphoma: Evaluation Based on Data From 1450 Patients.

Objective: To verify whether absolute monocyte count (AMC) and lymphocyte- monocyte ratio (LMR) at diagnosis are valid prognostic parameters in classical Hodgkin lymphoma (cHL).

Patients And Methods: Data were collected from 1450 patients with cHL treated in Israel and Italy from January 1, 1988, through December 31, 2007.

Results: The median age of the patients was 33 years (range, 17-72 years), and 70% (1017) of the patients had nodular sclerosis (NS); the median follow-up duration was 87 months.

Rituximab with cyclophosphamide, vincristine, non-pegylated liposomal doxorubicin and prednisone as first-line treatment for splenic marginal zone lymphoma: a Fondazione Italiana Linfomi phase II study.

Rituximab® provides high response rates and effective disease palliation in patients with splenic marginal zone lymphoma (SMZL). We conducted a phase II trial in patients with SMZL who were either untreated or were splenectomized but had shown disease progression within 1 year after splenectomy. Treatment consisted of six courses of Rituximab with cyclophosphamide, vincristine, non-pegylated liposomal doxorubicin and prednisone (R-COMP).

Two cases of q-Fever in hairy cell leukemia.

Hairy cell leukemia (HCL) is a rare B-cell lymphoproliferative disorder accounting for about 2% of all leukemias. The clinical course is indolent, however HCL patients are particularly susceptible to infections. Here we report two cases of Q-fever as first manifestation of disease in two patients affected by HCL.

Bone marrow stroma CD40 expression correlates with inflammatory mast cell infiltration and disease progression in splenic marginal zone lymphoma.

Splenic marginal zone lymphoma (SMZL) is a mature B-cell neoplasm characterized by rather indolent clinical course. However, nearly one third of patients experience a rapidly progressive disease with a dismal outcome. Despite the characterization of clone genetics and the recognition of deregulated immunologic stimulation in the pathogenesis of SMZL, little is known about microenvironment dynamics and their potential biological influence on disease outcome.

Treatment of elderly patients with chronic lymphocytic leukemia: an unmet cinical need.

In chronic lymphocytic leukemia (CLL), the most prevalent lymphoid malignancy in western countries, patients have a median age at diagnosis of 72 years. In the last few years, there has been remarkable progress in understanding the biology of CLL, the detection of molecular prognostic factors and the development of more effective therapies. However, many of the milestone studies were conducted in populations that were considerably younger than the average age of the CLL population.

Total body computed tomography scan in the initial work-up of Binet stage A chronic lymphocytic leukemia patients: Results of the prospective, multicenter O-CLL1-GISL study.

Total body computed tomography (TB-CT) scan is not mandatory in the diagnostic/staging algorithm of chronic lymphocytic leukemia (CLL). The aim of this study was to determine the value and prognostic significance of TB-CT scan in early stage CLL patients. Baseline TB-CT scan was performed in 240 Binet stage A CLL patients (179 Rai low- and 61 Rai intermediate-risk) included in a prospective multicenter observational study (clinicaltrial.

Efficacy and safety of bendamustine for the treatment of patients with recurring Hodgkin lymphoma.

The management of patients with Hodgkin lymphoma (HL) recurring after stem cell transplantation (SCT) and multiply relapsed disease remains challenging. We report on 41 such patients who received bendamustine hydrochloride, a bifunctional mechlorethamine derivative mechanistically unrelated to traditional alkylators, after a median of four prior chemotherapy lines, including SCT in 85% of cases. Bendamustine was given at doses of 90-120 mg/m(2) every 21 or 28 d.

Risk stratification for Splenic Marginal Zone Lymphoma based on haemoglobin concentration, platelet count, high lactate dehydrogenase level and extrahilar lymphadenopathy: development and validation on 593 cases.

This international retrospective study of 593 Splenic Marginal Zone Lymphoma (SMZL) patients aimed to identify factors that determine treatment initiation and influence lymphoma-specific survival (LSS). Logistic regression was used to identify the factors associated with treatment. A Cox regression was used to analyse LSS in a derivation cohort of 366 patients.

Tumor burden in Hodgkin's lymphoma can be reliably estimated from a few staging parameters.

The relative tumor burden (rTB), the tumor burden normalized to body surface area, is of prime clinical and prognostic value in Hodgkin's lymphoma. However, its measurement is rather complicated and a bedside computation cannot be proposed. We investigated the possibility of estimating, instead of measuring, rTB from elementary parameters of the initial staging.

Bendamustine with or without rituximab for the treatment of heavily pretreated non-Hodgkin's lymphoma patients : A multicenter retrospective study on behalf of the Italian Lymphoma Foundation (FIL).

Bendamustine is an alkylating agent with a nitrogen mustard group and a purine-like benzimidazole group. The aim of this study was to collect all the Italian experiences with this drug in order to evaluate the results in term of response to therapy and toxicities. We analyzed lymphoma patients treated in 24 Italian haematological centres with bendamustine alone or in combination with anti-CD20 antibody.

Tumour burden predicts treatment resistance in patients with early unfavourable or advanced stage Hodgkin lymphoma treated with ABVD and radiotherapy.

The purpose of the work was to investigate the factors predicting early resistance to treatment in Hodgkin lymphoma. Many staging parameters, including relative tumour burden (rTB), were analysed in 246 patients with Hodgkin lymphoma in relation to early failure, that is, less than complete remission (i.e.

Role of glutathione-S-transferase (GST) polymorphisms in patients with advanced Hodgkin lymphoma: results from the HD2000 GISL trial.

Polymorphisms of the Glutathione-S Transferase (GST) family may influence the prognosis in lymphoma patients. We aimed to validate the impact of GSTT1 and GSTM1 deletions and of the GSTP1Ile105Val polymorphism on outcome and toxicity in 140 patients with advanced Hodgkin's lymphoma enrolled in the prospective multicenter HD2000-GISL trial, comparing ABVD, BEACOPP and CEC regimens. Carriers of the GSTP1Ile105Val polymorphism had a higher rate of grade 3-4 anemia following treatment.

Bendamustine with or without rituximab in the treatment of relapsed chronic lymphocytic leukaemia: an Italian retrospective study.

To retrospectively assess the efficacy of bendamustine alone and with rituximab (R-B), 109 patients with relapsed chronic lymphocytic leukaemia (CLL) were enrolled in 24 Italian centres. The median age was 66 years (range 39-85). Forty-three percent of patients had relapsed and 57% were resistant (median previous therapies = 3; range 1-8).

How I diagnose and treat splenic lymphomas.

The incidental finding of an isolated splenomegaly during clinical assessment of patients evaluated for unrelated causes has become increasingly frequent because of the widespread use of imaging. Therefore, the challenging approach to the differential diagnosis of spleen disorders has emerged as a rather common issue of clinical practice. A true diagnostic dilemma hides in distinguishing pathologic conditions primarily involving the spleen from those in which splenomegaly presents as an epiphenomenon of hepatic or systemic diseases.

Gamma-delta T-cell lymphomas.

Peripheral T-cell lymphomas (TCLs) are uncommon neoplasms, accounting for about 12% of all lymphoid tumors worldwide. TCLs in which gammadelta T-cell receptors are expressed (gammadelta TCLs) are extremely aggressive and rare (<1% of lymphoid neoplasms). gammadelta TCLs originate from gammadelta T cells, a small subset of peripheral T cells with direct antigen recognition capability acting at the interface between innate and adaptive immunity.