Tumor microenvironment in Hodgkin lymphoma: novel prognostic factors for assessing disease evolution.

Hodgkin lymphoma (HL) has become one of the most curable hematological neoplasia. Clinical and biological factors remain the main pillars guiding therapeutic strategies in HL. Recent studies have improved our understanding of the phenotype, the characteristics of histogenesis, and other possible mechanisms of lymphomagenesis, including the role of Epstein-Barr virus (EBV) infection. Tumor cells manipulate the microenvironment, allowing them to develop their malignant phenotype and evade the attack of the host's immune response so that the interaction between tumor cells and the reactive microenvironment determines not only the histological features but also the clinical-pathological characteristics and prognosis of these patients - essential for the development of future therapies targeting various other cellular components of the tumor microenvironment. This article aimed to evaluate the characteristics of the tumor microenvironment and malignant cells using histopathology and immunohistochemistry (IHC) techniques to highlight the association of EBV and to study the expression of characteristic antigens in malignant and non-malignant cells within the tumor mass (overexpression of BCL2 (B-cell lymphoma 2) in malignant cells, presence of PD1 (Programmed cell death Protein 1) on T lymphocytes, CD68+ macrophages in the tumor microenvironment, and presence of EGFR (epidermal growth factor receptor). The analysis of the data collected in this paper highlights several key parameters with prognostic value and statistical significance: the EBV infection at diagnosis, its association with low-intensity BCL2(+), the presence of CD68 with rosette formation, and the identification of specific vascularization patterns. The development of prognostic systems that take into account the integration of biological prognostic markers seems essential for a better risk stratification.

LEAM vs. BEAM vs. CLV Conditioning Regimen for Autologous Stem Cell Transplantation in Malignant Lymphomas. Retrospective Comparison of Toxicity and Efficacy on 222 Patients in the First 100 Days After Transplant, On Behalf of the Romanian Society for Bone Marrow Transplantation.

High-dose chemotherapy (HDT) followed by autologous hematopoietic stem cell transplantation (ASCT) is widely used in patients with malignant lymphomas. In Europe over 8,000 ASCTs for lymphoma were performed out of a total of 40,000 transplants according to the European Bone Marrow Transplant (EBMT) activity survey in 2017. ASCT is considered the standard treatment for eligible patients failing to achieve remission after first line chemotherapy or patients with relapsed or refractory lymphomas, including classical Hodkin's lymphoma, diffuse large B-cell lymphoma, mantle cell lymphoma, and follicular lymphoma, as well as consolidation therapy in first remission in mantle cell lymphoma. BEAM (BCNU/carmustine, etoposide, cytarabine, and melphalan) is the most commonly used conditioning regimen for ASCT in patients with relapsed/refractory (R/R) lymphomas in Europe, whereas the CBV (cyclophosphamide, BCNU, and etoposide) regimen is also widely used in North America. Recently, concerns regarding BCNU toxicity as well as restricted availability of BCNU and melphalan has determined an increasing number of transplant centers to use alternative conditioning regimens. Currently, only a few comparative studies, most of them retrospective, between different conditioning protocols regarding efficacy and toxicity have been published. Thus, in the current manuscript, we report the experience of 2 transplant centers in ASCT in R/R lymphomas with three types of conditioning: BEAM, CLV (cyclophosphamide, lomustine, etoposide) and LEAM (lomustine, etoposide, cytarabine, and melphalan), with the aim to evaluate the results of alternative conditioning regimens using lomustine (LEAM and CLV) and compare them with the standard BEAM regarding early toxicity, engraftment, and transplant related mortality (TRM). All patients developed grade IV neutropenia, anemia with/without transfusion necessity. Severe thrombocytopenia with transfusion requirements is reported in most cases. Median time to platelet engraftment and neutrophil engraftment was 13 days (range) and 10 days (range), respectively. Gastrointestinal toxicity was the most common non-hematologic toxicity after all three conditioning regimens. Oral mucositis in various grades from I to IV was diagnosed in most cases. Other side effects include vomiting, diarrhea, colitis, and skin rash but with low severity grades. For the LEAM arm, one patient died after transplant, before engrafting, one patient didn't achieve platelet engraftment in day 100, one patient developed grade 3 upper gastrointestinal bleeding, one patient died (grade 5 toxicity) with acute renal failure, one patient developed hypoxic events up to grade 4 acute respiratory failure and one patient developed grade 3 itchy skin rash. For the CLV arm, one patient died after transplant, before engrafting, one patient developed grade 3 colitis, one patient with grade 3 hepatic cytolysis, one patient with cardiac toxicity followed by death (grade 5) caused by an acute myocardial infarction with ST elevation and one patient with pulmonary toxicity clinically manifested with grade 3 pleurisy. For the BEAM arm, one patient developed grade 3 cardiac toxicity with sinus bradycardia and afterwards grade 4 with acute pulmonary edema, three patients presented a grade 3 pruritic skin rash and two patients developed grade 3 seizures. In the present study we presented the differences that were observed between BEAM, LEAM, and CLV conditioning regimens offering clinical arguments for an SCT practitioner choice in the ideal situation, but also of choice for alternative regimens in the case that one regimen cannot be used.

Present and Future in Treatment of Hodgkin Lymphoma.

Hodgkin lymphoma is a highly curable malignant hemopathy, using chemotherapy, radiotherapy, target therapies and hematopoietic stem cell transplantation. Current research in this field focuses on identifying prognostic factors associated with the pathogenic characteristics of the tumoral process, enabling the therapy to be adjusted to each patient's degree of risk. The identification of biomarkers associated with the tumoral process is extremely important because these molecules can be targets for new biological therapies.

Hemophagocytic lymphohistiocytosis: a rare complication of autologous stem cell transplantation.

Hemophagocytic lymphohistiocytosis (HLH) is a very severe and rare syndrome of pathologic immune activation characterized by cytopenia and clinical signs and symptoms of extreme inflammation. HLH is usually fatal without treatment so that accurate and timely diagnosis is very important. The syndrome occurs as a familial disorder (familial HLH - FLH) or as an acquired condition (secondary - sHLH) in association with a variety of pathologic states: infections, rheumatologic, malignant or metabolic diseases. Malignancy associated HLH is primarily reported in T÷NK (natural killer)-cell malignancies but also in B-cell neoplasms and other types of cancer. HLH has also been reported in rare cases as a highly fatal and difficult to diagnose complication of stem cell transplantation (SCT). In this paper, we present the case of a young male patient who underwent autologous SCT as consolidation therapy for a T÷NK-cell lymphoma, complicated with graft failure due to HLH. The patient was successfully treated with corticosteroids, Etoposide, Cyclosporine and immunoglobulins. As a particularity, he developed a second B-cell neoplasia a few months after SCT.

Composite diffuse large B-cell lymphoma and follicular B-cell lymphoma - case report and review of literature.

Composite lymphoma refers to the co-occurrence of two or more morphologically and immunophenotypically separate lymphomas in the same topographic site at the time of clinical presentation. It is an infrequent type of lymphoid neoplasm, present in lymphoid tissue and may be due to the existence of two genetically related neoplasms such as transformation of a single lymphoma into another more aggressive lymphoma or be due to the presence of two clonally unrelated lymphomas. This paper is presenting a case of diffuse non-Hodgkin large B-cell lymphoma with areas of low grade and high grade follicular non-Hodgkin B-cell lymphoma in a retroperitoneal lymph node and spleen of an 62 year old woman. Histopathological examination and immunohistochemistry features proved the diagnosis of composite lymphoma.

Onset risk factors and treatment response features of refractory hodgkin lymphoma.

BACKGROUND: The International Prognostic Factors Project on Advanced Hodgkin lymphoma (HL) developed a seven factor prognostic score consisting of gender, age, stage, serum albumin, hemoglobin, leukocytosis and lymphocytopenia for the newly diagnosed Hodgkin disease patients in advanced stages, who receive chemotherapy. OBJECTIVES: The purpose of this study was to determine whether this prognostic score would also be useful for refractory Hodgkin lymphoma patients in monitoring response to treatment. MATERIAL AND METHOD: In the period 2000-2012, we performed a study on a group of 91 patients to show that the prognostic factors identified by the International Prognostic Factors (IPF) score affect the event- free survival (EFS) and the overall survival (OS). Our study also intends to show that the results of these factors change with the treatment response in patients with HL included in the category of patients with refractory disease. RESULTS: B symptoms, onset lymph node, more than 3 areas involved, bulky disease, extranodal involvement, low serum albumin, erythrocytes sedimentation rate (ESR), C reactive protein (CRP), lactic dehydrogenase (LDH) and anemia were associated with poorer EFS and OS. Male gender, stage, histological type, age (>45 years) and leukocytosis were not associated with significantly poorer outcomes. CONCLUSIONS: the prognostic score for advanced disease is also useful in predicting relapse in patients with HL and early detection of response in patients with refractory HL.