Gene expression profiling studies based on DNA microarrays have demonstrated their ability to define the interaction pathways between neoplastic and nonmalignant stromal cells in cancer tissues. During the past ten years, a number of approaches including microdissection have tried to resolve the variability in DNA microarray measurements stemming from cancer tissue sample heterogeneity. Another approach, designated as virtual or in silico microdissection, avoids the laborious and time-consuming step of anatomic microdissection. It consists of confronting the gene expression profiles of complex tissue samples to those of cell lines representative of different cell lineages, different differentiation stages, or different signaling pathways. This strategy has been used in recent studies aiming to analyze microenvironment alterations using gene expression profiling of nonmicrodissected classical Hodgkin lymphoma tissues in order to generate new prognostic factors. These recent contributions are detailed and discussed in the present paper.

Fran&#231;ois Bertucci

Bruno Chetaille

Luc Xerri

Gene Expression Profiling for In Silico Microdissection of Hodgkin's Lymphoma Microenvironment and Identification of Prognostic Features

We are reporting a case of a young woman with acute myelogenous leukemia status postallogeneic transplantation who developed multiply recurrent chloromas occurring along peripheral nerves in the absence of bone marrow relapse, all treated with radiation therapy. The patient is currently free of disease nearly four years after her first posttransplant chloroma. The case presented is unique for its isolated peripheral nervous system involvement, rare posttransplant occurrence, and indolent course without marrow relapse despite multiple extramedullary recurrences.

Richard Bakst

Ann Jakubowski

Joachim Yahalom

Recurrent Neurotropic Chloroma: Report of a Case and Review of the Literature

Epidemiological studies suggest unique occurrence patterns of Hodgkin lymphoma (HL) worldwide. In most Western countries there is a clear bimodal age distribution with an early peak in young adults followed by a second peak in older adults, particularly among males. In the Middle East and Asia, HL is more common in early childhood. There also are marked racial differences in the presentations of HL and HL subtypes, and particular single nucleotide polymorphisms (SNPs) have been identified as etiological factors suggesting that gene-gene and gene-environment interactions are involved. Personal health choices such as exercise and smoking may modify an individual's chances of developing HL. Numerous studies highlight the impact that exposure to Epstein-Barr virus and other environmental factors have on HL risk. Understanding the relative importance of each of these findings and their links to HL development and survival will help clinical researchers expand curative therapies and create preventative strategies for HL.

Alison Maggioncalda

Neha Malik

Pareen Shenoy

Melody Smith

Rajni Sinha

Christopher R. Flowers

Clinical, Molecular, and Environmental Risk Factors for Hodgkin Lymphoma

Classical Hodgkin lymphoma (CHL) is a relatively uncommon B  cell-derived neoplasm that presents with rare malignant cells in an abundant reactive background. The diagnosis of CHL currently relies on a combination of morphologic findings and immunohistochemical stains. With the exception of rare cases with dramatically increased malignant populations, isolation of pure viable tumor cells has not been historically possible. Recently, a reliable flow cytometric assay for direct detection and isolation of the malignant cells in this disease has been developed. This assay has proven useful diagnostically and has been clinically validated to have a very high sensitivity and nearly absolute specificity for the diagnosis of CHL in routine clinical samples. This paper describes the methodology for the flow cytometric detection of CHL in clinical samples as well as current state of evaluation of background lymphocytes as an adjunct diagnostic test. Also discussed are exciting research applications of the direct isolation of viable tumor cells in CHL. The current state of flow cytometric evaluation of nodular lymphocyte predominant Hodgkin lymphoma and T cell-rich large B cell lymphoma is also briefly discussed.

Mikhail Roshal

Brent L. Wood

Jonathan R. Fromm

Flow Cytometric Detection of the Classical Hodgkin Lymphoma: Clinical and Research Applications

Despite the favorable prognosis of most patients with Hodgkin's Lymphoma (HL), 15&#x2013;20&#x25; of patients remain refractory to chemoradiotherapy, and 20&#x2013;40&#x25; experience relapses following autologous stem cell transplantation (SCT) being used as salvage approach in this situation. Long-term survival of only 20&#x25; was reported for patients who failed this option. As some authors suggested the presence of a graft versus HL effect, allogeneic SCT was introduced as a further option. Myeloablative strategies were reported to be able to achieve cure in some younger patients, but high nonrelapse mortality remains a problem. Reduced intensity conditioning, in turn, was found to be associated with high posttransplant relapse rates. As there is currently no standard in the management of HL patients who failed autologous SCT, we here review the literature on allogeneic stem cell transplantation in HL patients with a special focus on the outcomes and risk factors being reported in the largest studies.

Evgeny Klyuchnikov

Ulrike Bacher

Nicolaus Kr&#xf6;ger

Ilya Kazantsev

Tatjana Zabelina

Francis Ayuk

Axel Rolf Zander

The Role of Allogeneic Stem Cell Transplantation in Relapsed/Refractory Hodgkin's Lymphoma Patients

Hodgkin&#39;s Lymphoma was incurable until the advent of effective therapeutic radiation around the first half of the 20th century. As survival rates improved, the long-term toxicities from radiotherapy began to emerge. This together with the availability of effective chemotherapy has encouraged a combined modality approach for early-staged disease and the omission of radiotherapy in advanced-staged disease. The differing toxicities of radiotherapy and chemotherapy has promoted ongoing research to identify the utility of each of these modalities in the modern management of Hodgkin&#39;s Lymphoma. 
This article will provide a critical review of the developments  and indications for modern radiotherapy, in context with advances in chemotherapy, for the treatment of Hodgkin&#39;s Lymphoma.

Kheng-Wei Yeoh

N. George Mikhaeel

Role of Radiotherapy in Modern Treatment of Hodgkin&#39;s Lymphoma

Thomas Hodgkin's and Samuel Wilks first recognized Hodgkin disease in the first half of the 19th century. Initially described as lymphogranulomatosis, it was later recognized to be a lymphoid neoplasm derived from B cells and was classified on the basis of its histopathological features. Hodgkin lymphomas are now regarded as encompassing two clearly defined entities according to the WHO classification: nodular lymphocyte-predominant Hodgkin Lymphoma (NLPHL) and classical Hodgkin Lymphoma (CHL). This paper focuses on the current knowledge about the biological features that characterize both NLPHL and CHL, highlighting those relevant to correct pathological diagnosis and those that might be associated with patient outcome.

S. Montes-Moreno

Hodgkin's Lymphomas: A Tumor Recognized by Its Microenvironment

In hematologic malignancies, the microenvironment is often characterized by nonneoplastic cells with peculiar phenotypic and functional features. This is particularly true in Hodgkin's lymphoma (HL), in which T lymphocytes surrounding Hodgkin's Reed-Sternberg cells are essentially polarized towards a memory T-helper type 2 phenotype. In this paper we will first evaluate the main processes modulating T-cell recruitment towards the lymph node microenvironment in HL, especially focusing on the role played by cytokines. We will then consider the most relevant mechanisms of immune escape exerted by neoplastic cells in order to evade antitumor immunity. The potential pathogenetic and prognostic impact of regulatory T cells in such a context will be also described. We will finally overview some of the strategies of cellular immunotherapy applied in patients with HL.

Claudio Fozza

Maurizio Longinotti

T-Cell Traffic Jam in Hodgkin's Lymphoma: Pathogenetic and Therapeutic Implications

Hodgkin&#39;s lymphoma is a hematolymphoid neoplasm, primarily of B cell lineage, that has unique histologic, immunophenotypic, and clinical features.  Neurologic complications of Hodgkin&#39;s Lymphoma can be separated into those that result directly from the disease, indirectly from the disease, or from its treatment.  Direct neurologic dysfunction from Hodgkin&#39;s Lymphoma results from metastatic intracranial spinal disease, epidural metastases causing spinal cord/cauda equina compression, leptomeningeal metastases, or intradural intramedullary spinal cord metastases.  Indirect neurologic dysfunction may be caused by paraneoplastic disorders (such as paraneoplastic cerebellar degeneration or limbic encephalitis) and primary angiitis of the central nervous system.  Hodgkin&#39;s lymphoma treatment typically includes chemotherapy or radiotherapy with potential treatment-related complications affecting the nervous system.  Neurologic complications resulting from mantle-field radiotherapy include the &#8220;dropped head syndrome,&#8221; acute brachial plexopathy, and transient ischemic attacks/cerebral infarcts.  Chemotherapy for Hodgkin&#39;s lymphoma may cause cerebral infarction (due to emboli from anthracycline-induced cardiomyopathy) and peripheral neuropathy.

Sean Grimm

Marc Chamberlain

Hodgkin&#39;s Lymphoma: A Review of Neurologic Complications

Hodgkin lymphoma (HL) represents one of the most common non-AIDS-defining cancers with an increasing incidence overtime. Clinically, patients present advanced stages of disease with extranodal involvement in the majority of cases. In the last years, significant improvements in the treatment of patients with HL and HIV infection have been achieved. In the lack of randomized trials, several phase II studies have showed that in the era of highly active antiretroviral therapy (HAART) the same regimens employed in HIV-negative patients with HL can be used in HIV setting with similar results. Moreover, in the last years the feasibility of high dose chemotherapy and peripheral stem cell rescue has allowed to save those patients who failed the upfront treatment.
Finally, in the near future, a better integration of diagnostic tools (including PET scan), chemotherapy (including new drugs), radiotherapy, HAART, and supportive care will significantly improve the outcome of these patients.

Michele Spina

Antonino Carbone

Annunziata Gloghini

Diego Serraino

Massimiliano Berretta

Umberto Tirelli

Hodgkin's Disease in Patients with HIV Infection

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Advances in Hematology publishes original research articles and&nbsp;review articles in all areas of hematology.

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Advances in Hematology - Table of contents 2011

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Advances in Hematology publishes original research articles and review articles in all areas of hematology.

Advances in Hematology