Christopher McNamara

ESMO Guidelines consensus conference on malignant lymphoma 2011 part 1: diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL)

To complete the existing treatment guidelines for all tumor types, ESMO organizes consensus conferences to better clarify open issues in each disease. In this setting, a consensus conference on the management of lymphoma was held on 18 June 2011 in Lugano, immediately after the end of the 11th International Conference on Malignant Lymphoma. The consensus conference convened ∼45 experts from all around Europe and selected six lymphoma entities to be addressed; for each of them three to five open questions were to be discussed by the experts. For each question, a recommendation should be given by the panel, supported by the strength of the recommendation based on the level of evidence. This consensus report focuses on the three most common lymphoproliferative malignancies: diffuse large B-cell lymphoma, follicular lymphoma and chronic lymphocytic leukemia. A second report will concentrate on mantle cell lymphoma, marginal zone lymphoma and T-cell lymphomas.

Excellent immunological recovery following CODOX-M/IVAC, an effective intensive chemotherapy for HIV-associated Burkitt's lymphoma.

Objective and design:To retrospectively describe the recovery of cellular immunity and the clinical outcome of 30 patients with HIV-associated Burkitts lymphoma (HIV-BL), who were treated with the intensive chemotherapy CODOX-M/IVAC and HAART as part of their standard care. Patients and methods:Seventy-three percent of the patients had high-risk disease, defined by stage, performance status, extranodal sites and lactate dehydrogenase. The median CD4 cell count at diagnosis of HIV-BL was 171/ml (range: 4–848) and the plasma HIV viral load was undetectable in five of 29 patients. Results:Nine patients died during treatment (disease progression, three; toxicity, five; central nervous system lesion not biopsied, one). Response rate was 70% (complete response/complete response uncertain, 17; partial response, 4). After a median follow-up of 22 months (range: 6–72), 18 patients remain alive without disease progression. The 3-year overall survival and event-free survival were 52 and 75%, respectively. Viral load was undetectable in 88% and CD4 cell count more than 200/ml in 58% of patients assessed 6 months after completing chemotherapy, and in 87 and 80% at 12 months, respectively. Conclusion:The intensive regimen CODOX-M/IVAC, a feasible and effective chemotherapy, is associated with an excellent immunological recovery in patients with HIV-BL on HAART.

Importance of Expert Central Review in the Diagnosis of Lymphoid Malignancies in a Regional Cancer Network

PURPOSE The accurate diagnosis of hematologic malignancies remains a challenging area for histopathologists. In 2003, the North Central London Lymphoma network was established to provide a centralized expert review service for general histopathologists based in peripheral nonspecialist hospitals. By studying samples sent for review, we sought to assess the diagnostic and clinical impact of centralized expert review in lymphoma diagnosis. METHODS A total of 1,949 patient samples were subject to expert review between 2003 and 2008. Diagnostic discordance rates were identified after expert review, and the impact on patient management was assessed by a hematologic oncology specialist. RESULTS An overall discordance rate of 27.3% was identified. Among the 10 most commonly referred lymphoid malignancies, the discordance rate varied between 3.6% and 34.1%. A small but significant number of reactive (n = 17) and malignant (n = 5) discordant diagnoses were also identified. Expert central review resulted in a major change to patient management in 2.1% of patients and prevented delays in treatment in 9.3% of patients. During the 6-year study, the discordance rate improved significantly, decreasing from 32% to 13%. Although centralized review incurred additional costs, these were relatively small compared with the costs associated with treatment. CONCLUSION This retrospective study demonstrates the importance of expert central review in the accurate diagnosis and timely management of lymphoid malignancies. Furthermore, it shows that where full centralization of services is not viable, a network comprising nonspecialist hospitals linked to a center providing expert review is a practical alternative to full unification of services at a single location and can help prevent local deskilling.

Guidelines on the investigation and management of follicular lymphoma.

The guideline group was selected to be representative of UK-based medical experts and patient’s representatives. MEDLINE and EMBASE were searched systematically for publications in English from 1980–2010 using the key words follicular lymphoma, non-Hodgkin lymphoma and low-grade lymphoma. The writing group produced the draft guideline, which was subsequently revised by consensus by members of the Haemato-oncology Task Force of the British Committee for Standards in Haematology (BCSH). The guideline was then reviewed by a sounding board of approximately 50 UK haematologists, the BCSH and the British Society for Haematology Committee and comments incorporated where appropriate. The objective of this guideline is to provide healthcare professionals with clear guidance on the management of patients with follicular lymphoma. The guidance is not appropriate for patients with other lymphoma subtypes and in all cases individual patient circumstances may dictate an alternative approach. Grading of evidence: These guidelines have used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) nomenclature for assessing levels of evidence and providing recommendations in the guidelines. See Appendix 1.

Primary follicular lymphoma of the testis and epididymis in adults.

Primary testicular lymphomas typically occur in patients over 60 years of age. Most are diffuse large B-cell lymphomas with frequent dissemination and a poor prognosis. Primary follicular lymphoma of the adult testis has not been well characterized. However, a small number of primary testicular follicular lymphomas have recently been described in children. These showed stage 1E disease, a lack of BCL2 gene rearrangement and Bcl-2 protein expression, and a good clinical outcome. Here, we describe 5 cases of primary follicular lymphoma of the testis and epididymis in adults. These presented as unilateral testicular masses 12 to 40 mm in diameter and were characterized histologically by small neoplastic follicles in a sclerotic background. The neoplastic cells expressed CD10 and Bcl-6, but not Bcl-2 and lacked t(14;18)(q32;q21)/IGH-BCL2 and BCL6 gene rearrangements. Four of the five patients were 35 years old or younger, and 4 presented with stage 1EA disease. Although follow-up is 12 months or less in 2 of the 5 patients, to date each has followed an indolent clinical course. These features are different from those of most adult nodal follicular lymphomas but are very similar to those of the pediatric primary testicular follicular lymphomas. Together, the pediatric and adult cases represent a discrete clinicopathologic entity of t(14;18)(q32;q21)/IGH-BCL2-negative primary follicular lymphoma of the testis and epididymis, which typically present as clinically indolent localized disease in young males and should be distinguished from the diffuse large B-cell lymphoma more frequently seen in the testes of older adults.

Routine bone marrow biopsy is not necessary in the staging of patients with classical Hodgkin lymphoma in the 18F-fluoro-2-deoxyglucose positron emission tomography era

Abstract Accurate staging of classical Hodgkin lymphoma (CHL) directs treatment intensity. Functional imaging can detect marrow/bone involvement making the role of bone marrow biopsy (BMB) unclear. We assessed current UK practice in CHL staging by questionnaire and retrospectively analyzed patients staged at a single center with BMB and 18F-fluoro-2-deoxyglucose positron emission tomography/computed tomography (FDG-PET/CT). From 34 questionnaire responses 50% used FDG-PET/CT routinely. BMB was employed in 97% with advanced-stage and 30% of patients with limited-stage disease (70% of those not using routine FDG-PET/CT). Ten out of 50 patients were BM+, all of which were identified by FDG-PET/CT (PET+). Conventional BMB changed management in 2% of cases. There were no clinically significant FDG-PET/CT false positives. Conventional routine BMB staging in CHL is extremely insensitive. FDG-PET/CT can rule out marrow/bone involvement in CHL. In the FDG-PET/CT staging era BMB should be targeted to a minority of patients with FDG-PET/CT + bone/marrow uptake and only when management would be altered by the result.

Pathology of bone marrow in human herpes virus‐8 (HHV8)‐associated multicentric Castleman disease

Human herpes virus‐8 (HHV8)‐associated multicentric Castleman disease (MCD) is an unusual systemic lymphoid hyperplasia induced by HHV8‐infected B cells. Most cases develop in the background of human immunodeficiency virus (HIV) infection. Despite the haematological problems at presentation and the difficulties in the initial diagnosis, the bone marrow appearances of MCD have not been described. In this study we examined the pathology of bone marrow in MCD with a view to identify the features that may be helpful in early diagnosis. Bone marrow aspirates and biopsies from 13 cases of MCD (11 of which were HIV+) and 66 control bone marrow biopsies from HIV‐infected cases were studied. The specimens were routinely processed and stained. Immunohistochemistry for HHV8, immunoglobulin light chains, B‐cell and plasma‐cell markers was performed. The most important features were the presence of characteristic MCD lymphoid follicles containing HHV8+ plasmablasts in three of 13 cases of MCD and scattered interstitial HHV8+ plasmablasts in 11 of 13 cases. In control cases, no such follicles were seen and interstitial HHV8+ plasmablasts were rarely detected (four of 66 cases). Our results suggest that the presence of HHV8+ plasmablasts within lymphoid follicles and/or interstitium of the bone marrow are helpful features for the early diagnosis of MCD.

Clinico-pathologic characteristics of patients with hepatic lymphoma diagnosed using image-guided liver biopsy techniques

Abstract Primary hepatic lymphoma is a rare presentation of a common disease. Diagnosis is difficult due to the risks of liver biopsy. We report the clinico-pathologic features of this presentation and specifically the utility of image-guided biopsy as a safe method of diagnosis. We retrospectively studied patients diagnosed with ‘hepatic lymphoma’ at a single center. Twenty-two patients fulfilled the criteria. Median age was 53 years (range 29–87). Nine patients were human immunodeficiency virus (HIV)-positive. The most frequent mode of presentation was with B-symptoms (15/22). All procedures were successful at obtaining diagnostic material with no complications. Six patients had synchronous bone marrow involvement. Nineteen patients received chemotherapy (10 had dose reductions) with an overall response rate of 74%. After a median follow-up of 19 months, 12 patients had died; the median overall survival (OS) was 4 months. Grade 3 or 4 aspartate transaminase (AST) abnormality was associated with very poor outcome. The OS of patients with hepatic lymphoma is poor. However, a response to modern induction therapies may predict a better outcome. The optimal dose adjustment of chemotherapy in this setting is unclear. In patients without readily accessible tissue, an image-guided core biopsy of hepatic lesions is a safe procedure with high diagnostic yield.

The Management of Classical Hodgkin's Lymphoma: Past, Present, and Future.

The management of classical Hodgkins lymphoma (CHL) is a success story of modern multi-agent haemato-oncology. Prior to the middle of the twentieth century CHL was fatal in the majority of cases. Introduction of single agent radiotherapy (RT) demonstrated for the first time that these patients could be cured. Developments in chemotherapy including the mechlorethamine, vincristine, procarbazine and prednisolone (MOPP) and Adriamycin, bleomycin, vinblastine and dacarbazine (ABVD) regimens have resulted in cure rates of over 80%. Even in relapse, CHL patients can be salvaged with high dose chemotherapy and autologous haematopoietic stem cell transplantation (ASCT). Challenges remain, however, in finding new strategies to manage the small number of patients who continue to relapse or progress. In addition, the young age of many Hodgkins patients forces difficult decisions in balancing the benefit of early disease control against the survival disadvantage of late toxicity. In this article we aim to summarise past trials, define the current standard of care and appraise future developments in the management of CHL.

Guidelines for the investigation and management of nodular lymphocyte predominant Hodgkin lymphoma.

Department of Haematology, Beatson West of Scotland Cancer Centre, Gartnavel Hospital, Glasgow, PETIC, Department of Radiology, University Hospital of Wales, Department of Clinical Oncology, Velindre Cancer Centre, Cardiff, UK, Paediatric Haematology/Oncology Unit, Children’s Hospital, John Radcliffe Hospital, Headington, Oxford, Department of Haematology, University College London Hospitals, Department of Pathology, University College London Hospitals, and Department of Haematology, The Royal Free London NHS Trust, London, UK