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NCI CANCERLIT^® Search: Hodgkin's Lymphoma - July 2002

National Cancer Institute^®
Last Modified: July 1, 2002

Hematopoietic stem cell transplantation in Hodgkin disease.
Expression pattern of MUM1/IRF4 in the spectrum of pathology of Hodgkin's disease.
Immunohistochemical detection of CD30 remains negative in nodular lymphocyte-predominant Hodgkin's disease using enhanced antigen
Virtual reality as a distraction intervention for older children receiving chemotherapy.
Solitary fibrous tumor of the orbit presenting 20 years after Hodgkin's disease.
Autotransplantation for advanced lymphoma and Hodgkin's disease followed by post-transplant rituxan/GM-CSF or radiotherapy and consolidation
The role of cytokines in classical Hodgkin lymphoma.
[The role of PET scan in the investigation of the lymphatic spreading of Hodgkin's disease]
Aggressive conventional chemotherapy compared with high-dose chemotherapy with autologous haemopoietic stem-cell transplantation for
Comparative treatment planning using secondary cancer mortality calculations.
Daily general anaesthesia for radiotherapy in unco-operative patients: ingredients for successful management.
Early lymphocyte recovery post-autologous haematopoietic stem cell transplantation is associated with better survival in Hodgkin's disease.
Hodgkin disease of thymic origin.
Pulmonary manifestations of Hodgkin's disease: radiographic and CT findings.
ChlVPP/EVA hybrid versus the weekly VAPEC-B regimen for previously untreated Hodgkin's disease.
Immunosuppressive non-myeloablative allografting as salvage therapy in advanced Hodgkin's disease.
Expression of Epstein-Barr virus in classical Hodgkin's lymphomas in Brazilian adult patients.
Hodgkin's lymphoma: basing the treatment on the evidence.
Multiple synchronous pigmented basal cell carcinomas following radiotherapy for Hodgkin's disease.
[Clinical course and treatment of Hodgkin's disease with concomitant bone marrow lesions]
[The role of indirect lower lymphoscintigraphy for radiotherapy planning in Hodgkin's lymphoma]
Challenges in treating hematologic malignancies.
Acquired inhibitor to factor VIII in a patient with Hodgkin's disease following treatment with interferon-alpha.
A population-based study of the outcome for patients with first relapse of Hodgkin's lymphoma.
Expression of SSX genes in the neoplastic cells of Hodgkin's lymphoma.
Hodgkin disease in adult and juvenile groups from two different geographic regions in Brazil: characterization of clinicopathologic
High numbers of active caspase 3-positive Reed-Sternberg cells in pretreatment biopsy specimens of patients with Hodgkin disease predict
Gene expression profiling defines molecular subtypes of classical Hodgkin's disease.
Common and differential chemokine expression patterns in rs cells of NLP, EBV positive and negative classical Hodgkin lymphomas.
B-cell markers in lymphocyte predominance Hodgkin disease.
The clinical course of nonsmall cell lung carcinoma in survivors of Hodgkin disease.
[Fournier's gangrene in a patient with Hodgkin's disease: a clinical case]
False-negative interpretation of FDG positron emission tomography in a patient with Hodgkin's lymphoma.
T-cell-rich B-cell lymphoma - diagnostic and therapeutic aspects.
[Successful neoplasm chemotherapy. Remission of Hodgkin's disease. V]
Up-front centralized data review and individualized treatment proposals in a multicenter pediatric Hodgkin's disease trial with 71 participating
[Hodgkin's disease with epitrochlear onset]
Loss of B cell identity correlates with loss of B cell-specific transcription factors in Hodgkin/Reed-Sternberg cells of classical

1
UI - 11880706
AU - Reece DE
TI - Hematopoietic stem cell transplantation in Hodgkin disease.
SO - Curr Opin Oncol 2002 Mar;14(2):165-70
AD - Department of Medical Oncology and Hematology, Princess Margaret Hospital, Toronto, Ontario, Canada. donna.reece@uhn.on.ca
Intensive therapy and autologous stem cell transplantation represent the standard of care in most patients whose Hodgkin disease has not been cured with conventional chemotherapy. With more prolonged follow-up of autografted patients, the problems with autologous stem cell transplantation are clear. In particular, recurrent disease and late transplant-related complications limit the effectiveness of this approach. A number of autologous stem cell transplantation studies have reported prognostic factors that will help identify patients at high risk for relapse. Several new approaches for decreasing recurrence rates are discussed, including novel immune strategies and re-evaluation of allogeneic stem cell transplantation. Although the risk of secondary malignancy and other causes of late morbidity and mortality after autologous stem cell transplantation is relatively low, current studies contribute to understanding of the pathogenesis of these complications and may diminish their impact in the future.

2
UI - 11972519
AU - Carbone A; Gloghini A; Aldinucci D; Gattei V; Dalla-Favera R; Gaidano G
TI - Expression pattern of MUM1/IRF4 in the spectrum of pathology of Hodgkin's disease.
SO - Br J Haematol 2002 May;117(2):366-72
AD - Division of Pathology, Centro di Riferimento Oncologico, IRCCS, Istituto Nazionale Tumori, via Pedemontali Occidentale, Aviano I-33081, Italy. acarbone@cro.it
Biological and clinical studies have shown that Hodgkin's disease (HD) can be divided into two major categories, termed nodular lymphocyte predominance HD (NLP HD) and classic HD (CHD). Within CHD four subtypes have been distinguished: nodular sclerosis, mixed cellularity, lymphocyte rich and lymphocyte depletion. To refine the histogenesis of the pathological spectrum of HD, 75 CHD and 13 NLP HD were analysed for the expression pattern of MUM1/IRF4 (Multiple Myeloma-1/Interferon Regulatory Factor-4), a lymphocyte-specific member of the IRF family, that is expressed by late centrocytes and post-germinal centre (GC) B cells. MUM1 reacted with Hodgkin's and Reed-Sternberg (HRS) cells of all CHD cases (75/75 cases), with a moderate to strong staining intensity. Conversely, lymphocyte and histiocyte (L & H) cells, the putative tumour cells of NLP HD, were negative for MUM-1 expression (9/13 cases) or displayed a weak reactivity for the antigen in < 10% neoplastic cells (4/13 cases). With respect to HD microenvironment, NLP HD displayed numerous MUM1-positive T lymphocytes located in close proximity to L & H cells whereas, in CHD, MUM1-positive T lymphocytes appeared to be distributed randomly with no specific relationship with HRS cells. Overall, this study shows that MUM1 expression differs in L & H cells versus HRS cells, corroborating the notion that NLP HD and CHD represent different stages of B-cell differentiation. As MUM1-positive T lymphocytes form rosettes around tumour cells of NLP HD, but not of CHD, these data point also to differences in the microenvironment of NLP HD and CHD, and postulate an interactive role of MUM1-positive T lymphocytes with L & H cells.

3
UI - 11952861
AU - Roberts C; Jack F; Angus B; Reid A; Thompson WD
TI - Immunohistochemical detection of CD30 remains negative in nodular lymphocyte-predominant Hodgkin's disease using enhanced antigen retrieval.
SO - Histopathology 2002 Feb;40(2):166-70
AD - Department of Pathology, Medical School, Foresterhill, Aberdeen, UK.
AIMS: The aims of this study were to confirm that CD30 is reproducibly negative in cases of nodular lymphocyte-predominant Hodgkin's disease (nLPHD), and its relationship to further antibody targets for the distinction of L&H cells from classical Hodgkin's and Reed-Sternberg cells. METHODS AND RESULTS: We examined 16 cases of nLPHD from two centres in the UK to characterize immunohistochemically L&H cells for CD30, EMA, J-chain and Oct2, using different methods of antigen retrieval, antigen amplification and antigen detection systems. Two cases could not be stained with J-chain and Oct2. All cases were negative for CD30 following manual and automated staining. Only one case became positive for EMA after manual staining using tyramide amplification. J-chain and Oct2 were negative in all cases following manual staining. J-chain showed a positive result of variable degree in all but one case using automated Dako ChemMate amplification system staining. Oct2 demonstrated a positive, albeit variable, staining pattern in all cases following automated staining. CONCLUSIONS: CD30 remains negative in L&H cells of nLPHD using enhanced antigen retrieval and can therefore reliably be used to distinguish nLPHD from classical Hodgkin's disease. The value of EMA in the diagnosis of nLPHD remains uncertain, as it does not reproducibly mark L&H cells, even after the use of enhanced antigen retrieval. J-chain and Oct2 appear to be useful markers in the diagnosis of nLPHD using enhanced immunostaining and should therefore be included in lymphoma panels. Automated enhanced staining, using standardized protocols, precoated slides and the full system of prepared reagents, further diminishes the occurrence of errors associated with manual staining, and thereby improves confidence and reliability in diagnosing nLPHD.

4
UI - 12026359
AU - Schneider SM; Workman ML
TI - Virtual reality as a distraction intervention for older children receiving chemotherapy.
SO - Pediatr Nurs 2000 Nov-Dec;26(6):593-7
AD - Oncology Program, Graduate School of Nursing, Duke University, Durham, NC, USA.
The purpose of this pilot study was to describe the perceived effectiveness and feasibility of using virtual reality (VR) as a distraction intervention for children, aged 10-17, receiving outpatient chemotherapy. Treatments for cancer are intensive and difficult to endure. Distraction interventions are effective because the individual concentrates on pleasant or interesting stimuli instead of focusing on unpleasant symptoms. VR is a computer-simulated technique allowing an individual to hear and feel stimuli that correspond with a visual image. Evaluation of the VR intervention demonstrated positive outcomes. Eighty-two percent of the children (n = 11) indicated the chemotherapy treatment with the VR was better than previous chemotherapy treatments. All subjects responded positively when asked if they would like to use the VR again. The intervention was easy to implement, did not require practice to be effective, and required minimal nursing time. Results from this pilot study suggest that VR as a distraction intervention has the potential to enhance positive clinical outcomes. This intervention warrants further investigation with both pediatric and adult populations.

5
UI - 12029582
AU - Holbach LM; Colombo F; Schlotzer-Schrehardt U; Kirchner T
TI - Solitary fibrous tumor of the orbit presenting 20 years after Hodgkin's disease.
SO - Orbit 2002 Mar;21(1):49-54
AD - Department of Ophthalmology & Eye Hospital, University of Erlangen-Nurnberg, Germany. leonard.holbach@augen.imed.unierlangen.de
A 54-year-old white male patient presented with a painless, slowly progressive proptosis and downward displacement of his right eye. He had been treated for Hodgkin's disease 20 years earlier. MRI revealed a well-circumscribed retro- and suprabulbar mass measuring 24 mm in its maximal diameter. The mass was isointense with brain on T1-weighted images, displayed a low signal on T2-weighted images and showed postcontrast enhancement. The tumor was removed in its entirety via an anterior orbitotomy. Histopathologic, immunohistochemical and ultrastructural studies revealed a solitary fibrous tumor. Both immunohistochemical and electron microscopic findings were essential in differentiating this entity from other similar soft-tissue lesions. Only 11 other cases of orbital solitary fibrous tumor have been reported in the literature. To our knowledge, this is the first one presenting after Hodgkin's disease.

6
UI - 11896427
AU - Rapoport AP; Meisenberg B; Sarkodee-Adoo C; Fassas A; Frankel SR;
TI - Mookerjee B; Takebe N; Fenton R; Heyman M; Badros A; Kennedy A; Jacobs M; Hudes R; Ruehle K; Smith R; Kight L; Chambers S; MacFadden M; Cottler-Fox M; Chen T; Phillips G; Tricot G Autotransplantation for advanced lymphoma and Hodgkin's disease followed by post-transplant rituxan/GM-CSF or radiotherapy and consolidation chemotherapy.
SO - Bone Marrow Transplant 2002 Feb;29(4):303-12
AD - Greenebaum Cancer Center and Stem Cell Transplantation Program, University of Maryland School of Medicine, Baltimore, MD, USA.
Disease relapse occurs in 50% or more of patients who are autografted for relapsed or refractory lymphoma (NHL) or Hodgkin's disease (HD). The administration of non-cross-resistant therapies during the post-transplant phase could possibly control residual disease and delay or prevent its progression. To test this approach, 55 patients with relapsed/refractory or high-risk NHL or relapsed/refractory HD were enrolled in the following protocol: stem cell mobilization: cyclophosphamide (4.5 g/m(2)) + etoposide (2.0 g/m(2)) followed by GM-CSF or G-CSF; high-dose therapy: gemcitabine (1.0 g/m(2)) on day -5, BCNU (300 mg/m(2)) + gemcitabine (1.0 g/m(2)) on day -2, melphalan (140 mg/m(2)) on day -1, blood stem cell infusion on day 0; post-transplant immunotherapy (B cell NHL): rituxan (375 mg/m(2)) weekly for 4 weeks + GM-CSF (250 microg thrice weekly) (weeks 4-8); post-transplant involved-field radiotherapy (HD): 30-40 Gy to pre-transplant areas of disease (weeks 4-8); post-transplant consolidation chemotherapy (all patients): dexamethasone (40 mg daily)/cyclophosphamide (300 mg/m(2)/day)/etoposide (30 mg/m(2)/day)/cisplatin (15 mg/m(2)/day) by continuous intravenous infusion for 4 days + gemcitabine (1.0 g/m(2), day 3) (months 3 + 9) alternating with dexamethasone/paclitaxel (135 mg/m(2))/cisplatin (75 mg/m(2)) (months 6 + 12). Of the 33 patients with B cell lymphoma, 14 had primary refractory disease (42%), 12 had relapsed disease (36%) and seven had high-risk disease in first CR (21%). For the entire group, the 2-year Kaplan-Meier event-free survival (EFS) and overall survival (OS) were 30% and 35%, respectively, while six of 33 patients (18%) died before day 100 from transplant-related complications. The rituxan/GM-CSF phase was well-tolerated by the 26 patients who were treated and led to radiographic responses in seven patients; an eighth patient with a blastic variant of mantle-cell lymphoma had clearance of marrow involvement after rituxan/GM-CSF. Of the 22 patients with relapsed/refractory HD (21 patients) or high-risk T cell lymphoblastic lymphoma (one patient), the 2-year Kaplan-Meier EFS and OS were 70% and 85%, respectively, while two of 22 patients (9%) died before day 100 from transplant-related complications. Eight patients received involved field radiation and seven had radiographic responses within the treatment fields. A total of 72 courses of post-transplant consolidation chemotherapy were administered to 26 of the 55 total patients. Transient grade 3-4 myelosuppression was common and one patient died from neutropenic sepsis, but no patients required an infusion of backup stem cells. After adjustment for known prognostic factors, the EFS for the cohort of HD patients was significantly better than the EFS for an historical cohort of HD patients autografted after BEAC (BCNU/etoposide/cytarabine/cyclophosphamide) without consolidation chemotherapy (P = 0.015). In conclusion, post-transplant consolidation therapy is feasible and well-tolerated for patients autografted for aggressive NHL and HD and may be associated with improved progression-free survival particularly for patients with HD.

7
UI - 12036854
AU - Skinnider BF; Mak TW
TI - The role of cytokines in classical Hodgkin lymphoma.
SO - Blood 2002 Jun 15;99(12):4283-97
AD - Amgen Research Institute, Ontario Cancer Institute, the Department of Medical Biophysics, University of Toronto, Ontario, Canada.
The clinical and pathologic features of classical Hodgkin lymphoma (cHL) reflect an abnormal immune response that is thought to be due to the elaboration of a variety of cytokines by the malignant Reed-Sternberg (RS) cells or surrounding tissues. The majority of cHL cases are characterized by expression of tumor necrosis factor receptor (TNFR) family members and their ligands, as well as an unbalanced production of Th2 cytokines and chemokines. Activation of TNFR members results in constitutive activation of nuclear factor-kappa B (NF-kappa B), a transcription factor important for the in vitro and in vivo growth of RS cell lines. The expression of Th2 cytokines and chemokines leads to the reactive infiltrate of eosinophils, Th2 cells, and fibroblasts characteristic of cHL, and can also contribute to a local suppression of Th1 cell-mediated cellular immune response. Another particularly important growth and survival factor for RS cell lines is the Th2 cytokine interleukin 13, which is also commonly expressed by primary RS cells. In approximately 40% of cHL cases, the presence of Epstein-Barr virus influences the Th1/Th2 balance toward the production of Th1 cytokines and chemokines, but this shift is apparently insufficient for the stimulation of an effective antitumor cell-mediated immune response. This review summarizes the current literature on cytokine expression by and activity on RS cell lines and primary cHL tissues, examines cytokine signaling pathways in RS cells, and discusses the role that cytokines play in the specific clinical and pathologic features of cHL.

8
UI - 12077912
AU - Lengyel Z; Rosta A; Deak B; Molnar Z; Schneider T; Varady E; Esik O;
TI - Szekely J; Tron L [The role of PET scan in the investigation of the lymphatic spreading of Hodgkin's disease]
SO - Orv Hetil 2002 May 26;143(21 Suppl 3):1268-72
AD - Debreceni Egyetem, Orvos- es Egeszsegtudomanyi Centrum, PET Centrum, Debrecen. hegel@pet.dote.hu
The authors investigated the role of PET, as a non-invasive diagnostic method, in the analysis of lymphatic spreading of Hodgkin's disease (HD). Whole-body FDG scans were carried out in 71 patients along with [11C]-methionine examinations, if necessitated by inconclusive FDG results. Based on these findings involvement-frequencies were calculated for each lymphatic region. The three most frequently involved lymphatic regions were the mediastinum (83.1%), the left cervical and left supraclavicular regions (78.9%) and the right cervical and right supraclavicular regions (76.1%). These data support the hypothesis that HD originates from the cervical or supraclavicular regions and reaches the distant sites by basically retrograde spreading in a non-random manner. The appropriate values of site involvement-rate were compared with those obtained by other authors based on pathologic staging and a good correlation was found. The high level of correspondence between these involvement-frequencies supported the general validity (i.e. valid for both treated and untreated cases) of the principles governing lymphatic spreading of HD.

9
UI - 12086759
AU - Schmitz N; Pfistner B; Sextro M; Sieber M; Carella AM; Haenel M;
TI - Boissevain F; Zschaber R; Muller P; Kirchner H; Lohri A; Decker S; Koch B; Hasenclever D; Goldstone AH; Diehl V; German Hodgkin's Lymphoma Study Group; Lymphoma Working Party of the European Group for Blood and Marrow Transplantation Aggressive conventional chemotherapy compared with high-dose chemotherapy with autologous haemopoietic stem-cell transplantation for relapsed chemosensitive Hodgkin's disease: a randomised trial.
SO - Lancet 2002 Jun 15;359(9323):2065-71
AD - Department of Internal Medicine II, University of Kiel, Kiel, Germany
BACKGROUND: High-dose chemotherapy followed by transplantation of autologous haemopoietic stem cells (BEAM-HSCT) is frequently used to treat patients with relapsed Hodgkin's disease. We aimed to compare this treatment with conventional aggressive chemotherapy without stem-cell transplantation (Dexa-BEAM). METHODS: 161 patients between 16 and 60 years of age with relapsed Hodgkin's disease were randomly assigned two cycles of Dexa-BEAM (dexamethasone and carmustine, etoposide, cytarabine, and melphalan) and either two further courses of Dexa-BEAM or high-dose BEAM and transplantation of haemopoietic stem cells. Only patients with chemosensitive disease (complete or partial remission after two courses of Dexa-BEAM) proceeded to further treatment. The primary endpoint was freedom from treatment failure for patients with chemosensitive disease. Analysis was per protocol. FINDINGS: 17 patients were excluded from the study after randomisation (ten given Dexa-BEAM and seven given BEAM-HSCT). Median follow-up was 39 months (IQR 3-78). Freedom from treatment failure at 3 years was significantly better for patients given BEAM-HSCT (55%) than for those on Dexa-BEAM (34%; difference -21%, 95% CI -39.87 to -2.13; p=0.019). Overall survival of patients given either treatment did not differ significantly. INTERPRETATION: High-dose BEAM and transplantation of haemopoietic stem cells improves freedom from treatment failure in patients with chemosensitive first relapse of Hodgkin's disease irrespective of length of initial remission.

10
UI - 11770547
AU - Schneider U; Lomax A; Lombriser N
TI - Comparative treatment planning using secondary cancer mortality calculations.
SO - Phys Med 2001;17 Suppl 1():97-9
AD - Division of Medical Physics, Department of Radiation Oncology and Nuclear Medicine, City Hospital Triemli, Zurich, Switzerland.
Calculations of mortality due to secondary cancer have been investigated for its use in comparative treatment planning. A patient with Hodgkin's disease has been chosen as an example and has been planned with different radiation treatment modalities using photons and protons. The ICRP calculation scheme has been used to calculate mortality from dose distributions. To this purpose target volumes as well as critical structures have been outlined in the CT set of a patient with Hodgkin's disease. Dose distributions have been calculated using conventional as well as intensity modulated treatment techniques using photon and proton radiation. From the mean doses of each organ the mortality has been derived. Our work suggests that calculations of mortality can be useful in comparative treatment planning. Such mortality calculations can be helpful to find decisions between radiotherapy treatment techniques (intensity modulated or conventional treatment) or between different types of radiation (photons, electrons, protons, neutrons).

11
UI - 11824877
AU - Tsang RW; Solow HL; Ananthanarayan C; Haley S
TI - Daily general anaesthesia for radiotherapy in unco-operative patients: ingredients for successful management.
SO - Clin Oncol (R Coll Radiol) 2001;13(6):416-21
AD - Princess Margaret Hospital, University of Toronto, Canada. richard.tsang@rmp.uhn.on.ca
An unco-operative patient requiring daily radiation therapy presents a difficult clinical problem. After reviewing the paediatric oncology literature addressing the use of general anaesthesia for short medical procedures, we have developed checklists of procedural guidelines and monitoring equipment for the safe use of daily anaesthesia in adult patients who require a fractionated course of radiation therapy. We illustrate this by describing the successful treatment of a woman with autism and Hodgkin's disease who required daily general anaesthesia for immobilization during a 4-week course of radiation therapy. Propofol was used as the primary drug and was not associated with any adverse side-effects. There was no development of tolerance.

12
UI - 12028034
AU - Porrata LF; Inwards DJ; Micallef IN; Ansell SM; Geyer SM; Markovic SN
TI - Early lymphocyte recovery post-autologous haematopoietic stem cell transplantation is associated with better survival in Hodgkin's disease.
SO - Br J Haematol 2002 Jun;117(3):629-33
AD - Division of Hematology and Internal Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
A retrospective study of 82 patients was conducted to determine the relationship of absolute lymphocyte count (ALC) recovery with clinical outcome after autologous stem cell transplantation (ASCT) in Hodgkin's disease (HD). The median overall (OS) and progression-free survival (PFS) times from the day of transplantation were significantly better for the 41 patients with ALC > or = 0.5 x 10(9) cells/l compared with the 41 patients with ALC < 0.5 x 10(9) cells/l ("not yet reached" versus 42 months, P < 0.0001; 57 versus 15 months, P < 0.002 respectively). Thus, ALC recovery on day 15 post ASCT in HD is associated with better survival and requires further study.

13
UI - 12063471
AU - Rios Zambudio A; Torres Lanzas J; Galindo Fernandez PJ; Roca Calvo MJ;
TI - Parilla Paricio P Hodgkin disease of thymic origin.
SO - J Thorac Cardiovasc Surg 2002 Jun;123(6):1208-10
AD - Department of General and Thoracic Surgery, Virgen de la Arrixaca University Hospital, Murcia, Spain. ARZRIOS@teleline.es

14
UI - 11702175
AU - Diederich S; Link TM; Zuhlsdorf H; Steinmeyer E; Wormanns D; Heindel W
TI - Pulmonary manifestations of Hodgkin's disease: radiographic and CT findings.
SO - Eur Radiol 2001;11(11):2295-305
AD - Department of Clinical Radiology, University of Munster, Albert-Schweitzer-Strasse 33, 48129 Munster, Germany. stefan.diedrich@unilateral-muenster.de
The aim of this study was to assess the radiological and CT findings in patients with pulmonary Hodgkin's disease and to analyse to what extent CT provides more diagnostic information. In 37 patients with 41 episodes of pulmonary manifestation of Hodgkin's disease (histological diagnosis: 11, clinical diagnosis: 30) 39 radiographs and 33 CT scans were analysed by two readers in consensus. Pulmonary nodules were recorded in 77% of radiographs (CXR) and 88% of CT scans. Nodules were multiple in 67% (CXR) and 86% (CT) and bilateral in 43% (CXR) and 66% (CT) of cases, respectively. Nodule size ranged from 2 to 100 mm. Of the nodules, 83% at radiography and CT, respectively, were < or =30 mm, and again 83% at radiography and CT, respectively, were irregularly marginated. Diffuse infiltration with and without nodules was less common. With pulmonary manifestations at initial diagnosis of Hodgkin's disease there was always hilar or mediastinal lymphadenopathy. Of 20 episodes, in which radiograph and CT had been obtained within 8 days, CT demonstrated pulmonary involvement when chest radiography was normal in 3 cases and demonstrated more lesions in 12 cases. The typical appearance of pulmonary HD consisted of multiple, irregularly marginated pulmonary nodules. Diffuse infiltration was less common. Computed tomography was superior to radiography not only in characterization of lesions but could also demonstrate pulmonary involvement when the radiograph was normal and should, therefore, be used liberally in addition to radiography.

15
UI - 12089229
AU - Radford JA; Rohatiner AZ; Ryder WD; Deakin DP; Barbui T; Lucie NP; Rossi
TI - A; Dunlop DJ; Cowan RA; Wilkinson PM; Gupta RK; James RD; Shamash J; Chang J; Crowther D; Lister TA ChlVPP/EVA hybrid versus the weekly VAPEC-B regimen for previously untreated Hodgkin's disease.
SO - J Clin Oncol 2002 Jul 1;20(13):2988-94
AD - Department of Medical Oncology, Christie Hospital, Manchester, UK. john.radford@man.ac.uk
PURPOSE: To test the hypothesis that a chemotherapy regimen of relatively low toxicity and 11 weeks' duration (doxorubicin, cyclophosphamide, etoposide, vincristine, bleomycin, and prednisolone [VAPEC-B]) is at least as effective in terms of disease control as 6 months' treatment with chlorambucil, vinblastine, procarbazine, and prednisone/etoposide, vincristine, and doxorubicin (ChlVPP/EVA hybrid), which is associated with a high risk of permanent sterility. PATIENTS AND METHODS: Two hundred eighty-two patients with previously untreated Hodgkin's disease, clinical stages I/II (plus mediastinal bulk and/or B symptoms) and clinical stages III/IV were randomized at three United Kingdom and one Italian center to receive either six monthly cycles of ChlVPP/EVA hybrid or 11 weekly cycles of VAPEC-B. After chemotherapy and a restaging evaluation, radiotherapy was administered to sites of previous bulk or residual radiographic abnormality before patients were observed off treatment. RESULTS: Further accrual to the trial was halted follow-up of 4.9 years, freedom from progression (FFP), event-free survival (EFS), and overall survival (OS) are all significantly better in the population treated with ChlVPP/EVA than VAPEC-B, where the comparative 5-year results are 82% and 62% (FFP), 78% and 58% (EFS), and 89% and 79% (OS), respectively. The superiority of ChlVPP/EVA was seen in both low-risk and intermediate/high-risk patients, although subset analysis suggested that ChlVPP/EVA and VAPEC-B produce equivalent results in the best-prognosis patients (Hasenclever score 16
UI - 11694399
AU - Carella AM; Beltrami G; Carella M Jr; Corsetti MT; Scalzulli RP; Greco M
TI - Immunosuppressive non-myeloablative allografting as salvage therapy in advanced Hodgkin's disease.
SO - Haematologica 2001 Nov;86(11):1121-3

17
UI - 11694413
AU - Vassallo J; Metze K; Traina F; de Souza CA; Lorand-Metze I
TI - Expression of Epstein-Barr virus in classical Hodgkin's lymphomas in Brazilian adult patients.
SO - Haematologica 2001 Nov;86(11):1227-8

18
UI - 11722984
AU - Connors JM; Noordijk EM; Horning SJ
TI - Hodgkin's lymphoma: basing the treatment on the evidence.
SO - Hematology (Am Soc Hematol Educ Program) 2001;():178-93
AD - B.C. Cancer Agency, Vancouver Clinic, BC, Canada.
This paper examines the evidence available to guide treatment decisions in three areas of Hodgkin's lymphoma management. In Section I Dr. Evert Noordijk describes evolving strategies for patients with early stage disease outlining the eras during which the focus has changed from initially accomplishing cure through refining and intensifying the treatment to one of maximizing cure rates and finally into a patient-oriented era in which the twin goals of maintaining high rates of cure and minimizing late toxicity are being achieved. In Section II Dr. Sandra Horning reviews the way in which the cooperative groups of North America and Europe have built upon initial observations from single centers to assemble the trials that have defined the treatment for advanced stage Hodgkin's lymphoma. Over a period of almost three decades, these well-constructed trials have defined a current standard of treatment, ABVD chemotherapy and are now investigating innovative approaches to move beyond this standard. She also indicates the need to appreciate diagnostic factors and the implications of prognostic factor models for the design and interpretation of clinical trials. In Section III Dr. Joseph Connors summarizes the evidence available to inform our choice of treatment for the uncommon but important entity of lymphocyte predominance Hodgkin's lymphoma. Once again, the guidance that can be derived from carefully conducted clinical investigation is used to address the issues surrounding choice of treatment, reasonable monitoring in long term follow-up and the clear-cut need to base diagnosis on objective immunohistochemical evidence.

19
UI - 12031028
AU - Stante M; Salvini C; De Giorgi V; Carli P
TI - Multiple synchronous pigmented basal cell carcinomas following radiotherapy for Hodgkin's disease.
SO - Int J Dermatol 2002 Apr;41(4):208-11
AD - Department of Dermatology, University of Florence, Via degli Altani 37, 50121 Florence, Italy. marcellostante@tin.it
BACKGROUND: Multiple basal cell carcinomas (BCCs) are infrequently seen in patients under 30 years of age. Their occurrence at a young age is often linked to some genodermatosis, including Nevoid Basal Cell Carcinoma Syndrome (NBCCS). The exposure to ionizing radiation is also considered to be a predisposing factor in the development of BCCs. METHODS: We report the case of a 35-year-old patient who presented with seven synchronous, nodular, brownish-pigmented BCCs, confined within the radiation-treated cutaneous areas, 15 years after receiving Cobalt-60 (60Co) irradiation for Hodgkin's disease. RESULTS: On the basis of clinical, radiological, and anamnestic data we excluded a NBCCS, thus proposing irradiation as the cause of the multiple synchronous pigmented BCCs. CONCLUSIONS: Previous therapeutic ionizing radiation leads to an increased risk of BCCs confined to the region of the body to which radiotherapy was delivered. We consider our patient's BCCs represents a late adverse effect of the treatment with Cobalt-60.

20
UI - 12101562
AU - Gershanovich ML; Kanaev SV; Filatova LV; Novikov SN; Leenman EE;
TI - Pozharisskii KM [Clinical course and treatment of Hodgkin's disease with concomitant bone marrow lesions]
SO - Vopr Onkol 2002;48(1):29-36
AD - N.N. Petrov Research Institute of Oncology, Ministry of Health of the RF, St. Petersburg.
Fifty patients with confirmed local multiple lesions of bone marrow were selected by 99mTc scintigraphy, magnetic resonance imaging and morphologically-supported trepan biopsy from 155 cases of Hodgkin's disease stage II-IVAB. Bone marrow lesions were relatively more common in younger patients 1-11 months after primary tumor detection (an average of 6.5 months). They were detected within 12-156 months (an average of 48 months) among relapsing patients with nodal sclerosis and mixed-cell tumors stage III-IVAB, mostly concomitant with anemia and lymphopenia. Standard combination chemotherapeutical regimens for primary patients (MOPP, ABVD and LOPP) and relapsing ones (CCNU-OPP and ABVD) were effective in those with bone marrow lesions. Side-effects (myelodepression) did not exceed normal levels, provided human recombinant interleukin-1 beta (beta-leukin) was administered for protection and leukopoietic stimulation.

21
UI - 12101563
AU - Kanaev SV; Novikov SN; Semenov II; Zhukova LA
TI - [The role of indirect lower lymphoscintigraphy for radiotherapy planning in Hodgkin's lymphoma]
SO - Vopr Onkol 2002;48(1):37-42
AD - N.N. Petrov Research Institute of Oncology, Ministry of Health of the RF, St. Petersburg.
The feasibility of application of indirect lower lymphoscintigraphy (ILLSG) was assessed in 202 patients with Hodgkin's disease. Its high diagnostic potential was demonstrated by comparison with direct X-ray contrast lymphography: ILLSG's sensitivity was 91.5%, specificity--76.1% and overall accuracy--88.4%. The procedure used for topometric preparation prior to exposure of paraaortal and ileaco-inguinal lymph nodes proved instrumental in designing individual irradiation fields: their boundaries were altered in 21.6% on the basis of ILLSG data.

22
UI - 12082652
AU - Voliotis D; Diehl V
TI - Challenges in treating hematologic malignancies.
SO - Semin Oncol 2002 Jun;29(3 Suppl 8):30-9
AD - Clinic I for Internal Medicine, University of Cologne, Cologne, Germany.
During the past 40 years substantial progress has been made in the treatment of hematologic malignancies, particularly in some subgroups of patients. Today, cure is attainable for patients with Hodgkin's disease and a considerable proportion of patients with high-grade non-Hodgkin's lymphoma. Prognosis is improving in patients with acute promyelocytic leukemia and, to some extent, those with acute lymphoblastic and myeloid leukemias. However, the majority of patients who suffer from a hematologic malignancy live with incurable disease. In CLL, outside the setting of a clinical trial, it is advisable to postpone treatment until the manifestation of clinical symptoms. It is yet to be determined whether treatment strategies based on new prognostic parameters such as cytogenetics can change the course of disease. In indolent lymphomas, cure is not attainable for the vast majority of patients; the median survival of 9 to 10 years has remained unchanged for several decades. Nevertheless, there has been a dramatic change in therapeutic paradigms in the past few years. For the first time, with the use of new cytostatic drugs and recombinant monoclonal antibodies, it is possible to achieve molecular remissions. Whether this will translate into cure or prolonged survival is still to be determined. In Hodgkin's disease, which is curable when treated with radiotherapy, chemotherapy, or combined therapy, depending on the stage of disease, the focus of future studies must be on prevention of early relapse and on primary resistant disease, both of which present a very poor prognosis. Finally, regardless of underlying malignancy and prognosis, the preservation of quality of life is of major consideration in the setting of hematologic malignancies. Copyright 2002, Elsevier Science (USA). All rights reserved.

23
UI - 11554946
AU - Regina S; Colombat P; Fimbel B; Guerois C; Gruel Y
TI - Acquired inhibitor to factor VIII in a patient with Hodgkin's disease following treatment with interferon-alpha.
SO - Haemophilia 2001 Sep;7(5):526-7
AD - Department of Hematology-Haemostasis, University Hospital, Tours, France.
We describe a young woman who developed acquired haemophilia after 18 months of interferon (IFN-)-alpha therapy. This patient had been monitored since 1992 for Hodgkin's disease initially treated by chemotherapy. After two relapses, she received intensive chemotherapy followed by an autologous peripheral progenitor cell graft. IFN-alpha was then administered for 18 months. Bleeding of the limbs and tongue occurred 1 month after withdrawal of IFN-alpha and high titres (123 Bethesda units) of autoantibody to factor VIII (FVIII):C were measured. Prednisone (1 mg kg(-1) day(-1)) achieved rapid cessation of the bleeding and FVIII autoantibodies were undetectable 5 months later. This case report suggests that the activated partial thromboplastin time should be regularly checked in every patient treated with IFN-alpha in cases of unexplained bleeding, together testing for antibodies to FVIII if the bleeding is prolonged.

24
UI - 12071938
AU - Amini RM; Glimelius B; Gustavsson A; Ekman T; Erlanson M; Haapaniemi E;
TI - Enblad G A population-based study of the outcome for patients with first relapse of Hodgkin's lymphoma.
SO - Eur J Haematol 2002 Apr;68(4):225-32
AD - Department of Oncology and Regional Oncological Centre, University Hospital of Uppsala, Sweden. Rose-Marie.Amini@genpat.uu.se
BACKGROUND: Our aims were to evaluate the response to salvage treatment in relation to initial treatment and to evaluate prognostic factors at the time of relapse in an unselected population of relapsing patients with Hodgkin's lymphoma (HL). PATIENTS AND METHODS: In total, 124 patients younger than 60 yr of age with initial diagnosis of HL in Sweden relapsed between 1985 and 1995. RESULTS: Fifty-eight patients relapsed after initial treatment with radiotherapy (RT) only, 62 after combination chemotherapy (CT), of whom 30 had received additional involved-field RT, and four after a short course of CT followed by extended-field RT. For 37 patients among the 58 relapsers after initial RT treated according to the recommendations of the National guidelines, the 5-yr Hodgkin-specific survival (HLS) was 85%, overall survival (OS) 73% and event-free survival (EFS) 62%, which is not inferior to survival in patients with primarily advanced stages. It was poorer in the 21 patients who initially had received RT only, even though they had been recommended for more extensive treatment. For patients initially treated with a full course (6-8 cycles) of CT the 5-yr HLS was 60%, OS 58% and EFS 22%. Bulky disease and age at diagnosis strongly affected survival in a multivariate analysis. CONCLUSIONS: Patients initially treated with RT who relapse have a favourable outcome, provided they have been treated according to the recommendations of the guidelines at the time of diagnosis. Initially bulky disease and, as a consequence, additional RT as part of the initial treatment negatively affect survival at relapse in patients initially treated with a full course of CT.

25
UI - 12094374
AU - Colleoni GW; Capodieci P; Tickoo S; Cossman J; Filippa DA; Ladanyi M
TI - Expression of SSX genes in the neoplastic cells of Hodgkin's lymphoma.
SO - Hum Pathol 2002 May;33(5):496-502
AD - Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
The cancer/testis antigen (CTA) group of tumor-associated proteins have been reported to be expressed in various cancers and in adult testis but they are essentially not found in any other normal adult nonneoplastic tissues. Prompted by the frequent detection of SSX1 in a previous comprehensive expression profile of the Hodgkin's lymphoma (HL) cell line L428, we analyzed SSX expression by nonnested reverse-transcription polymerase chain reaction (RT-PCR) in 4 HL cell lines (L428, L540, HD-MY-Z, and KM-H2) and 32 tumor samples of HL. The cellular localization of SSX expression in the tumor samples was further analyzed by in situ hybridization (ISH). All 4 HL cell lines were positive by RT-PCR using SSX consensus primers. Using primers specific to individual SSX genes, all 4 cell lines expressed multiple SSX family members. Five tumor samples (15.6%) were positive by RT-PCR using SSX consensus primers and direct sequencing of the RT-PCR products showed that 4 of 5 expressed more than 1 SSX family member. ISH confirmed that SSX expression originated in HL cells in all 5 RT-PCR-positive tumor samples. Furthermore, ISH demonstrated SSX-positive HL cells in 6 of 11 cases (55%) that were negative by RT-PCR. Our results suggest that members of the SSX family of CTA are expressed in most HL. This subset of HL may be a candidate for immunotherapy approaches directed at SSX proteins. Copyright 2002, Elsevier Science (USA). All rights reserved.

26
UI - 12109852
AU - Elgui de Oliveira D; Bacchi MM; Abreu ES; Niero-Melo L; Bacchi CE
TI - Hodgkin disease in adult and juvenile groups from two different geographic regions in Brazil: characterization of clinicopathologic aspects and relationship with Epstein-Barr virus infection.
SO - Am J Clin Pathol 2002 Jul;118(1):25-30
AD - Department of Pathology, Botucatu School of Medicine, UNESP, Sao Paolo, Brazil.
We analyzed clinicopathologic data, immunophenotype, and Epstein-Barr virus (EBV) status in 96 cases of Hodgkin disease (HD) in juveniles (younger than 20 years) and adults (20 years or older) from 2 distinctive states in Brazil. We studied 34 juvenile (group 1) and 16 adult (group 2) cases from Ceara and 31 juvenile (group 3) and 15 adult (group 4) cases from Sao Paulo. Ceara has a socioeconomic profile similar to a developing country; Sao Paulo is in better economic condition. Mixed cellularity (MC) was the major histologic subtype among groups 1 (22 [65%]), 3 (21 [68%]), and 4 (7 [47%]); nodular sclerosis (NS) was more frequent in group 2 (8 [50%]). EBV infection was observed in 61 cases (64%), including the following (among others): group 1, MC, 22 (65%) and NS, 4 (12%); group 2, NS, 3 (19%) and MC, 2 (12%); group 3, MC, 16 (52%) and NS, 1 (3%); and group 4, MC, 7 (47%). There was predominance of EBV+ HD cases in group 1 compared with group 3. HD in Brazilian patients is highly associated with EBV infection, but geographic differences reflect histologic subtypes and age distribution.

27
UI - 12070005
AU - Dukers DF; Meijer CJ; ten Berge RL; Vos W; Ossenkoppele GJ; Oudejans JJ
TI - High numbers of active caspase 3-positive Reed-Sternberg cells in pretreatment biopsy specimens of patients with Hodgkin disease predict favorable clinical outcome.
SO - Blood 2002 Jul 1;100(1):36-42
AD - Department of Pathology, VU Medical Centre, Amsterdam, The Netherlands.
In vitro studies suggest that resistance to the apoptosis-inducing effect of chemotherapy might explain poor responses to therapy in fatal instances of Hodgkin disease (HD). Execution of apoptosis depends on proper functioning of effector caspases, in particular caspase 3, which is activated on the induction of apoptosis through either the stress-induced pathway or the death receptor-mediated pathway. Thus, high levels of caspase 3 activation should reflect proper functioning of one or both identified apoptosis pathways, resulting in chemotherapy-sensitive neoplastic cells and thus a favorable clinical response to chemotherapy. We tested this hypothesis by quantifying active caspase 3-positive tumor cells in primary biopsy specimens of HD and compared these numbers to clinical outcomes. Using an immunohistochemical assay, activation of caspase 3 was detected in 0% to 13% of neoplastic cells. High numbers of active caspase 3-positive tumor cells (5% or more) correlated with excellent clinical prognosis; 0 of 22 patients with 5% or more active caspase 3-positive cells died compared with 11 of 41 patients with less than 5% positive cells (P =.007). Proper functioning of active caspase 3 was demonstrated by the detection of one of its cleaved substrates, PARP-1/p89, in similar percentages of neoplastic cells. High levels of active caspase 3-positive neoplastic cells were associated with the expression of p53 and its downstream effector molecule p21, suggesting proper functioning of the stress-induced apoptosis pathway. In conclusion, high numbers of active caspase 3-positive neoplastic cells predict a highly favorable clinical outcome in HD patients, supporting the notion that an (at least partially) intact apoptosis cascade is essential for the cell killing effect of chemotherapy.

28
UI - 12082542
AU - Devilard E; Bertucci F; Trempat P; Bouabdallah R; Loriod B; Giaconia A;
TI - Brousset P; Granjeaud S; Nguyen C; Birnbaum D; Birg F; Houlgatte R; Xerri L Gene expression profiling defines molecular subtypes of classical Hodgkin's disease.
SO - Oncogene 2002 May 2;21(19):3095-102
AD - Department of Pathology, Institut Paoli-Calmettes, 232 Boulevard de Sainte-Marguerite, BP 156, 13273 Marseille Cedex, France.
Although the prognosis of Hodgkin's disease is relatively good, around 20% of patients do not benefit from current therapies and succumb to their disease. A large-scale molecular characterization of disease might help improve HD management. Using cDNA arrays, we studied the mRNA expression levels of approximately 1000 selected genes in 34 benign and malignant lymphoid samples including 21 classical Hodgkin's disease (HD) tissue samples. Hierarchical clustering identified three main molecular groups of HD tumours relevant with respect to histology and clinical outcome (response to therapy and survival). Samples from all bad outcome HD (BOHD) patients clustered in one group whereas the two other groups contained most good outcome HD (GOHD) cases. The nodular sclerosis GOHD samples overexpressed genes involved in apoptotic induction and cell signalling, including cytokines, while the BOHD samples were characterized by the upregulation of genes involved in fibroblast activation, angiogenesis, extracellular matrix remodelling, cell proliferation, and the downregulation of tumour suppressor genes. Our results establish a molecular taxonomy of HD correlating with response to therapy and clinical outcome, thereby suggesting the possibility of improving the current prognostic classification.

29
UI - 12115499
AU - Maggio EM; Van Den Berg A; Visser L; Diepstra A; Kluiver J; Emmens R;
TI - Poppema S Common and differential chemokine expression patterns in rs cells of NLP, EBV positive and negative classical Hodgkin lymphomas.
SO - Int J Cancer 2002 Jun 10;99(5):665-72
AD - Department of Pathology and Laboratory Medicine, University Hospital Groningen, Groningen, The Netherlands.
Hodgkin lymphoma (HL) is characterized by a minority of neoplastic cells, the so-called Reed-Sternberg (RS) cells and a vast majority of reactive cells. RS cells produce chemokines that can attract subsets of peripheral blood cells into HL tissues. To gain insight in the chemokines involved in HL, 16 chemokines were selected based on their ability to recruit different subsets of cells. Five HL, 5 non-HL-derived cell lines, 22 HL, 5 non-HL and 3 control tissues were analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR). Products for 13 of these 16 chemokines were detected in 1 or more of the cell lines tested. No or only very faint signals were obtained in HL for CXCL12, CCL7 and CCL8, but CXCL10, CCL5, CCL13, CCL17 and CCL22 were highly or differentially expressed in HL cell lines and tissues. Immunohistochemistry was performed with antibodies reactive with the latter 5 chemokines on paraffin sections of 21 cases of HL. CCL17 and CCL22 had the highest signals in RS cells at gene expression and at protein levels. CCL17 was specific for the classic HL subtypes, whereas CCL22 also had low signals in NLP samples, as well as in some non-HL. CXCL10 was expressed in a large proportion of HL cases with a predominant expression in EBV-positive cases. The results indicate that RS cells produce a complex pattern of chemokines that are involved in the recruitment of reactive cells and contribute to the paradox of an extensive but ineffective host immune response. Copyright 2002 Wiley-Liss, Inc.

30
UI - 12123231
AU - Torlakovic E; Torlakovic G
TI - B-cell markers in lymphocyte predominance Hodgkin disease.
SO - Arch Pathol Lab Med 2002 Jul;126(7):862-3
AD - Department of Pathology, The Norweigian Radium Hospital, Oslo, Norway. emina.torlakovic@labmed.uio.no

31
UI - 12115325
AU - Laurie SA; Kris MG; Portlock CS; Rosenzweig KE; Miller VA; Krug LM;
TI - Rusch VW The clinical course of nonsmall cell lung carcinoma in survivors of Hodgkin disease.
SO - Cancer 2002 Jul 1;95(1):119-26
AD - Thoracic Oncology Service, Division of Solid Tumor Oncology, Memorial Sloan-Kettering Cancer Center, Weill Medical College of Cornell

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