• [Giant cell lymphosarcoma or lymphogranulomatosis variants?]

• CD34(+) cell enrichment depletes atypical CD30(+) cells from PBPC grafts in patients with HD.

• Eosinophilic folliculitis occurring in a patient affected by Hodgkin lymphoma.

• Second malignant neoplasms among long-term survivors of Hodgkin's disease: a population-based evaluation over 25 years.

• Long-term survival of a patient with human immunodeficiency virus infection and Hodgkin's lymphoma.

• Challenging cases and diagnostic dilemmas: case 1. Tracheal compression in Hodgkin's disease.

• PET predicts prognosis after 1 cycle of chemotherapy in aggressive lymphoma and Hodgkin's disease.

• Trends in mortality from Hodgkin's disease in western and eastern Europe.

• Role of radiation therapy in advanced Hodgkin's disease--as yet, an answer? Still a question?

• Fifteen-year secondary leukaemia risk observed in 761 patients with Hodgkin's disease prospectively treated by MOPP or ABVD chemotherapy

• Interleukin 6 expression by Hodgkin/Reed-Sternberg cells is associated with the presence of 'B' symptoms and failure to achieve complete

• Correlation of blood lymphocyte CTLA-4 (CD152) induction in Hodgkin's disease with proliferative activity, interleukin 2 and interferon-gamma

• Semen cryopreservation, utilisation and reproductive outcome in men treated for Hodgkin's disease.

• Hodgkin's disease following methotrexate therapy for rheumatoid arthritis.

• Primary mediastinal large B-cell lymphoma: a comparative study with nodular sclerosis-type Hodgkin's disease.

• Clonal relation in a case of CLL, ALCL, and Hodgkin composite lymphoma.

• Stage I-III Hodgkin's disease: outcome and pattern of failure following treatment with radiation therapy and chemotherapy in a modern era.

• From chronic lymphocytic leukemia to Hodgkin's disease: a case of prognostically favorable transformation.

• Hodgkin's lymphoma in first relapse following chemotherapy or combined modality therapy: analysis of outcome and prognostic factors after

• Paraneoplastic cerebellar degeneration and nephrotic syndrome preceding Hodgkin's disease: case report and review of the literature.

• EMMPRIN (CD 174) is expressed in Hodgkin's lymphoma and anaplastic large cell lymphoma. An immunohistochemical study of 60 cases.

• Lung function and serum concentrations of different cytokines in patients submitted to radiotherapy and intermediate/high dose

• Epstein-barr virus-associated non-Hodgkin's lymphoma of B-cell origin, Hodgkin's disease, acute leukemia, and systemic lupus erythematosus: a

• Ofuji papuloerythroderma associated with Hodgkin's lymphoma.

• Aberrantly expressed c-Jun and JunB are a hallmark of Hodgkin lymphoma cells, stimulate proliferation and synergize with NF-kappa B.

• LMP1-induced downregulation of CD99 molecules in Hodgkin and Reed-Sternberg cells.

• Is it wise to eliminate lymphography from the staging of Hodgkin's disease?

• Hodgkin's disease: unsuspected minimal activity in patients that die from causes other than tumoral progression.

• Randomized trial of chemotherapy versus chemotherapy plus radiotherapy for stage III-IV A & B Hodgkin's disease.

• Defective IkappaBalpha in Hodgkin cell lines with constitutively active NF-kappaB.

• Mutations in the IkBa gene in Hodgkin's disease suggest a tumour suppressor role for IkappaBalpha.

• Inhibition of NF-kappaB, clonogenicity, and radiosensitivity of human cancer cells.

• Clonal deleterious mutations in the IkappaBalpha gene in the malignant cells in Hodgkin's lymphoma.

• Differential effects of CD30 activation in anaplastic large cell lymphoma and Hodgkin disease cells.

• Epstein-Barr virus latent membrane protein-1 activates CD25 expression in lymphoma cells involving the NFkappaB pathway.

• Value of fine needle aspiration cytology in the initial diagnosis of Hodgkin's disease. Analysis of 188 cases with an emphasis on diagnostic

• Fine needle aspiration in Hodgkin's disease.

• Expression pattern of MUM1/IRF4 in the spectrum of pathology of Hodgkin's disease.

• Multiple cavitating pulmonary nodules and clubbing in a 12-year-old girl.

• Sternal osteomyelitis caused by Aspergillus fumigatus in a patient with previously treated Hodgkin's disease.

• Vascular endothelial growth factor (VEGF) is expressed by neoplastic Hodgkin-Reed-Sternberg cells in Hodgkin's disease.

• Interventions for early stage Hodgkin's disease in children.

• Interventions for early stage Hodgkin's disease in children.

• Miller-Fisher syndrome and Hodgkin's disease.

• CD44 variant exons in leukemia and lymphoma.

• Utility and outcomes of fine-needle aspiration biopsy in Hodgkin's disease.

• Pediatric Hodgkin's disease--up, up, and beyond.

• Viruses and Hodgkin disease: no evidence of novel herpesviruses in non-EBV-associated lesions.

• T-cell variant of classical Hodgkin's lymphoma with nodal and cutaneous manifestations demonstrated by single-cell polymerase chain reaction.

• [Acquired ichthyosis disclosing Hodgkin's disease. Simultaneous recurrence]

• Different incidence and pattern of p15INK4b and p16INK4a promoter region hypermethylation in Hodgkin's and CD30-Positive non-Hodgkin's lymphomas.

• Expression of gene MAGE-A4 in Reed-Sternberg cells.

• Breast cancer after mantle irradiation for Hodgkin's disease: correlation of clinical, pathologic, and molecular features including

• In regard to Gaffney et al., IJROBP 2001;49:539-546.

• [Tumor of the nasopharyngeal wall. Hodgkin lymphoma (Hodgkin disease), nodular sclerosis, grade 1, stage Ia, primary manifestation of the

• High-dose therapy and autologous stem cell transplantation for high-risk Hodgkin's lymphoma: a single center experience.

• Radiotherapy for early stage of Hodgkin's disease at Kuwait Cancer Control Center, Kuwait.

1
UI - 12181835
AU - Kremenetskaia AM; Vorob'ev AI; Kharazishvili DV; Frank GA; Vorob'ev IA;
TI - Kaplanskaia IB; Kravchenko SK; Moiseeva TN; Shklovskii-Kordi NE; Chernova NG; Lorie IuIu [Giant cell lymphosarcoma or lymphogranulomatosis variants?]
SO - Ter Arkh 2002;74(7):48-52

2
UI - 12171718
AU - Blystad AK; Torlakovic E; Holte H; Kvaloy S; Lenschow E; Kvalheim G
TI - CD34(+) cell enrichment depletes atypical CD30(+) cells from PBPC grafts in patients with HD.
SO - Cytotherapy 2001;3(4):295-305
AD - Department of Oncology, The Norwegian Radium Hospital, Oslo, Norway.
BACKGROUND: European Group for Blood and Marrow Transplantation (EBMT) registry data indicate that patients with relapsed HD given high-dose therapy (HDT), supported with PBPC might have a poorer outcome compared with those given BM. Since this can be due to the infusion of contaminating tumor cells in the PBPC products, we studied the presence of minimal residual disease and tested whether CD34(+) cell enrichment was able to remove atypical CD30(+) cells from PBPC grafts. METHODS: Eighteen HD patients eligible for HDT were included in the study. By the use of immunocytochemistry (ICC), mononuclear cells from BM and peripheral blood (PB) before mobilization, PBPC products and selected CD34(+) fractions were stained using anti-CD30 MAb (Ber-H2) and the APAAP (alkaline phosphatase-anti-alkaline phosphatase) method. Cells scored as atypical CD30(+) cells were large- to medium-sized, with membranous, cytoplasmatic and/or Golgi positivity for CD30. RESULTS: Nine out of 11 BM tested were positive, while 14 of 14 PB and 18 of 18 PBPC contained atypical CD30(+) cells. The total number of atypical CD30(+) cells was significantly higher in PBPC than in the corresponding BM. CD34(+) cell enrichment employing ISOLEX 300I gave a purity and yield of 99.2% (range 97.8-99.7) and 49.6% (range 30.0-78.4), respectively. After HDT a median of 5.8 x 10(6) (range 2.7-20) CD34(+) cells/kg was infused. Neutrophil counts of > 0.5 x 10(9)/L and platelet counts of > 20 x 10(9)/L were achieved at Day 12 (range 10-17) and at Day 10 (range 7-15), respectively. Sixteen of 18 CD34(+) selected products had no detectable atypical CD30(+) cells, while two had a low number. After HDT, the overall survival was 80% and the event-free survival was 69%, with a median follow-up of 24 months (range 1-36). DISCUSSION: We show that contaminating atypical CD30(+) cells in PBPC can efficiently be removed by CD34(+) cell enrichment, and the use of such grafts following HDT gives fast and sustained engraftment.

3
UI - 12100711
AU - Vassallo C; Ciocca O; Arcaini L; Brazzelli V; Ardigo M; Lazzarino M;
TI - Borroni G Eosinophilic folliculitis occurring in a patient affected by Hodgkin lymphoma.
SO - Int J Dermatol 2002 May;41(5):298-300
AD - Department of Dermatology, and the Institute of Hematology, University of Pavia, Policlinico S. Matteo-IRCCS, Italy. cvassallo@yahoo.com

4
UI - 12177110
AU - Dores GM; Metayer C; Curtis RE; Lynch CF; Clarke EA; Glimelius B; Storm
TI - H; Pukkala E; van Leeuwen FE; Holowaty EJ; Andersson M; Wiklund T; Joensuu T; van't Veer MB; Stovall M; Gospodarowicz M; Travis LB Second malignant neoplasms among long-term survivors of Hodgkin's disease: a population-based evaluation over 25 years.
SO - J Clin Oncol 2002 Aug 15;20(16):3484-94
AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Executive Plaza South, Suite 7039, Bethesda, MD 20892, USA. doresg@mail.nih.gov
PURPOSE: To quantify the relative and absolute excess risks (AER) of site-specific second cancers, in particular solid tumors, among long-term survivors of Hodgkin's disease (HD) and to assess risks according to age at HD diagnosis, attained age, and time since initial treatment. PATIENTS AND METHODS: Data from 32,591 HD patients (1,111 25-year survivors) reported to 16 population-based cancer registries in North America and Europe (1935 to 1994) were analyzed. RESULTS: Two thousand one hundred fifty-three second cancers (observed-to-expected ratio [O/E] = 2.3; 95% confidence interval [CI] = 2.2 to 2.4), including 1,726 solid tumors (O/E = 2.0; 95% CI, 1.9 to 2.0) were reported. Cancers of the lung (observed [Obs] = 377; O/E = 2.9), digestive tract (Obs = 376; O/E = 1.7), and female breast (Obs = 234; O/E = 2.0) accounted for the largest number of subsequent malignancies. Twenty-five years after HD diagnosis, the actuarial risk of developing a solid tumor was 21.9%. The relative risk of solid neoplasms decreased with increasing age at HD diagnosis, however, patients aged 51 to 60 years at HD diagnosis sustained the highest cancer burden (AER = 79.2/10,000 patients/year). After a progressive rise in relative risk and AER of all solid tumors over time, there was an apparent downturn in risk at 25 years. Temporal trends and treatment group distribution for cancers of the esophagus, stomach, rectum, female breast, bladder, thyroid, and bone/connective tissue were suggestive of a radiogenic effect. CONCLUSION: Significantly increased risks of second cancers were observed in all HD age groups. Although significantly elevated risks of stomach, female breast, and uterine cervix cancers persisted for 25 years, an apparent decrease in relative risk and AER of solid tumors at other sites is suggested.

5
UI - 12190241
AU - Diwan AH; Umbreit J; Nelson BP
TI - Long-term survival of a patient with human immunodeficiency virus infection and Hodgkin's lymphoma.
SO - South Med J 2002 Aug;95(8):943-4
AD - Department of Pathology, University of South Alabama, Mobile, USA.
When patients infected with human immunodeficiency virus (HIV) are found to have Hodgkin's lymphoma (HL), it is generally advanced, with involvement of extranodal sites including bone marrow, spleen, and liver, and prognosis tends to be unfavorable. We present the case of a 38-year-old white man who had HIV and HL diagnosed in 1990. Despite presenting with stage IV HL, having recurrence of HL after initially attaining remission, and being hospitalized on several occasions for opportunistic infections, he ultimately achieved complete remission of HL and is alive 9 years after initial diagnosis. This case illustrates that although unusual, prolonged survival of an HIV-infected patient with HL associated with poor prognostic features is possible.

6
UI - 12149308
AU - Garrison MA; Glanton C; Rasnke M; Smith ME; Ornstein DL
TI - Challenging cases and diagnostic dilemmas: case 1. Tracheal compression in Hodgkin's disease.
SO - J Clin Oncol 2002 Aug 1;20(15):3344-7
AD - Brooke Army Medical Center and Wilford Hall Medical Center, San Antonio, TX, USA.

7
UI - 12163626
AU - Kostakoglu L; Coleman M; Leonard JP; Kuji I; Zoe H; Goldsmith SJ
TI - PET predicts prognosis after 1 cycle of chemotherapy in aggressive lymphoma and Hodgkin's disease.
SO - J Nucl Med 2002 Aug;43(8):1018-27
AD - Division of Nuclear Medicine, Department of Radiology, Weill Medical College of Cornell University and New York Presbyterian Hospital, New York, New York 10021, USA. lak2005@mail.med.cornell.edu
Early identification of chemotherapy-refractory lymphoma patients provides a basis for alternative treatment strategies. Metabolic imaging with (18)F-FDG PET offers functional tissue characterization that is useful for assessing response to therapy. Our objective was to determine the predictive value of (18)F-FDG PET early during chemotherapy (after 1 cycle) and at the completion of chemotherapy for subsequent progression-free survival (PFS) in patients with aggressive non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD). METHODS: (18)F-FDG PET (dual-head coincidence camera with attenuation correction) was performed before and after 1 cycle of chemotherapy on 30 patients (17 NHL, 13 HD; mean age, 52.3 +/- 16.0 y). For 23 of the 30 patients, (18)F-FDG PET data were also obtained after the completion of chemotherapy. The patients had a median follow-up of 19 mo (range, 18-24 mo). Follow-up of PFS was compared between patients with positive and negative (18)F-FDG PET results obtained after the first cycle of chemotherapy and at the completion of chemotherapy. RESULTS: Positive (18)F-FDG PET results obtained both after the first cycle and at the completion of therapy were associated with a shorter PFS (median, 5 and 0 mo, respectively) than were negative (18)F-FDG PET results (PFS medians not reached). A statistically significant difference in PFS between positive and negative (18)F-FDG PET results was obtained both after the first cycle and at the completion of chemotherapy (P < or = 0.001). The PFS and (18)F-FDG PET results obtained after the first cycle correlated better than those obtained after the completion of chemotherapy (r(2) = 0.45 vs. 0.17). (18)F-FDG PET had more false-negative results after the last cycle (6/17 cases, or 35%) than after the first cycle (2/13 cases, or 15%). Thus, (18)F-FDG PET had greater sensitivity and positive predictive values after the first cycle (82% vs. 45.5% and 90% vs. 83%, respectively) than after the last cycle. CONCLUSION: (18)F-FDG PET after 1 cycle of chemotherapy is predictive of 18-mo outcome in patients with aggressive NHL and HD and may earlier identify patients who would benefit from more intensive treatment programs.

8
UI - 12177797
AU - Levi F; Lucchini F; Negri E; Boyle P; La Vecchia C
TI - Trends in mortality from Hodgkin's disease in western and eastern Europe.
SO - Br J Cancer 2002 Jul 29;87(3):291-3
AD - Cancer Epidemiology Unit and Cancer Registries of Vaud and Neuchatel, Institut universitaire de medecine sociale et preventive, CHUV-Falaises 1, 1011 Lausanne, Switzerland. Fabio.Levi@inst.hospvd.ch
Hodgkin's disease mortality rates steadily declined by about 75% between the late 1960's and the late 1990's in the current European Union countries and the USA, and Japan. Eastern European countries, however, showed only an approximately 40% decline between the late 1960's and the early 1990's, and no further fall thereafter. Copyright 2002 Cancer Research UK

9
UI - 1498069
AU - Sutcliffe SB
TI - Role of radiation therapy in advanced Hodgkin's disease--as yet, an answer? Still a question?
SO - Ann Oncol 1992 Jul;3(7):499-501

10
UI - 12100147
AU - Delwail V; Jais JP; Colonna P; Andrieu JM
TI - Fifteen-year secondary leukaemia risk observed in 761 patients with Hodgkin's disease prospectively treated by MOPP or ABVD chemotherapy plus high-dose irradiation.
SO - Br J Haematol 2002 Jul;118(1):189-94
AD - Department of Hematology, Hopital J.Bernard, Poitiers, France.
Between 1972 and 1988, 869 adult patients received MOPP (mechlorethamine, vincristine, procarbazine and prednisone; 462 patients) or ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine; 373 patients) and subsequent high-dose irradiation for Hodgkin's disease. Nine patients developed a leukaemia after MOPP and four after ABVD; 11 patients were diagnosed as acute non-lymphoblastic leukaemia (ANLL) and two as acute lymphoblastic leukaemia (ALL). Both cases of ALL were observed after ABVD and were associated with a 11q23 translocation. The 15-year actuarial risk of secondary leukaemia was 2.4% for the whole group of patients, 3.4% after MOPP and 1.3% after ABVD. For the MOPP subgroup, the risk of leukaemia was significantly associated with the extent of irradiation: 2.4% for limited irradiation and 13.9% for extended irradiation (P < 0.001). For the ABVD subgroup, this risk remained low (1.3%) whatever the type of irradiation. Concerning ANLL, the MOPP regimen was significantly associated with a higher risk: 3.4% versus 0.7% for ABVD (P11
UI - 12100148
AU - Reynolds GM; Billingham LJ; Gray LJ; Flavell JR; Najafipour S; Crocker
TI - J; Nelson P; Young LS; Murray PG Interleukin 6 expression by Hodgkin/Reed-Sternberg cells is associated with the presence of 'B' symptoms and failure to achieve complete remission in patients with advanced Hodgkin's disease.
SO - Br J Haematol 2002 Jul;118(1):195-201
AD - The Liver Research Laboratories, CRC Institute for Cancer Studies, Department of Pathology, University of Birmingham, Edgbaston, UK.
Interleukin 6 (IL-6) is a potent immunomodulatory cytokine that has pathogenic and prognostic significance in a number of disorders. Previous studies in Hodgkin's disease (HD) have demonstrated the association between elevated serum levels of IL-6 and unfavourable prognosis, including advanced stage and the presence of 'B' symptoms and with reduced survival. Although IL-6 expression has been demonstrated in both the malignant Hodgkin/Reed-Sternberg (HRS) cells and in the various non-malignant cells present in HD biopsies, a relationship between expression of IL-6 by the tumour and outcome measures has not been established. The study group comprised of 97 patients with advanced HD who were recruited to two related clinical trials. IL-6 expression was determined on paraffin-wax sections of biopsy material by means of an immunohistochemical assay. Of the 97 patients, 27 (28%) showed staining for IL-6 in HRS cells. IL-6 expression by HRS cells was significantly correlated with a decreased likelihood of achieving a complete response to chemotherapy (P = 0.02) and with an increased prevalence of 'B' symptoms (P = 0.04). IL-6 expression by HRS cells was not associated with Epstein-Barr virus status (P = 0.57). In summary, the results suggest that IL-6 expression by HRS cells may contribute to the presence of 'B' symptoms and to a decreased likelihood to achieve a complete remission in HD patients.

12
UI - 12100149
AU - Kosmaczewska A; Frydecka I; Bocko D; Ciszak L; Teodorowska R
TI - Correlation of blood lymphocyte CTLA-4 (CD152) induction in Hodgkin's disease with proliferative activity, interleukin 2 and interferon-gamma production.
SO - Br J Haematol 2002 Jul;118(1):202-9
AD - Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
Expression of the downregulatory CTLA-4 molecule was determined on unstimulated and anti-CD3 + recombinant interleukin 2 (rIL-2)-stimulated peripheral blood T cells in Hodgkin's disease (HD) and correlated with the T-cells' proliferative activity, IL-2 and interferon (IFN)-gamma production. There was a negligible percentage of CTLA-4+/CD3+ cells before culture. The mean percentage of CTLA-4+/CD3+ lymphocytes increased gradually, peaked after 72 h of stimulation and returned to basal values after 96 h of stimulation. The mean proportion of CTLA-4+/CD3+ cells from untreated patients was significantly higher after 24, 48 and 72 h of stimulation compared with controls. The mean percentage of CTLA-4+/CD3+ cells from patients in clinical remission (CR) was lower than that of untreated patients, but remained significantly higher compared with controls. Lymphocytes from untreated HD patients showed impaired proliferative activity, IL-2 and IFN-gamma production compared with controls. The proliferative activity of the lymphocytes, IL-2 and IFN-gamma production remained significantly lower in CR compared with controls. The proportion of CTLA-4+/CD3+ cells negatively correlated with proliferative activity, IL-2 and IFN-gamma production in HD patients and controls. However, some untreated patients as well as patients in CR with normal mean fluorescence intensity values of CTLA-4 showed unimpaired T-cell function tests. Our study provides the first evidence of an increased expression of downregulatory CTLA-4 molecule on stimulated T-cells in HD, which could be one of the mechanisms of immune deficiency in this disease.

13
UI - 12177773
AU - Blackhall FH; Atkinson AD; Maaya MB; Ryder WD; Horne G; Brison DR;
TI - Lieberman BA; Radford JA Semen cryopreservation, utilisation and reproductive outcome in men treated for Hodgkin's disease.
SO - Br J Cancer 2002 Aug 12;87(4):381-4
AD - Cancer Research UK Department of Medical Oncology, Christie Hospital NHS Trust, Wilmslow Road, Manchester M20 4BX, UK.
Between 1978 and 1990, 122 men underwent semen analysis before starting sterilising chemotherapy for Hodgkin's disease. Eighty-one (66%) had semen quality within the normal range, 25 were oligospermic (<20 x 10(6) sperm per ml) and five were azoospermic (no sperm in the ejaculate). Semen from 115 men was cryopreserved and after a median follow-up time of 10.1 years, 33 men have utilised stored semen (actuarial rate 27%) and nine partners have become pregnant resulting in 11 live births and one termination for foetal malformation. Actuarial 10 year rates of destruction of semen before death or utilisation and death before utilisation are 19% and 13% respectively. This retrospective cohort study demonstrates that approximately one-quarter of men utilising cryopreserved semen after treatment for Hodgkin's disease obtain a live birth. The high non-utilisation rate is intriguing and warrants further investigation.

14
UI - 12199007
AU - Jardine DL; Colls BM
TI - Hodgkin's disease following methotrexate therapy for rheumatoid arthritis.
SO - N Z Med J 2002 Jun 21;115(1156):293-4
AD - Department of General Medicine, Christchurch Hospital, Christchurch. David.Jardine@cdhb.govt.nz

15
UI - 11594519
AU - Yonetani N; Kurata M; Nishikori M; Haga H; Ohmori K; Yamabe H; Uchiyama
TI - T; Ohno H Primary mediastinal large B-cell lymphoma: a comparative study with nodular sclerosis-type Hodgkin's disease.
SO - Int J Hematol 2001 Aug;74(2):178-85
AD - Department of Internal Medicine, Faculty of Medicine, Kyoto University, Japan.
The clinicopathological features of 10 patients with primary mediastinal large B-cell lymphoma (PMLBCL) are described. The patients were aged 19 to 63 years, with a median age of 25.5 years. There were 5 men and 5 women. All patients presented with chest symptoms, and 6 presented with superior vena cava syndrome. Nine patients had bulky mediastinal tumors. The disease was confined within the thorax and contiguous lymph nodes, although multiple liver tumors were observed in 1 patient. Laboratory findings included high lactate dehydrogenase levels and elevated C-reactive protein levels. The soluble interleukin 2-receptor level was high in 6 patients tested. A comparative study of PMLBCL and nodular sclerosis-type Hodgkin's disease (NS-HD) with a mediastinal mass revealed substantial overlap in clinical features. Histopathological examination of biopsy specimens of PMLBCL revealed clusters of CD20+ large cells; however, CD30+ Hodgkin/Reed-Sternberg-like cells were occasionally seen, raising the potential to misdiagnose PMLBCL as NS-HD. The patients with PMLBCL were treated with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone), biweekly CHOP, or MACOP-B (methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisolone, and bleomycin) regimen, and 6 received consolidation radiotherapy to the involved field. With the exception of 1 patient who was primarily refractory to therapy, 9 patients (90%) achieved complete response and 7 (70%) remain in continuous remission with a mean follow-up of 24 months.

16
UI - 12149227
AU - van den Berg A; Maggio E; Rust R; Kooistra K; Diepstra A; Poppema S
TI - Clonal relation in a case of CLL, ALCL, and Hodgkin composite lymphoma.
SO - Blood 2002 Aug 15;100(4):1425-9
AD - Department of Pathology and Laboratory Medicine, University and University Hospital Groningen, Groningen, The Netherlands.
Large cell lymphomas and Hodgkin disease may develop during the course of chronic lymphocytic leukemia (CLL). In some cases the transformed cells are Epstein-Barr virus (EBV)-positive and not clonally related to the CLL cells. In other cases the transformed cells have the same clonal rearrangements as the CLL cells. Here we describe a composite lymphoma in a patient with CLL that exhibits a combination of CLL/small lymphocytic lymphoma, large cell lymphoma with anaplastic morphology, and Hodgkin lymphoma (HL). Although the large cell lymphoma cells are CD45R0 and TIA-1-positive, suggesting a T- or 0-cell anaplastic large cell lymphoma (ALCL), the genetic analysis demonstrates immunoglobulin heavy chain (IgH) gene rearrangements for both alleles, carrying the same somatic mutations as observed in the CLL component. The Reed-Sternberg (R-S) cells in the Hodgkin component also strongly express TIA-1 but differ from the anaplastic large cells by the expression of CD15 and TARC and the presence of a prominent lymphocytic infiltrate. The ALCL and HL components both are EBV negative. Analysis of the IgH gene rearrangements in micromanipulated R-S cells revealed identical Ig gene rearrangements carrying the same somatic mutations as the CLL and the large cell components. The findings indicate transformation of the CLL cells into a large cell lymphoma with anaplastic morphology and a Hodgkin component.

17
UI - 12171776
AU - Zapatero A; Lopez MA; Cerezo L; De Vidales CM; MarIn A; Perez-Torrubia A
TI - Stage I-III Hodgkin's disease: outcome and pattern of failure following treatment with radiation therapy and chemotherapy in a modern era.
SO - Hematol 2002 Feb;7(1):43-50
AD - Department of Radiation Oncology, Hospital Universitario de la Princesa, Madrid, Spain. azapatero@hlpr.inscelud.es
PURPOSE: To analyse the long term outcome, pattern of failure and treatment related complications after radiation therapy (RT) with or without chemotherapy for stage I-III Hodgkin's disease (HD). MATERIAL AND METHODS: Detailed records from 86 patients with stage I-III HD treated between 1989 and 1998, were retrospectively reviewed. Seventeen patients with favourable stage I-IIA were treated with RT alone, and the remaining 69 patients with combined modality treatment (CMT). Patients treated with RT received extended-field or subtotal nodal irradiation (STNI) to a total dose of 36-54 Gy, and patients with CMT, received involved-field irradiation to a lower doses, 26-40 Gy. The median follow-up time was 50 months (range 16-180). RESULTS: The 10-year overall survival (OS) for the whole group was 96% (SE 2%), 100% for stage I, 95% for stage II and 100% for stage III patients. Of potential prognostic factors analysed for statistical significance, only the response to chemotherapy (p=0.0393) was found to influence significantly OS rates. Twelve patients (13.9%) relapsed. Salvage treatment was effective in 10 of the 12 relapsed patients. The 10-year freedom from treatment failure (FFTF) was 79% (SE 6%). Although 8 (9.6%) of the 83 surviving patients developed late effects that could represent toxicity from the treatment, no patient died of late complications. CONCLUSIONs: RT alone for favourable early stage HD attains good survival rates with a modest treatment related morbidity. For patients with unfavourable stage II and stage III HD, CMT with limited RT provides a good to excellent prognosis.

18
UI - 12191574
AU - Zinzani PL; Tani M; Stefoni V; Piccaluga PP; Baccarani M; Ascani S;
TI - Pileri S From chronic lymphocytic leukemia to Hodgkin's disease: a case of prognostically favorable transformation.
SO - Leuk Res 2002 Aug;26(8):775-6

19
UI - 12144535
AU - Vassilakopoulos TP; Angelopoulou MK; Siakantaris MP; Kontopidou FN;
TI - Dimopoulou MN; Boutsis DE; Anargyrou K; Kokoris SI; Giannakakis A; Karkantaris C; Kyrtsonis MC; Tsaftaridis P; Rombos J; Variamis E; Korkolopoulou P; Kittas C; Pangalis GA Hodgkin's lymphoma in first relapse following chemotherapy or combined modality therapy: analysis of outcome and prognostic factors after conventional salvage therapy.
SO - Eur J Haematol 2002 May;68(5):289-98
AD - Hematology Section, First Department of Internal Medicine, National and Kapodistrian University of Athens, Laikon General Hospital, 16 Sevastoupoleos Street, Athens, Greece.
OBJECTIVES: To investigate the prognosis of patients with Hodgkin's lymphoma (HL) who relapse following a complete remission (CR) achieved by chemotherapy with or without radiotherapy (CT+/-RT), and to identify prognostic factors for freedom from second progression (FF2P). METHODS: We analyzed the prognostic significance of the initial CT regimen (4 vs. 7-8 drugs), treatment-free interval (TFI), and demographic, clinical, and laboratory factors at the time of relapse and diagnosis, in 113 patients with HL, who relapsed after a CR achieved by CT+/-RT. RESULTS: Conventional salvage CT+/-RT was administered in 107 patients, while six received RT only. The 5-yr FF2P was 24%, while the 10-yr survival after relapse (O2S) was 39% and was not afffected by the initial CT regimen. Multivariate analysis revealed that extranodal disease at relapse (P<0.001), TFI<6 month (P<0.001), > or =5 involved sites at diagnosis (P=0.04) and anemia at relapse (P=0.03) were independent predictors of FF2P. 55% of patients had 0 or 1 of these adverse prognostic factors. The 5-yr FF2P of patients with 0, 1 or 2 adverse factors was 58%, 34% and 5% (P<0.0001). The corresponding rates for 10-yr O2S were 68%, 51% and 25%, respectively (P=0.002). CONCLUSIONS: Our data confirmed the significance of TFI and extranodal relapse and demonstrated a potential role for anemia at relapse and number of involved sites at diagnosis, for the prognosis of patients with HL relapsing after CT+/-RT. The combination of these prognostic factors defines a sizeable subgroup of patients with favorable outcome following conventional salvage therapy.

20
UI - 12144540
AU - Spyridonidis A; Fischer KG; Glocker FX; Fetscher S; Klisch J; Behringer
TI - D Paraneoplastic cerebellar degeneration and nephrotic syndrome preceding Hodgkin's disease: case report and review of the literature.
SO - Eur J Haematol 2002 May;68(5):318-21
AD - Departmentof Hematology/Oncology, University Medical Center Freiburg, Hugstetter Strasse 55, D-79106 Freiburg, Germany.
A patient presented with symptoms of cerebellar degeneration and nephrotic syndrome. A work-up at that time failed to reveal an underlying disease; however, 20 months later Hodgkin's disease was diagnosed. Hodgkin's lymphadenopathy developed 2 wk after prednisone therapy for the nephrotic syndrome had been discontinued. Systemic polychemotherapy resulted in complete remission of both Hodgkin's disease and nephrotic syndrome, while the neurological deficit persisted. Patients with unexplained cerebellar degeneration and/or nephrotic syndrome demand extensive evaluation for the presence of Hodgkin's disease, and steroid therapy may delay diagnosis.

21
UI - 12174874
AU - Thorns C; Feller AC; Merz H
TI - EMMPRIN (CD 174) is expressed in Hodgkin's lymphoma and anaplastic large cell lymphoma. An immunohistochemical study of 60 cases.
SO - Anticancer Res 2002 Jul-Aug;22(4):1983-6
AD - Institute of Pathology, Medical University of Luebeck, Germany. thorns@patho.mu-luebeck.de
BACKGROUND: Matrix metalloproteinases are involved in tumor invasion and metastatic spread. Expression of metalloproteinases is induced by the extracellular matrix metalloproteinase inducer (EMMPRIN). Their activity can be inhibited by several tissue inhibitors of metalloproteinases (TIMP1-to-4). Whereas TIMP-1 expression is described for high-grade malignant lymphomas and seems to be correlated with unfavourable prognosis, there are no data on the expression of EMMPRIN in malignant lymphoma. MATERIALS AND METHODS: We investigated 60 cases of Hodgkin's lymphoma and anaplastic large cell lymphoma for TIMP-1 and EMMPRIN expression using immunohistochemistry. RESULTS: EMMPRIN was expressed in all but four cases. EMMPRIN and TIMP-1 were co-expressed in two-thirds of the Hodgkin's lymphomas and anaplastic large cell lymphomas. CONCLUSION: This is the first report on the expression of EMMPRIN in malignant lymphoma. We speculate that EMMPRIN and TIMP-1 may be important in the pathogenesis of anaplastic large cell lymphoma and Hodgkin's disease.

22
UI - 12174934
AU - Villani F; Viola G; Vismara C; Laffranchi A; Di Russo A; Viviani S;
TI - Bonfante V Lung function and serum concentrations of different cytokines in patients submitted to radiotherapy and intermediate/high dose chemotherapy for Hodgkin's disease.
SO - Anticancer Res 2002 Jul-Aug;22(4):2403-8
AD - U.O. di Pneumologia e Fisiopatologia Respiratoria, Istituto Nazionale per lo Studio e la Cura dei Tumor, Milano, Italy.
The aim of the present investigation was to evaluate lung function and the time course of serum concentration of selected cytokines known to be involved in pulmonary fibrosis, in 39 patients with stages IIB, III and IV Hodgkin's disease submitted to intermediate-high dose chemotherapy, (epirubicin, vincristine, cyclophosphamide, etoposide, prednisone) followed by radiotherapy. Lung function tests were performed before, at the end of treatment and after a follow-up of more than 12 months from the end of the combined therapy. Tumor necrosis factor alpha, fibronectin and Interleukins 4, 6 and 8 were determined on serum samples collected at the same time intervals. In the patients, spirometric parameters apparently improved whereas diffusing capacity for CO (DLCO) decreased, TNF-alpha concentrations constantly decreased, fibronectin and IL-8 showed a tendency to increase, but Interleukins 4 and 6 did not show significant modifications. No significant correlations were observed between the changes of lung function tests and serum cytokine concentrations, probably because cytokine serum levels were not able to reflect events occurring in the alveolar phase.

23
UI - 12188384
AU - Mitarnun W; Pradutkanchana J; Takao S; Saechan V; Suwiwat S; Ishida T
TI - Epstein-barr virus-associated non-Hodgkin's lymphoma of B-cell origin, Hodgkin's disease, acute leukemia, and systemic lupus erythematosus: a serologic and molecular analysis.
SO - J Med Assoc Thai 2002 May;85(5):552-9
AD - Department of Pathology, Faculty of Medicine, Prince of Songkla University, Thailand.
Parallel studies of (a) patients with Epstein-Barr virus (EBV)-associated peripheral T-cell proliferative disease/lymphomas and (b) a group of patients with a prolonged fever from other causes were conducted at Songklanagarind University Hospital from 1997 through 2000. (Reports on EBV-associated peripheral T-cell and NK-cell proliferative disease/lymphomas have been published elsewhere) In this study, the authors identified 58 patients; 14 were non-Hodgkin's lymphoma of B-cell origin (NHL-B), 8 were Hodgkin's disease, 6 were acute leukemia, 9 were systemic lupus erythematosus (SLE), and 21 were patients with other diseases. Serologic tests for the EBV infection, the study of EBV genome in circulating non-T-cells (CD3-cells) and T-cells (CD3+ cells), and the EBV-RNA study in the tumor cells were performed. EBV internal repeat-1 region (IR-1) in peripheral blood CD3+ cells was detected in 10 of 14 patients (71.5%) with NHL-B, 3 of 8 patients (37.5%) with Hodgkin's disease, 1 of 6 patients (16.7%) with acute leukemia, 4 of 9 patients (44.5%) with SLE, and was not detected in any of the 21 patients with other diseases. Anti-viral capsid antigen-IgG was significantly elevated in hematologic malignancy patients with EBV IR-1 genome in the peripheral blood CD3+ cells when compared to hematologic malignancy patients with a negative result, whereas there was no significant difference in anti-EBV nuclear antigen among these two groups. EBV-RNA expression in tumor cells by in situ hybridization was detected in 4 of 13 patients (31%) with NHL-B (all showed EBV IR-1 genome in peripheral blood CD3+ cells), and 3 of 5 patients (60%) with Hodgkin's disease (only two showed EBV IR-1 genome in peripheral blood CD3+ cells). These data support the theory that chronic EBV infection is often found in association with cases of NHL-B, Hodgkin's disease, acute leukemia, and SLE.

24
UI - 12100217
AU - de Vries HJ; Koopmans AK; Starink TM; Mekkes JR
TI - Ofuji papuloerythroderma associated with Hodgkin's lymphoma.
SO - Br J Dermatol 2002 Jul;147(1):186-7

25
UI - 12145210
AU - Mathas S; Hinz M; Anagnostopoulos I; Krappmann D; Lietz A; Jundt F;
TI - Bommert K; Mechta-Grigoriou F; Stein H; Dorken B; Scheidereit C Aberrantly expressed c-Jun and JunB are a hallmark of Hodgkin lymphoma cells, stimulate proliferation and synergize with NF-kappa B.
SO - EMBO J 2002 Aug 1;21(15):4104-13
AD - Max-Delbruck-Center for Molecular Medicine and Universitatsklinikum Charite, Robert-Rossle-Klinik, Humboldt University, Lindenberger Weg 80, D-13125 Berlin.
AP-1 family transcription factors have been implicated in the control of proliferation, apoptosis and malignant transformation. However, their role in oncogenesis is unclear and no recurrent alterations of AP-1 activities have been described in human cancers. Here, we show that constitutively activated AP-1 with robust c-Jun and JunB overexpression is found in all tumor cells of patients with classical Hodgkin's disease. A similar AP-1 activation is present in anaplastic large cell lymphoma (ALCL), but is absent in other lymphoma types. Whereas c-Jun is up-regulated by an autoregulatory process, JunB is under control of NF-kappa B. Activated AP-1 supports proliferation of Hodgkin cells, while it suppresses apoptosis of ALCL cells. Furthermore, AP-1 cooperates with NF-kappa B and stimulates expression of the cell-cycle regulator cyclin D2, proto-oncogene c-met and the lymphocyte homing receptor CCR7, which are all strongly expressed in primary HRS cells. Together, these data suggest an important role of AP-1 in lymphoma pathogenesis.

26
UI - 11697486
AU - Lee IS; Shin YK; Chung DH; Park SH
TI - LMP1-induced downregulation of CD99 molecules in Hodgkin and Reed-Sternberg cells.
SO - Leuk Lymphoma 2001 Aug;42(4):587-94
AD - Department of Pathology, Seoul National University College of Medicine, Korea.
Hodgkin's and Reed-Sternberg (H-RS) cells are morphological hallmarks of Hodgkin's disease (HD). So far, several characteristics frequently seen in H-RS cells from different origins have been described, such as the high expression of Epstein-Barr virus latent membrane protein 1 (LMP1), the elevation of NF-kappaB activity, and the aberrant expression of molecules such as CD15, CD30, and CD99. Despite extensive studies on the nature of H-RS cells, the molecular mechanism by which H-RS cells are generated remained elusive. Recently, the forced down-regulation of CD99 was reported to induce typical H-RS phenotypes in vitro in a B cell line. Furthermore, it was revealed that LMP1 markedly reduces the CD99 expression at the transcriptional level. Since the presence of LMP1 is known to be associated with the H-RS cell formation, the data provide a possibility of linkage between LMP1 and HD via CD99, thus suggesting that, at least in part, the loss of CD99 may play a critical role in the pathogenic sequence to the formation of H-RS cells in HD. In this review, the role of CD99 in the generation of H-RS cells and its molecular mechanism will be suggested.

27
UI - 11697494
AU - Guermazi A
TI - Is it wise to eliminate lymphography from the staging of Hodgkin's disease?
SO - Leuk Lymphoma 2001 Aug;42(4):655-60
AD - Department of Radiology Saint-Louis University Hospital, Paris, France. guermazi@chu-stlouis.fr
We believe that lymphography and CT are complementary rather than mutually exclusive techniques for the diagnosis and staging of HD. Unfortunately, it seems that many radiologists and clinicians disregard the ability of lymphography to provide qualitative information on lymph node architecture, which is not available by CT. The use of lymphography is declining in several teaching centers throughout the world. This makes it difficult for young radiologists to acquire the skills needed to perform and interpret lymphographies successfully. In turn, radiologists who have little experience with lymphography are less likely to use the technique. Because most of the treatment-related morbidity in HD is dose-related, and because lymphography helps to avoid over- and undertreatment, we believe that high-quality lymphography continues to have a significant role in the staging of selected HD patients. Moreover. lymphography may reduce both the cost of management and the morbidity rate in many HD patients. One solution would be to continue to use lymphography in a small number of institutions specialized in the management of HD.

28
UI - 11697495
AU - Provencio M; Espana P; Salas C; Sanchez A; Bonilla F
TI - Hodgkin's disease: unsuspected minimal activity in patients that die from causes other than tumoral progression.
SO - Leuk Lymphoma 2001 Aug;42(4):661-4
AD - Department of Oncology, Hospital Universitario Clinica Puerta de Hierro, Madrid, Spain.
Hodgkin's disease (HD) is a curable disease. However, there are still many questions that remain unanswered in this illness, such as the appearance of unsuspected microscopic active illness a long time after the conclusion of treatment, We do not know of any recent publications that have microscopically studied the presence of unsuspected HD activity in patients who died from causes other than tumoral progression. This aspect was analysed in our series of patients with HD. We studied 486 patients with a median follow-up of 8 years. Autopsy was performed in 40 of 144 non-surviving patients. Active HD was found in 60% (24/40) of the patients at autopsy. Of these, 10 patients (25%, 10/40) with active HD died from causes other than tumoral progression. Six patients had minimal clinically unsuspected isolated tumor foci. In spite of technical advances and the introduction of modern and more aggressive chemotherapy, the discovery of minimal unsuspected residual HD continues in an considerable percentage of patients who die from causes other than tumoral progression.

29
UI - 1498073
AU - Pavlovsky S; Santarelli MT; Muriel FS; Fernandez I; Garcia I; Schwartz
TI - L; Montero C; Sanahuja FL; Magnasco H; Costa A; et al Randomized trial of chemotherapy versus chemotherapy plus radiotherapy for stage III-IV A & B Hodgkin's disease.
SO - Ann Oncol 1992 Jul;3(7):533-7
AD - Grupo Argentino de Tratamiento de Leucemia Aguda (GATLA), Buenos Aires.
A total of 151 patients with previously untreated Hodgkin's disease, clinical stages III-IV A & B, were randomized to receive CVPP for 6 cycles, or CVPP plus RT 3000 cGy to previously involved areas between the 3rd and 4th cycles. CVPP consists of cyclophosphamide 600 mg/m2/i.v., vinblastine 6 mg/m2/i.v. on day 1, procarbazine 100 mg/m2/p.o. and prednisone 40 mg/m2/p.o. on days 1 to 14. Both groups displayed similar clinical characteristics at diagnosis. Sixty-six were treated with CVPP + RT (52 St III and 14 St IV) and 85 with CVPP alone (68 St III and 17 St IV). Complete remission was obtained in 57 (86%) of 66 patients who received CVPP plus RT, and in 62 (73%) of 85 patients treated with CVPP. Five and sixteen patients, respectively, achieved partial responses, while 2 in each group died during treatment. At 7 years, duration of complete remission and failure-free survival were: 51% and 45% for those treated with CVPP plus RT, and 23% and 21% with CVPP alone (p = 0.0150 and P = 0.0016, respectively). Overall survival at 7 years was 71% and 58%, respectively (p = 0.1488). A dose analysis performed in 84 pts showed that 91% and 88% received full protocol doses of CPM and PCZ, respectively, in the CVPP + RT group, and 95% and 94% for CVPP. The WBC nadir was 3.5 and 3.7 x mm3, respectively. Of 25 pts on CVPP + RT who relapsed, 9 are now disease-free, 5 are alive with disease and 11 have died, and with CVPP, of 37 relapsing pts, 18 are disease-free, 5 are alive with disease and 14 are dead.(ABSTRACT TRUNCATED AT 250 WORDS)

30
UI - 9572494
AU - Wood KM; Roff M; Hay RT
TI - Defective IkappaBalpha in Hodgkin cell lines with constitutively active NF-kappaB.
SO - Oncogene 1998 Apr 23;16(16):2131-9
AD - Department of Pathology, Royal Victoria Infirmary, Newcastle upon Tyne, England.
The molecular mechanisms underlying Hodgkin's disease remain obscure, but it has been recognized that the neoplastic cells display high levels of constitutively active nuclear NF-kappaB. Here we demonstrate that although nuclear NF-kappaB is transcriptionally active, the Hodgkin cells fail to activate NF-kappaB dependent transcription in response to CD40 ligand. In three Hodgkin cell lines examined each had abnormalities in expression of IkappaBalpha which could account for the deregulated NF-kappaB. Although all three cell lines had greater than normal levels of IkappaBalpha mRNA no IkappaBalpha protein could be detected in the KM-H2 cells, while the L428 cell line contains a C-terminally truncated IkappaBalpha species that fails to associate with NF-kappaB. The HDLM-2 cell line contains a more slowly migrating form of IkappaBalpha that can associate with NF-kappaB, but increasing the level of this protein within the cell fails to inhibit nuclear NF-kappaB. Addition of recombinant IkappaBalpha to nuclear extracts from all three cell lines resulted in complete inhibition of NF-kappaB DNA binding activity and introduction of a plasmid expressing IkappaBalpha into the cells inhibited the transcriptional activity of an NF-kappaB dependent reporter plasmid. Thus the constitutive expression of NF-kappaB in Hodgkin cells is a direct consequence of the abnormal expression of IkappaBalpha rather than changes in NF-kappaB that render it refractory to inhibition by IkappaB proteins. These changes could, at least in part, account for the characteristic activated phenotype of Hodgkin cells and their pattern of cytokine secretion, which determine the pathological appearance and clinical manifestations of Hodgkin's disease.

31
UI - 10340377
AU - Cabannes E; Khan G; Aillet F; Jarrett RF; Hay RT
TI - Mutations in the IkBa gene in Hodgkin's disease suggest a tumour suppressor role for IkappaBalpha.
SO - Oncogene 1999 May 20;18(20):3063-70
AD - School of Biomedical Science, University of St Andrews, Fife, UK.
The NF-kappaB/Rel family of transcription factors regulates a wide variety of genes whose products play a fundamental role in inflammatory and immune responses. The implication of NF-kappaB/Rel proteins and their IkappaB regulatory subunits in the control of cellular growth and oncogenesis, was suggested by the induction of fatal lymphomas in birds by the v-rel oncoprotein, and the rearrangement and amplification of several genes encoding the NF-kappaB/Rel/IkappaB signal transduction factors in human malignancies, primarily of lymphoid origin. Hodgkin's disease (HD) is a lymphoma characterized by a low frequency of malignant Hodgkin and Reed-Sternberg (H/RS) cells in a reactive background of non-neoplastic cells. The peculiar activated phenotype of Hodgkin and Reed-Sternberg cells and their pattern of cytokine secretion are believed to be a consequence of constitutive activation of the NF-kappaB transcription factor. Here, we report the detection of mutations of the IkBa gene, in two HD-derived cell lines and in two out of eight biopsy samples from patients with relapsed Hodgkin's disease. The presence of defective IkappaBalpha is thus likely to explain the constitutive activation of NF-kappaB in these cells and suggests that IkappaBalpha is a tumour suppressor controlling the oncogenic activation of NF-kappaB in Hodgkin and Reed-Sternberg cells.

32
UI - 10564680
AU - Pajonk F; Pajonk K; McBride WH
TI - Inhibition of NF-kappaB, clonogenicity, and radiosensitivity of human cancer cells.
SO - J Natl Cancer Inst 1999 Nov 17;91(22):1956-60
AD - Department of Radiation Oncology, Experimental Division, University of California at Los Angeles School of Medicine 10833, USA. fpajonk@u

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