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NCI CANCERLIT® Search: Hodgkin|s Disease - September 2001

Last Modified: November 1, 2001

Table of Contents

CancerMail from the National Cancer Institute

1
UI - 21062261
AU - Soriano Guillen L; Munoz Calvo MT; Pozo Roman J; Contra Gomez T; Buno Soto M; Argente Oliver J
TI - [Changes in gonadal function in post-pubertal male survivors of acute lymphoblastic leukemia and Hodgkin's disease]
SO - An Esp Pediatr 2000 Oct;53(4):318-23

AD - Secciones de Endocrinologia y Oncologia Pediatricas. Hospital Universitario Nino Jesus. Universidad Autonoma. Madrid.
AIM: To study gonadal function in male patients surviving acute lymphoblastic leukemia (ALL) or Hodgkins disease (HD). PATIENTS AND METHODS: Thirteen postpubertal males were studied (Tanner stage V), 9 with ALL and 4 with HD, who had received polychemotherapy during the pre-puberal period. The control group was composed of 13 male volunteers of similar ages and with complete pubertal development. Testicular size, spermiogram, serum levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) before and after stimulus with gonadotropin-releasing hormone (GnRH), and serum testosterone levels were determined. The germinal epithelium was believed to be damaged when at least one of the following criteria was present: 1) oligospermia/azoospermia, 2) increase in serum FSH levels before or after GnRH, or 3) reduction in testicular volume. Lesions in Leydig's cells were thought to exist when serum testosterone levels were reduced or when serum LH levels, before or after stimulus, increased. RESULTS: Patients with HD presented clear alterations in germinal function and, to a lesser degree, in the function of Leydig's cells. Significant differences compared with the control group (p < 0.001) were found in peak FSH (19.7 +/- 18 vs 4.8 +/- 1.8 microUI/mL), peak LH (49.2 +/- 31 vs 33.4 +/- 10.0 microUI/mL), serum testosterone (4.1 +/- 0.6 vs 5.9 +/- 0.3 ng/mL) and testicular volume (16.6 +/- 2.8 vs 22.5 +/- 2.4 mL). Of the four patients with HD, three presented azoospermia and one oligospermia. No significant differences in any of the clinical or biochemical parameters studied were found in patients surviving ALL compared with the control group, but two of the nine patients studied presented oligospermia. CONCLUSIONS: The chemotherapy protocols used in the treatment of HD and ALL produced a high incidence of germinal cell damage and subclinical alterations in the Leydig's cell function in males with HD. In patients with ALL, the germinal line was only mildly affected. Prepubertal state does not protect the testes from the harmful effects of chemotherapy.

2
UI - 21319816
AU - Wheeler C; Khurshid A; Ibrahim J; Elias A; Mauch P; Ault K; Antin J
TI - Incidence of post transplant myelodysplasia/acute leukemia in non-Hodgkin's lymphoma patients compared with Hodgkin's disease patients undergoing autologous transplantation following cyclophosphamide, carmustine, and etoposide (CBV).
SO - Leuk Lymphoma 2001 Feb;40(5-6):499-509

AD - Beth Israel Deaconess Medical Center, Division of Hematology/Oncology, Farber Cancer Institute, MA, USA.
Secondary malignancies, particularly myelodysplasia (MDS), are serious events following high dose therapy with autologous stem cell support. We observed a higher frequency of secondary malignancies in patients with Hodgkin's disease (HD) than in patients with non-Hodgkin's lymphoma (NHL) undergoing high dose therapy with the same non-TBI conditioning regimen. Three hundred patients with Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) were treated with cyclophosphamide, carmustine and etoposide and autologous stem cell support from 1986 through 1994. Median follow up of survivors is 3.9 years. Five-year survival is 51% for HD and 48% for NHL. Eleven patients developed second malignancies (9/150 treated for HD vs. 2/150 treated for NHL) a median of 2.4 years from transplantation and 5.2 years from initial diagnosis. Six patients had myelodysplasia or acute leukemia (MDS/AML) and 5 had lymphomas or solid tumors. Actuarial risk of MDS/AML at five years for patients transplanted for non-Hodgkin's lymphoma is 3% (95% CI 0.6-9.6%). HD patients had significantly different pretreatment characteristics than patients with NHL. A Cox model showed that greater number of prior relapses and prior radiation therapy were significant risk factors for the development of MDS/AML. These data suggest that CBV is associated with a lower risk of secondary MDS/AML than TBI containing regimens and that much of the risk is associated with the pre-transplantation therapy. The use of autotransplantation early in the course of therapy for relapsed lymphoma might prevent some cases of MDS/AML.

3
UI - 21397970
AU - Chapman AL; Rickinson AB; Thomas WA; Jarrett RF; Crocker J; Lee SP
TI - Epstein-Barr virus-specific cytotoxic T lymphocyte responses in the blood and tumor site of Hodgkin's disease patients: implications for a T-cell-based therapy.
SO - Cancer Res 2001 Aug 15;61(16):6219-26

AD - CRC Institute for Cancer Studies, University of Birmingham, Vincent Drive, Edgbaston, Birmingham, B15 2TT, United Kingdom.
Approximately 40% of Hodgkin's disease (HD) cases carry EBV in the malignant Hodgkin-Reed Sternberg (H-RS) cells, with expression of viral latent membrane proteins (LMPs) 1 and 2. These viral proteins are targets for CTLs in healthy EBV carriers, and their expression in EBV-associated HD raises the possibility of targeting them for a CTL-based immunotherapy. Here we characterize the CTL response to EBV latent antigens in both the blood and tumor-infiltrating lymphocytes of HD patients using two approaches: (a) in vitro reactivation of CTLs by stimulation with the autologous EBV-transformed lymphoblastoid cell line; and (b) an enzyme-linked immunospot assay to quantify frequencies of CTLs specific for known LMP1/2 epitopes. We detected EBV-specific CTLs in blood and biopsy samples from both EBV-negative and EBV-positive HD patients. However, as in healthy EBV carriers, LMP-specific CTL precursors occurred only at low frequency in the blood of HD patients, and with the exception of one EBV-negative HD case, were undetectable in the tumor. These data give rise to two considerations: (a) they may explain why EBV-positive tumor cells persist in the presence of an existing EBV-specific immune response; and (b) they provide a rationale for selectively boosting/eliciting LMP-specific CTL responses as a therapy for EBV-positive HD.

4
UI - 21379834
AU - Flavell KJ; Biddulph JP; Powell JE; Parkes SE; Redfern D; Weinreb M; Nelson P; Mann JR; Young LS; Murray PG
TI - South Asian ethnicity and material deprivation increase the risk of Epstein-Barr virus infection in childhood Hodgkin's disease.
SO - Br J Cancer 2001 Aug 3;85(3):350-6

AD - School of Health Sciences, University of Wolverhampton, Wolverhampton, WV1 1DJ.
In order to further define the factors associated with the observed variations in the Epstein-Barr virus-positive rate in childhood Hodgkin's disease, we have studied the effect of material deprivation (measured by the Townsend score) and ethnic origin on the frequency of Epstein-Barr virus-positivity in 55 cases of childhood Hodgkin's disease, diagnosed between 1981 and 1999, from a multi-ethnic region of the United Kingdom. Epstein-Barr virus status was determined by immunohistochemistry for the Epstein-Barr virus-encoded latent membrane protein-1. 62% of cases were Epstein-Barr virus-positive. Ethnic group was the strongest predictor of Epstein-Barr virus-positivity, with South Asians having a more than 20-fold risk of being Epstein-Barr virus-positive compared with non-South Asians. An increased risk was still present after adjusting for deprivation. Townsend scores were significantly higher (indicating more deprivation) in the Epstein-Barr virus-positive group, particularly in males. The relative risk of Epstein-Barr virus-positivity showed a gradient with increasing Townsend score; the risk being 7-times higher in the most deprived quartile compared with the least deprived group. Although the association between Townsend score and Epstein-Barr virus-positivity was reduced after adjusting for ethnic group, the risk of Epstein-Barr virus-positivity was still 3-times higher in the most deprived compared with the least deprived quartile. In addition, cases having 2 or more siblings were 5-times as likely to be Epstein-Barr virus-positive as those from smaller families. These results provide the first evidence of a strong association between Epstein-Barr virus-positive Hodgkin's disease and South Asian children from the United Kingdom. In addition, deprivation may increase the likelihood of Epstein-Barr virus-positive disease independently of ethnicity. Copyright 2001 Cancer Research Campaign.

5
UI - 21175031
AU - Metkar SS; Manna PP; Anand M; Naresh KN; Advani SH; Nadkarni JJ
TI - CD40 Ligand--an anti-apoptotic molecule in Hodgkin's disease.
SO - Cancer Biother Radiopharm 2001 Feb;16(1):85-92

AD - Immunology Division, Cancer Research Institute, Tata Memorial Centre, Parel, Mumbai 400 012, India.
The expression of CD40L was investigated in HD involved lymph nodes by flow cytometry (FCM) and reverse transcriptase polymerase chain reaction (RT-PCR). Also an investigation of the role of CD40L in upregulation of the anti-apoptotic gene BclxL in a Hodgkin's disease (HD) derived cell line was undertaken. HD patients (n = 18) had significantly higher numbers of activated CD4+ and CD8+ T cells in the tumor microenvironment as compared to controls (n = 8). HD patients also demonstrated higher numbers of CD4+, CD8+ and CD19+ lymphocytes co-expressing CD40L as compared to controls. The CD40L signal was consistently and significantly upregulated in HD patients (n = 5) as compared to controls (n = 3) at the mRNA level. RT-PCR and FCM analysis revealed that soluble CD40L upregulated BclxL levels in the Fas-sensitive HD cell line HDLM2. We conclude that CD40L can act as an important anti-apoptotic molecule by upregulating BclxL expression in Reed-Sternberg cells of HD and may be partly responsible for their survival 'in-vivo'.

6
UI - 21265627
AU - Miyata A; Kojima K; Yoshino T; Fujii S; Shinagawa K; Ichimura K
TI - Concurrent Hodgkin's disease (mixed cellularity type) and T-cell chronic lymphocytic leukemia/prolymphocytic leukemia.
SO - Int J Hematol 2001 Feb;73(2):230-5

AD - Department of Internal Medicine, Chugoku Central Hospital of the Mutual Aid Association of Public School Teachers, Hiroshima, Japan. myatak@mint.ocn.ne.jp
We describe a patient with leukopenic T-cell chronic lymphocytic leukemia/prolymphocytic leukemia (T-CLL/PLL), according to the Revised European-American Classification of Lymphoid Neoplasms. This patient simultaneously developed classic Hodgkin's disease (HD), a combination previously unreported. The leukemic cells were small and mature, did not have cytoplasmic granulation, and appeared similar to B-cell chronic lymphocytic leukemia. Immunophenotyping of the bone marrow-infiltrating cells revealed a postthymic suppressor/cytotoxic phenotype of CD2+, CD3+, CD4, CD5+, CD8+, CD25-, TCR-alpha beta. A lymph node biopsy showed the histological features of HD (mixed cellularity) with infiltrating CD8+ lymphocytes, and immunohistochemical examination revealed the following phenotype of Reed-Sternberg cells: LeuM1/CD15+, BerH2/CD30+, L26/PanB-, UCHL-1/CD45RO-, cyCD3-, CD4, CD8-, CD20-, CD79a-, EMA-, EBER-1+, LMP-1+. Southern blot analysis of the bone marrow and lymph node revealed the same rearrangement of bands of T-cell-receptor genes. Although the HD was treated with chemotherapy that resulted in complete remission, the T-PLL/CLL took an indolent course. This case may suggest the existence of a subtype of T-CLL/PLL with leukopenia and an indolent clinical course. Both diseases were believed to be independent and not a transformation of one to the other.

7
UI - 21265628
AU - Uehira K; Amakawa R; Ito T; Uehira T; Ozaki Y; Shimizu T; Fujimoto M; Inaba M; Fukuhara S
TI - A Hodgkin's disease cell line, KM-H2, shows biphenotypic features of dendritic cells and B cells.
SO - Int J Hematol 2001 Feb;73(2):236-44

AD - First Department of Internal Medicine, Kansai Medical University, Osaka, Japan.
The origin of Reed-Sternberg (RS) cells, the neoplastic cells of Hodgkin's disease, has long remained controversial. Dendritic cells (DCs) are highly specialized antigen-presenting cells that have the unique capacity to prime naive T cells, and they may be progenitors of RS cells in a population of Hodgkin's disease cells. In this study, the KM-H2 cell line, previously established from a patient with Hodgkin's disease of mixed cellularity, was reevaluated for its cellular derivation, particularly in terms of DCs. KM-H2 cells were demonstrated to carry the newly proposed DC-associated molecules fascin, CD83, and DEC-205, as well as costimulatory molecules such as CD40, CD80, and CD86. In addition, KM-H2 cells were shown to be able to potently stimulate peripheral blood T cells and to have the strong endocytotic activity of fluorescein isothiocyanate-dextran. On the other hand, KM-H2 cells were shown to have variable-diversity-joining recombination of the immunoglobulin H gene, although they did not express any subclasses of immunoglobulin and they were negative for CD79a and CD79b. In addition, KM-H2 cells produced the messenger RNA of the Pax-5 gene. These findings lead to a hypothesis that KM-H2 cells originated from the cells that had differentiated through the possible common DC-B-cell progenitors along the newly proposed pathway.

8
UI - 21353425
AU - Amakawa R
TI - [Latest findings on Hodgkin's disease]
SO - Nippon Naika Gakkai Zasshi 2001 Jun 10;90(6):977-82

9
UI - 21353427
AU - Kinoshita T
TI - [Prognostic factor and models for prognosis of malignant lymphoma]
SO - Nippon Naika Gakkai Zasshi 2001 Jun 10;90(6):988-91

10
UI - 21353429
AU - Hotta T
TI - [Standard treatment of malignant lymphoma (Hodgkin's and non-Hodgkin's lymphoma)]
SO - Nippon Naika Gakkai Zasshi 2001 Jun 10;90(6):997-1002

11
UI - 21361177
AU - Kube D; Holtick U; Vockerodt M; Ahmadi T; Haier B; Behrmann I; Heinrich PC; Diehl V; Tesch H
TI - STAT3 is constitutively activated in Hodgkin cell lines.
SO - Blood 2001 Aug 1;98(3):762-70

AD - Klinik fur Innere Medizin I, Zentrum fur Molekulare Medizin der Universitat Koln, Germany. dieter.kube@uni-tuebingen.de
Hodgkin disease (HD) represents a malignant lymphoma in which the putative malignant Hodgkin and Reed-Sternberg cells are rare and surrounded by abundant reactive nonmalignant cells. It has been suggested that cytokines such as interleukin-6 (IL-6) are involved in the pathogenesis of the disease. The expression of the IL-6 receptor (IL-6R) complex and its link to the activation of signal transducers and activators of transcription (STAT) molecules in HD cell lines was investigated. Gel retardation and Western blot analyses revealed a high level of constitutively activated STAT3 in 5 of 7 HD cell lines, which could not be detected in Burkitt lymphoma cell lines. Different levels of IL-6R protein were measured in various HD cell lines: L428 and Dev cells were characterized by very low levels of gp80 and gp130, on KMH2 cells only gp130 but no gp80 was detected, whereas L540, L591, HDLM2, and L1236 were positive for both gp80 and gp130, suggesting a possible autocrine stimulation of STAT3. However, a further increase in STAT3 activation on IL-6 or IL-6/soluble IL-6R stimulation was not observed. Neutralizing monoclonal antibodies against IL-6, gp80, gp130, or both receptor subunits did not affect the proliferation or the constitutive activation of STAT molecules in HD cell lines. However, the tyrosine kinase inhibitor AG490 blocked the constitutive activation of STAT3 and inhibited spontaneous growth of HD tumor cells. The evidence suggests abnormal STAT signaling and growth regulation in Hodgkin cell lines. (Blood. 2001;98:762-770)

12
UI - 21243438
AU - Altundag O; Celik I; Kars A
TI - Recurrent asymptomatic bradycardia episodes after cisplatin infusion.
SO - Ann Pharmacother 2001 May;35(5):641-2

13
UI - 21383897
AU - Hirschi S; Lange F; Battesti JP; Lebargy F
TI - [Pulmonary sarcoid-like granulomatosis associated with Hodgkin's disease and complicated by bleomycin-induced pulmonary nodules]
SO - Ann Med Interne (Paris) 1998 Apr;149(3):164-6

AD - Service de Pneumologie, Hopital Avicenne, 125, route de Stalingrad, 93009 Bobigny.
We report the case of a man in whom multiple lung macronodules developed after chemotherapy containing bleomycin for Hodgkin's disease, which was itself shortly preceded by a pulmonary sarcoid-like granulomatosis. Biopsy of the nodules showed fibrotic and granulomatous lesions. The etiological diagnosis is discussed.

14
UI - 21417929
AU - Baird D; Anderson R; Hamish Wallace W
TI - Autotransplantation of ovarian tissue.
SO - Lancet 2001 Aug 18;358(9281):588

15
UI - 21319923
AU - Matsubara K; Nigami H; Harigaya H; Osaki M; Baba K
TI - Peroneal mononeuropathy in pediatric Hodgkin's disease.
SO - Leuk Lymphoma 2000 Dec;40(1-2):205-7

AD - Department of Pediatrics, Nishi-Kobe Medical Center, Kobe, Japan. kskmatsu@portnet.ne.jp
A 12-year-old boy with Hodgkin's disease developed left peroneal nerve palsy during combination therapy with chemotherapy and low-dose irradiation. The palsy occurred twice; around 1-2 weeks after the second administration of vincristine in the second and third COPP (cyclophosphamide, vincristine, prednisolone, and procarbazine) regimens. Without any treatment, the peroneal neuropathy completely resolved clinically three months and electromyographically six months after the onset. He used to play television games for more than 6 hours a day with the legs crossed while sitting on the bedside. Compared to adult patients, little is known about the relationship between peroneal neuropathy and systemic malignant diseases in pediatric patients. This case shows for the first time that habitual leg crossing during potentially neurotoxic chemotherapy could induce peroneal mononeuropathy in a pediatric cancer patient.

16
UI - 21274940
AU - Lopez M
TI - [Successful cancer chemotherapy. The cure of Hodgkin's disease. III]
SO - Clin Ter 2001 Jan-Feb;152(1):57-63

AD - Istituto Regina Elena per lo Studio e la Cura dei Tumori, Roma, Italia.

17
UI - 21260583
AU - Balfour JA; Goa KL
TI - Bendamustine.
SO - Drugs 2001;61(5):631-8; discussion 639-40

AD - Adis International Limited, Auckland, New Zealand.
Bendamustine is a bifunctional alkylating agent with cytotoxic activity against human ovarian and breast cancers in vitro. It shows only partial in vitro cross-resistance with cyclophosphamide, melphalan, carmustine and cisplatin. Bendamustine as monotherapy or as part of combination chemotherapy protocols for first-line or subsequent treatment produced objective response rates of 61 to 97% in patients with Hodgkin's disease or non-Hodgkin's lymphoma (NHL) [41 to 48% in high grade NHL]. In patients with multiple myeloma, a bendamustine/prednisone regimen produced a higher rate of complete response (32 vs 11%) and more durable responses than a melphalan/prednisone regimen. Substitution of bendamustine for cyclophosphamide in a standard first-line COP regimen (cyclophosphamide, vincristine and prednisolone) yielded similar response rates in patients with advanced low grade NHL. Substituting bendamustine for cyclophosphamide in the CMF protocol (cyclophosphamide, methotrexate and fluorouracil) prolonged remission from 6.2 to 15.2 months in patients with metastatic breast cancer. The most common adverse events in patients receiving bendamustine are haematological events and gastrointestinal disturbances. Bendamustine has a relatively low propensity to induce alopecia.

18
UI - 21324125
AU - Andres E; Vinzio S; Maloisel F; Carre S; Perrin AE; Goichot B; Schlienger JL
TI - [Autoimmune peripheral neuropathies with anti-MAG antibodies and hematological disorders. Five cases]
SO - Ann Med Interne (Paris) 2001 Apr;152(3):147-51

AD - Services de Medecine Interne et Nutrition, Clinique Medicale B, Hopital, 67091 Strasbourg Cedex, France.
OBJECTIVE: The aim of this study was to report our experience with autoimmune neuropathies associated with hematological disorders and to describe their etiological and clinical polymorphism. PATIENTS AND METHODS: A retrospective study was conducted in five patients with autoimmune peripheral neuropathies with anti-MAG (myelin-associated glycoprotein) antibodies. RESULTS: Autoimmune neuropathies were associated with Waldenstrom's macroglobulinemia (n=2), Hodgkin disease (n=1), chronic lymphocytic leukemia (n=1) and idiopathic polyclonal B lymphoproliferation (n=1). Most of the patients had a sensorial polyneuropathy, predominant in the legs, exhibiting slow progress. Our patients showed a disappointing response to chemotherapy with stabilization or short response.

19
UI - 21340652
AU - Ansen S; Engert A; Wolf J; Sieber M; Paulus U; Diehl V
TI - [German Hodgkin's Lymphoma Study Group]
SO - Onkologie 2001 Feb;24 Suppl 1():35-48

AD - Klinik I fur Innere Medizin, Universitat zu Koln.

20
UI - 21381774
AU - Bonci A; Di Lernia V; Merli F; Lo Scocco G
TI - Erythema nodosum and Hodgkin's disease.
SO - Clin Exp Dermatol 2001 Jul;26(5):408-11

AD - Operative Unit of Dermatology, 1st Medical Department, Arcispedale Santa Maria Nuova, Reggio Emilia, Italy.
A 27-year-old woman with a 5-month history of recurrent erythema nodosum was found to have Hodgkin's disease. A temporal relationship between the two disorders suggested a causative role of the lymphoma. A review of the literature yielded 15 cases of this association, suggesting that the diagnosis of Hodgkin's disease should be considered in patients with unexplained erythema nodosum.

21
UI - 21353885
AU - Saint-Cyr I; Vezon G; Boisseau-Garsaud AM; Cales-Quist D; Panelatti G; Ossondo M
TI - [Panniculitis induced by MINE chemotherapy]
SO - Ann Dermatol Venereol 2001 Jun-Jul;128(6-7):756-8

AD - Service de Dermatologie, CHU de Fort-de-France, Hopital Pierre-Zobda-Quitman, BP 632, 97261 Fort de France Cedex, Martinique.
BACKGROUND: Drug-induced panniculitis are uncommon. We report the second case of panniculitis induced by MINE chemotherapy. CASE REPORT: A 31-year-old woman with relapsed Hodgkin disease was treated with MINE cytostatic regimen. Multiple erythematous and painful nodules of panniculitis developed on her chest, abdomen and thighs fifteen days after the beginning of drug administration with a second flare up after second administration of the same drugs. The eruption cleared slowly after treatment withdrawal. DISCUSSION: To our knowledge, our case is the second reported case of panniculitis induced by MINE chemotherapy. Drug-induced panniculitis is uncommon and usually induced by steroid treatment. Some cases of panniculitis induced by atenolol, potassium bromide, apomorphine, interferon alpha and interleukin 2 have been described. Few cutaneous adverse effects are reported with MINE chemotherapy: rash, erythema and swelling of extremities. A case of inflammatory swelling of thighs with hemorrhagic panniculitis due to this treatment has been described recently.

22
UI - 21447479
AU - Nitschke R
TI - Cyclophosphamide-based, seven-drug hybrid and low-dose involved field radiation for the treatment of childhood and adolescent Hodgkin disease.
SO - J Pediatr Hematol Oncol 2001 Aug-Sep;23(6):368-9

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