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Abramson Cancer CenterNCI CANCERLIT® Search: Hodgkin's Disease - April 2002
National Cancer Institute®
Last Modified: April 1, 2002
Table of Contents
1
UI - 11764714
AU - Zebrack B
TI -
An advocate's perspective on cancer survivorship.
SO - Semin Oncol Nurs 2001 Nov;17(4):284-7
AD - Division of Cancer Prevention and Control Research, University of
California-Los Angeles, Johsson Comprehensive Cancer Center, Los
Angeles, CA, USA.
OBJECTIVE: To illustrate the scope of advocacy in cancer survivorship
and to emphasize the critical role that health care providers play to
help improve the quality of life of cancer survivors. DATA SOURCES:
Published articles, government reports, and books. CONCLUSIONS: The
delivery of quality cancer care requires not only an understanding of
cancer survivorship issues but also a strategy for advocacy efforts for
cancer survivors and their families. IMPLICATIONS FOR NURSING PRACTICE:
Advocacy efforts involve individual interventions and family-focused
support, public and professional education, and programs and policies
that enhance cancer care and quality of life.
2
UI - 11788819
AU - Spaepen K; Mortelmans L
TI -
Evaluation of treatment response in patients with lymphoma using
[18F]FDG-PET: differences between non-Hodgkin's lymphoma and Hodgkin's
disease.
SO - Q J Nucl Med 2001 Sep;45(3):269-73
AD - Department of Nuclear Medicine, University Hospital Gasthuisberg,
Leuven, Belgium.
Fluorine-18fluorodeoxyglucose positron emission tomography
([18F]FDG-PET) has become a very useful technique for the therapy
monitoring of patients with lymphoma. It provides unique information
about the metabolic behavior of the disease independent of morphological
criteria. In recent years, [18F]FDG-PET has proven to be a technique
with high sensitivity for the detection of residual tumor. Therefore,
[18F]FDG-PET seems to be the ideal tool for the evaluation of treatment
response. However, most recent published studies included both HD and
NHL, although [18F]FDG-PET scan results in Hodgkin's disease (HD) has a
different impact than in Non Hodgkin's Lymphoma (NHL). In this paper, we
summarize our findings on the role of [18F]FDG-PET in the therapy
evaluation of lymphoma patients in a large group of patients and
highlight the differences between the interpretations of the results of
HD and NHL patients. Finally, a strategy for the implementation of
[18F]FDG-PET in the management of lymphoma patients is proposed.
3
UI - 11891176
AU - Gan YJ; Razzouk BI; Su T; Sixbey JW
TI -
A defective, rearranged Epstein-Barr virus genome in EBER-negative and
EBER-positive Hodgkin's disease.
SO - Am J Pathol 2002 Mar;160(3):781-6
AD - Department of Microbiology and Immunology, Louisiana State University
Health Sciences Center, Shreveport, Louisiana 71130, USA.
A ubiquitous herpesvirus that establishes life-long infection, the
Epstein-Barr virus (EBV) has yielded little insight into how a single
agent in general accord with its host can produce diverse pathologies
ranging from oral hairy leukoplakia to nasopharyngeal carcinoma, from
infectious mononucleosis to Hodgkin's disease (HD) and Burkitt's
lymphoma. Its pathogenesis is further confounded by the less than total
association of virus with histologically similar tumors. In other viral
systems, defective (interfering) viral genomes are known to modulate
outcome of infection, with either ameliorating or intensifying effects
on disease processes initiated by prototype strains. To ascertain
whether defective EBV genomes are present in HD, we examined
paraffin-embedded tissue from 56 HD cases whose EBV status was first
determined by cytohybridization for nonpolyadenylated EBV RNAs (EBERs).
Using both standard polymerase chain reaction (PCR) and PCR in situ
hybridization, we successfully amplified sequences that span abnormally
juxtaposed BamHI W and Z fragments characteristic of defective
heterogeneous (het) EBV DNA from 10 of 32 (31%) EBER-positive tumors. Of
24 EBER-negative HD, 8 yielded PCR products indicating presence of het
EBV DNA. Two of these contained defective EBV in the apparent absence of
the prototype virus. Of the 42 tumors analyzed for defective EBV by both
PCR techniques, there was concordance of results in 38 (90%). Detection
of defective EBV genomes with the potential to disrupt viral gene
regulation suggests one mechanism for pathogenic diversity that may also
account for loss of prototypic EBV from individual tumor cells.
4
UI - 11781645
AU - Blystad AK; Holte H; Kvaloy S; Smeland E; Delabie J; Kvalheim G
TI -
High-dose therapy in patients with Hodgkin's disease: the use of
selected CD34(+) cells is as safe as unmanipulated peripheral blood
progenitor cells.
SO - Bone Marrow Transplant 2001 Nov;28(9):849-57
AD - Department of Oncology, The Norwegian Radium Hospital, Oslo, Norway.
Register data suggest that patients with Hodgkin's disease (HD) given
high-dose therapy (HDT) with peripheral blood progenitor cells (PBPC)
have a less favourable prognosis as compared to those given bone marrow
as stem cell support. Since this can be due to infusion of tumour cells
contaminating the PBPC grafts, we initiated a feasibility study in which
PBPC grafts from HD patients were purged by CD34(+) cell enrichment.
Controversy exists about whether the use of CD34(+) enriched stem cells
leads to a delayed haematological and immune reconstitution. We compared
these parameters, including risk of infections and clinical outcome
after HDT, in patients with HD given either selected CD34(+) cells or
40 HD patients with primary refractory disease or relapse were treated
with HDT and supported with either selected CD34(+) cells (n = 21) or
unmanipulated PBPC (n = 19) as stem cell support. All patients had
chemosensitive disease at the time of transplantation. A median of 5.8
(range 2.7-20.0) vs 4.5 (range 2.3-17.6) x 10(6) CD34(+) cells per kilo
were reinfused in the CD34(+) group and PBPC group, respectively. No
difference was observed between the two groups with regard to time to
haematological engraftment, reconstitution of B cells, CD56(+) cells and
T cells at 3 and 12 months and infectious episodes after HDT. Two (5%)
treatment-related deaths, one in each group, were observed. The overall
survival at 4 years was 86% for the CD34(+)group and 74% for the PBPC
group with a median follow-up of 37 months (range 1-61) and 46 months
(range 4-82), respectively (P = 0.9). The results of this study
demonstrate that the use of CD34(+) cells is safe and has no adverse
effects either with respect to haematological, immune reconstitution or
to infections after HDT.
5
UI - 11781653
AU - Cornely OA; Pels H; Bethe U; Seibold M; Toepelt K; Soehngen D;
TI -
Ritzkowsky A
A novel type of metastatically spreading subcutaneous aspergillosis
without epidermal lesions following allogeneic stem cell
transplantation.
SO - Bone Marrow Transplant 2001 Nov;28(9):899-901
AD - Department I of Internal Medicine, Hematology, Oncology and Infectious
Diseases, University of Cologne, Cologne, Germany.
Systemic mycosis is among the most feared opportunistic infections in
the immunocompromised host. Difficulty and delay in diagnosis and
treatment often result in poor outcomes. In this communication a
metastatically spreading form of subcutaneous aspergillosis developed in
a patient with a history of allogeneic stem cell transplantation for
relapsed Hodgkin's lymphoma. Strikingly, necrotizing cutaneous papules
or ulcerating lesions were absent. Diagnosis was accomplished after
excision of a clinically non-suggestive subcutaneous nodule. Despite
prompt initiation of antimycotic therapy the outcome was fatal; dosage
of conventional and liposomal amphotericin B was limited due to
treatment-related toxicities. This case report describes a novel form of
aspergillosis and underlines the need for an aggressive diagnostic
approach in severely immunocompromised patients.
6
UI - 11870170
AU - Rassidakis GZ; Medeiros LJ; Viviani S; Bonfante V; Nadali GP;
TI -
Vassilakopoulos TP; Mesina O; Herling M; Angelopoulou MK; Giardini R;
Chilosi M; Kittas C; McLaughlin P; Rodriguez MA; Romaguera J; Bonadonna
G; Gianni AM; Pizzolo G; Pangalis GA; Cabanillas F; Sarris AH
CD20 expression in Hodgkin and Reed-Sternberg cells of classical
Hodgkin's disease: associations with presenting features and clinical
outcome.
SO - J Clin Oncol 2002 Mar 1;20(5):1278-87
AD - Department of Lymphoma-Myeloma, The University of Texas M.D. Anderson
Cancer Center, Houston, TX 77030, USA.
PURPOSE: CD20 can be expressed in Hodgkin and Reed-Sternberg (HRS) cells
of classical Hodgkin's disease (HD), but its clinical significance
remains controversial. Therefore, we correlated CD20 expression with
presenting features and clinical outcome of untreated patients with
classical HD. PATIENTS AND METHODS: Patients were eligible if they were
previously untreated and human immunodeficiency virus-1 negative, had
biopsy-proven classical HD, and if pretreatment paraffin-embedded tumor
tissue was available. CD20 expression was determined by
immunohistochemistry without knowledge of clinical outcome. A tumor was
considered positive if any HRS cells expressed CD20, but other cutoffs
for number of CD20-positive HRS were also investigated. RESULTS: We
identified 598 patients whose median age was 30 years and of whom 55%
were male. HRS cells expressed CD20 in 132 (22%) of 598 patients with
classical HD. When any percentage of CD20 expression in HRS cells was
used as a cutoff, the 5-year failure-free survival (FFS) for positive
versus negative tumors was 86% versus 84%, respectively, for 302
patients treated with doxorubicin, bleomycin, vinblastine, and
dacarbazine or equivalent regimens (P =.7 by log-rank test), 74% versus
77%, respectively, for 181 patients treated with mitoxantrone,
vincristine, vinblastine, and prednisone and radiotherapy (P =.7 by
log-rank test), 74% versus 84%, respectively, for 54 patients treated
with MOPP (P =.4 by log-rank test), and 77% versus 88% for 53 patients
treated only with radiotherapy (P =.5 by log-rank test). The 5-year FFS
was not statistically different when cutoffs of 5% up to 50% for
CD20-positive HRS cells were used. CONCLUSION: CD20 is expressed by HRS
cells in 22% of patients with classical HD but is not associated with
different FFS after treatment with equivalent regimens.
7
UI - 11920535
AU - Wilder RB; Schlembach PJ; Jones D; Chronowski GM; Ha CS; Younes A;
TI -
Hagemeister FB; Barista I; Cabanillas F; Cox JD
European Organization for Research and Treatment of Cancer and Groupe
d'Etude des Lymphomes de l'Adulte very favorable and favorable,
lymphocyte-predominant Hodgkin disease.
SO - Cancer 2002 Mar 15;94(6):1731-8
AD - Department of Radiation Oncology, The University of Texas M.D. Anderson
Cancer Center, Houston, Texas 77030-4009, USA. rwilder@mdanderson.org
BACKGROUND: Lymphocyte-predominant Hodgkin disease (LPHD) is rare and
has a natural history different from that of classic Hodgkin disease.
There is little information in the literature regarding the role of
chemotherapy in patients with early-stage LPHD. The objective of this
study was to examine recurrence free survival (RFS), overall survival
(OS), and patterns of first recurrence in patients with LPHD who were
treated with radiotherapy alone or with chemotherapy followed by
radiotherapy. METHODS: From 1963 to 1996, 48 consecutive patients ages
16-49 years (median, 28 years) with Ann Arbor Stage I (n = 30 patients)
or Stage II (n = 18 patients), very favorable (VF; n = 5 patients) or
favorable (F; n = 43 patients) LPHD, according to the European
Organization for Research and Treatment of Cancer and Groupe d'Etude des
Lymphomes de l'Adulte (EORTC-GELA) criteria, received radiotherapy alone
(n = 37 patients) or received chemotherapy followed by radiotherapy (n =
11 patients). The percentages of patients with VF disease (11% vs. 9% in
the radiotherapy group vs. the chemotherapy plus radiotherapy group,
respectively) or F disease (89% vs. 91%, respectively) within the two
treatment groups were similar (P = 1.00). A median of three cycles of
chemotherapy with mechlorethamine, vincristine, procarbazine, and
prednisone (MOPP) or with mitoxantrone, vincristine, vinblastine, and
prednisone (NOVP) was given initially to six patients and five patients,
respectively. A median total radiotherapy dose of 40 grays (Gy) given in
daily fractions of 2.0 Gy was delivered to both treatment groups.
RESULTS: The median follow-up was 9.3 years, and 98% of patients were
observed for > or = 3.0 years. RFS was similar for patients who were
treated with radiotherapy alone and patients who were treated with
chemotherapy followed by radiotherapy (10-year survival rates: 77% and
68%, respectively; P = 0.89). The OS rate also was similar for the two
groups (10-year survival rates: 90% and 100%, respectively; P = 0.43).
MOPP or NOVP chemotherapy did not reduce the risk of recurrence outside
of the radiotherapy fields. CONCLUSIONS: MOPP or NOVP chemotherapy did
not improve RFS or OS significantly in patients with VF or F LPHD,
although the statistical power was limited. Ongoing clinical trials will
help to clarify the role of a watch-and-wait strategy or systemic
therapy, including anthracycline (epirubicin or doxorubicin), bleomycin,
and vinblastine-based chemotherapy or antibody-based approaches, in the
treatment of these patients. Copyright 2002 American Cancer Society.
8
UI - 11920510
AU - Wang J; Weiss LM; Chang KL; Slovak ML; Gaal K; Forman SJ; Arber DA
TI -
Diagnostic utility of bilateral bone marrow examination: significance of
morphologic and ancillary technique study in malignant.
SO - Cancer 2002 Mar 1;94(5):1522-31
AD - Division of Pathology, City of Hope National Medical Center, Duarte,
California 91010, USA.
BACKGROUND: To retrospectively evaluate the significance of morphologic
examination and ancillary studies performed on bilateral bone marrow
biopsy specimens, 1864 bone marrow samples were studied. METHODS:
Bilateral bone marrow biopsy specimens included 883 specimens that were
evaluated for involvement by non-Hodgkin lymphoma (NHL); 381 specimens
that were evaluated for involvement by carcinoma (CA); 362 specimens
that were evaluated for involvement by Hodgkin disease (HD); 94
specimens that were evaluated for involvement by sarcoma (SA); 56
specimens that were evaluated for involvement by multiple myeloma (MM);
53 specimens that were evaluated for involvement by acute and chronic
leukemia, myelodysplasia, and/or myeloproliferative disorders (LEUK);
and 35 specimens that were evaluated for other reasons. RESULTS: Of all
1864 specimens, 410 samples (22.0%) were positive for disease, including
77% of MM samples, 58% of LEUK samples, 29.6% of NHL samples, 14% of SA
samples, 9.9% of HD samples, and 6.8% of CA samples. A discrepancy
between the left and right sides was identified in 48 specimens (11.7%
of positive samples). The discrepancy rate was 39% for HD samples, 29%
for SA samples, 23% for CA samples, and 9.2% for NHL samples. No
morphologic discrepancies between bilateral samples were found in MM
samples or LEUK samples. Bilateral flow cytometric studies (n = 113
samples) were positive in 11 samples (9.7%; all morphologically
positive), with two discrepancies detected between bilateral samples.
Bilateral cytogenetic studies (n = 74 samples) were positive in 5
samples (7%), and there were no discrepancies. Bilateral molecular
studies (n = 16 samples) were positive in 7 samples (44%), and there
were 3 discrepancies. CONCLUSIONS: Bilateral morphologic evaluation is
useful in the evaluation of patients with NHL, HD, CA, and SA and is not
indicated for patients with acute or chronic leukemia, myelodysplasia,
MM, and other diseases. Bilateral flow cytometric or cytogenetic studies
of bone marrow did not provide additional information in this population
to justify bilateral samples. The role of bilateral molecular analysis
needs to be defined further, but pooled samples for molecular studies
may be adequate. Copyright 2002 American Cancer Society.
9
UI - 11912994
AU - Kramer K; O'Brien A
TI -
Progressive wheeze, dry cough: what lies beneath? Hodgkin's disease.
SO - Postgrad Med 2002 Mar;111(3):101-2, 105
AD - Division of Pulmonary and Critical Care Medicine, Veterans Affairs
Medical Center and Rhode Island Hospital, Providence, USA.
10
UI - 11601135
AU - Ohno T; Huang JZ; Wu G; Park KH; Weisenburger DD; Chan WC
TI -
The tumor cells in nodular lymphocyte-predominant Hodgkin disease are
clonally related to the large cell lymphoma occurring in the same
individual. Direct demonstration by single cell analysis.
SO - Am J Clin Pathol 2001 Oct;116(4):506-11
AD - Department of Pathology and Microbiology, University of Nebraska Medical
Center, Omaha, NE 68198-3135, USA.
Large cell lymphoma (LCL) sometimes occurs concurrently or subsequently
in patients with nodular lymphocyte-predominant Hodgkin disease (NLPHD).
Although there is evidence of a clonal relationship between LCL and
NLPHD, there has been no direct demonstration that the lymphocytic and
histiocytic (L&H) cells in NLPHD are related to the tumor cells in LCL.
We identified 2 cases of NLPHD with an associated LCL. Single L&H cells,
the Reed-Sternberg cell variants in NLPHD, were isolated from
immunostained tissue sections by micromanipulation, and the
immunoglobulin heavy chain gene (IgH) complementarity determining region
(CDR) III of the cells was amplified by the polymerase chain reaction
(PCR). The products were compared with those obtained from
microdissected LCL cells using polyacrylamide gel electrophoresis and
nucleotide sequencing. The IgH CDRIII sequences from the L&H cells were
related to each other, but also showed nucleotide substitutions,
consistent with a germinal center origin. The sequences from the L&H
cells also were related to those from the corresponding LCL cells. We
have provided direct evidence through sequence analysis of the IgH
CDRIII that the L&H cells are clonally related to the corresponding LCL
arising in 2 cases of NLPHD.
11
UI - 11911042
AU - Yang CM; Yang YH; Lin YT; Lu MY; Chiang BL
TI -
Natural killer cell deficiency associated with Hodgkin's lymphoma: a
case report.
SO - J Formos Med Assoc 2002 Jan;101(1):73-5
AD - Department of Pediatrics, National Taiwan University Hospital, 7 Chung
Shan South Road, Taipei, Taiwan.
Natural killer (NK) cells are large granular lymphocytes that play
important roles in immunity against viral infection. NK cell deficiency
is associated with recurrent episodes of severe herpes group virus
reactivation. Few cases of NK cell deficiency have been reported. Here,
we report the case of a Taiwanese girl who had suffered from severe
atopic dermatitis since infancy, and recurrent episodes of herpes virus
reactivation since the age of 3 years old. NK cell deficiency was
diagnosed based on the finding of persistently low NK cell counts in
peripheral blood. Hodgkin's lymphoma developed when she was 6 years old.
The present case suggests that NK cell deficiency may be an important
risk factor in the development of Hodgkin's lymphoma.
12
UI - 11122844
AU - Weiss LM
TI -
Epstein-Barr virus and Hodgkin's disease.
SO - Curr Oncol Rep 2000 Mar;2(2):199-204
AD - City of Hope National Medical Center, 1500 East Duarte Road, Duarte, CA
91010, USA. lweiss@coh.org
Approximately 40% to 50% of cases of Hodgkin's disease occurring in
Western populations are associated with the Epstein-Barr virus (EBV). In
these cases, EBV is found in the neoplastic elements, the Reed-Sternberg
and Hodgkin's cells. EBV is probably not present in all cases, but
neither have any other viruses been found in the cases that are
EBV-negative. EBV may play a role in the pathogenesis of Hodgkin's
disease by the activation of anti-apoptotic factors in a premalignant
germinal center B-lymphocyte. Regardless of their role in etiology or
pathogenesis, EBV-latent antigens may represent a target for possible
immune therapy.
13
UI - 11920454
AU - Kostakoglu L; Leonard JP; Kuji I; Coleman M; Vallabhajosula S; Goldsmith
TI -
SJ
Comparison of fluorine-18 fluorodeoxyglucose positron emission
tomography and Ga-67 scintigraphy in evaluation of lymphoma.
SO - Cancer 2002 Feb 15;94(4):879-88
AD - Division of Nuclear Medicine, Department of Radiology, Weill Medical
College of Cornell University, New York, New York 10021, USA.
lak2005@columbia.edu
BACKGROUND: The accuracy of fluorodeoxyglucose positron emission
tomography (FDG-PET; dual-head camera with attenuation correction) and
Ga-67 scintigraphy was compared to identify disease sites in patients
with Hodgkin disease (HD) and intermediate and high-grade non-Hodgkin
lymphoma (NHL) at initial diagnosis or clinical recurrence. METHODS:
Fifty-one contemporaneous FDG-PET and Ga-67 scintigraphies were
performed on patients with NHL (35 intermediate grade, 3 high grade) or
HD (13 patients). Sites of disease were correlated on a site-by-site
basis on FDG-PET and Ga-67 images. Tumor-to-background (T/B) ratios were
obtained for both techniques. Discordant FDG-PET and Ga-67 findings were
correlated with computed tomography findings or clinical evaluation
including repeat FDG-PET scans obtained after therapy. RESULTS:
Fluorodeoxyglucose positron emission tomography was positive at all 158
sites in 51 patients compared with 113 sites in 41 positive studies with
Ga-67 scintigraphy (single positron emission computed tomography [SPECT]
and/or planar images). In 44 patients who had complete Ga-67 SPECT data
on all tumor sites, FDG-PET was positive at 126 sites and Ga-67 SPECT
was positive at 81 sites. Ga-67 SPECT failed to demonstrate disease at
45 sites (35.7%). In 10 of 44 patients, Ga-67 SPECT completely failed to
detect any disease at 22 of 45 sites (17.5%) and partially identified
disease sites at 23 of 45 sites (18.2%) in 11 patients regardless of the
tumor site and histology. In these patients, the lesions measured
between 0.6 and 14.0 cm by CT. Fluorodeoxyglucose positron emission
tomography revealed higher stage disease in 13 patients compared with
Ga-67 imaging. Tumor-to-background ratios were statistically different
between the two techniques with higher ratios obtained with FDG-PET (P <
0.0001). CONCLUSIONS: In imaging aggressive lymphoma and HD before
therapy, FDG-PET has significantly higher site and patient sensitivity
than Ga-67 scintigraphy (100% vs. 71.5% and 100% vs. 80.3%,
respectively). The change in disease stage by FDG-PET may result in a
change in therapy strategy. Copyright 2002 American Cancer Society. DOI
10.1002/cncr.10336
14
UI - 11807629
AU - Sevilla J; Rodriguez A; Hernandez-Maraver D; de Bustos G; Aguado J;
TI -
Ojeda E; Arrieta R; Hernandez-Navarro F
Secondary acute myeloid leukemia and myelodysplasia after autologous
peripheral blood progenitor cell transplantation.
SO - Ann Hematol 2002 Jan;81(1):11-5
AD - Banco de Sangre, Hospital Nino Jesus, Av/Menendez Pelayo 65, Madrid
28009, Spain. jsevilla@hnjs.insalud.es
Secondary myelodysplastic syndrome (MDS) and acute leukemia (AL) are
well-known complications of antineoplastic therapy. The incidence of
these serious complications after autologous hematopoietic
transplantation ranges from 1.1% to 24%. Prior chemotherapy is its most
likely cause, but other variables related to these long-term
complications are seriously discussed. There is evidence that priming of
progenitor cells isolated from peripheral blood with chemotherapy is
also related to a higher risk of secondary MDS/AL. Whether progenitor
cells isolated from bone marrow or peripheral blood after mobilization
only with cytokines are related to higher risk is a controversial issue.
In this paper, we analyze the incidence and variables related to these
complications in a series of 99 patients diagnosed with lymphoma or
multiple myeloma who underwent autologous transplantation using
hematopoietic progenitors isolated from peripheral blood mobilized with
granulocyte colony-stimulating factor (G-CSF). The probability of MDS/AL
in patients alive 5 years after transplant in our series is 8.58%,
similar to that reported in other series using bone marrow grafts. The
total dose of cyclophosphamide ( p=0.099), the number of chemotherapy
cycles ( p=0.04) received before transplant, and the total dose of
mononuclear cells infused at the time of transplant were the only
variables associated with secondary MDS/AL. Autologous transplantation
with progenitor cells isolated from peripheral blood after mobilization
with cytokines has probability and risk factors for secondary MDS/AL
development similar to bone marrow grafts when compared with other
published series.
15
UI - 11807631
AU - Weihrauch MR; Re D; Bischoff S; Dietlein M; Scheidhauer K; Krug B;
TI -
Textoris F; Ansen S; Franklin J; Bohlen H; Wolf J; Schicha H; Diehl V;
Tesch H
Whole-body positron emission tomography using 18F-fluorodeoxyglucose for
initial staging of patients with Hodgkin's disease.
SO - Ann Hematol 2002 Jan;81(1):20-5
AD - Department of Internal Medicine I, University of Cologne,
Immunologisches Labor Haus 16, Joseph-Stelzmann-Str. 9, 50924 Cologne,
Germany. martin.weihrauch@uni-koeln.de
An accurate initial staging of patients with Hodgkin's disease (HD) is
important for the evaluation of clinical stage and risk factors, which
are crucial for the choice of an appropriate treatment.
18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is
useful for detecting active tumor tissue in patients with
lymphoproliferative diseases and may contribute to conventional staging
methods in patients with HD. Twenty-two patients who presented with
newly diagnosed HD underwent conventional staging methods including
computed tomography (CT) as well as FDG PET. Lesions apparent in FDG PET
and CT were correlated to each other. Seventy-seven lesions were
observed either in PET or CT or in both. In 48 (62%) lesions PET and CT
were both positive. In 20 (26%) sites, PET was positive and CT negative.
Of 22 patients (18%) 4 were upstaged due to these positive PET findings,
and as a result one patient received a different therapeutic regimen.
PET failed to detect nine (12%) CT-positive sites in six patients.
Statistically, these data are reflected by a sensitivity for PET and CT
of 88% and 74%, respectively. Specificity of both imaging modalities was
100%. PET can contribute valuable information as an additional staging
examination and led to an upstaging in some patients with primary HD.
However, PET should not be used as the only imaging modality as it
failed to detect CT-positive, active tumor regions in some cases.
16
UI - 11807639
AU - Komurcu S; Ozet A; Altundag MK; Arpaci F; Ozturk B; Celasun B; Tezcan Y
TI -
Vanishing bile duct syndrome occurring after high-dose chemotherapy and
autologous peripheral stem cell transplantation in a patient with
Hodgkin's disease.
SO - Ann Hematol 2002 Jan;81(1):57-8
17
UI - 11907792
AU - Robin V; Lebacq J; Michaux L; Ferrant A
TI -
Hodgkin's disease and hypothermia: case report and review of the
literature.
SO - Ann Hematol 2002 Feb;81(2):106-7
AD - Cliniques Universitaires Saint-Luc, Service d'Hematologie, Avenue
Hippocrate 10, 1200 Bruxelles, Belgium. ferrant@sang.ucl.ac.be
We report the development of hypothermia following induction
chemotherapy in a patient with stage IV Hodgkin's disease, fever, and
hypotension. A link between hypothermia, hypotension, and sensory
neuropathy is possible. Acute autonomic neuropathy is the suggested
cause.
18
UI - 11907790
AU - Hanel M; Kroger N; Sonnenberg S; Bornhauser M; Kruger W; Kroschinsky F;
TI -
Hanel A; Metzner B; Birkmann J; Schmid B; Hoffknecht MM; Fiedler F;
Ehninger G; Zander AR
Busulfan, cyclophosphamide, and etoposide as high-dose conditioning
regimen in patients with malignant lymphoma.
SO - Ann Hematol 2002 Feb;81(2):96-102
AD - Medical Clinic and Policlinic I, University Hospital Carl Gustav Carus,
Dresden, Germany.
We investigated the efficacy and toxicity of the combination of
busulfan, cyclophosphamide, and etoposide (Bu/Cy/VP-16) as a preparative
regimen prior to autologous hematopoietic stem cell transplantation
(ASCT) in patients with Hodgkin's disease (HD) or non-Hodgkin's lymphoma
(NHL). Fifty-three patients with recurrent ( n=30), refractory ( n=20),
or high-risk ( n=3) lymphoma were enrolled. The 10 patients with HD and
43 with NHL (median age: 46 years, range: 18-64) received busulfan (16
mg/kg), cyclophosphamide (120 mg/kg), and etoposide (30 or 45 mg/kg)
followed by ASCT. A total of 50 patients (94%) were consolidated in
complete ( n=25) or partial ( n=25) remission, whereas 3 patients had
chemoresistant disease before Bu/Cy/VP-16. Thirty-five patients (66%)
had received prior radiotherapy (RT) excluding total body irradiation
(TBI) as part of the conditioning regimen. The main nonhematological
toxicities (grade II-IV according to the Bearman score) in 52 evaluable
patients were mucositis (79%) and hepatic toxicity (15%). Severe
veno-occlusive disease (VOD) occurred in three patients (5.8%) including
one treatment-related death caused by VOD. Overall, treatment-related
mortality was 3.8%. After a median follow-up for surviving patients of
21 months (range: 6-118), 20 patients (38%) are in continuous complete
remission, 8 patients (15%) are alive in relapse, and 25 patients (47%)
died. Probabilities of relapse, event-free survival, and overall
survival at 3 years were 63% [95% confidence interval (CI): 48-79%], 31%
(95% CI: 17-46%), and 43% (95% CI: 27-59%), respectively. In conclusion,
Bu/Cy/VP-16 is an effective and well-tolerated conditioning regimen in
patients with HD and NHL. Both toxicity and outcome were not
significantly different in patients treated with 30 mg/kg and 45 mg/kg
etoposide, respectively. The observed long-term results are even
comparable to those published for other established high-dose protocols,
including TBI-based regimens. However, further investigations are
necessary to evaluate the value of Bu/Cy/VP-16 as a high-dose protocol
for malignant lymphoma, especially in patients who have already received
extensive RT.
19
UI - 11745901
AU - Donfrancesco A; Ilari I; Miano C
TI -
Sternal lesions in children.
SO - Med Pediatr Oncol 2001 Dec;37(6):558
20
UI - 11133768
AU - Skinnider BF; Elia AJ; Gascoyne RD; Trumper LH; von Bonin F; Kapp U;
TI -
Patterson B; Snow BE; Mak TW
Interleukin 13 and interleukin 13 receptor are frequently expressed by
Hodgkin and Reed-Sternberg cells of Hodgkin lymphoma.
SO - Blood 2001 Jan 1;97(1):250-5
AD - Amgen Institute, Ontario Cancer Institute, the Department of Medical
Biophysics, University of Toronto, Ontario, Canada.
Hodgkin lymphoma (HL) is characterized by the abnormal expression of
multiple cytokines, accounting for its unique clinicopathologic
features. We have previously shown that interleukin-13 (IL-13) is
secreted by HL cell lines and may serve as an autocrine growth factor.
To determine the frequency of IL-13 expression in lymphoma patients,
tissue sections from 36 patients with classical HL, 5 patients with
nodular lymphocyte predominance HL (NLPHL), and 23 patients with
non-Hodgkin lymphoma (NHL) were subjected to in situ hybridization. In
31 of 36 cases (86%) of classical HL patients of all histologic
subtypes, between 25% to almost 100% of Hodgkin and Reed Sternberg (HRS)
cells were positive for IL-13 expression. In contrast, in no case of
NLPHL and in only 4 of 23 NHL cases (1 of 5 T-cell-rich B-cell
lymphomas, 2 of 5 anaplastic large cell lymphomas, and 1 of 5 peripheral
T-cell lymphomas) did the neoplastic cells express IL-13. The expression
of the IL-13 receptor chain alpha1 (IL-13Ralpha1) was also analyzed by
in situ hybridization. In 24 of 27 (89%) cases of classical HL, between
25% to 75% of HRS cells, as well as a high frequency of lymphocytes and
histiocytes, were positive for IL-13Ralpha1 expression. These results
were confirmed by the construction of complementary DNA libraries from
single HRS cells, followed by polymerase chain reaction analysis, in
which IL-13Ralpha1 transcripts were found to be present in all 6 cases
of HL. These data indicate that expression of IL-13 and IL-13Ralpha1 is
a common feature of HRS cells in HL, consistent with the hypothesis that
IL-13 may play a role in autocrine growth in classical HL.
21
UI - 11697338
AU - Fiumara P; Cabanillas F; Younes A
TI -
Interleukin-13 levels in serum from patients with Hodgkin disease and
healthy volunteers.
SO - Blood 2001 Nov 1;98(9):2877-8
22
UI - 10515679
AU - Barth S; Matthey B; Huhn M; Diehl V; Engert A
TI -
CD30L-ETA': a new recombinant immunotoxin based on the CD30 ligand for
possible use against human lymphoma.
SO - Cytokines Cell Mol Ther 1999 Jun;5(2):69-78
AD - Medizinische Klinik I de Universitat zu Koln, Cologne, Germany.
Recombinant DNA technology makes it possible to genetically fuse V genes
or cytokines to toxin domains, resulting in immunotherapeutics for
selective destruction of tumor cells. Since recombinant immunotoxins can
be easily manipulated in terms of affinity or cytotoxic potency and
produced in large quantities, we have developed a new CD30 ligand-based
fusion toxin (CD30L-ETA'). Human CD30L cDNA was ligated into a pET-based
expression plasmid and thereby fused to a modified Pseudomonas
aeruginosa exotoxin A (ETA') lacking its cell-binding domain I. After
IPTG-indiced expression in E. coli strain BL21(DE3), the 60 kDa
His-tagged fusion protein (CD30L-ETA') was isolated from inclusion
bodies. Denatured protein was renatured in the presence of 0.4 M
arginine and a glutathione redox system. Refolded protein was purified
and concentrated by ion-exchange chromatography on a HiTrap Q column.
The binding properties of CD30L-ETA' were evaluated by competitive
ELISA, immunohistochemical staining, and FACS analysis on
CD30-expressing cells. The in vitro toxicity of the fusion protein was
then tested on the CD30+ Hodgkin-derived cell line L540cy and the
Burkitt's lymphoma cell line BL38. CD30L-ETA' exhibited specific
cytotoxicity against L540cy cells (IC50 = 24 ng/ml) as determined by
[3H]leucine uptake assays. This is the first report on the specificity
and cytotoxic potency of a chimeric CD30L fusion toxin against Hodgkin's
disease-derived cells.
23
UI - 10971392
AU - Bolognesi A; Polito L; Tazzari PL; Lemoli RM; Lubelli C; Fogli M; Boon
TI -
L; de Boer M; Stirpe F
In vitro anti-tumour activity of anti-CD80 and anti-CD86 immunotoxins
containing type 1 ribosome-inactivating proteins.
SO - Br J Haematol 2000 Aug;110(2):351-61
AD - Dipartimento di Patologia Sperimentale and Istituto di Ematologia e
Oncologia medica 'L. & A. Seragnoli', Universita di Bologna, Bologna,
Italy. bolo@alma.unibo.it
Immunotoxins specific for the CD80 and CD86 antigens were prepared by
linking three type 1 ribosome-inactivating proteins (RIPs), namely
bouganin, gelonin and saporin-S6, to the monoclonal antibodies M24
(anti-CD80) and 1G10 (anti-CD86). These immunotoxins showed a specific
cytotoxicity for the CD80/CD86-expressing cell lines Raji and L428. The
immunotoxins inhibited protein synthesis by target cells with IC50s
(concentration causing 50% inhibition) ranging from 0.25 to 192 pmol/l
as RIPs. The anti-CD80 immunotoxins appeared 1-2 log more toxic for
target cells than the anti-CD86 ones. Immunotoxins containing saporin
and bouganin induced apoptosis of target cells. The toxicity for bone
marrow haemopoietic progenitors of these conjugates was also evaluated.
Bouganin and related immunotoxins at concentrations up to 100 nmol/l did
not significantly affect the recovery of committed progenitors or of
more primitive cells. The saporin-containing immunotoxins at
concentrations >/= 1 nmol/l showed some toxicity on colony-forming unit
cells (CFU-C). The expression of the CD80 and CD86 molecules is
prevalently restricted to antigen-presenting cells and is also strong on
Hodgkin and Reed-Sternberg cells in Hodgkin's disease. Present results
suggest that immunotoxins targeting type 1 ribosome-inactivating
proteins to these antigens could be considered and further studied for
the therapy of Hodgkin's disease or other CD80/CD86-expressing tumours.
24
UI - 11378550
AU - Ohshima K; Sugihara M; Haraoka S; Suzumiya J; Kanda M; Kawasaki C;
TI -
Shimazaki K; Kikuchi M
Possible immortalization of Hodgkin and Reed-Sternberg cells: telomerase
expression, lengthening of telomere, and inhibition of apoptosis by
NF-kappaB expression.
SO - Leuk Lymphoma 2001 Apr;41(3-4):367-76
AD - Department of Pathology, School of Medicine, Fukuoka University,
Fukuoka, Japan.
Telomerase, an enzyme associated with cellular immortality, is expressed
on malignant tumor cells. Deregulation of telomerase is thought to
facilitate tumorigenesis and cellular immortality by providing cancer
cells with unlimited proliferation capacity. Hodgkin and Reed-Sternberg
(H&RS) cells are generally considered as neoplastic cells in Hodgkin's
disease (HD), however, such cells are only found in a minority of HD
lesions. In addition, H&RS cells with mitotic features are rare and
mummified forms are occasionally encountered. There are no available
data on the relationship between telomerase activity and apoptosis in
HD. We studied 14 cases with Hodgkin's disease (mixed cellularity type,
nine cases; nodular sclerosis type, five cases) to clarify the
relationship between telomerase activity and apoptosis using in situ
hybridization of human telomerase reverse transcriptase (hTERT), reverse
transcriptase-polymerase chain reaction (RT-PCR) of hTERT, using
extracted RNA and immunohistochemistry of nuclear factor-?B (NF-?B), and
TdT-mediated dUTP-digoxigenin nick end-labeling (TUNEL) technique for
apoptosis. We also analyzed the telomere length, using sorted H&RS
cells. TUNEL showed a few apoptotic H&RS cells, but the cells frequently
expressed hTERT, as confirmed by ISH and RT-PCR. Lengthening of the
telomere of H&RS cells was noted in ten cases. In addition, H&RS cells
frequently expressed NF-?B, which is known as an inducible transcription
factor and inhibitor of apoptosis. Our findings of telomerase activity
in H&RS cells indicate that these cells are neoplastic and are
potentially immortal. In addition, NF-?B expression on H&RS cells
suggests its possibility in inhibition of apoptosis of these cells.
25
UI - 11675352
AU - Fiumara P; Snell V; Li Y; Mukhopadhyay A; Younes M; Gillenwater AM;
TI -
Cabanillas F; Aggarwal BB; Younes A
Functional expression of receptor activator of nuclear factor kappaB in
Hodgkin disease cell lines.
SO - Blood 2001 Nov 1;98(9):2784-90
AD - Department of Lymphoma and Myeloma, Head and Neck Surgery, and
Bioimmunotherapy, University of Texas M. D. Anderson Cancer Center,
Houston, TX 77030, USA.
The malignant Hodgkin and Reed-Sternberg (H/RS) cells of Hodgkin disease
(HD) express several members of the tumor necrosis factor (TNF) receptor
family, including CD30 and CD40, and secrete several cytokines and
chemokines. However, little is known about what regulates cytokine and
chemokine secretion in H/RS cells. Although H/RS cells are predominantly
of B-cell origin, they frequently share phenotypic and functional
features with dendritic cells (DCs). Previous studies reported that
receptor activator of nuclear factor kappaB (NF-kappaB) (RANK), a member
of the TNF receptor family, is expressed on DCs, and that RANK ligand
(RANKL) enhances DC survival and induces them to secrete cytokines. This
study reports that, similar to DCs, cultured H/RS cells expressed RANK.
However, unlike DCs, H/RS cells also expressed RANKL. Soluble RANKL
activated NF-kappaB and induced messenger RNA expression of
interferon-gamma, interleukin-8 (IL-8), IL-13, IL-9, IL-15, and RANTES,
in addition to the receptors for IL-9, IL-13, IL-15, and CCR4. RANKL
increased IL-8 and IL-13 levels in the supernatants of H/RS cell lines,
an effect that was blocked by soluble RANK. Furthermore, soluble RANK
decreased the basal level of IL-8 in one cell line, suggesting that IL-8
was induced by an autocrine RANKL/RANK loop. RANKL had no effect on H/RS
cell survival in culture, and it did not modulate the expression of
bcl-2, bcl-xL, bax, or inhibitors of apoptosis proteins. These data
provide evidence of further functional similarities between DCs and H/RS
cells. The coexpression of RANK and RANKL in H/RS cells suggests that
they may regulate cytokine and chemokine secretion in H/RS cells by an
autocrine mechanism.
26
UI - 11924013
AU - De Greslan T; Coste S; Ferreira A; Renard JL; Bequet D; Felten D
TI -
[Radicular pain revealing Hodgkin's disease]
SO - Rev Neurol (Paris) 2001 Nov;157(11 Pt 1):1430-2
AD - Service de Neurologie, Hopital du Val-de-Grace, Paris.
We report on a case of Hodgkin's disease, revealed in a 52 year-old
woman by isolated neurological signs. Sciatica is an uncommon pattern of
discovery that is particularly misleading. It may lead to a delayed
diagnosis all the more prejudicial since it discloses an advanced stage
of the disease. The neurological involvement is always associated with a
bone lesion. This latter can be discovered at an early stage through
magnetic resonance imaging.
27
UI - 11886375
AU - Pilatrino C; Cataldi A; Guerrasio A; Saglio G
TI -
Renal Hodgkin's disease.
SO - Br J Haematol 2002 Mar;116(4):732
AD - Ospedale S Luigi Gonzaga, University of Turin, Italy.
28
UI - 11886379
AU - Sjoberg J; Andersson M; Garcia C; Palucka KA; Bjorkholm M;
TI -
Porwit-MacDonald A; Pisa P
Expression of the signal transduction molecule zeta in peripheral and
tumour-associated lymphocytes in Hodgkin's disease in relation to the
Epstein-Barr virus status of the tumour cells.
SO - Br J Haematol 2002 Mar;116(4):765-73
AD - Department of Medicine, Pathology and Oncology, Radiumhemmet, Karolinska
Hospital, Karolinska Institutet, Stockholm, Sweden. jan.sjoberg@ks.se
We investigated whether the described immune evasion of Epstein-Barr
virus (EBV)-infected malignant Hodgkin and Reed-Sternberg (HRS) cells in
Hodgkin's disease (HD) is paralleled by a disturbed expression of the
signal transduction molecule zeta associated with CD3 and CD16 in
tumour-associated T lymphocytes (TAL). Flow cytometric analysis revealed
a significantly lower zeta expression in CD3+/4+, CD3+/8+ and CD16+
patient peripheral blood lymphocytes (PBL; n = 10) compared with normal
donor PBLs (n = 11). When patient PBLs were compared with the
corresponding TAL, the latter showed a significantly higher (CD3+/4+) or
equal (CD3+/8+) zeta expression. The EBV status of the tumours did not
correlate with zeta expression in the TAL. Immunohistochemical staining
revealed zeta-positive lymphocytes among the adjacent bystander cells of
the HRS cells in all analysed tumours (n = 8), irrespective of tumour
EBV status. In conclusion, these results do not support downregulation
of zeta in TAL as a critical mechanism contributing specifically to the
immune escape of EBV+ HRS cells.
29
UI - 11883035
AU - Vetter C
TI -
[High healing chances in Hodgkin disease, but: now health insurance is
turning off the money faucet]
SO - MMW Fortschr Med 2002 Jan 31;144(5):4-6
30
UI - 11883038
AU - Diehl V
TI -
[Interview with Professor Dr. Volker Diehl, Cologne. Hodgkin disease: on
the path to causal therapy? (interview by Christine Vetter)]
SO - MMW Fortschr Med 2002 Jan 31;144(5):8
31
UI - 11896065
AU - Pileri SA; Ascani S; Leoncini L; Sabattini E; Zinzani PL; Piccaluga PP;
TI -
Pileri A Jr; Giunti M; Falini B; Bolis GB; Stein H
Hodgkin's lymphoma: the pathologist's viewpoint.
SO - J Clin Pathol 2002 Mar;55(3):162-76
AD - Pathologic Anatomy and Haematopathology, Bologna University, Policlinico
S. Orsola, Via Massarenti 9, 40138 Bologna, Italy.
pileri@almadns.unibo.it
Despite its well known histological and clinical features, Hodgkin's
lymphoma (HL) has recently been the object of intense research activity,
leading to a better understanding of its phenotype, molecular
characteristics, histogenesis, and possible mechanisms of
lymphomagenesis. There is complete consensus on the B cell derivation of
the tumour in most cases, and on the relevance of Epstein-Barr virus
infection and defective cytokinesis in at least a proportion of
patients. The REAL/WHO classification recognises a basic distinction
between lymphocyte predominance HL (LP-HL) and classic HL (CHL),
reflecting the differences in clinical presentation and behaviour,
morphology, phenotype, and molecular features. CHL has been classified
into four subtypes: lymphocyte rich, nodular sclerosing, with mixed
cellularity, and lymphocyte depleted. The borders between CHL and
anaplastic large cell lymphoma have become sharper, whereas those
between LP-HL and T cell rich B
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