New Aspects in the Diagnosis and Treatment of Hodgkin’s Disease

286 Pages·1989·5.927 MB·English

by  D. H. Wright (auth.), Professor Dr. med. Volker Diehl, Professor Dr. med. Michael Pfreundschuh, Dr. med. Dipl. Phys. Markus Loeffler (eds.)

Recent Results 117
in Cancer Research
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v.
Diehl M. Pfreundschuh
M. Loeffler (Eds.)
New Aspects in the
Diagnosis and Treatment
of Hodgkin's Disease
With 71 Figures and 91 Tables
Springer-Verlag Berlin Heidelberg New York
London Paris Tokyo Hong Kong
Professor Dr. med. Volker Diehl
Professor Dr. med. Michael Pfreundschuh
Dr. med. Dip!. Phys. Markus Loeffler
I. Medizinische UniversiUitsklinik Kaln
loseph-Stelzmann-Stra13e 9, 5000 Kaln 41, FRG
ISBN-13: 978-3-642-83783-8 e-ISBN-13 :978-3-642-83781-4
DOl: 10.1007/978-3-642-83781-4
Library of Congress Cataloging-in-Publication Data
New aspects in the diagnosis and treatment of Hodgkin's disease/V. Diehl,
M. Pfreundschuh, M. Loeffler (eds.). p.cm.-(Recent results in cancer research: 117)
Based on the First International Symposium on Hodgkin's Lymphoma in Cologne,
Oct., 2-3, 1987. Includes Index.
ISBN-I3:978-3-642-83783-8 (U. S.: alk. paper)
1. Hodgkin's disease-Congresses. I. Diehl, V. (Volker), 1938-. II. pfreundschuh, M.
(Michael) III. Loeffler, M. (Markus), 1954-. IV. International Symposium on Hodgkin's
Lymphoma (1st: 1987: Cologne, Germany) V. Series.
[DNLM: 1. Hodgkin's Disease-diagnosis-congresses. 2. Hodgkin's Disease-therapy
congresses. WI RE106P v. 117/WH 500 1987] RC261.R35 vol. 117 [RC644] 616.99'4
s-dc20 [616.99'446] DNLM/DLC 89-11302
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Preface
In the field of Hodgkin's lymphoma, many new data have been
collected during the last decade both on the cell of origin of this
disease and on more effective therapies to cure the majority of pa
tients even in the advanced stages. Therefore, it seems to be justi
fied to compile these new data in a special volume of Recent Re
sults in Cancer Research. This volume summarizes the contribu
tions presented at the First International Symposium on Hodgkin's
Disease that took place in Cologne (FRG) on October 2-3, 1988.
There is little doubt that the Hodgkin and Reed-Sternberg (H
and RS) cells and their variants represent the malignant population
in Hodgkin's lymphoma; however, there is still a fierce debate as to
the possible cell of origin of Hand RS cells. Many of the problems
confounding earlier research into this question were related to the
difficulty or virtual impossibility, of obtaining purified populations
of Hand RS cells. Most of the recent progress stems from the
establishment of permanent cell lines of Hand RS cells in culture.
Though permanent cell lines may degenerate from their ancestors
and may not be representative of the original cells, the data accu
mulated demonstrate that the cells in vitro reflect very well the bio
logical and immunological aspects of Hand RS cells in vivo. The
marker spectrum of Hodgkin-derived cell lines in vitro and that of
Hand RS cells in vivo, as well as gene rearrangement studies of
the cell lines, suggest that Hand RS cells in vivo are lymphoid in
origin. Even though gene rearrangement studies of biopsy material
are not yet conclusive, immunological marker studies with mono
clonal antibodies suggest that Hand RS cells are activated lym
phoid cells of either T- or B-cell type. Taking into account the data
presented and summarized in this volume, we cannot totally ex
clude the derivation of Hand RS cells from other cells (e. g., mac
rophages), especially in the light of some functional studies (e. g.,
antigen presentation) and the reactivity with monoclonal anti
bodies that recognize antigens related to the monocytoid/myeloid
VI Preface
lineage. However, all contributors agree upon the conclusion that
at the current state of our knowledge we must regard Hand RS
cells as lymphoid.
Just as revolutionary as the new data concerning the cell of ori
gin in Hodgkin's lymphoma have been the changes in the diagnos
tic and therapeutic approaches to this disease. The safest ground
for diagnosing Hodgkin's disease is still conventional morphology,
but immunohistology is of help in confirming the diagnosis, espe
cially in cases which cannot be classified using morphological cri
teria. Diagnostic laparotomy with splenectomy is no longer gener
ally recommended. The new diagnostic strategies presented here -
immunoscintigraphy and bone marrow scintigraphy with magnetic
resonance imaging - may possibly help to replace this invasive
method completely in the near future.
The improvement of therapy in Hodgkin's lymphoma during the
last two decades is mostly due to the development of effective
combination chemotherapy protocols. More than 20 years after its
inauguration, MOPP is still the golden standard by which all new
chemotherapy protocols have to be measured. The gains accom
plished by new drug combinations, if they exist at all, are minor if
they are projected onto the total population of patients with Hodg
kin's disease. With remission rates between 70% and 90% and cure
rates less than 50%, the major challenge for clinical research of
Hodgkin's lymphoma in the 1990s is the definition of prognostic
subgroups by clinical or laboratory parameters in order to select
patients who benefit from more aggressive therapy and those in
whom the intensity, and thus the toxicity of treatment can be re
duced.
Oncologists dealing with adult patients are impressed by the re
sults obtained in pediatric patients, which are presented here. Of
course, the approaches used for children cannot simply be trans
ferred to adult patients, but much can be learned from the tailoring
of the diagnostic and therapeutic strategy to the individual pa
tient's needs. The recent results of clinical trials demonstrate the
value of risk factor analysis. It becomes evident that the staging
system according to Ann Arbor may no longer serve as a strategy
for making therapeutic decisions, and a more refined system of
prognostic subgrouping is badly needed. The problem is that dif
ferent risk factors were reported for different treatment strategies.
To define intrinsic or therapy-independent risk factors, we need an
intergroup analysis of risk factors. Such an analysis can only be ac
complished by accumulating the data of several large international
study groups. It is one of the most important results of the First In
ternational Symposium on Hodgkin's Lymphoma that the participat
ing representatives of the most important institutions and coopera
tive groups have agreed to contribute their data for an internation
al workshop on risk factor analysis which is now being carried out.
Preface VII
Failure of primary treatment need no longer be fatal. The thera
peutic advances of conventional salvage therapy and the innova
tive approach of bone marrow transplantation are discussed in a
special section. Finally, the psychological problems that arise in
treating our patients and the intermediate and long-term sequelae
of treatment deserve further attention. These sequelae will answer
the question whether our therapeutic efforts, which succeed in cur
ing most of the patients, are really worthwhile. This can only be the
case if we not only free the patients from their disease but also pro
vide them with a psychological and somatic quality of life that jus
tifies the efforts and the costs involved in conquering the disease.
The attendance and the enthusiastic comments made us believe
that the First International Symposium on Hodgkin's Lymphoma
in Cologne succeeded in summarizing the most important goals
that we have achieved during the last two decades and in defining
the questions that remain to be answered in the future to complete
our knowledge for the sake of the patients.
I do not want to finish this preface without first thanking the
Ministry of Research and Technology of the Federal Government
(BMFT), The German Research Society (DFG), the Thyssen Foun
dation, the Boehringer-Ingelheim Foundation, the German Asso
ciation of Medical Oncology (Ala), and the City of Cologne for
their financial and administrative support. My personal thanks go
to our Hodgkin Study Group team, especially to Mrs. Nisters
Backes and Olga Pavlovic and to our students, who guaranteed the
flawless organization of a meeting that we hope many of the parti
cipants will remember for a long time to come.
Cologne, March 1989 For the editors
Volker Diehl
Contents
Pathology and Cell Biology of Hodgkin's Disease 1
D. H. Wright
Pathology of Hodgkin's Disease: Anything New? . 3
H. Stein, R. Schwarting, F. Dallenbach, and D. Dienemann
Immunology of Hodgkin and Reed-Sternberg Cells .... 14
A. C. Feller and H. Griesser
DNA Gene Rearrangement Studies in Hodgkin's Disease and
Related Lymphomas: A Contribution to Their Cellular Origin. 27
C. Fonatsch, G. Gradl, and J. Rademacher
Genetics of Hodgkin's Lymphoma. . . . . . . . . . . . . . .. 35
Hodgkin's Disease Derived Cell Lines. . . . . . . . . . . . . . . . .. 51
M. Schaadt, H. Burrichter, M. Pfreundschuh, E. Schell-Frederick,
H. Tesch, C. Fonatsch, H. Stein, and V Diehl
Biology of Hodgkin Cell Lines .................. . 53
D. B. Jones, A. J. W Furiey, J. Gerdes, M. F. Greaves, H. Stein, and
D. H. Wright
Phenotypic and Genotypic Analysis of Two Cell Lines Derived from
Hodgkin's Disease Tissue Biopsies . . . . . . . . . . . . . . . . .. 62
S. Poppema, L. Visser, B. de Jong, M. Brinker, J. Atmosoerodjo, and
W Timens
The Typical Reed-Sternberg Phenotype and I g Gene
Rearrangements of Hodgkin's Disease Derived Cell Line ZO
Indicating a B-Cell Origin . . . . . . . . . . . . . . . . . . . . . 67
H. G. Drexler, S. M. Gignac, A. V HoJjbrand, B. F. Leber, J. Norton,
M. S. Lok, and J. Minowada
Characterization of Hodgkin's Disease Derived Cell Line HDLM-2. 75
X Contents
H. Kamesaki, S. Fukuhara, H. Uchino, and T Nosaka
A New Hypothesis on the Cellular Origin of Reed-Sternberg and
Hodgkin Cells Based on the Immunological and Molecular Genetic
Analysis of the KM-H2 Line. . . . . . . . . . . . . . . . . . . . .. 83
E. Paietta, R. J. Stockert, A. Morell, J. Racevskis, and P. H. Wiernik
A Marker and Putative Pathoantigen of Hodgkin's Cells . . . . . .. 91
Development in Diagnostic Procedures. . . . . . . . . . . . . . . . .. 99
P. Carde, M. Pfreundschuh, L. da Costa, L. Manil, J. D. Lumbroso,
B. Ca illou , C. Parmentier, J. C. Saccavini, and V. Diehl
Radiolabeled Monoclonal Antibodies Against Reed-Sternberg Cells
for in Vivo Imaging of Hodgkin's Disease by Immunoscintigraphy 101
H. Schicha, M. Franke, J. Smolorz, A. Linden, W Waters, and
V. Diehl
Diagnostic Strategies and Staging Procedures for Hodgkin's
Lymphoma: Bone Marrow Scintigraphy and Magnetic Resonance
Imaging .................................. 112
Therapeutic Strategies 121
Overviews. 123
H. Sack
Radiotherapy Trials in Hodgkin's Disease 123
P. H. Wiernik
Current Status of Chemotherapy for Hodgkin's Disease ....... 132
Report on Recent and Current Clinical Trials . .............. 142
M. Loeffler, M. Pfreundschuh, U. Ruhl, E. Hiller, H. Gerhartz,
R. Roloff, M. Adler, W Schoppe, U. Hagen-Aukamp, G. Schmitt,
J. Teichmann, V Brust, R. Fuchs, B. Makoski, H. Bartels, J. Entzian,
G. Kuhn, A. Hellriegel, H. Kirchner, H. Emminger, G. Dolken,
W Oertel, W Wilhelmy, B. Kruger, S. Petsch, H. f1luger,
R. Hinterberger, P. Worst, W GajJmann, K. Smith, D. Hasenclever,
and V. Diehl
Risk Factor Adapted Treatment of Hodgkin's Lymphoma:
Strategies and Perspectives. . . . . . . . . . . . . . . . . . . 142
M. Herold, G. Anger, K. Keinert, D. Hache, R. Kastner, and K. Wutke
Reduced Combined Radiotherapy and Chemotherapy for
Hodgkin's Disease - Risk-Adapted Treatment Approach ....... 163
Contents XI
G. Bonadonna. P. Valagussa. A. Santoro. S. Viviani. V. Bonfante. and
A. Banfi
Hodgkin's Disease: The Milan Cancer Institute Experience with
MOPP and ABVD ............................ 169
R. Somers. M. Tubiana. and M. Henry-Amar
EORTC Lymphoma Cooperative Group Studies in Clinical
Stage I-II Hodgkin's Disease - 1963 1987 . . . . . . . . . .. '" 175
R. T Hoppe. S. J. Horning. S. L. Hancock. and S. A. Rosenberg
Current Stanford Clinical Trials for Hodgkin's Disease. . . . . 182
D. J. Straus. J. Gaynor. J. Myers. D. Merke. D. Chapman. J. Caravelli.
L. Z. Nisce. B. J. Lee. and B. D. Clarkson
Results and Prognostic Factors Following Optimal Treatment in
Advanced Hodgkin's Disease ...................... 191
L. M. Fuller and F. B. Hagemeister
Two Cycles of MOPP and Definitive Radiotherapy for Stage IlIA
and III B Hodgkin's Disease. . . . . . . . . . . . . . . . . . . .. . 197
G. Schellong. I. Hornig. E. W Schwarze. and M. Wannenmacher
Risk Factor Adapted Treatment of Hodgkin's Lymphoma in
Childhood: Strategies and Results of Three Consecutive Multicenter
Studies in the Federal Republic of Germany . . . . . . . . . . . . . . 205
J. Lemerle. O. Oberlin. G. Schaison. G. Leverger. D. Olive. M. Bonnet.
D. Dufillot. and L. de Lumley
Hodgkin's Disease in Children: Adaptation of Treatment to Risk
Factors ................................... 214
Role of Bone Marrow Transplantation in the Treatment of Hodgkin's
Lymphoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 223
M.J1reundschuh. M. Schaadt. and V. Diehl
Conventional Salvage Therapy for Hodgkin's Lymphoma . 225
J. A. Spinolo. S. Jagannath. K. A. Dicke. K. E. Smith. F. Cabanillas.
F. B. Hagemeister. L. J. Horwitz. P. McLaughlin. F. Swan. and
G. Spitzer
High-Dose Combination Chemotherapy with Cyclophosphamide,
Carmustine, Etoposide, and Autologous Bone Marrow
Transplantation in 60 Patients with Relapsed Hodgkin's Disease:
The M. D. Anderson Experience .................... 233
A. M. Carella and A. M. Marmont
Treatment of Resistant Hodgkin's Lymphoma with Bone Marrow
Transplantation in Italy ......................... 239