Advances in Hematopoietic Stem Cell Transplantation and Molecular Therapy

159 Pages·1998·4.357 MB·English

by  Priv.-Doz. Dr. med. Rainer Haas, Dr. med. Ralf Kronenwett, Priv.-Doz. Dr. rer. nat. Georg Sczakiel (auth.)

Recent Results 144
in Cancer Research
Managing Editors
P. Schlag, Berlin· H.-J. Senn, St. Gallen
Associate Editors
V. Diehl, Cologne . D.M. Parkin, Lyon
MJ. Rajewsky, Essen . R. Rubens, London
M. Wannenmacher, Heidelberg
Founding Editor
P. Rentchnik, Geneva
Springer
Berlin
Heidelberg
New York
Barcelona
Budapest
Hong Kong
London
Milan
Paris
Santa Clara
Singapore
Tokyo
R. Haas R. Kronenwett
G. Sczakiel (Eds.)
Advances in Hematopoietic
Stem Cell Transplantation
and Molecular Therapy
With 47 Figures and 8 Tables
, Springer
Priv.-Doz. Dr. med. Rainer Haas
Dr. med. Ralf Kronenwett
Deutsches Krebsforschungszentrum
Klinische Kooperationseinheit
Molekulare Hamatologie/Onkologie (460)
1m Neuenheimer Feld 280
D-69120 Heidelberg
Priv.-Doz. Dr. rer. nat. Georg Sczakiel
Deutsches Krebsforschungszentrum
Forschungsschwerpunkt Angewandte
Tumorvirologie
1m Neuenheimer Feld 242
D-69120 Heidelberg
ISBN-13 :978-3-642-46838-4 e-TSBN-13 :978-3-642-46836-0
DOT: 10.1007/978-3-642-46836-0
Library of Congress Cataloging-in-Publication Data applied for
Die Deutsche Bibliothek - CIP-Einheitsaufnahme
Advances in hematopoietic stem cell transplantation and molecular therapy: with 8
tables 1 R. Haas ... (ed.). - Berlin; Heidelberg; New York; Barcelona; Budapest; Hong
Kong; London; Milan; Paris; Santa Clara; Singapore; Tokyo: Springer, 1997
(Recent results in cancer research; Vol. 144)
This work is subject to copyright. All rights are reserved, whether the whole or part of
the material is concerned, specifically the rights of translation, reprinting, reuse of illus
trations, recitation, broadcasting, reproduction on microfilm or in any other way, and
storage in data banks. Duplication of this publication or parts thereof is permitted only
under the provisions of the German Copyright Law of September 9, 1965, in its current
version, and permission for use must always be obtained from Springer-Verlag. Viola
tions are liable for prosecution under the German Copyright Law.
© Springer-Verlag Berlin· Heidelberg 1998
Softcover reprint of the hardcover 1st edition 1998
The use of general descriptive names, registered names, trademarks, etc. in this publica
tion does not imply, even in the absence of a specific statement, that such names are
exempt from the relevant protective laws and regulations and therefore free for general
use.
Product liability: The publisher cannot guarantee the accuracy of any information about
dosage and application contained in this book. In every individual case the user must
check such information by consulting the relevant literature.
Typesetting: K+ V Fotosatz, Beerfelden
SPIN 10558982 19/3133-5 4 3 2 1 0 - Printed on acid-free paper
Preface
In 1985 when the first peripheral blood stem cell transplantation
was carried out in Heidelberg one could not foresee the success
of this therapeutic principle. Today, it is an established therapeu
tic option in the treatment of human diseases. In the interim,
molecular therapeutic approaches such as the application of anti
bodies or gene therapy have become promising alternatives to
the classical treatment of cancer. In 1995, the Clinical Coopera
tion Unit Molecular Hematology/Oncology was founded at the
German Cancer Research Center to combine experience in clini
cal hematology and oncology and advances in basic research. To
date several cooperative projects have been started which aim to
facilitate the transfer of new developments in basic sciences to
clinical applications. On September 13th and 14th 1996, an inter
national symposium was held in Heidelberg at which clinical and
basic scientists were invited to update and discuss the recent ad
vances in hematopoietic stem cell tra!lsplantation and molecular
therapy. The proceedings of this symposium are summarized in
this book. Eighteen articles give an overview of the biology of
hematopoietic stem cells, peripheral blood stem cell transplanta
tion in patients with hematological malignancies, recent develop
ments in molecular diagnosis, and gene therapeutic concepts.
The symposium made transparent that successful future develop
ments require cooperative research connecting basic science with
clinical expertise.
We wish to thank the authors of the articles for their contribu
tions and the publisher for support and cooperation.
Heidelberg, July 1997 R. Haas
R. Kronenwett
G. Sczakiel
Contents
Mobilization and Selection of CD34+ Cells ................. .
S. Hohaus, S. Murea, M. T. Voso, and R. Haas
Autologous Stem Cell Transplantation for Chronic Myeloid Leukemia 8
F. Mahon, G. Marit, ]. M. Boiron, P. Cony-Makhoul,
P. Agape, A. Pigneux, A. Broustet, and ]. Reiffers
Autologous Stem Cell Transplantation
in Aggressive Non-Hodgkin's Lymphoma. . . . . . . . . . . . . . . . . . .. 15
C. Gisselbrecht
Peripheral Blood Progenitor Cell Transplantation
in Multiple Myeloma Following High-Dose Melphalan-Based Therapy .. 27
H. Goldschmidt, U. Hegenbart, M. Wallmeier, S. Hohaus,
R. Engenhart, M. Wannenmacher, and R. Haas
Molecular Monitoring of Residual Disease
in Chronic Myelogenous Leukemia Patients After Therapy . . . . . . . .. 36
A. Hochhaus, A. Reiter, H. Skladny, A. Reichert,
S. SaufJele, and R. Hehlmann
Delineation of Genomic Regions in Chromosome Band 7q22
Commonly Deleted in Myeloid Leukemias . . . . . . . . . . . . . . . . . .. 46
K. Fischer, ]. Brown, S. W. Scherer, P. Schramm, ]. Stewart,
G. Fugazza, U. Pascheberg, W. Peter, I.-c. Tsui, P. Lichter,
and H. Dohner
Molecular Cytogenetic Analysis of Low-Grade B-Cell Neoplasias:
a Comparative Genomic Hybridization Study ................. 53
C. A. Werner, H. Dohner, T. F. E. Barth, S. Stilgenbauer,
A. Plesch, P. Lichter, and M. Bentz
Applications of Gene Transfer in Hematologic Malignancy . . . . . . . .. 61
M. K. Brenner
VIII Contents
Dendritic Cells for Somatic Gene Therapy ................... 70
J. Westermann, A. Aicher, and A. Pezzutto
Construction of Immunogenic Tumor Cell Surfaces
by Somatic Gene Transfer . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 78
S. C. Meuer, B. Guckel, M. Lindauer, W. Rudy,
and U. Moebius
Adeno-associated Virus Type 2 Vector for Transduction
of Hematopoietic Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 86
E. Ogniben and R. Haas
Protection of Hematopoietic Stem Cells from Chemotherapy-Induced
Toxicity by Multidrug-Resistance 1 Gene Transfer .............. 93
S. Fruehauf, K. Wermann, E. C. Buss, P. Hundsdoerfer,
M.R. Veldwijk, R. Haas, and w.]. Zeller
Regulated Gene Expression After Retroviral Vector-Mediated Delivery
of Cancer-Relevant Therapeutic Genes ..................... 116
W. H. Gunzburg, P. Karle, S. Mrochen, G. Sparmann,
R. Saller, D. Klein, W. Uckert, and B. Salmons
Specific bcr-ab/-Directed Antisense Nucleic Acids and Ribozymes:
A Tool for the Treatment of Chronic Myelogenous Leukemia? 127
R. Kronenwett and R. Haas
The Use of Ribozymes in Gene Therapy Approaches to AIDS . . . . . .. 139
W. James
Subject Index .................................... 147
List of Contributors *
Agape, P. R Lichter, p.46, 53
Aicher, A. 70 Lindauer, M.78
Barth, T. F. E. 53 Mahon, F. 8
Bentz, M.53 Marit, G.8
Boiron, J. M. 8 Meuer, S. C. 78
Brenner, M. K. 61 Moebius, U. 78
Broustet, A.8 Mrochen, S.116
Brown, J.46 Murea, S.I
Buss, E. C. 93 Ogniben, E.86
Cony-Makhoul, p.8 Pascheberg, U. 46
Dohner, H.46, 53 Peter, W.46
Engenhart, R.27 Pezzutto, A.70
Fischer, K.46 Pigneux, A.8
Fruehauf, S.93 Plesch, A.53
Fugazza, G. 46 Reichert, A.36
Gisselbrecht, C. 15 Reiffers, J. 8
Goldschmidt, H.27 Reiter, A.36
Giickel, B.78 Rudy, W.78
Giinzburg, W. H. 116 Saller, R. 116
Haas, R. 1, 27, 86, 93, 127 Salmons, B. 116
Hegenbart, U. 27 SauBele, S.36
Hehlmann, R.36 Scherer, S. W. 46
Hochhaus, A.36 Schramm, p.46
Hohaus, S. 1, 27 Skladny, H.36
Hundsdoerfer, p.93 Sparmann, G.116
James, W.139 Stewart, J.46
Karle, p.116 Stilgenbauer, S.53
Klein, D.116 Tsui, L.-c. 46
Kronenwett, R.127 Uckert, W.116
* The address of the principal author is given on the first page of each con
tribution.
1 Page on which contribution begins.
X List of Contributors
Veldwijk, M. R. 93 Wermann, K.93
Voso, M.T.l Werner, C. A. S3
Wallmeier, M. 27 Westermann, J.70
Wannenmacher, M.27 Zeller, W. J. 93
Mobilization and Selection of CD 34+ Cells
S. Hohaus, S. Murea, M. T. Voso and R. Haas
Department of Internal Medicine V, University of Heidelberg, HospitalstraBe 3,
69115 Heidelberg, Germany
High-risk patients with hematological malignancies and solid tumors may
benefit from dose-escalated cytotoxic chemotherapy, provided that the tumor
cells are chemosensitive as reflected by a dose-response relationship between
the cytotoxic drugs administered and the degree of cell kill achieved. Since
the first transplantation of peripheral blood stem cells (PBSC) in 1985, mobi
lized peripheral blood has gradually replaced the bone marrow as a source
of hematopoietic stem cells (Korbling et aI. 1986; Reiffers et aI. 1986; Kes
singer et aI. 1988; see also Mahon et aI., Gisselbrecht, and Goldschmidt et aI.,
this volume). The faster hematological reconstitution after transplantation of
PBSC compared to bone marrow ameliorates the dose-limiting myelotoxicity
of high-dose regimens and results in a significant reduction of nonhematolo
gical toxicity (To et al. 1992; Schmitz et al. 1995). The use of hematopoietic
growth factors is essential for efficient mobilization of PBSC (Haas et al.
1990; Hohaus et al. 1993; Haas and Murea 1995; Hohaus et al. 1997a). In this
setting, flow cytometry analysis with CD 34 staining permits counting of
PBSC in a rapid and reliable fashion (Siena et al. 1991; Haas et al. 1994). It
has become apparent that a minimum or threshold number of transplanted
CD 34+ cells are needed for rapid and sustained hematological recovery
(Hohaus et aI. 1993; Haas et al. 1994; Schwartzberg et al. 1993; Weaver et al.
1995; Bensinger et aI. 1993).
Additionally, blood-derived autografts contain fewer tumor cells than bone
marrow in some malignancies such as breast cancer (Passos-Coelho et al.
1995; Ross et al. 1993). Further reduction of tumor cells in the transplant can
be achieved using monoclonal antibodies for the purging of tumor cells or
positive enrichment of CD34+ cells (Berenson et aI. 1991; Gorin et aI. 1995;
Hardwick et al. 1992). A purified population of CD34+ cells is a sufficient
autograft for the support of any high-dose therapy (Hohaus et al. 1977b;
Brugger et al. 1994). Improvement of mobilization conditions may help to
provide blood-derived hematopoietic grafts with these characteristics.
Recent Results in Cancer Research, Vol. 144
© Springer-Verlag Berlin· Heidelberg 1998