Aplastic Anemia and Other Bone Marrow Failure Syndromes

250 Pages·1990·7.71 MB·English

by  Mehdi Tavassoli (auth.)

Aplastic Anemia and
Other Bone Marrow
Failure Syndromes
Nasrollah T. Shahidi
Editor
Aplastic Anemia and
Other Bone Marrow
Failure Syndromes
With 39 Illustrations
Springer-Verlag
New York Berlin Heidelberg
London Paris Tokyo
N. T. Shahidi
Department of Pediatrics
University of Wisconsin-Madison
Madison. Wisconsin 53792
U.S.A.
Library of Congress Cataloging in Publication Data
Aplastic anemia and other bone marrow failure syndromes I N.T.
Shahidi. editor.
p. cm.
Based on an international symposium held Dec. 5. 1987 in
Washington. D.C.
ISBN -13: 978-1-4612-7935-8
I. Aplastic anemia-Congresses. 2. Bone marrow-Diseases
Congresses. I. Shahidi. Nasrollah T.
[DNLM: I. Anemia. Aplastic-congresses. 2. Bone Marrow Diseases
congresses. WH 175 A6423 1988)
RC64I.7.A6A65 1989
616.1 '52-dc20
DNLMIDLC
for Library of Congress 89-21857
CIP
Printed on acid-free paper.
© 1990 by Springer-Verlag Inc.
Sof teover reprint of the hardcover 1s t edition 1990
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ISBN-13:978-1-4612-7935-8 e-ISBN-13:978-1-4612-3254-4
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Introduction
During the past decade, there have been numerous direct and indirect
scientific contributions to both the etiology and therapy of aplastic anemia
and related bone marrow failure syndromes. Clinical observations, such as
autologous bone marrow recovery after conditioning with immunosup
pressive agents for bone marrow transplantation; failure to achieve en
graftment in some identical twins without prior immunosuppressive ther
apy; and hematologic response to immunosuppressive agents, have led to
the concept of immune-mediated etiology of acquired aplastic anemia.
Such a concept was further strengthened by laboratory findings, implicat
ing the role of activated cytotoxic T lymphocytes and abnormal produc
tion of inhibitory lymphokines. The immunologic mechanisms may also
apply to the idiosyncratic bone marrow aplasias associated with drugs,
toxic chemicals, and viruses. These agents may alter normal cellular recog
nition sites by interacting with cellular components and result in loss of self
tolerance.
Immunologic mechanisms have long been advocated in many other
organ failures, and the hemopoietic organ is no exception. It is of interest
that parallel clinical and laboratory investigations in juvenile diabetes
mellitus type I and in rodent models of this disease have yielded results
compatible with the same pathogenic mechanisms. The infiltration of
pancreatic islets by activated T lymphocytes, functional and morphological
alterations of islet cells upon incubation with lymphokines such as gamma
interferon and tumor necrosis factor, and clinical response to cyclosporine
are a few examples.
Finally, with greater insight into the structure and function of the bone
marrow microenvironment, it has become increasingly apparent that stem
cell proliferation is regulated by locally produced stimulators and inhibi
tors. The possibility of genetically or environmentally-induced imbalance
in the production of these factors should also be considered.
Despite significant progress in the specific therapy and supportive mea
sures for patients with aplastic anemia, whether acquired or constitutional,
the mortality remains high. Consequently, a judicious choice of various
v
vi Introduction
therapeutic options available is extremely important. Furthermore, aplas
tic anemia is a relatively rare disorder. In order to evaluate the efficacy of
various therapeutic modalities and to ascertain the superiority of one over
another under various specific circumstances, collaborative efforts are of
paramount importance.
Recently, a number of well known scientists with expertise in the field of
aplastic anemia and related bone marrow failure syndromes presented the
results of many years of their laboratory and clinical research at an interna
tional symposium. * It is hoped that collective publication of the latest
scientific achievement by these scientists will lead to greater collaboration,
to better understanding of the pathophysiology of this heterogenous group
of pancytopenias, and ultimately, to improved survival.
Nasrollah T. Shahidi
*This symposium was made possible through an educational grant by Sandoz
Corporation.
Contents
Introduction v
Chapter 1. Bone Marrow and Hemopoiesis
Mehdi Tavassoli
Chapter 2. Acquired Aplastic Anemia: Classification and
Etiologic Considerations
Nasrollah T. Shahidi 25
Chapter 3. Constitutional Aplastic Anemia
Blanche P. Alter 38
Chapter 4. Cytogenetics in Constitutional Aplastic Anemia
Arleen D. Auerbach 51
Chapter 5. Cellular Interactions in the Suppression of
Hematopoiesis
F. Roy MacKintosh, Jean C. Schulman, and
Esmail D. Zanjani 63
Chapter 6. Flow Cytofiuorometric Analysis of Patient
Mononuclear Cells and Clinical Response to
Antithymocyte Globulin
Beverly Torok-Storb and Gretchen G. Johnson 82
Chapter 7. Prospects for the Treatment of Aplastic Anemia
Neal S. Young 88
Chapter 8. Treatment of Severe Aplastic Anemia: A 12-Year
Follow-Up of Patients after Bone Marrow
Transplantation or after Therapy with
Antilymphocyte Globulin
Bruno Speck, Andre Tichelli, Alois Gratwohl, and
Caterina Nissen 96
VII
viii Contents
Chapter 9. Long-Term Comparison of Immunosuppressive
Therapy with Antithymocyte Globulin to Bone
Marrow Transplantation in Aplastic Anemia
Kristine C. Doney. Kenneth Kopecky. Rainer Storb.
C. Dean Buckner. Jack W. Singer.
Claudio Anasetti. Frederick R. Appelbaum.
Patrick Beatty. William I. Bensinger.
Ronald Berenson. Reginald A. Clift.
Hans Joachim Deeg. John A. Hansen. Roger Hill.
Thomas P. Loughran. Paul Martin.
Finn Bo Petersen. George E. Sale. Jean Sanders.
Keith M. Sullivan. Patricia Stewart.
Paul L. Weiden. Robert P. Witherspoon. and
E. Donnall Thomas 104
Chapter 10. Treatment of Severe Aplastic Anemia (SAA) with
Bone Marrow Transplantation (BMT) or
Immunosuppression: A Report of the EBMT SAA
Working Party
Andrea Bacigalupo. Jill M. Hows. Andreas Wursh.
Caterina Nissen. E. Gluckman. Agnes Devergie.
Judith C. W. Marsh. M. Teresa van Lint.
Marina Congiu. Alberto Granena.
Mariet M. de Planque. Peter Ernst. Sean McCann.
Aruna Raghavachar. N. Frickho/en.
Edward C. Gordon Smith. and Alberto M. Marmont 115
Chapter 11. Treatment of Aplastic Anemia: Bone Marrow
Transplantation, Immunomodulatory Therapy, and
Hematopoietic Growth Factors
Richard E. Champlin 121
Chapter 12. Bone Marrow Transplantation for Fanconi Anemia
E. Gluckman 134
Chapter 13. The Use of Etiocholanolone and Antithymus
Globulin to Treat Aplastic Anemia: An
Uncontrolled Comparative Study
Frank H. Gardner and Harinder S. Juneja 145
Chapter 14. Treatment of Acquired Aplastic Anemia with
Cyclosporine and Androgens
Nasrollah T. Shahidi. Winfred C. Wang.
Susan B. Shurin. Jonathan L. Finlay.
Paul M. Sondel. and Patricia Anne Dinndorf 155
Contents IX
Chapter 15. Congenital Hypoplastic Anemia (Diamond-Blackfan
Anemia)
Berti! E. Glader 166
Chapter 16. Pure Red Cell Aplasia
Emmanuel N. Dessypris 179
Chapter 17. The Preleukemic Syndrome (Hematopoietic
Dysplasia)
Grover C. Bagby, Jr. 199
Chapter 18. Summary and Conclusions
David G. Nathan 224
Index 231
Contributors
BLANCHE P. ALTER, M.D.
Departments of Medicine and Pediatrics, Polly Annenberg Levee
Hematology Center, Mount Sinai School of Medicine, New York, New
York 10029-6574, U.S.A.
CLAUDIO ANASETTI, M.D.
Fred Hutchinson Cancer Research Center, Seattle, Washington 98104,
U.S.A.
FREDERICK R. ApPELBAUM, M.D.
Department of Medicine, University of Washington, Seattle, Washington
98108, and Fred Hutchinson Cancer Research Center, Seattle,
Washington 98104, U.S.A.
ARLEEN D. AUERBACH, Ph.D.
Laboratory for Investigative Dermatology, The Rockefeller University,
New York, New York 10021-6399, U.S.A.
ANDREA BACIGALUPO, M.D.
Department of Hematology, San Martino Hospital, 16132 Genoa, Italy
GROVER C. BAGBY, JR., M.D.
Department of Medicine and Medical Genetics, Division of Hematology
and Medical Oncology, Oregon Health Sciences University, Portland,
Oregon 97201 and Section of Hematology and Medical Oncology,
Veterans Administration Medical Center, Portland, Oregon 97201, U.S.A.
PATRICK BEATTY, M.D., Ph.D.
Department of Medicine, University of Washington, Seattle, Washington
98108, and Fred Hutchinson Cancer Research Center, Seattle,
Washington 98104, U.S.A.
xi
Contributors
XlI
WILLIAM I. BENSINGER, M.D.
Department of Medicine, University of Washington, Seattle, Washington
98108, and Fred Hutchinson Cancer Research Center, Seattle,
Washington 98104, U.S.A.
RONALD BERENSON, M.D.
Department of Medicine, University of Washington, Seattle, Washington
98108, and Fred Hutchinson Cancer Research Center, Seattle,
Washington 98104, U.S.A.
C. DEAN BUCKNER, M.D.
Department of Medicine, University of Washington, Seattle, Washington
98108, and Fred Hutchinson Cancer Research Center, Seattle,
Washington 98104, U.S.A.
RICHARD E. CHAMPLIN, M.D.
Department of Medicine, Division of Hematology/Oncology, UCLA
School of Medicine, Los Angeles, California 90024, U.S.A.
REGINALD A. CLIFT, F.I.M.L.S.
Fred Hutchinson Cancer Research Center, Washington 98104, U.S.A.
MARINA CONGIU, M.D.
Department of Hematology, San Martino Hospital, 16132 Genoa, Italy
HANS JOACHIM DEEG, M.D.
Bone Marrow Transplantation Department, Lombardi Cancer Research
Center, Washington, District of Columbia 20007, U.S.A.
EMMANUEL N. DESSYPRIS, M.D.
Department of Medicine, Vanderbilt University, Nashville, Tennessee
37240, and Veterans Administration Medical Center, Nashville,
Tennessee 37212, U.S.A.
AGNES DEVERGIE, M.D.
Department of Hematology, Saint Louis Hospital, Paris, France
PA TRICIA ANNE DINNDORF, M.D.
Department of Pediatrics, University of Wisconsin-Madison, Madison,
Wisconsin 53792, U.S.A.
KRISTINE C. DONEY, M.D.
Department of Medicine, University of Washington, Seattle, Washington
98108, and Fred Hutchinson Cancer Research Center, Seattle,
Washington 98104, U.S.A.