Table Of ContentR Schmalzl G.1. Mufti (Eds.)
Myelodysplastic
Syndromes
With 66 Figures and 87 Tables
Springer-Verlag
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Prof. Dr. med. Franz Schmalzl
Interne Abteilung
A. 6. Bezirkskrankenhaus Hall in Tirol
Milser StraBe 10
6060 Hall in Tirol, Austria
Dr. G. J. Mufti
Department of Haematology
King's College School of Medicine and Dentistry
Denmark Hill
London SE5 8RX, UK
ISBN-13 : 978-3-540-52966-8 e-ISBN-13 : 978-3-642-75952-9
DOl: 10.1007/978-3-642-75952-9
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Preface
The myelodysplastic syndromes pose important clinical and scientific chal
lenges which in recent years have attracted growing interest within haemato
oncology and molecular genetics. Their potential as a model for the study of
human leukaemogenesis makes this one of the most exciting fields in
contemporary haematology. Rapid progress towards understanding these
disorders had created the need for international interdisciplinary communi
cation. In order to fulfil this need the First International Symposium on
Myelodysplastic Syndromes was organized in Innsbruck, Austria, in June
1988. The substantial number of excellent speakers and of participants
manifested the great international interest on the topic.
The present volume consists of the contributions of most of the speakers at
this Symposium. We wish to thank all those who submitted their manus
cripts.
G.]. Mufti Franz Schmalzl
Contents
Classification and Cytopathology of Myelodysplastic Syndromes
The Classification of Myelodysplastic Syndromes
J. M. Bennett . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
Discussion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
Classification of Myelodysplastic Syndromes in Clinical Practice:
Frequency of Subtypes
G. Flandrin ............. : . . . . . . . . . . . . . . . . . . . . . . . . . .. 15
Pathogenesis of Anaemia in the Myelodysplastic Syndrome
A. Jacobs .......................................... 20
Immunological Abnormalities in the Myelodysplastic Syndrome
T. J. Hamblin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 25
Pediatric Experiences in Myelodysplastic Syndrome
H. Gadner . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 31
Myelodysplastic Syndromes in Childhood: Description of 11 Cases
E. T. van't Veer-Korthof . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 38
The Value of Cytochemical Investigations in the Diagnosis
of the Myelodysplastic Syndromes
F. Schmalzl . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 44
Enzyme Cytochemical Studies in Myelodysplastic Syndromes
A. De Pasquale and D. Quaglino ......................... 51
Immunological Phenotyping of Blood and Bone Marrow Cells From
Patients with Myelodysplastic Syndromes
U. Koeller, O. Krieger, O.A. Haas, P. Bettelheim, O. Majdic,
and W. Knapp . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 60
VIII Contents
Bone Marrow Biopsy in RAEB and RAEB-t Myelodysplastic
Syndromes
G. Lambertenghi-Deliliers, D. Soligo, C. Annaloro, E. Pozzoli,
and A. Riva . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 67
Discussion of Poster Session I
D. Quaglino and F. Schmalzl ............................ 74
Cyto- and Histopathology of Myelodysplastic Syndrome
Maturation Pattern and Evolution of Leukemia in the
Myelodysplastic Syndrome
P. Dormer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81
Therapy-Related Myelodysplastic Syndromes and Acute Myeloid
Leukemia
R. D. Brunning ...................................... 90
The Prognostic Value of Abnormal Localization of Immature
Precursors in the Myelodysplastic Syndromes
G.J. Tricot, M. T. Rizzo, and C. De Wolf-Peeters. . . . . . . . . . . . .. 99
Bone Marrow Histology in Myelodysplastic Syndromes: An Update
B. Frisch and R. Bartl ................................. 103
Evolution of Myelodysplastic Syndromes
R. Bartl, B. Frisch, and Ch. Schmid ....................... 107
Conversion of Myelodysplastic Subtypes to Acute Leukemia:
A Follow-Up Study
Ch. Schmid, R. Bartl, K. Jager, A. Beham, H. Seewann, G. Kettner,
and B. Frisch. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 114
Primary Myelodysplastic Syndromes and Chronic Myelofibrosis
S. Sisti, G. Campanati, P. Leoni, M. Montillo, S. Rupoli, V. Vasi,
G. Biagini, and G. M. Mariuzzi . . . . . . . . . . . . . . . . . . . . . . . . . .. 121
Myelodysplastic Syndrome with Myelofibrosis: A Report of Seven
Cases
A. Shibata, M. Takahashi, T. Koike, M. Narita, and Y. Moriyama 125
Contents IX
Chronic Myelomonocytic Leukemia
Chronic Myelomonocytic Leukaemia and Atypical Chronic Myeloid
Leukaemia
I. Krsnik, P. C. Srivastava, and D. A. G. Galton .............. 131
Chronic Myelomonocytic Leukemia with Lymphadenopathy
M. Bizet, M. P. Callat, J. Goasguen, R. Garand, J. L. Bremond,
J. Gardais, and C. Duval ............................... 140
Generalized Lymphadenopathy in Juvenile Chronic Myelomonocytic
Leukemia Is Due to Lymph Node Infiltration with Myelomonocytic
Cells and Immature T Cells
O. A. Haas, A. Zoubek, U. Koller, A. Martins da Cunha,
T. Radaszkiewicz, C. R. Bartram, l. Mutz, and H. Gadner ....... 146
Impaired MonocytelMacrophage Differentiation
in the Myelodysplastic Syndromes
H. Zwierzina, N. Sepp, E. Ringler, and Schmalzl . . . . . . . . . . . . .. 155
Discussion of Poster Session II
A. Jacobs and Zwierzina ............................... 159
Cytogenetic Anomalies and Molecular Biology of Myelodysplastic
Syndromes
Myelodysplastic Syndromes: Cytogenetic Anomalies and Their
Clinical Significance
A. A. Sandberg and B. Wullich .......................... 165
Genetic Consequences of Chromosomal Abnormalities
in the Myelodysplastic Syndromes
M. Thangavelu and M. M. Le Beau . . . . . . . . . . . . . . . . . . . . . . .. 178
ras Mutations in the Myelodysplastic Syndromes
A. Jacobs, R. A. Padua, G. Carter, D. Hughes, C. Farr, D. Oscier,
D. Bowen, and J. F. McCormick .. . . . . . . . . . . . . . . . . . . . . . . .. 187
Study of the Rearrangement of Proto-oncogene MET in 88 Cases
of Myelodysplastic Syndromes
M. Collyn-d'Hooghe, P. Fenaux, J. L. Lai, F. Bauters,
M. H. Loucheux-Lefebvre, and K. P. Kerckaert . . . . . . . . . . . . . . .. 193
X Contents
In Vitro-Culture Studies in Myelodysplastic Syndromes
ras Oncogenes in Myelodysplastic Syndromes
D. M. Layton and C. R. Bartram . . . . . . . . . . . . . . . . . . . . . . . . . 201
Growth Factors in Myelodysplastic Syndromes.
D. S. Rosenthal, W. Holmes, and J. H. Antin ................. 215
In Vitro Granulopoiesis in Myelodysplastic Syndromes According
to the F AB Classification
L. Fiorensa, S. Woessner, R. Lafuente, J. Bux6, J. Almarcha,
M. R. Marill, and J. Sans-Sabrafen ........................ 222
Therapy of Myelodysplastic Syndromes:
Supportive Care and Chemotherapy
Therapeutic Implications of Understanding Pathogenesis:
Clinical Relevance of Prognostic Factors
G.J. Mufti. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 235
Supportive Therapy and Bone Marrow Transplantation in MDS
H. Heimpel ......................................... 240
Retinoic Acid Therapy in the Myelodysplastic Syndrome
A. Jacobs .......................................... 248
Phase III Evaluation of Low-Dose Cytosine Arabinoside Versus Sup
portive Care in the Treatment of Adults With Myelodysplastic Syn
drome:
An Intergroup Study by the Eastern Cooperative Oncology Group
and the Southwest Oncology Group - Preliminary Results
J. M. Bennet, K. B. Miller, K. Kim, F. S. Morrison, J. N. Winter,
P. Cassileth, R. S. Neiman, and D. Head .................... 253
Intensive Chemotherapy in Myelodysplastic Syndromes
H. Loffler . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 259
Therapeutic Effects of Low-Dose Cytosine Arabinoside Without or
With 1,25-Dihydroxyvitamin D3 in Myelodysplastic Syndromes
and in Elderly Acute Nonlymphocytic Leukemia
C. Bernasconi, E. P. Alessandrino, P. Bernasconi, M. Lazzarino,
D. Inverardi, and E. Orlandi ............................ 263
Contents XI
Low-Dose Cytosine Arabinoside Regimen Adapted to the FAB
Classifications of Myelodysplastic Syndromes: Is it Superior to
Uniform Treatment for all Types of MDS?
R. Schlag, R. Zankovich, J. Walther, C. Fonatsch, J. Thiele, W. Hill,
R. Bernsmeier, V. Diehl, and E. Thiel . . . . . . . . . . . . . . . . . . . . .. 268
Results of Low-Dose Cytosine Arabinoside and Agressive
Chemotherapy in Patients with Advanced Myelodysplastic
Syndromes
C. Au/-and W. Schneider ............................... 274
Aggressive Chemotherapy in Adult Primary Myelodysplastic
Syndromes: A Report on 29 Cases
P. Fenaux, J. L. Lai, M. H. Estienne, M. Deminatti, and F. Bauters. 282
Therapy of Myelodysplastic Syndromes:
Biological Response Modifiers and Growth Factors
Recombitant <X.2b-Interferon in the Management of Myelodysplastic
Syndromes
S. M. Donohue, S. Lim, and B. J. Boughton ................ 291
A Phase II Clinical Trial of Recombinant Interferon-yon
Myelodysplastic Syndromes
M. Ogawa, Y. Yoshida, Y. Moriyama, K. Ezaki, M. Shimoyama,
H. Mizoguchi, l. Urushizaki, T. Miyazaki, Y. Yoshida, A. Togawa,
K. Toyama, Y. Kuraishi, T. Nakamura, K. Tamura and H. Sato ... 294
Treatment of Patients with Myelodysplastic Syndromes with
Recombinant Human GranulocytelMacrophage Colony-Stimulating
Factor: A Phase IIII Trial
A. Ganser, B. Volkers, J. Greher, O. G. Ottmann, F. Walther,
R. Becher, L. Bergmann, G. Schulz, and D. Hoelzer ........... 300
Combined Treatment Modality with Recombinant Human
GranulocytelMacrophage Colony-Stimulating Factor and Low-Dose
Cytosine Arabinoside in Patients with Myelodysplastic Syndromes
D. Hoelzer, A. Ganser, O. P. Ottmann and G. Schulz. . . . . . . . . .. 315
xn Contents
GM-CSF Combined with Low-Dose Cytosine Arabinoside:
A Trial Proposed for High-Risk Myelodysplastic Syndromes
and Results of a Dose-Finding Study
H. H. Gerhartz, H. Schmetzer, B. Wolf-Hornung, and A. C. Stern .. 321
Discussion of Poster Session III
T. Hamblin and O. Krieger. . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 330
Subject Index ....................................... 332
