Table Of ContentI
MINIMAL RESIDUAL DISEASE IN ACUTE LEUKEMIA 1986
II
DEVELOPMENTS IN ONCOLOGY
F.J. Cleton and J.W.I.M. Simons, eds., Genetic Origins of Tumour Cells. ISBN 90-247-2272-1
J. Aisner and P. Chang, eds., Cancer Treatment Research. ISBN 90-247-2358-2
B.W. Ongerboer de Visser, D.A. Bosch and W.M.H. van Woerkom-Eykenboom, eds., Neuro
oncology: Clinical and Experimental Aspects. ISBN 90-247-2421-X
K. Hellmann, P. Hilgard and S. Eccles, eds., Metastasis: Clinical and Experimental Aspects.
ISBN 90-247-2424-4
H.F. Seigler, ed., Clinical Management of Melanoma. ISBN 90-247-2584-4
P. Correa and W. Haenszel, eds., Epidemiology of Cancer of the Digestive Tract. ISBN 90-247-2601-8
L.A. Liotta and I.R. Hart, eds., Tumour Invasion and Metastasis. ISBN 90-247-2611-5
J. Banoczy, ed., Oral Leukoplakia. ISBN 90-247-2655-7
C. Tijssen, M. Halprin and L. Endtz, eds., Familial Brain Tumours. ISBN 90-247-2691-3
F.M. Muggia, C.W. Young and S.K. Carter, eds., Anthracycline Antibiotics in Cancer.
ISBN 90-247-2711-1
B.W. Hancock, ed., Assessment of Tumour Response. ISBN 90-247-2712-X
D.E. Peterson, ed., Oral Complications of Cancer Chemotherapy. ISBN 0-89838-563-6
R. Mastrangelo, D.G. Poplack and R. Riccardi, eds., Central Nervous System Leukemia. Prevention
and Treatment. ISBN 0-89838-570-9
A. Polliack, ed., Human Leukemias. Cytochemical and Ultrastructural Techniques in Diagnosis and
Research. ISBN 0-89838-585-7
W. Davis, C. Maltoni and S. Tanneberger, eds., The Control of Tumor Growth and its Biological
Bases. ISBN 0-89838-603-9
A.P.M. Heintz, C.Th. Griffiths and J.B. Trimbos, eds., Surgery in Gynecological Oncology.
ISBN 0-89838-604-7
M.P. Hacker, E.B. Double and I. Krakoff, eds., Platinum Coordination Complexes in Cancer
Chemotherapy. ISBN 0-89838-619-5
M.J. van Zwieten, The Rat as Animal Model in Breast Cancer Research: A Histopathological Study
of Radiation-and Hormone-Induced Rat Mammary Tumors.
ISBN 0-89838-624-1
B. Lowenberg and A. Hagenbeek, eds., Minimal Residual Disease in Acute Leukemia.
ISBN 0-89838-630-6
I. van der Waal and G.B. Snow, eds., Oral Oncology. ISBN 0-89838-631-4
B.W. Hancock and A.H. Ward, eds., Immunological Aspects of Cancer. ISBN 0-89838-664-0
K.V. Honn and B.F. Sloane, Hemostatic Mechanisms and Metastasis. ISBN 0-89838-667-5
K.R. Harrap, W'. Davis and A.H. Calvert, eds., Cancer Chemotherapy and Selective Drug Devel.
opment. ISBN 0-89838-673-X
C.J.H. van de Ve1de and P.H. Sugarbaker, eds., Liver Metastasis. ISBN 0-89838-648-5
D.J. Ruiter, K. Welvaart and S. Ferrone, eds., Cutaneous Melanoma and Precursor Lesions.
ISBN 0-89838-689-6
S.B. Howell, ed., Intra-arterial and Intracavitary Cancer Chemotherapy. ISBN 0-89838-691-8
D.L. Kisner and J.F. Smyth, eds., In',te"rfre ro"n ",A :l-p'h.a -2: Pre-Clinical and Clinical Evaluation.
ISBN 0-89838-701-9 :,'w;""~ '#,
P. Furmanski, J .C. Hager and M.A. Rich, eds., RNA Tumor Viruses, Oncogenes, Human Cancer and
Aids: On the Frontiers of Understanding. ISBN 0-89838-703-5
J. Talmadge, I.J. Fidler and R.K. Oldham, Screening for Biological Response Modifiers: Methods and
Rationale. ISBN 0-89838-712-4
J.C. Bottino, R.W. Opfell and F.M. Muggia, eds., Liver Cancer. ISBN 0-89838-713-2
P.K. Pattengale, R.J. Lukes and C.R. Taylor, Lymphoproliferative Diseases: Pathogenesis, Diag
nosis, Therapy. ISBN 0-89838-725-6
F. Cavalli, G. Bonadonna and M. Rozencweig, eds., Malignant Lymphomas and Hodgkin's Disease:
Experimental and Therapeutic Advances. ISBN 0-89838-727-2
J.G. McVie, W. Bakker, Sj.Sc. Wagenaar and D. Carney, eds., Clinical and Experimental Pathology
of Lung Cancer. ISBN 0-89838-764-7
D.G. Poplack, L. Massimo and P. Cornaglia-Ferraris, eds., The Role of Pharmacology in Pediatric
Oncology. ISBN 0-89838-795-7
A. Hagenbeek and B. Lowenberg, eds., Minimal Residual Disease in Acute Leukemia 1986.
ISBN 0-89838-799-x
III
MINIMAL RESIDUAL
DISEASE IN ACUTE
LEUKEMIA 1986
edited by
Anton Hagenbeek, MD, PhD
Bob Lowenberg, MD, PhD
The Dr. Daniel den Hoed Cancer Center, Rotterdam
The Netherlands
1986 MARTIN US NIJHOFF PUBLISHERS .-
II
a member of the KLUWER ACADEMIC PUBLISHERS GROUP
DORDRECHT / BOSTON / LANCASTER
IV
Distributors
for the United States and Canada: Kluwer Academic Publishers, 190 Old Derby
Street, Hingham, MA 02043, USA
for the UK and Ireland: Kluwer Academic Publishers, MTP Press Limited,
Falcon House, Queen Square, Lancaster LA1 1RN, UK
for all other countries: Kluwer Academic Publishers Group, Distribution Center,
P.O. Box 322, 3300 AH Dordrecht, The Netherlands
Library of Congress Cataloging in Publication Data
Minimal residual disease in acute leukemia, 1986.
(Developments in oncology)
Includes bibliographies and index.
1. Leukemia--Relapse. I. Hagenbeek, A. (Anton)
II. Lowenberg, B. (Bob), 1946- • II. Series.
[DNLM: 1. Bone Marrow--transplantation. 2. Leukemia-
diagnosis. 3. Leukemia--therapy. 4. Neoplasm
Recurrence, Local--diagnosis. 5. Neoplasm Recurrence,
Local--therapy. Wl DE998N / WH 250 M665]
RC643.M54 1986 616.99'41906 86-851
ISBN-13: 978-94-010-8398-0 e-ISBN-13: 978-94-009-4273-8
001: 10.1007/978-94-009-4273-8
Copyright
© 1986 by Martinus Nijhoff Publishers, Dordrecht.
Softcover reprint of the hardcover 1s t edition 1986
All rights reserved. No part of this publication may be reproduced, stored in a
retrieval system, or transmitted in any form or by any means, mechanical,
photocopying, recording, or otherwise, without the prior written permission of
the publishers,
Martinus Nijhoff Publishers, P.O. Box 163, 3300 AD Dordrecht,
The Netherlands.
v
PREFACE
Relapse of leukemia following successful remission-induction therapy
remains a major obstacle in the treatment of patients with acute leukemia.
Leukemia recurs most frequently in patients with acute myeloblastic
leukemia (AML) and high risk acute lymphoblastic leukemia (ALL) following
chemotherapy and less often in patients with low risk ALL and particularly
in patient groups> submitted to allogeneic marrow transplantation.' It is
likely that the great majority of these recurrences originate from residual
leukemic cells that survive initial remission-induction chemotherapy.
Today, several research groups throughout the world place emphasis on
studies concerned with the detection and treatment of 'minimal residual
disease' (MRD). These investigations are conducted with the common
objective to tackle the remaining cells. 'Minimal Residual Disease in Acute
Leukemia: 1986' summarizes the fast advancements in this area.
Several disciplines are concerned with the analysis of leukemic cells. The
perspectives of cytogenetic and molecular genetic approaches for applica
tion in the detection of MRD are reviewed. In this respect, modern cyto
genetics provide highly specific tumor markers. The resolution of cyto
genetic methods can be particularly improved when combined with other
techniques which select relevant subpopulations of cells. Characterization
of oncogenes and gene rearrangements, including those of immunoglobulin and
T-cell receptor genes, and the measurement of gene products, have been
established. Techniques based on these approaches offer interesting tools
for the detection of MRD. New possibilities of employing monoclonal anti
bodies are also presented. The reagents are applied to enriched subpopula
tions and hold promise for tracing leukemic cells with specific phenotypes.
Some of these studies especially focus on the detection of in vitro clono
genic leukemic cells.
As regards the treatment of 'minimal residual disease', new strategies of
chemotherapy of acute myeloblastic and lymphoblastic leukemia are under
investigation. These include high-dose cytosine arabinoside, and high-dose
treatment followed by autologous bone marrow transplantation (ABMT). The
developments of immunological and pharmacological means to eliminate
residual leukemic cells from autologous marrow grafts, are highlighted and
discussed in the context of a comprehensive survey of the results of ABMT
employing 'unpurged' marrow.
A considerable amount of data on the long-term outcome of HLA-matched
allogeneic bone marrow transplantation is now becoming available. Commu
cations from major studies deal with the incidence of leukemia relapses
and with the causes of mortality among patients surviving five years or
more after transplantation. A section of this book is devoted to the pre
vention of graft-versus-host disease (GvHD) after allogeneic bone marrow
transplantation. This section focusses in particular on the physico
chemical and immunological methods by means of T-lymphocytes which are
removed from the marrow graft. From the results of these investigations it
becomes clear that GvH~can be prevented to a significant extent. These
results show that allogeneic marrow transplantation is becoming safer.
VI
This opens perspectives for a wider application of bone marrow transplanta
tion, regarding a crossing of the histocompatability barrier and applica
tion of the procedure in relation to older patients.
The gradually increasing experiences with 'Mismatched Bone marrow trans
plantation' are updated in this book. The achievements of the continuous
research in this field are numerous and exciting. We have become impressed
by the speed at which progress has been made, considering that only two
years have elapsed since the first volume on 'Minimal Residual Disease in
Acute Leukemia' was published.
Anton Hagenbeek and Bob Lowenberg
January 1986
VII
CONTENTS
Preface v
Contents VII
List of First Authors with Co-Authors XI
Part I - Detection of Minimal Residual Disease in Acute Leukemia
New possibilities for cytogenetic analysis of leukemic cells
A. Hagemeyer, H.J. Adriaansen, C.R. Bartram
Breakpoint analysis in CML: potentials for detection of minimal residual
disease
G.C. Grosveld, D. Bootsma, A. de Klein, N. Heisterkamp, K. Stam,
J. Groffen 12
The mammalian ETS genes: two unique chromosomal locations in cat, mice and
man and novel translocated position in human leukemias
T.S. Papas, O.K. Watson, N. Sacchi, S.J. O'Brien, R. Ascione 23
Activated RAS oncogenes in acute leukemia
J.L. B~ M. Verlaan-de Vries, A.J. van der Eb, R. Delmel, B. Lowenberg,
S. Rodenhuis, J.W.G. Janssen, L.P. Colly 43
DNA rearrangements as unique markers of clonal evolution, recurrence and
translocation
J.J. Wrigth, D.G. Poplack, A. Bakhshi, S.J. Korsmeyer 51
The application of monoclonal antibodies for the detection and classifica
tion of AML
J.D. Griffin 58
Towards detection of minimal disease: discrimination of AML precursors fron
normal myeloid precursors using a combination of surface makers
R. Delwel, I. Touw, B. Lowenberg 68
An immunological approach to analyse the kinetics of minimal residual
disease in acute leukemia
A. Hagenbeek, A.C.M. Martens 76
Visualization of minor cell populations with simultaneous three-parameter
flow cytometry: BN rat marrow and spleen model
A.K. Sullivan, A. Brox, G. Price 86
Growth kinetics of minimal residual disease in the brown Norway rat acute
myelocytic leukemia
F.W. Schultz, A.C.M. Martens, A. Hagenbeek 97
VIII
Detection of minimal residual acute lymphoblastic leukemia by immunological
marker analysis: possibilities and limitations
J.J.M~ van Dongen, H. Hooijkaas, H.J. Adriaansen, K. Hahlen,
G.E. van Zanen 113
Surveillance of terminal deoxynucleotidyl transferase-positive cells in
peripheral blood of patients with acute lymphoblastic leukemia
R.G. Smith, M.L. Hetherington, P.R. Huntsman, G.R. Buchanan 134
In vitro colony forming cells of acute lymphoblastic leukemia: analysis nf
24 cases with recombinant interleukin 2 as growth stimulus
I. Touw, W. Hofhuis, G.E. van Zanen, R. Delwel, B. Lowenberg 141
Part II - Intensive Chemotherapy Regimens for 'Minimal Residual Disease' in
Acute Myeloblastic and Lymphoblastic Leukemia
Biologic and treatment determinants of curability in acute myologenous
leukemia
M.J. Keating, K.B. McCredie, E.J. Freireich 148
High-dose cytosine-arabinoside plus AMSA for reinduction or consolidation
maintenance in acute myelogenous leukemia
R. Zittoun 159
Treatment of residual disease in AML: interim analysis of a southeastern
cancer study group prospective randomized clinical trial
R.S. Weiner, M. Raney, G.J. Elfenbein, B.S. Kramer, W.R. Vogler,
E.F. Winton, D.C. Shina 167
L-20 protocol for adult patients with acute lymphoblastic leukemia: a
protocol utilizing prognostic factors, intensive chemotherapy and autologus
"purged" marrow transplantation to eradicate minimal residual disease
T. Gee, S. Gulati, B.D. Clarkson 180
Treatment of minimal residual disease in adult ALL: the German national
study
D. Hoelzer, E. Thiel, H. Loffler, Th. Buchner, D. Bodenstein,
R. Engelhardt, H. Ruhl, A. Ganser, D. Messerer for the BMFT ALL/AUL
Study Group 196
Treatment of minimal residual disease in "poor risk" acute lymphoblastic
leukaemia with high-dose cytosine arabinoside
M.J. Barnett, J.E. Kingston, A. Miller, A.Z.S. Rohatiner, M.A. Horton,
M.F. Greaves, J.S. Malpas, T.A. Lister 205
Part III Autologous Bone Marrow Transplantation for the Eradication of
'Minimal Residual Leukemia'
Autologous bone marrow transplantation in first remission AML using non
purged marrow - update
A.K •. Burnett, S. McKinnon 211
Double autografting: a potential curative regimen for acute leukaemia?
C.C. Anderson, D.C. Linch, A.H. Goldstone for the Bloomsbury Transplant
W
~~
IX
Autologous bone marrow transplantation in acute nonlymphocytic leukemia. A
study of ex vivo marrow treatment with 4-hydroperoxycyclophosphamide
A.M. Yeager, H. Kaizer, H.G. Braine, M. Colvin, S.D. Rowley, R. Saral,
D.J. Fuller, R.F. Ambinder, W.H. Burns, S. May, L. Sensenbrenner,
R.K. Stuart, G.B. Vogelsang, J.R. Wingard, G.W. Santos 234
Attempts to eliminate residual acute myeloid leukemia from autologous bone
marrow grafts through in vitro chemotherapy - a review
P. Herve, E. Tamayo, J.Y. Cahn, E. Plouvier, M. Flesch, A. Peters
Technical assistance: M.C. Charvat 248
Monoclonal antibody purged autologous bone marrow transplantation for
relapsed non T-cell acute lymphoblastic leukemia
T. Takvorian, S. Sallan, J. Ritz 266
Allogeneic and autologous marrow transplantation: ex vivo purging with
monoclonal antibody or immunotoxins to remove leukemic cells or to prevent
graft versus host disease
J. Kersey, T. LeBien, D. Vallera, A. Filipovich, P. McGlave, T. Kim,
N. Ramsay 275
Detection and selective destruction of tumor cells by the lipophilic dye,
merocyanine 540
F. Sieber 282
Part IV Allogeneic Bone Marrow Transplantation for the Eradication of
'Minimal Residual Leukemia'
Factors influencing long-term leukemia-free survival after allogeneic bone
marrow transplantation for acute leukemia
F.E. Zwaan, J. Hermans, A. Lyklema for the EBMT Leukemia Working Party 295
Bone marrow transplantation with HLA identical donors in the acute
leukemias - Baltimore experience
G.W. Santos, R. Saral, W.H. Burns, H.G. Braine, L.L. Sensenbrenner,
J.R. Wingard, A.M. Yeager, R.F. Ambinder, S.D. Rowley, S. May,
305
G.B. Vogelsang
Results of allogeneic marrow transplantaton in patients transplanted for
acute leukemia: a long-term follow-up
R.P. Witherspoon, C.D. Buckner, E.D. Thomas, H.J. Deeg, K. Sullivan,
R. Clift, K. Doney, N. Flournoy, F. Appelbaum, J. Clark, J. Sanders,
R. Storb 318
Bone marrow transplantation in first CR of acute leukaemia using T-depleted
marrow from HLA identical sibling donors
H.G. Prentice, M.K. Brenner, J-P. Grob, G. Janossy, J. Wimperis,
A.V. Hoffbrand, J. Patterson, M. Gilmore, A.E. Thomas, J. Hancock,
J.K. Pattinson, N. Bell, D. Skeggs 323
Soybean lectin agglutination and E-rosette depletion for removal of T-cells
from HLA-identical marrow grafts: results in 60 consecutive patients
transplanted for hematologic malignancy
R.J. O'Reilly, N.H. Collins, J. Brochstein, N. Kernan, C. Keever, 337
x
H. Castro-Malaspina, N. Flomenberg, J. Laver, S. Gulati, J. Burns,
D. Emanual, C. Bordignon, T. Small, D. Hornick, B. Kushner, B. Shank
Allogeneic bone marrow transplantation in adult leukemia: result of T-cell
depletion by soybean lectin fractionation
G.W. Slocombe, N.W.J. Yeatman, M.G. Macey, A.C. Newland 345
Rapid lymphocyte depletion by a new elutriator rotor for the prevention of
acute graft versus host disease after allogeneic bone marrow
transplantation
T. de Witte, J. Janssen, A. Plas, J. Wessels, C. Haanen 355
Problems and prospect of histoincompatible bone marrow transplantation
studied in rhesus monkeys
G. Wagemaker 363
Allogeneic marrow transplantation for the treatment of leukemia. Role of
the major histocompatibility complex
J.A. Hanssen, P.G. Beatty, R.A. Clift, E.D. Thomas 374
Summing up
Minimal residual disease in leukemia: 1986
R.P. Gale 386
Index of subjects 388
