The Leukemias: Etiology, Pathophysiology, and Treatment

685 Pages·1957·17.559 MB·English

by  John W. Rebuck, Frank H. Bethell and Raymond W. Monto (Eds.)

Previous Henry Ford Hospital Symposia
1. The Dynamics of Virus and Rickettsial Infection
2. The Hypophyseal Growth Hormone, Nature and Actions
3. Cardiovascular Surgery: Recent Studies in Physiology,
Diagnosis, and Techniques
4. Enzymes: Units of Biological Structure and Function
HENRY FORD HOSPITAL
International Symposium
THE LEUKEMIAS:
Etiology, Pathophysiology,
and Treatment
Edited by
John W. Rebuclc
Division of Hematology
Department of Laboratories
Henry Ford Hospital
Detroit
Frank H. Bethell
The Thomas Henry Simpson Memorial Institute
for Medical Research
Ann Arbor
Raymond W. Monto
Division of Hematology
Department of Medicine
Henry Ford Hospital
Detroit
1957
ACADEMIC PRESS INC. ' PUBLISHERS ' NEW YORK
Copyright ©, 1957,
by
ACADEMIC PRESS INC.
Ill FIFTH AVENUE
NEW YORK 3, N. Y.
All Rights Reserved
NO PART OF THIS BOOK MAY BE REPRODUCED
IN ANY FORM, BY PHOTOSTAT, MICROFILM, OR
ANY OTHER MEANS, WITHOUT WRITTEN PERMIS-
SION FROM THE PUBLISHERS.
Library of Congress Catalog Card Number: 57-8380
PRINTED IN THE UNITED STATES OF AMERICA
Participants
Awapara, Jorge Houston, Texas
Berman, Lawrence Detroit, Michigan
Bessis, Marcel C. Paris, France
Bethell, Frank H. Ann Arbor, Michigan
Bierman, Howard R. Duarte, California
Brown, George B. New York, New York
Buchanan, John M. Cambridge, Massachusetts
Burchenal, Joseph H. New York, New York
Butler, John B. Rochester, New York
Craddock, Jr., Charles G. Fort Ord, California
Dameshek, William Boston, Massachusetts
DeMarsh, Q. B. Seattle, Washington
Doan, C. A. Columbus, Ohio
Dougherty, T. F. Salt Lake City, Utah
Ellison, Rose Ruth New York, New York
Farber, Sidney Boston, Massachusetts
Finch, Stuart C. New Haven, Connecticut
Furth, Jacob Boston, Massachusetts
Gellhorn, Alfred New York, New York
Goldthwait, David A. Cleveland, Ohio
Gordon, Albert S. New York, New York
Gross, Ludwik New York, New York
Hamilton, L. D. New York, New York
Hauschka, Theodore S. Buffalo, New York
Hayhoe, F. G. J. Cambridge, England
Hill, Joseph M. Dallas, Texas
Hitchings, George H. Tuckahoe, New York
Hopps, H. D. Oklahoma City, Oklahoma
Hutchison, Dorris J. New York, New York
Jacobson, L. O. Chicago, Illinois
Jones, Oliver P. Buffalo, New York
Kaplan, Henry S. San Francisco, California
Kieler, J0rgen Copenhagen, Denmark
Kirschbaum, A. Houston, Texas
Krakoff, I. W. New York, New York
Law, L. W. Bethesda, Maryland
Martin, Samuel P. Durham, North Carolina
Moeschlin, Sven Solothurn, Switzerland
Moore, Carl V. St. Louis, Missouri
Nichol, Charles A. New Haven, Connecticut
Osgood, E. E. Portland, Oregon
Richter, Maurice N. New York, New York
Rossiter, Roger London, Canada
Rouser, George L. Duarte, California
Schrek, Robert Hines, Illinois
Skipper, Howard E. Birmingham, Alabama
Storti, Edoardo Modena, Italy
Tullis, James L. Jamaica Plain, Massachusetts
Valentine, William N. Los Angeles, California
Vilter, Richard W. Cincinnati, Ohio
Waisman, Harry A. Madison, Wisconsin
Weisberger, A. S. Cleveland, Ohio
Will, John J. Cincinnati, Ohio
Wintrobe, M. M. Salt Lake City, Utah
Winzler, Richard J. Chicago, Illinois
Witts, L. J. Oxford, England
Zuelzer, Wolf W. Detroit, Michigan
PREFACE
In the last two decades most of the medical disciplines have made
dramatic and far-reaching advances toward the control and cure of a
major share of the diseases which appropriately pertain to them. In
that portion of medical science which concerns itself with the leukemias,
the advances have been complex. It could hardly have been otherwise.
Hematologists in the previous generation had achieved a higher insight
into free-celled leukocytic structure than was true in the tissue-organ
areas of other disciplines. Consequently, cytologie objectives whose
functional significance was barely appreciated elsewhere, were common-
place here.
This volume accomplishes two purposes. It gives the present complex
position of leukemic etiology and pathophysiologic disturbance, a much
needed knowledge of detailed leukocytic functions and comprehensive
thought on the therapy of the leukemias. It establishes a basis of com-
parison with the earlier works of Downey and Forkner in this field in
the late thirties and thus makes it possible to see with some clarity the
extent of progress made. Actually the progress has been extensive and
at an accelerated rate of speed.
Perusal of the material contained in this volume suggests some fas-
cinating and challenging problems ahead. When hematology struggled
for tools and methods other than the blood smear or the counting
chamber, its choices and decisions were limited. Once this point was
passed, however, each investigator was faced with a new question:
"What kind of approach do I wish to take?" The hematologist may
literally choose for example between electron microscopic, immunologie,
biochemical, metabolic, microbiologie, endocrine, genetic, toxicologie,
and isotopic routes. Each investigator makes these choices according to
his training and objectives. This volume details in quiet pages, the
aggregate achievements stemming from these personal decisions.
Coming a century after Virchow's and Bennett's recognition of leu-
kemia, this book as a whole—as well as almost every individual chapter
—is in a very real sense the result of cooperative effort. The content
of this volume arises from the proceedings of an International Sym-
posium on The Leukemias: Etiology and Pathophysiology held at
Henry Ford Hospital, Detroit, March 8-10, 1956. It is significant that
this symposium was suggested and sponsored by the members of the
clinical staff of Henry Ford Hospital and its Executive Director, Dr.
Robin C. Buerki. It is a pleasure to acknowledge their consideration as
well as the initiative and effort of the members of the program commit-
tee, the fifty-six participants and the more than four hundred fellow
scientists who were in attendance.
Detroit, Michigan J. W. REBUCK
January, 1957
The Symposium was sponsored by the Henry Ford
Hospital, Detroit, Michigan, and held at the Hospital,
March 8, 9, 10, 1956.
Program Committee
Advisory: Local:
FRANK H. BETHELL RAYMOND W. MONTO
HOWARD R. BIERMAN JOHN W. REBUCK
JOSEPH H. BURCHENAL WOLF W. ZUELZER
SIDNEY FÄRBER
CARL V. MOORE
I
Electron Microscopy of Normal and Leulcemic Leukocytes
MARCEL C. BESSIS
National Blood Transfusion Center, Paris, France
General Considerations
The ability to make very thin preparations is one of the principal
difficulties which interferes with the use of the electron micro-
scope. This problem has been solved only since 1954, when a technique
for obtaining extremely thin sections was developed.
Formerly one had to use the technique of spreading and the technique
of casting and shadowing which can be applied to isolated cells only.
In this way one can obtain excellent pictures of the cell surface. This
process has led, for example, to the study of the surface of cells sampled
by sternal puncture. But the casting technique does not show anything
about what is inside the cell, and here lies the enormous advance ac-
complished by the ultrathin section technique. It is now possible to ob-
tain preparations, the thickness of which is in the neighborhood of
0.02 μ. As a result a white cell may be sliced into 800 sections. To get
this surprising result took only a few improvements in the usual section-
ing technique. The first and most important is the use of very hard em-
bedding substances. After various researches in the paraffin field, embed-
ding in plastic has been adopted, the specific substance being butyl
methacrylate. After dehydration the fragments which are to be sec-
tioned are soaked in monomeric methacrylate which is later polymerized.
The necessity of obtaining ultrathin sections led also to special adjust-
ments of the microtomes. Ordinary microtomes with mechanical ad-
vance were used at first. These were replaced by the principle of thermic
advances in which the block-holder is tied to a metallic rod which is
slowly heated by an appropriate apparatus, and which expands out in
proportion to the heat. In this way one avoids the inconveniences of
mechanical advance, always allowing a certain amount of slackening.
1
2 MARCEL C. BESSIS
Nevertheless, for the time being, good results may be obtained with
either of these two types of microtomes.
a a * a a
It is important to appreciate that electron microscope sections cannot
be interpreted in the same way as sections seen with an ordinary micro-
scope. A fundamental point which distinguishes them lies in the stain-
ing process applied to the latter, and this, in reality, consists of two
processes. The first is well enough known: The proteins which make up
the various structures of cells and tissues have variable properties as
regards their chemical combination with, or adsorption of, more or less
specific stains. The second, which is generally overlooked, is very im-
portant and depends on the fact that Canada balsam (or a similar
mounting medium) is used; this, because of its refractive index, sup-
presses everything which has not been fixed by the stain, thus rendering
the stained material all the more clear. The fundamental technique of
classical hematology, indeed, is to show up structures which stain and
suppress those which do not.
The structures which are suppressed in this way represent the con-
fused mass of cellular and tissue proteins which have been coagulated
and deformed by fixation and which, if seen, would appear in a very
different form from that in which they normally exist. These are what
are called artifacts. One forgets them because one does not see them;
the observer takes into account only the material which is stained, and
not the surrounding unstained material which is rendered invisible by
the mounting medium. Although the unstained material is not seen, it
nevertheless exists.
When phase contrast is used, otherwise unperceived differences of
refractive index are revealed, and these artifacts appear distinctly. The
importance of structures which classical staining techniques render in-
visible now becomes apparent, and it will be clear that the images fur-
nished by staining techniques are simple and definite but also in-
complete.
If this is true when ordinary histological preparations are examined
with phase contrast instead of the ordinary microscope, it is even more
true when the electron microscope is used, for the latter shows up the
smallest artifact due to technique, and the important problem of histo-
logical fixation has to be looked into anew from the standpoint of elec-
tron microscope technique.
There is a second fact which must be appreciated and which has to
do with the physical conditions under which the image is formed in the