Blood, 1955, Vol. 10, No. 3, pp. 197-227.
© 1955 American Society of Hematology, Inc.
The Auto-Immune Hemolytic Anemia of Malignant
Lymphocytic Disease
MARTIN C. ROSENTHAL 1,
ANTHONY V. PISCIOTTA 1,
ZACHARIAS D. KOMNINOS 1,
HENRY GOLDENBERG 1, and
WILLIAM DAMESHEK 1
1 Ziskind Laboratories (Hematology Section) of the Joseph H. Pratt and New
England Center Hospitals, and the Department of Medicine, Tufts College Medical School.
Twenty-four cases of malignant lymphocytic disease associated with frank
hemolytic anemia are reviewed. Four cases were associated with some form of
lymphosarcoma and twenty cases appeared in conjunction with chronic lymphocytic leukemia.
In the latter cases, the hemolytic process was detected in eleven patients from
one-half to five years after the original diagnosis had been established. In three
patients, a positive Coombs’ test antedated the development of any other evidence of a hemolytic process by either several months or a year. In a significant
number of cases, x-ray therapy seemed to precipitate the appearance of the
abnormal hemolysis. In nine other patients, only when symptoms referable to
hemolytic anemia necessitated medical aid, was the lymphocytic leukemia
detected.
Of the four patients with lymphosarcoma, three presented themselves initially
as cases of hemolytic anemia. The primary diagnosis was uncovered only after
lymph node biopsy or laparotomy.
The physical examination in both disease groups represented a combination
of the findings associated with hemolytic anemia and lymphocytic disease. In
the cases of chronic lymphocytic leukemia, this led to splenomegaly of unusual
degree and disproportionate to the size of the lymphadenopathy.
The laboratory findings likewise combined the features of both the primary
lymphocytic disorder and hemolytic anemia. Anemia, reticulocytosis, spherocytosis, and bilirubinemia of the indirect type were present, and in the cases of
lymphocytic leukemia, elevated white cell counts with diminished platelet
counts were found. The bone marrow in many instances represented a "duality
of proliferation", hyperplasia of erythroid and lymphoid elements existing side
by side.
Immunologic studies clearly indicated that the mechanism of hemolysis in
these cases differed in no respect from that of "idiopathic" auto-immune hemolytic anemia. The direct Coombs’ test was positive in all twenty cases in which it
was employed, and circulating hemagglutinins were demonstrated in eleven of
nineteen cases so tested.
The multiplicity of laboratory indications of hemolysis, as well as the distinct
immunologic mechanism, distinguish these cases of hemolysis from the so-called "occult" hemolytic anemia. The term "overt" hemolytic anemia has
been used to emphasize the difference.
The role of the lymphoid apparatus in the production of such auto-immune
hemolytic anemia is discussed. The bulk of evidence would seem to implicate
some cellular component of the lymphoid system, although not the adult lymphocyte, as the producer of antibody. The architectural disruption of this system in
malignant lymphocytic disease might well have a functional counterpart with
respect to its immunologic duty. The resultant aberration may manifest itself
clinically as auto-immune hemolytic anemia.
At present the therapy of choice for control of the hemolytic process is ACTH,
Compound E or Compound F. Transfusions and splenectomy are useful ancillary
measures when hormonal therapy is either partially or totally unsuccessful. The
hemolytic component should be treated independently of the lymphocytic
proliferation since control of both cannot be established by any one agent currently available.
Submitted on May 25, 1954
Accepted on July 14, 1954
