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.