Martin R. Klemperer

Epstein-Barr virus-induced diseases in boys with the X-linked lymphoproliferative syndrome (XLP): Update on studies of the registry

Analyses of 100 subjects with the X-linked lymphoproliferative syndrome (XLP) in 25 kindreds revealed four major interrelated phenotypes: infectious mononucleosis, malignant B-cell lymphoma, aplastic anemia, and hypogammaglobulinemia. Eighty-one of the patients died. Two male subjects were asymptomatic but showed immunodeficiency to Epstein-Barr virus (EBV). Seventy-five subjects had the infectious mononucleosis phenotype and concurrently, 17 subjects of this group had aplastic anemia. All subjects with aplastic anemia died within a week. Aplastic anemia did not accompany hypogammaglobulinemia or malignant lymphoma phenotypes. Hypogammaglobulinemia had been detected before infectious mononucleosis in three subjects, after infectious mononucleosis in five subjects, and was not associated with infectious mononucleosis in 11 boys with hypogammaglobulinemia. In nine subjects infectious mononucleosis appeared to have evolved into malignant lymphoma; however, the majority of patients with malignant lymphoma showed no obvious antecedent infectious mononucleosis. One subject had infectious mononucleosis following recurrent malignant lymphoma. Twenty-six of 35 lymphomas were in the terminal ileum. Results of immunologic and virologic studies of 15 survivors revealed combined variable immunodeficiency and deficient antibody responses to EBV-specific antigens. Mothers of boys with XLP exhibited abnormally elevated titers of antibodies of EBV. Subjects of both sexes with phenotypes of XLP should be investigated for immunodeficiency to EBV. Persons with inherited or acquired immunodeficiency may be vulnerable to life-threatening EBV-induced diseases.

Hereditary deficiency of the sixth component of complement in man. II. Studies of hemostasis.

Prompted by previous observations of defective blood clotting in rabbits deficient in the sixth component of complement (C6), an evaluation was made of the hemostatic functions of the homozygous proband of a newly recognized human kindred with hereditary C6 deficiency. This human subject, who had no clinical evidence of a bleeding disorder, exhibited a total lack of C6 by functional and immunoprecipitin assays of serum or plasma. Standard tests of hemostatic function were normal; however, when the whole blood clotting time was measured at 25 degrees C in plastic tubes, it was at the upper range of our normal values. In confirmation of this observation, prothrombin consumption, when performed at 37 degrees C in plastic tubes, was at the lower range of normal. Inulin and endotoxin, in concentrations shown to cause activation of human complement, had little or no effect on clotting times or prothrombin consumption of normal or C6-deficient human blood. These observations indicate that absence of C6 does not have a significant effect on hemostatic function in man. In the light of other investigations, the observed differences in clotting function between C6-deficient human blood and C6-deficient rabbit blood could be due to species differences governing the susceptibility of platelets to complement activation.

Evidence of clastogens in acute leukemia. Chromosomal abnormalities in healthy parents of congenital leukemic patients.

If leukemia is caused by an “agent” which can pass through the placenta, it could produce leukemic transformation in the maternal cells. Cytogenetic studies were carried out in 5 acute lymphoblastic leukemic children and their parents. Significant abnormalities were found in 3 of the fathers, 4 of the mothers, and all the leukemic children. All but one abnormal metaphase from the mothers of the 2 leukemic boys had a XX sex pattern, indicating that these abnormal metaphases originated in the mother and probably were caused by a chromosomal breaking agent. The abnormal metaphases found in the fathers suggests that they too were exposed to this agent. Therefore, this agent must be present in the immediate environment, and this can pass from the maternal circulation to the fetus through the placenta and affect the fetus cells. The failure of the infant to eradicate these abnormal cells results in the phenotypical expression of clinical leukemia. Cancer 46:109–117, 1980.

Survival prediction based on morphology of lymphoblasts.

Following publication of the paper entitled “Subdivision of Classical Varieties of Acute Leukemia. Correlation with Prognosis and Cure Expectancy” by G. Mathe et al. [1], considerable interest has been rekindled regarding the ability to 1. subclassify acute lymphocytic leukemia and 2. correlate the cell type with prognosis. The following study was an attempt to utilize the Mathe nomenclature of prolymphoblastic, macrolymphoblastic, microlymphoblastic, and prolymphocytic cell types in a series of acute lymphocytic leukemias of childhood (under 14 years of age) treated by the Pediatric-Hematology Unit of the University of Rochester School of Medicine.