Gregg T. Aspnes

Chronic neurologic disturbance in childhood leukemia.

Twenty‐three leukemic children were studied prospectively to detect chronic effects of therapy. All patients received CNS prophylaxis, including 2400 R cranial irradiation, and intermittent maintenance therapy with intravenous methotrexate, cyclophosphamide and cytosine arabinoside. Neurologic symptoms were observed in 12 patients, all of whom had intermittent limping and mild incoordination, between the 10th and 18th month of maintenance therapy. Five of the 12 sustained seizures and four of these had subsequent abnormalities in motor, perceptual, behavioral or language development. Three school‐aged children have learning disability and perceptual‐motor defects. Studies of CSF folate and MTX content are presented but are not helpful in delineating the etiology of these neurologic symptoms.

Prospective study of sickle cell anemia in infancy.

Twelve infants with sickle cell anemia identified in the course of a cord blood screening program have been followed prospectively for up to three years of age. The development of hemolytic anemia paralleled the postnatal decline in fetal hemoglobin and was evident in all infants by 12 weeks of age. Vasoocclusive episodes occurred in more than half the infants and seven aplastic crises were documented in four patients. Febrile illnesses were common and one of the twelve infants developed pneumococcal sepsis. This study also demonstrated that functional asplenia is an acquired defect in sickle cell disease. The onset of functional asplenia was documented with splenic scans in six of the nine infants followed for more than one year after birth. There have been no deaths in this series.

Cytophilic Antibodies in Man

Abstract Antibodies cytophilic for macrophages, mediating attachment of immunologically naive macrophages to leukemic cells, were found in the serum of 25 patients with acute myelocytic or lymphocy...

COMPREHENSIVE TESTING FOR THALASSEMIA TRAIT

The thalassemias are a group of hereditary blood conditions that occur with considerable frequency in ethnic groups tracing their origins to countries that border the Mediterranean Sea, the Middle East, and Southeast Asia.l The conditions result from genetic defects causing deficient synthesis of hemoglobin polypeptide chains, and are manifested by microcytic, hypochromic anemias of varying degrees of severity. In the homozygous state, thalassemia genes cause severe and often lethal diseases for which there is no cure.2 The heterozygous state, thalassemia trait, is usually benign, but has clinical and genetic implications. Diagnosis of thalassemia trait is suggested by a familial microcytosis and is usually confirmed by demonstration of characteristic changes in the proportions of Hgb A? and F or unbalanced polypeptide chain synthe~is .~-~ These latter diagnostic tests are somewhat complicated and expensive, and this has inhibited the screening of populations at risk for these defects. Techniques for rapid, accurate electronic measurement of red cell size have recently become available. A preliminary study at this institution by one of us (P.M.) indicated that about 25% of hospital patients with microcytosis determined with an electronic cell counter (Coulter Model S) had thalassemia trait.6 This suggested that measurement of mean corpuscular volume (MCV) might be used as a screening test for thalassemia trait but did not indicate its reliability. The present report describes a comprehensive testing program for thalassemia trait in high-risk populations. This program included education, voluntary testing with evaluation of several screening methods, and individual genetic counseling. The program was designed to conform with the recommendations of the Institute of Society, Ethics and Life Sciences regarding the initiation and operation of genetic screening programs.’

NEUROTOXICITY IN LEUKEMIC CHILDREN RECEIVING PROPHYLACTIC CRANIAL IRRADIATION AND MAINTENANCE HIGH DOSE METHOTREXATE

Non-leukemic neurologic abnormalities may be produced or enhanced in children with lymphoblastic leukemia receiving prophylactic CNS therapy and high-dose maintenance methotrexate (MTX). 22 children given cranial irradiation and intrathecal MTX after remission induction were maintained for 1-3 years with biweekly intravenous MTX, 125-450 mg./m2; cyclophosphamide, 200 mg./m2, and cytosine arabinoside, 100 mg./m2. Eight children (36%) suffered transient encephalopathy, previously described by Aur, et al., during the second month after irradiation. Other neurologic abnormalities were observed 6-24 months after CNS prophylaxis, during which time dosage of MTX was increased to tolerance. Four children developed a seizure disorder and perceptual-motor deficits; two improved clinically after discontinuation of parenteral MTX. McCarthy tests administered to 18 patients revealed gross and fine motor or perceptual-motor deficits in 9 (50%). Insidious limping of uncertain etiology was persistent in 8 children (36%). CSF folate levels fell to less than 10 ng./ml. in 13 (59%), and transient, mild EEG changes occurred in 8 asymptomatic patients. The combination of high-dose parenteral MTX following CNS prophylaxis may be causally related to subsequent non-leukemic neurologic disturbances.

SPLENIC FUNCTION AND HEMATOLOGIC CHANGES DURING THE FIRST YEAR OF LIFE IN SICKLE CELL ANEMIA

Seven infants with sickle cell anemia have been identified in routine screening of cord blood from 1500 neonates. These children have been followed serially for up to 2 years. Hemoglobin levels fell most rapidly during the first 3 months and then declined more slowly, stabilizing between 7 and 10 gm% by 10 months of age. The post natal decline of Hgb F was slower than normal but showed considerable variability. There was close correlation between the rate of fall of Hgb F and the development and severity of hemolysis. Clinical vasocclusive symptoms occurred as early as 4 months but were also variable. 99mTc colloid scans showed normal splenic activity in all infants before 6 months. The onset of functional asplenia was documented in four infants at 7, 8, 10 and 11 months. Thus, functional asplenia is an acquired defect in sickle cell anemia. Howell-Jolly bodies were noted prior to the abnormal scan. Functional asplenia occurred when Hgb F fell below 20%. Two infants retain normal splenic function at 12 and 20 months. These observations indicate variability in the development of hematologic and splenic abnormalities in children with homozygous Hgb S disease. The fact that splenic dysfunction, with resultant susceptibility to overwhelming sepsis may occur as early as 7 months of age in this disease, provides impetus for early diagnosis.