Mills, Stephen D.

THE RECENT publications of Farber and co-workers dealing with the treatment of acute leukemia in children have awakened widespread interest. Their investigations have stimulated hope for the amelioration of symptoms of this fatal disease and indicated the possibility of provoking remissions that lengthen the lives of those patients affected by it, while making them more comfortable at the same time. In investigating leukemia and allied conditions of a neoplastic nature, Farber and co-workers noted what they termed an "acceleration phenomenon" in the blood and bone marrow of leukemic children treated with folic acid or its conjugates such as diopterin (pteroyldiglutamic acid) or teropterin (pteroyltriglutamic acid). There was marked hyperplasia of the marrow as well as of other sites of leukemic involvement at postmortem examination. They reasoned that if folic acid or its conjugates speeded up the leukemic process, an antagonist to folic acid might be devised in order to retard the progress of the disease or stop it altogether. Through co-operation with the research division of one of the major pharmaceutical firms, a series of folic acid antagonists was soon developed. One of these was aminopterin (4-aminopteroylglutamic acid). It differs from folic acid only in the substitution of the NH2 group for the OH radical in the fourth position of the pteridine group. Of several compounds synthetically made, it has been the most effective and yet most toxic agent in its action on the leukemic process. Farber and co-workers first employed aminopterin in the treatment of acute leukemia of children in December 1947.

Osteoid osteoma is a small, benign tumor usually of endochondral bone, affecting mainly the long bones of the extremities and occurring not uncommonly among children. It produces pain which may disturb sleep and interfere with normal activities. The roentgenogram reveals a radiolucent area surrounded by osteosclerosis. This is suggestive of osteoid osteoma but differential diagnosis from certain other neoplastic, inflammatory and metabolic lesions of bone must be made. Thirteen children with osteoid osteoma have been treated by excision of the lesion at the Mayo Clinic. The results have been uniform alleviation of symptoms. This experience and that obtained elsewhere has shown that incomplete removal of the nidus may lead to recurrence of the symptoms.

Abstract The effect of 6-MP therapy on the duration of remissions induced by adrenal corticosteroids has been studied as a model for testing of new agents. Ninetytwo patients under age 20 entered the study and were accepted for analysis. Sixty-two (67 per cent) had complete or partial remissions induced by corticosteroids. Patients in remission were randomly assigned to maintenance therapy with either 6-MP or placebo. The median duration of 6-MP-maintained complete remissions was 33 weeks and for placebo, 9 weeks. A sequential experimental design was used to analyze remission times while the study was in progress. This resulted in the study being stopped after analysis of the remission times of 21 pairs of patients (42 patients). Overall survival was not significantly different for the two treatment programs, since patients maintained on placebo were treated with 6-MP when relapse occurred. The activity of the known active antileukemic compound 6-MP was readily detected by this experimental design without compromise of optimal survival. Such a design should prove useful for the evaluation of new agents and also permit study of the remission maintenance activity of a compound separately from its remission inducing activity.

Although most patients with coarctation of the aorta survive to early adult life, it has been adequately demonstrated that some patients die in infancy and early childhood as a result of their coarctation. In selected cases, then, operation is advisable at a very early age. Cardiac failure in a 10 week old infant necessitated operation at this age in the case reported.