Summary. The purpose of this study was to elucidate the effect of neuraminidase on circulating platelets in rats and the pathogenesis of this effect. Injection of bacterial, purified bacterial and viral neuraminidase caused thrombocytopenia of various degrees. Thrombocytopenia was less pronounced in rats given viral neuraminidase and in splenectomized animals. A dose‐response effect was seen only with purified bacterial neuraminidase injected intravenously. Ultrastructural studies of blood platelets were performed after injection of neuraminidase. Fifteen minutes after injecting neuraminidase, before a definite fall in the count, platelets showed evidence of structural damage such as irregular shapes, centripetal migration and fusion of granules and bleb formation. The structural alterations were progressive, reaching a maximum at about 2–4 hr. At no time were large platelet aggregates observed in the circulating blood. Four hours after injection of neuraminidase, when the platelet count dropped significantly, many platelets had normal ultrastructurc. By 24 hr, the majority of circulating platelets appeared normal; however, the splenic sinusoids and macrophages contained platelets with the same structural abnormalities seen in the circulation 15 min to 2 hr after injection of neuraminidase. We conclude that neuraminidase alters the platelet membrane resulting in its rapid and permanent removal by the reticuloendothelial system.

The initial features, response to therapy, complications, cause of death, and prognostic factors of 171 consecutive children with ANLL are described and compated to historical data for adults with ANLL and for children with ALL. Major differences between children and adults with ANLL include a higher frequency of CNS leukemia and a lower frequency of early deaths in the children. The most important differences between children with ANLL and ALL are the absence of a peak age of incidence in ANLL and the far better response to therapy in ALL. Among features present at 100,000/mm3 or above, and no palpable hepatomegaly had significantly longer survivals, while patients with platelet counts below 10,000/mm3 had significantly shorter survivals. The frequency and duration of remission were significantly better with three protocols used since 1968 than previously. However, even with these protocols, the results were far from satisfactory, with a complete remission frequency of 66%, a median duration of hematological remission of 6 months, and a median duration of survival of 10 months. The striking contrast of these results in childhood ANLL with current results in childhood ALL underscores the need for novel, imaginative therapeutic approaches for ANLL.

Asparaginase was administered to children with acute lymphocytic leukemia in dosages less than those generally used. The objectives were to determine whether toxicity of the enzyme could be reduced without loss of efficacy, and to compare weekly with twice weekly administration. In five of 11 children who received 5,000 international units (IU)/sq m twice weekly for four doses and four of ten who received 10,000 IU/sq m once weekly for two doses, examination of bone marrow showed complete remission. Although the usual asparaginase-induced toxic reactions occurred, there were no deaths due to toxic reaction and no clinical signs of pancreatic dysfunction. Toxic reactions were comparable in the once weekly and twice weekly groups. Toxicity can be decreased without loss of efficacy by using these reduced dosage schedules.The enzyme asparaginase has been demonstrated to produce com¬ plete remission on bone marrow ex¬ amination in approximately 50% of children with acute lymphocytic leu¬ kemia refractory to conventional treatment.1" However, toxic reac¬ tions have been considerable. The en¬ zyme consistently produced fatty metamorphosis of the liver with de¬ rangement of hepatic function.:J-e-8-u Acute necrotizing pancreatitis was found in 10% of patients who failed to survive after asparaginase treatFollowing two to three weeks of enzyme therapy, anaphylac¬ toid reactions were common.'-17-9'"Abnormalities of blood coagulation factors1" were encountered frequent¬ ly but rarely were associated with fatal hemorrhage. In a previous study9 we found that weekly administration of asparagin¬ ase was as effective as a daily sched¬ ule in producing remissions and was accompanied by less toxic reaction.We also observed that treatment with asparaginase beyond two weeks did not result in further marrow im¬ provement when only partial remis¬ sions occurred.The objectives of this study were (1) to determine whether lower dos¬ age of asparaginase over shorter periods of time would result in de¬ creased toxicity without reduced fre¬ quency of remission induction, and(2) to compare once weekly and twice weekly administration with regard to efficacy and toxicity. Materials and MethodsAmorphous Escherichia coli asparagin¬ ase in vials containing 10,000 in¬ ternational units (IU) of the lyophilized powder was used. Specific activity of this preparation was 363 IU/mg protein. Prior to administration, 5 ml of water for in¬ jection was added to each vial and the cal¬ culated total dose was withdrawn. Each dose was further diluted with 5% dextrose in water to a total volume of 12 ml. This was administered intravenously over a pe¬ riod of five minutes.Patients were assigned by a randomiza¬ tion card technique to receive 10,000 IU/sq m of body surface area in¬ travenously weekly for two doses, or 5,000 IU/sq m twice weekly for four doses. Toxicity and response were evaluated follow¬ ing two weeks of treatment.Marrow response was quantitated ac¬ cording to the following criteria used at St. Jude Children's Research Hospital: (1) Complete remiss...

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