Hodgkin's disease developed in a girl 8 years 9 months of age with the physical and hematologic stigmata of Chediak-Higashi syndrome. The association of malignant lymphoma with Chediak-Higashi syndrome has been reported previously, but to our knowledge, no case of Hodgkin's disease has been described to date.
Children with Hodgkin's disease had significantly elevated serum IgG and IgA levels but normal IgM and IgD levels when compared with healthy age- and sex-matched controls. The increased serum IgG and IgA levels occurred in all four clinical stages of Hodgkin's disease but were not related to histologic cell type. Following staging splenectomy, serum IgG, IgA, and IgD levels fell by 20% in patients who recieved radiation therapy then returned to preoperative levels; by contrast, serum IgM levels fell by 50% and remained there for at least 36 months. Patients who received chemotherapy had a persistent decline in serum levels of all immunoglobulin classes by at least 40%. Thus, staging splenectomy per se appears to be at least partly responsible for the postoperative decline in serum IgM levels and this effect is enchanced by aggressive treatment of the Hodgkin's disease.
2-Amino-6-mercapto-9 β -d-ribofuranosylpurine (thioguanosine) has been used orally and intravenously in the treatment of 82 patients with leukemias and disseminated tumors.
The oral dose of thioguanosine required to produce toxic or therapeutic responses was less than half the oral dose of thioguanine necessary to produce comparable results calculated on a molar basis. However, the two compounds were equally active when given by the intravenous route, indicating that the difference in oral dosage of the two compounds was due to a difference in absorption.
Remissions have occurred in diseases which might have been expected to respond to the purine antagonists (acute leukemia in children and adults and chronic granulocytic leukemia) and only in cases which had not already become resistant to 6-mercaptopurine. Thioguanosine therefore appeared to have no qualitative or quantitative advantages over the previously available purine analogs.
Actinomycin D has a slight but definite effect in producing regression of tumors in patients with cancer. Wilms' tumor and lymphomas have shown better response than other tumors. Although the effect of the combination of actinomycin D and x-ray therapy is difficult to evaluate, these agents appear to be additive in producing temporary regression of the tumor in some patients. The usual single course of actinomycin D intravenously is 75 µ.g/kg of body weight divided into four or five daily doses. The oral dose of actinomycin D is 3 to 10 mg daily. About 5% of actinomycin D given orally is absorbed as evidenced by production of systemic toxicity. However, severe local gastrointestinal effect usually prevents adequate oral administration of the drug. The toxic effects of actinomycin D are local on the gastrointestinal tract with ulceration of the mouth, nausea, vomiting, anorexia, occasional abdominal pain and diarrhea; exacerbation of skin reaction in previously irradiated areas; alopecia; decrease in leukocyte and platelet counts. The toxicity after intravenous administration of actinomycin D usually develops within the first 2 weeks and disappears within the next 2 weeks. The duration of improvement after a single course of actinomycin D intravenously was usually from 1 to 10 weeks. Two children, one with Wilms' tumor and one with embryonal carcinoma, had no recurrence for 24 and 7 months, respectively. Both received maintenance doses of actinomycin D orally.
2'-Fluoro-5-iodo-1-beta-D-arabinofuranosylcytosine (FIAC) is a potent selective inhibitor of the replication of herpes simplex virus types 1 and 2 (HSV-1, HSV-2), varicella zoster virus, and cytomegalovirus in cell culture systems. FIAC produces an unequivocal therapeutic effect in mice that have been inoculated with a lethal burden of HSV-1. We have administered FIAC to 32 host compromised patients, 30 with advanced cancer, who were experiencing acute herpesvirus infections (varicella zoster, 29; HSV-1, 2; HSV-2, 1); the drug was given by 20 min i.v. infusion twice a day for 7 days. The dosage levels explored were 60, 120, 240, 400, and 600 mg/sq m/day. Drug-induced myelosuppression became evident at 600 mg/sq m/day; thrombocytopenia exceeded leukopenia. The toxic low dose was 400 mg/sq m/day with mild nausea and rare myelosuppression. All 24 varicella zoster patients with cutaneous disease receiving FIAC, greater than or equal to 120 mg/sq m/day, experienced stabilization of cutaneous lesions within 48 to 72 hr; healing began promptly thereafter.
A THERAPEUTIC SYNERGISTIC EFFECT IS SEEN IN ANIMAL MODELS when vinca alkaloids are administered after methotrexate. To examine further this interaction in clinical studies, a phase I-II trial was conducted in children with hematologic malignancies in the Department of Pediatrics at Memorial Sloan-Kettering Cancer Center. A schedule of sequential of methotrexate and vindesine was developed which showed effect in acute lymphoblastic leukemia in children in relapse and which was relatively nontoxic. The regimen has also been useful for reinduction for patients who are candidates for bone marrow transplant.
