Joseph H. Kushner

Childhood non-Hodgkin's lymphoma. The results of a randomized therapeutic trial comparing a 4-drug regimen (COMP) with a 10-drug regimen (LSA2-L2).

Members of the Childrens Cancer Study Group treated 234 eligible patients in a randomized trial designed to study the relative effectiveness of two therapy programs for the treatment of childhood and adolescent non-Hodgkins lymphoma. Two chemotherapeutic strategies were compared: a 4-drug regimen (COMP) and a 10-drug regimen (modified LSA2-L2). Failure-free survival for all patients was 60 per cent at 24 months. In patients with disseminated disease treatment success was influenced by both the histologic subtype of disease and the therapeutic regimen followed. The 10-drug program was more effective than the 4-drug program in patients with disseminated lymphoblastic disease (two-year failure-free survival rate, 76 vs. 26 per cent, respectively; P = 0.0002), whereas the 4-drug program was more effective than the 10-drug program in those with nonlymphoblastic disease (57 vs. 28 per cent, respectively, P = 0.008). The less toxic, more easily administered 4-drug regimen was as effective as the 10-drug regimen in patients with localized disease (89 vs. 84 per cent, respectively).

Human Leukocyte Interferon for the Treatment of Varicella in Children with Cancer

Human leukocyte interferon was evaluated as a treatment for varicella in a randomized double-blind, placebo-controlled study carried out in two phases. A total of 44 children being treated for cancer were enrolled within 72 hours of the appearance of the exanthem. The mean number of days of new lesion formation was 3.8 +/- 1.89 (+/- S.D.) in the interferon recipients and 5.3 +/- 2.56 in the placebo recipients (P less than 0.05). Eighty-one per cent of the interferon recipients had had no new lesions for 24 hours by Day 7, as compared with 56 per cent of the placebo recipients (P less than 0.025). In the second, higher-dose phase of the study 92 per cent of the interferon recipients had had no new lesions for 24 hours by Day 6, as compared with 45 per cent of the placebo recipients (P less than 0.025). Three of 21 placebo recipients died of progressive varicella. Two of the 23 interferon recipients died two to three weeks after the onset of varicella; viral cultures were negative in one of these patients, and the second had recurrent viremia at the end of the treatment period. Among the survivors, treatment with interferon reduced the number of patients who had life-threatening dissemination (none of 21 vs. three of 18; P = 0.053). We conclude that interferon had an antiviral effect against varicella virus in immunocompromised patients.

Studies on the pathology of non‐Hodgkin's lymphoma of childhood: I. The role of routine histopathology as a prognostic factor a report from the childrens cancer study group

Between April 1977, and August 1980, the Childrens Cancer Study Group (CCSG) conducted a clinical trial of childhood non‐Hodgkins lymphoma (NHL), randomizing 256 patients to one of two treatment regimens. A 4‐drug regimen (regimen 1, modified cyclophosphamide, Oncorin [vincristine], methotrexate, prednisone [COMP]) was compared with a 10‐drug regimen (regimen 2, modified LSA2‐I2). Using the Rappaport classification, the review pathologist diagnosed the 213 evaluable tissue specimens as follows: lymphoblastic (LC), 73; Burkitts tumor (BT), 40; “undifferentiated” non‐Burkitts type (NB), 67; large cell or “histiocytic” lymphoma (HI), 29; and other types (OT), 4. Concurrence in classification between the review and institutional pathologists was poor when using the above four categories; however, concurrence was 88% between the review pathologist and other hematopathologists, and 99% when classifying the specimens as lymphoblastic or nonlymphoblastic. For patients with nonlocalized disease, this randomized controlled study demonstrated a new important correlation of histopathology with the effectiveness of treatment. When analyzed without stratification into lymphoblastic and nonlymphoblastic types, the two regimens showed identical relapse free survival (RFS) curves for patients with nonlocalized involvement. However, when patients were stratified according to histologic classification, regimen 2 was superior to regimen 1 for patients with lymphoblastic lymphoma, achieving 74% RFS at 30 months compared to 31% for regimen 1 (P = 0.001). Conversely, those with nonlymphoblastic types (BT, NB, HI) treated with regimen 1 had a 58% RFS at 30 months compared to 32% for those treated on regimen 2 (P = 0.01). This study demonstrates that proper, routine histopathologic classification of NHL is the best criterion for choice of therapy in children with nonlocalized involvement. As a result of this study, all patients with nonlocalized disease, diagnosed after August 1980, were no longer randomized but were assigned to the appropriate treatment regimen based on prospective review of histopathology.

Dental involvement in histiocytosis

Abstract Fifty consecutive patients with histiocytosis were studied for dental involvement of this symptom complex. More than one third had oral manifestations of this disease, and 16 per cent had a chief complaint of oral pain. Since lesions associated with gingiva, jawbones, and teeth are often seen either as the first manifestation of histiocytosis or as a complication of the disease, the dentist is implicated in the diagnosis and management.

Histiocytosis X: occurrence and oral involvement in six adolescent and adult patients.

Six cases of adolescent- and adult-onset histiocytosis X with oral involvement and their evaluation are described. Clinical findings can be mistaken for dental infection. Management involved a combination of low-dose radiation and chemotherapeutic drugs. The extreme variability of clinical signs and symptoms and the extent and progression of the disease suggest that the classic classification of histiocytosis X is inappropriate.

Treatment of Metastatic Wilms's Tumor

Whole lung irradiation (1,500 rads in 10 fractions) was combined with dactinomycin in the treatment of 17 children with metastatic Wilmss tumor. Seven patients (54%) remained disease-free for at least two years. In addition, liver metastases developed in 2 of these survivors who were effectively treated with surgery, irradiation, and chemotherapy. Our control rate is similar to rates found in the literature, which demonstrates that an aggressive treatment approach for patients with metastatic disease by a multidisciplinary pediatric oncology group is worthwhile.

Partial hepatectomy in metastatic Wilms' tumor

REFERENCES 1. Freireich, E. J., Whang, J., Tjio, J. H., Levin, R. H., Brittin, G. M., and Frei, E., 111: Refractory anemia, granulocytic hyperplasia of bone marrow, and a missing chromosome in marrow cells. A new clinical syndrome? Clin, Res. 12: 284, 1964 (abst.). 2. Teasdale, J. M., Worth, A. J., and Corey, M_ J.: A missing group C chromosome in the bone marrow cells of tht~ee children with myeloproliferative disease, Cancer 25: 1468, 1970. 3. McClure, P. D., Thaler, M. M., and Cohen, P. E.: Chronic erythroleukemia with chromosome mosaicism: Report of a case in a 5-year-old boy, Arch. Intern. Med. 115: 697, 1965. 4. Holden J. D., Garcia, F. U., Samuels, M., Dupin, C., Stallworth, B., and Anderson, E.: Myelofibrosis with C monosomy of marrow elements in a child, Am. J. Clin. Pathol. 55: 573, 1971. 5. Humbert, J. R., Hathaway, W. E., Robinson, A., Peakman, D. C., and Githens, J. H.: Pre-leukaemia in children with a missing bone marrow C chromosome and a myeloproliferative disorder, Br. J. Haematol. 21: 705, 1971. 6. Moorhead, P. S., Nowell, P. C., Mellman, W. J., Battips, D. M., and Hungerford, D. A.: Chromosome preparations of leukocytes cultured from human peripheral blood, Exp. Cell Res. 20: 613, 1969. 7. Schmid, N.: DNA replication patterns of human chromosomes, Cytogenetics 2: 175, 1963. 8. Lin, C. C., Uchida, I. A., and Byrnes, E.; A suggestion for the nomenclature of the fluorescent banding patterns in human metaphase chromosomes, Can. J. Genet. Cytol. 13: 361, 1971. 9. Patil, S., Merrick, S., and Lubs, H. A.: Identification of each human chromosome with a modified giemsa stain, Science 173: 821, 1971. 10. Schwartz, A. D., Zelson, J. H., and Pearson, H. A.: Acute myelogenous leukemia with compensatory but ineffective erythropoiesis: Di Guglielmos syndrome, J. PEDIATR. 77: 653, 1970. 11. Roloff, J. N., and Lukens, J. N.: Dissociation of e ry throblas t ic and myeloblas t ic prol i fera t ion in erythroleukemia, Am. J. Dis. Child. 123: 11, 1972.

ALPHA-INTERFERON IN SIMIAN AND HUMAN VARICELLA

ABSTRACT: The efficacy of alpha-interferon administration was demonstrated during an epizootic of simian varicella and in primary varicella in children with cancer. Twenty-eight patas monkeys were enrolled in a randomized placebo controlled trial of interferon prophylaxis during a naturally occurring outbreak of simian varicella. Among animals who were seronegative at entry, 17% interferon recipients developed symptoms compared to 80% of placebo recipients. Forty-four children with cancer were enrolled in two consecutive randomized placebo-controlled trials. The duration of new lesion formation was diminished in the interferon-treated patients. Serious dissemination or fatal infection occurred in 6 of 21 placebo recipients compared to 2 of 23 interferon recipients. These studies suggest that alpha interferon therapy can significantly alter the course of primary varicella infection in immunosuppressed patients and in the simian form of the infection.