The Childrens Cancer Study Group conducted four therapeutic studies on a total of 1006 children with acute nonlymphocytic leukemia from 1972 to 1983. This report describes the therapeutic strategies of these studies and examines trends in induction rates and long-term outcome over this period. The remission induction rate has changed from 58% in 1972 to 1975 to 80% for the period 1980 to 1983, and the induction mortality dropped from 20% to 6%. Four-year survival probabilities from time of diagnosis have almost doubled from 19% to 36%. Few deaths occurred more than 5 years after diagnosis: children surviving in first remission beyond 5 years had a 92% survival rate and an 86% relapse-free survival rate over the next 5 years. In contrast, median survival after a marrow relapse was less than 6 months and the 6-year survival probability was 4%. The leukocyte count was a significant prognostic factor, and although the mortality for infants was high initially, long-term survival was not decreased.

Thirty-one adults with Wilms tumor were reported to the National Wilms Tumor Study from 1968 to 1979. Treatment and survival data for these patients were analyzed and compared to similar information derived from children enrolled in the first National Wilms Tumor Study. The ages of the 31 adults ranged from 17 to 63 years (mean 29 years). All but 3 patients had surgical resection or excision of tumor, 7 did not receive postoperative irradiation and all but 1 had chemotherapy. Actinomycin D and vincristine were the drugs used most commonly, 26 of the 31 patients receiving both agents. Advanced disease at diagnosis (6 stage III and 9 stage IV versus 9 stage I and 5 stage II--in 2 cases stage was not known) was found more often than in children in whom stages III and IV disease made up 27 per cent of the first National Wilms Tumor Study population. The 3-year actuarial survival rate for the 31 adults was 24 per cent: 48 per cent for stages I and II disease and 11 per cent for Stage IV disease. Comparable data for children in the first National Wilms Tumor Study, adjusted for stage, were 74, 87 and 53 per cent, respectively. It is concluded that adults with Wilms tumor treated as were these have a worse prognosis than children managed according to the first National Wilms Tumor Study regimen. However, those adults in this series who were treated aggressively, that is surgical excision, postoperative irradiation and multi-agent chemotherapy, appeared to have fared better than adults treated in the pre-chemotherapy era. It is concluded that aggressive therapy should be given to all adults with Wilms tumor irrespective of stage.

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Seven patients with hematologic malignancy refractory to conventional therapy were treated with 1000 rads midpoint tissue dose of whole-body irradiation followed by infusion of marrow from an HL-A matched sibling. Three patients with advanced leukemia showed histologic evidence suggestive of engraftment but the graft did not function and they died after 18, 26, and 30 days. Four patients, three with acute lymphoblastic leukemia and one with Hodgkin’s disease, treated while in good clinical condition, showed evidence of a functioning marrow graft within 3 wk. Engraftment was proved by cytogenetic analysis in three cases with donors of the opposite sex. One patient died with graft-vs.-host disease (GVH) after 37 days. The other three had mild to moderate GVH. Two patients showed recurrent leukemia and died after 85 and 102 days. In one of these patients, a girl, the recurrent leukemia was in male donor cells. One patient, a boy, is alive and well after 200 days with only female donor cells in the marrow. He shows no evidence of GVH and, as yet, no leukemia.

Multivariate analyses of the clinical course of 1537 children with acute lymphoblastic leukemia (ALL) identified a subgroup which experienced short remission duration and a high incidence of extramedullary relapse. The patients differed from other ALL patients by the presence at diagnosis of two or more of a constellation of clinical and laboratory features: organomegaly or mass disease, E-rosette positivity, hemoglobin level greater than 10 g/dl, leukocyte count greater than 50,000/microliters, male predominance, and older age. This type of presentation of ALL is referred to as the "lymphoma syndrome" (LS) since such patients exhibit a pattern of several clinical and laboratory features which were observed repeatedly but in differing combinations, and some of which clinically resemble lymphoma. A subsequent database from 2231 patients was analyzed. Patients with a mediastinal mass, massive splenomegaly, or massive adenopathy, alone or in combination, had a worse outcome when the patient also had either leukocytosis, E-rosette-positive lymphoblasts, or a normal or near normal hemoglobin (Hb) level at diagnosis. Similarly, the above three laboratory features alone or in combination did not predict less than 40% disease-free survival (DFS) unless they were accompanied by at least one of the clinical features of mass disease. When at least one clinical feature and at least one laboratory feature were present, the overall DFS was 36% 6 years after diagnosis versus 64% for all other patients. The association of these features with poor prognosis remained significant after adjusting for the level of leukocyte count at diagnosis, age at diagnosis, and sex of the patients. Patients with this recurrent syndrome of features do not represent a homogeneous biologic entity but they constitute a subgroup of patients with ALL having a high risk of treatment failure using current therapies, including failure to achieve remission, early relapse, and increased frequency of relapse in extramedullary sites. They deserve early recognition at diagnosis and selection of treatment strategies appropriate for very high risk ALL.