Of 48 children with acute lymphocytic leukemia 11 had blast cells with receptors for sheep erythrocytes in their initial bone-marrow aspirates and 37 did not. A comparison of selected clinical features indicated striking differences between the two groups. Leukemia with the receptors was associated with a high proportion of older children, predominantly boys, a thymic mass, and a high white-cell count at diagnosis. In contrast, the 37 children with leukemia without the receptors were generally less than five years of age, with a nearly equal distribution of boys and girls; all but one had normal chest roentgenograms, and only one had a white-cell count greater than 100,000. Thus, the presence or absence of lymphoblasts with sheep erythrocyte receptors--a T-cell marker--distinguishes two forms of childhood acute lymphocytic leukemia, each with a distinct distribution of age and sex as well as other characteristic clinical features.

Children with acute lymphocytic leukemia in complete remission were randomized between 2 combination chemotherapy schedules for continuation of their remissions. One group received full dosage of 4 antileukemic drugs, and the other received half dosage of the same compounds. Median durations of complete remission and of hematologic remission were longer in the full‐dosage than half‐dosage group. Four out of 21 patients in the full‐dosage group continue in their initial complete remission for 40 to 48 months and have been off treatment for 3 months to 1 year. Nine in the full‐dosage group and 4 in the half‐dosage group remain in continuous hematologic remission for 40 to 55 months. Review of results of previous combination chemotherapy studies of childhood lymphocytic leukemia at this hospital indicated a 17 per cent 5‐year leukemia‐free survival rate.

In earlier combination chemotherapy regimens for childhood acute lymphocytic leukemia, nervous system leukemia terminated complete remission in over half the patients in a median time of 11 months. In the present study, cranial radiation (2400 R, 60Co) and intrathecal methotrexate given early in remission were added to combination chemotherapy in an attempt to prevent or delay central nervous system relapse and termination of complete remission. Of 35 consecutive children with previously untreated acute lymphocytic leukemia, 20 of 30 who attained remission and received all initial phases of therapy have been in continuous complete remission for 23 to 30 months. Complete remission was terminated by nervous system relapse in three patients and by hematological relapse in five. Two patients died in complete remission of viral infections and others experienced reversible drug toxicity. We conclude that this combined therapy reduces the incidence of nervous system relapse in the first 2 years and prolongs complete remission.

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One hundred seventy-seven children with acute lymphoblastic leukemia (ALL) were admitted to a study designed to determine whether pulses of cytosine arabinoside (ara-C) and cyclophosphamide (cyclo) would improve disease-free survival (DFS). All patients received vincristine, prednisone, and asparaginase for remission induction, CNS prophylaxis with cranial irradiation and intrathecal methotrexate, and continuation therapy with 6-mercaptopurine plus methotrexate. Forty-seven of 101 patients with non-T ALL and 18 of 26 patients with T-cell ALL received ara-C/cyclo pulses every eight weeks during continuation therapy. The age, sex, and initial white cell count distributions were similar in both treatment groups. Patients with non-T-cell ALL had similar DFS with or without ara-C/cyclo pulses (36% versus 48%; P = 0.32). Ara-C/cyclo pulses significantly improved DFS in children with T-cell ALL (36% versus 0%; P = 0.015). Toxicities of the ara-C/cyclo pulses included reversible pancytopenia, drug induced fever, fever associated with neutropenia, and death in one patient from systemic candidiasis while neutropenic. This is the first clinical evidence to indicate that the combination of ara-C/cyclo used during continuation therapy is selectively beneficial in T-cell ALL.

The proportion of pretreatment bone marrow macrolymphoblasts was determined in a total of 93 children with acute lymphoblastic leukaemia (ALL) in order to assess the validity of cell size as a prognostic indicator. A macrolymphoblast (MLb) was defined as having a diameter greater than 12 mum, and patient samples were divided simply on the basis of whether they had more or less than 10% MLb present at diagnosis. In a retrospective study of a sample of 47 children treated according to Total Therapy Study VII, the continuous complete remission duration, survival and incidence of CNS disease bore no relationship to the cell size distribution present at diagnosis. A second sample of 46 current patients with untreated ALL was examined both for the presence of surface markers for T- and B-cells and for cell size. Bone marrow blasts from 10 of these 46 children formed rosettes with sheep erythrocytes (E)-- a T-cell marker. E-rosette formation was associated with a constellation of adverse prognostic factors, including older age, very high initial WBC counts, organomegaly, and mediastinal enlargement; yet the presence of this T-cell marker was unrelated to cell size. We conclude that pretreatment lymphoblast cell size is not a reliable prognostic indicator in childhood ALL.

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