Kenneth A. Starling

A staging system for histiocytosis X: A southwest oncology group study

Patients with generalized histiocytosis X may be divided into three prognostic groups based on age at the time of diagnosis and presence or absence of organ dysfunction. These variables are independent. Favorable response to initial chemotherapy was shown to be associated with improved survival and overall disease control.

L-asparaginase therapy in children with advanced leukemia. The Southwest Cancer Chemotherapy Study Group.

Each of 105 children with advanced acute leukemia in relapse was randomly assigned to one of three treatment schedules utilizing L‐asparaginase. L‐asparaginase used alone induced bone marrow remissions in 43% of all cases and 54% of evaluable cases. L‐asparaginase combined with vincristine and prednisone induced remissions in a significantly greater number of children—50% of all cases and 77% of evaluable cases: There was a suggestive advantage in survival experience for patients receiving the 3‐drug combination compared with L‐asparaginase alone. Survival in this study population was clearly related to the length of disease prior to start of therapy, the longer survivals occurring in those with longer prestudy duration of disease. Fourteen of 17 children who had relapsed following inductions of remissions with the first course of L‐asparaginase treatment had remissions again following retreatment with a second course. These results indicate that L‐asparaginase has considerable therapeutic activity in children with advanced leukemia.

Cyclophosphamide-asparaginase-vincristine-prednisone induction therapy in childhood acute lymphocytic and nonlymphocytic leukemia

A remission‐induction regimen for childhood leukemia using cyclophosphamide, asparaginase, vincristine, and prednisone (CAVP) was compared to standard vincristine‐prednisone (VP) induction. The more intensive regimen was associated with a lower complete remission rate (81% vs 93%) and a higher early death rate from infection (15% vs 5%) for acute lymphocytic leukemia. In contrast, complete remission was achieved in 58% of children with acute nonlymphocytic leukemia treated with CAVP compared to 18% for VP. Early death rates were similar (27% vs 25%). These observations corroborate previous studies in childhood nonlymphocytic leukemia showing activity for asparaginase. Preliminary analysis of remission duration and survival for responders shows no advantage for those who survived the more intensive induction.

Mitoxantrone in refractory acute leukemia in children: A phase I study

SummaryNine children with acute non-lymphocytic leukemia (ANLL), ages 16 months to 16 years (median 7 years), and 15 children with acute lymphocytic leukemia (ALL), ages 10 months to 18 years (median 5 years), were treated with 5-day courses of mitoxantrone (Novantrone®; dihydroxyanthracenedione) as induction therapy. All the children had leukemia which was resistant to conventional therapy and all but one patient had received anthracycline therapy prior to the initiation of this trial. Three patients (two with ANLL, one with ALL) received the drug at a dose of 6 mg/m2/day i.v. for 5 days. Both patients with ANLL achieved partial remissions (PR) (105 and 87 days duration). The child with ALL failed to respond to two courses of the drug, and died of progressive disease 45 days after the institution of therapy. Twenty-one patients (14 with ALL, seven with ANLL) were treated with 8 mg/m2/day i.v. mitoxantrone for 5 days. There were three early deaths (all ALL) which were not felt to be secondary to drug toxicity. Four of the 18 children achieved complete remission (CR) (one ANLL — 35 days; three ALL — 39, 31 and 13 days). One child with ANLL achieved a PR (13 days) and one child with ALL showed improvement in his bone marrow status. Twelve children failed to respond to this therapy.Dose-limiting toxicity was not seen among the patients who received 6 mg/m2/day for 5 days. There were five patients who had mucositis and one patient who had nausea and vomiting among those patients who received 8 mg/m2/day for 5 days. Four of these children had significant decreases in the myocardial shortening fraction as measured by echocardiography. None of these patients had clinical signs of cardiotoxicity.The CR plus PR rate for both dose levels is 33%. Mitoxantrone appears to be an effective agent for remission induction in children with late stage ALL and ANLL. Toxicity was not a significant problem at the doses used in this trial.

Adriamycin in the treatment of childhood acute leukemia. A Southwest Oncology Group study.

Sixty‐six children with acute leukemia, in advanced stages of their disease and resistant to conventional chemotherapy, received adriamycin for remission induction. Seventeen of 46 (37%) evaluable children with acute lymphocytic leukemia achieved a complete remission, and 5 (11%) achieved a partial remission. Two of 12 evaluable children with acute myelogenous leukemia achieved a complete remission, while an additional 3 achieved a partial remission. Two children with erythroleukemia also achieved a complete remission. Previous therapy with daunorubicin did not affect the response rate. The main toxicities observed with adriamycin were myelosuppression, fever, nausea and vomiting, stomatitis, alopecia, and cardiac toxicity (ST segment changes and arrhythmias).

Anti-LW Antibody Production in a Child with Combined Immune Deficiency Disease (Thymic Alymphoplsia)

IN 1967 a six-month-old boy was evaluated for severe moniliasis and persistent pneumonia. A diagnosis of thymic alymphoplasia was established by the following data: low gamma-globulin levels, absen...

LEUKEMIC PULMONARY INFILTRATES AS A CAUSE OF RESPIRATORY DISTRESS IN CHILDREN

The clinical and pathological findings in 284 children with acute leukemia who had autopsies over a 22-year period were examined to determine the incidence of pulmonary leukemic infiltrates at the time of death. Six children (2.1%) had acute monocytic leukemia (AMoL), 33 (11.6%) had acute myelogenous or acute monomyelogenous leukemia (AMML) and 245 (86.3%) had acute lymphoid leukemia (ALL). Forty-one of 284 children (14.4%) were found to have 3 distinctive patterns of pulmonary infiltrate. Eleven children (6 ALL, 4 AMML, 1 AMoL) had interstitial infiltrates with or without pleural infiltrates. Seven children (4 ALL, 3 AMML) had parenchymal nodules. Twenty-three children (20 ALL, 2 AMoL, 1 AMML) had perivascular infiltrates with or without peribronchial infiltrates. The presence or absence of infiltrates could not be correlated with leukemic cell type, immunologic phenotype, sex, or white blood cell count at the time of death. Ten of 41 children had respiratory distress (RD) prior to death; however, only 2 of 41 (4.9%) or 2 of 284 (0.7%) had RD which was not explained by active pulmonary infection. We conclude that despite reports of leukemic infiltrates presenting as interstitial pneumonia, pulmonary leukemic infiltrates are a rare cause of RD in the terminally ill child with leukemia.

Toxicity Study of Cytosine Arabinoside and Methotrexate in the Maintenance Therapy of Childhood Leukemia. A Southwest Oncology Group Study

In a toxicity study to determine the feasibility of treating patients with acute lymphocytic leukemia (ALL) using an intravenous combination of cytosine arabinoside (Ara-C) and methotrexate (MTX), the drugs were given either simultaneously or sequentially every two weeks. Twenty-nine patients were studied, 17 treated simultaneously, 12 treated sequentially. The tolerated doses of Ara-C and MTX were 60 mg/m2 and 90 mg/m2, respectively, for the simultaneous treatment schedule and 90 mg/m2 and 150 mg/m2, respectively, for the sequential treatment schedule. The dose-limiting factor of the drug combination was gastrointestinal toxicity. The observed recurrent vomiting on both schedules rendered the treatment unsuitable for maintenance therapy.

Effects of continuous or discontinuous maintenance therapy on subsequent remission maintenance in childhood leukemia.

This study was designed to determine if resistance to a standard drug during the second remission of children with acute leukemia was reduced by discontinuation of therapy during the initial remission. The initial maintenance therapy was either 6‐mercaptopurine (6‐MP), methotrexate (MTX), or cyclophosphamide (CYC) given continuously to relapse or discontinued (at random) at 2 or 6 months. Following the initial relapse and after induction of a second complete remission, 72 evaluable patients received (continuously to relapse) either 6‐MP (53 patients) or CYC (19 patients) for the second remission maintenance. Resistance to 6‐MP occurred during the second maintenance, regardless of the drug used during the initial maintenance, in that the length of second remissions was significantly shorter than the length of first remissions. However, this resistance was most pronounced in patients who initially relapsed while on continuous 6‐MP maintenance (medium duration of remission [MDR] of 9 weeks). Patients whose initial relapse occurred after the discontinuation of 6‐MP had a MDR of 23 weeks and patients whose second remission was maintained with CYC (after relapse from initial continuous remission on 6‐MP) had a MDR of 25 weeks.

832 ABNORMAL CT BRAIN SCANS IN CHILDREN WITH ACUTE LYMPHOBLASTIC LEUKEMIA (ALL)

The results of CT brain scans in 2 groups of children with ALL are reviewed. In Group I, 25 asymptomatic children 3-5 yrs from initial diagnosis were studied upon discontinuation of therapy. Mild ventricular dilation (5/25) and cerebral calcifications (1/25) were noted. Of the 6 patients with abnormal CT scans, radiotherapy + intrathecal methotrexate were used in 4/6 patients and intrathecal therapy alone in 2/6 patients. Subsequent neurological complications were uncommon (1/25). In Group II, 14 children who developed neurologic syndromes were studied while still receiving therapy. Leukoencephalopathic syndromes were diagnosed in 10/14 children; central nervous system (CNS) leukemia occurred in 6/10 children. CT scan abnormalities occurred in 9/10 patients. CT scans indicated ventricular dilation alone in 1 patient, and both ventricular and subarachnoid space dilation in 8 patients; in addition, 2 patients had areas of intracerebral calcification in areas of decreased attenuation coefficient. CNS infections were subsequently identified in 2/10 patients (toxoplasmosis and St. Louis encephalitis). Significant CT scan abnormalities are more likely to be seen in patients with antecedent clinical problems or in patients receiving more intensive CNS therapy.