1. Combinations of effective agents produce at least an additive increase in complete remission rates over that which can be achieved when the agents are used individually. 2. Patients who do not achieve complete remission with initial treatment have a significantly shorter survival. 3. Alternating MTX and 6-MP at 28-day intervals during remission does not prolong the duration of remission over that of combined concurrent 6-MP and MTX. 4. The administration of folic acid antagonists intrathecally at 28-day intervals during antimetabolite maintained remission did not prolong the duration of remission. Meningeal leukemia, however, occurred significantly less frequently in these patients. 5. The duration of combined 6-MP and MTX maintained remission is not greater than that of 6-MP maintained remission. 6. The toxicity of 6-MP and MTX in combination in patients in remission is additive. The above conclusions were drawn from this comparative study of combinations of chemotherapeutic agents in children with acute lymphocytic leukemia.
The effect of 6-MP therapy on the duration of remissions induced by adrenal corticosteroids has been studied as a model for testing of new agents. Ninetytwo patients under age 20 entered the study and were accepted for analysis. Sixty-two (67 per cent) had complete or partial remissions induced by corticosteroids. Patients in remission were randomly assigned to maintenance therapy with either 6-MP or placebo. The median duration of 6-MP-maintained complete remissions was 33 weeks and for placebo, 9 weeks. A sequential experimental design was used to analyze remission times while the study was in progress. This resulted in the study being stopped after analysis of the remission times of 21 pairs of patients (42 patients). Overall survival was not significantly different for the two treatment programs, since patients maintained on placebo were treated with 6-MP when relapse occurred. The activity of the known active antileukemic compound 6-MP was readily detected by this experimental design without compromise of optimal survival. Such a design should prove useful for the evaluation of new agents and also permit study of the remission maintenance activity of a compound separately from its remission inducing activity.
Pulmonary alveolar proteinosis is a rare disease in childhood, generally found in infants less than 1 year old. Survival time averages less than one year after the onset of symptoms, which consist mainly of cough and dyspnea. Of the 23 patients with pulmonary alveolar proteinosis, seven had thymic alymphoplasia (30%); this association leads to speculation that the immuno-logic system may be incompetent or contribute to the etiology of the disease. The diagnosis of pulmonary alveolar proteinosis is confirmed by biopsy, although chest roentgenograms and sputum staining may be helpful. Therapy consists of the use of steroids, antibiotics, and inhalation therapy; bronchopulmonary lavage has been unsuccessful in children. Si nce the original description of pulmonary alveolar proteinosis by Rosen et al1 in 1958, 139 adult cases have been reported.2 The dis¬ ease is rarer in childhood, and only 22 cases have been reported to date.1-3-12 We present the 23rd case and a review of the previous 22 cases. Report of a CaseA white girl, 7 years 2 months old, was first referred to this clinic when she was 6 years 2 months old because of pneumonia in the middle lobe of the right lung, leuko¬ penia, and fever. At the age of 5 years, she was given griseofulvin for a ring¬ worm-like lesion of the abdomen. At that time, leukopenia was first noted (white blood cell count [WBC] 3,000/cu mm). A biopsy of the lesion reportedly showed nonspecific vasculitis, and the child was treated with steroids for ten days. Dur¬ ing the next year, the lesion disappeared spontaneously, but upper-respiratory tract infection recurred and the leukopenia per¬ sisted.On first admission to our clinic, June 26, 1969, she was in moderate respiratory dis¬ tress and had a temperature of 103 F (39.4 C) and rales in both lung bases. A chest roentgenogram showed a diffuse in¬ terstitial infiltrate (Fig 1, left). Cultures of blood and bronchial washings were negative, and bone marrow examination showed no abnormality. Multiple skin tests for fungi and tubercle bacilli were negative. Tests for rheumatoid factor and lupus erythematosus cells were negative. Serum IgA, IgM, and IgG concentrations were, respectively, 1.45, 1.35, and 14.5 mg/100 ml. The leukopenia persisted (3,000 WBC /cu mm), with a normal differential cell count. Open lung biopsy showed a recent and an old intraalveolar hemorrhage suggestive of pulmonary hemosiderosis, as well as mild subacute and chronic interstitial pneumonitis. Gas¬ tric aspirates were negative for hemosiderin. Treatment consisted of ampicillin and supportive therapy. The fever sub¬ sided, and she was dismissed on July 3, at which time she was receiving 30 nig of prednisone per day. Three episodes of bronchitis, pneu¬ monitis, and fever occurred before her final admission on May 9, 1970, at the age of 7 years. Figure 1, center, shows a chest x-ray film that was taken during one of those episodes. At the final admission, the chief complaints were fever, dyspnea, cyanosis, and cough productive of clear sputum. There was no hemoptysis. ...
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