Abnormal CT scans of the brain in asymptomatic children with acute lymphocytic leukemia after prophylactic treatment of the central nervous system with radiation and intrathecal chemotherapy.

Thirty-two asymptomatic patients with acute lymphocytic leukemia, who had received prophylactic cranial radiation (2400 rads) and either intrathecal methotrexate or cytosine arabinoside were studied by computed tomography of the brain 19 to 67 months after initiation of prophylaxis. Seventeen of 32 (53 per cent) had one or more abnormal findings. Dilatation of the ventricles (eight patients) and widening of the subarachnoid spaces (nine patients) were equally distributed among patients in both intrathecal-chemotherapy groups.

Acceleration of myeloid recovery from cyclophosphamide-induced leukopenia by pretreatment with Bacillus Calmette-Guérin.

Treatment of C57BL/6 mice with Bacillus Calmette-Guérin i.p. 8 days prior to the induction of leukopenia by cyclophosphamide (300 mg/kg i.

Immunodeficiency in familial erythrophagocytic lymphohistiocytosis.

4 children with familial erythrophagocytic lymphohistiocytosis and hyperlipidaemia were found to have a previously unrecognised immunological deficiency syndrome which included defects in both humoral and cellular immunity and a plasma inhibitor of in-vitro lymphocyte blastogenesis. The inhibitory activity was proportional to the increase in the triglyceride concentration in the patients' plasma. Immunological deficiency, to which hyperlipidaemia may be a contributing factor, appears to be a significant feature of familial erythrophagocytic lymphohistiocytosis.

Prolonged complete remission following high dose chemotherapy of Burkitt's lymphoma in relapse.

Fourteen patients with American Burkitt's lymphoma resistant to conventional chemotherapy were treated with high-dose combination chemotherapy and intensive supportive care. Four patients died shortly after chemotherapy, 3 of an acute carditis. All ten remaining patients demonstrated tumor regression and 3 remain in prolonged complete unmaintained remission 29+, 19+, and 9+ months after treatment.

Sequential combination chemotherapy (containing high-dose cyclophosphamide) for metastic osteogenic sarcoma.

Eleven patients with metastatic osteogenic sarcoma were treated with cyclophosphamide, adriamycin, and, in some cases, high-dose methotrexate. In the event of metastatic progression, the dose of cyclophosphamide was escalated by increasing the number of consecutive daily infusions (dose, 45 mg/kg/day). The results indicate that metastatic osteogenic sarcoma is marginally responsive to adriamycin and cyclophosphamide but rarely responsive to high-dose methotrexate as administered in this trial.

Characterization of a suppressor-cell leukemia. Evidence for the requirement of an interaction of two T cells in the development of human suppressor effector cells.

To characterize the suppressor activity of neoplastic T cells from a child with acute lymphoblastic leukemia and hypogammaglobulinemia, we applied an in vitro assay that determines the capacity of pokeweed-mitogen-stimulated lymphocytes to mature into immunoglobulin-secreting cells. The geometric mean synthesis by peripheral blood lymphocytes from 12 normal persons was 3200 ng for IgM, 2447 ng for IgG and 1825 for IgA (2 X 10(6) cells per 12 days in culture). The patient's leukemic cells produced no detectable immunoglobulin and depressed the immunoglobulin production of normal lymphocytes by 85 to 100 per cent in co-culture experiments.

Characteristics of long-term survivors in AML.

We examined the records of all patients with a diagnosis of acute myelogenous leukemia or acute myelo-monocytic leukemia seen between 1963--1975. Of 211 patients, 12 are alive and in complete remission from 179--48 months since diagnosis. Life table analysis reveals a survival plateau of 4--5% after five years.

Chronic ventricular cerebrospinal fluid sampling, drug injections, and pressure monitoring using subcutaneous reservoirs in monkeys.

Animal models enabling reliable access to ventricular cerebrospinal fluid (CSF) are crucial to the study of neuropharmacological and neurotoxicological effects of cytotoxic agents used to treat central nervous system neoplasms. This investigation concludes that 4th ventricular catheterization using subcutaneous CSF reservoirs in rhesus monkeys: (a) provides chronic access to sterile CSF without chronic immobilization, (b) enables mixing of injected drugs with lateral ventricular CSF, (c) permits sensitive monitoring of intraventricular pressure and (d) does not produce tissue damage during cannula implantation or breakdown of the blood-brain barrier.

A primate model for study of methotrexate pharmacokinetics in the central nervous system.

A new technique enabling repetitive sampling of cerebrospinal fluid (CSF) in unanesthetized rhesus monkeys was developed to study the pharmacokinetics of methotrexate (MTX) in the CSF. CSF and plasma MTX levels were monitored following intraventricular and intravenous MTX administration. CSF and plasma MTX disappearance curves in the monkey were virtually identical to curves generated in humans, suggesting that the mechanisms of transport between the CSF and plasma compartments are similar in both species.

Effect of Corynebacterium parvum, methanol-extraction residue of BCG, and levamisole on macrophage random migration, chemotaxis, and pinocytosis.

Three parameters of macrophage function: random migration, chemotaxis, and pinocytosis, were studied in the guinea pig after administration of Corynebacterium parvum, methanol-extraction residue of BCG, and levamisole (LMS), a synthetic anthelmintic. Macrophage migration studies were performed with a modified Boyden chamber. Pinocytosis was assessed by the uptake of colloidal 198Au.

Computer assisted tomography in methotrexate encephalopathy.

Five children with acute lymphocytic leukemia (ALL) developed encephalopathy following treatment with intrathecal or intraventricular methotrexate (MTX). In these patients computer assisted tomography was informative by revealing areas of decreased attenuation coefficient located periventricularly and in each centrum semiovale (three cases) and calcifications, mostly in the deep and cortical gray matter (two cases), as well as ventricular dilatation (four cases). Contrast injection used in one of these five patients, as well as in another child (not affected by ALL) with MTX encephalopathy, failed to reveal enhancement.

Primate model for long-term study of intraventricularly or intrathecally administered drugs and intracranial pressure.

Meaningful pharmacokinetic investigations require animal systems which approximate the human situation. This report describes a primate model in which silicone catheters are placed into the fourth ventricle and the spinal subarachnoid space and connected to subcutaneous cerebrospinal fluid without tissue damage, prod, enables spinoventricular perfusion, and permits ventricular cerebrospinal fluid sampling over extended periods in unanethetized rhesus monkeys. This animal system may provide intraventricular pressure recordings and pharmacokinetic data similar to that obtained in man.

Blindness during remission in two patients with acute lymphoblastic leukemia: a possible complication of multimodality therapy.

Two patients with acute lymphoblastic leukemia treated on the same protocol became blind during complete remission. Therapy consisted of systemic combination chemotherapy, prophylactic central nervous system irradiation and monthly intrathecal cytosine arabinoside. Eight months after CNS irradiation visual acuity in both patients began to decrease.

Monocyte-mediated antibody-dependent cellular cytotoxicity: a clinical test of monocyte function.

The lack of a simple, rapid, and quantitative test of the functional activity of the monocyte has hampered studies of the contribution of this cell type to host defense and human disease. This report describes an assay of antibody-dependent cellular cytotoxicity, which depends exclusively upon the monocyte as the effector cell and therefore provides a convenient test of monocyte function. In this system, mononuclear leukocytes (MNL) obtained by Ficoll-Hypaque separation of whole blood are cytotoxic for 51Cr-labeled human erythrocyte targets coated with anti-blood group antibody.

Hepatitis B virus infection in the Wiskott-Aldrich syndrome.

Testing of paired serum samples of 12 children with the Wiskott-Aldrich syndrome for the presence of hepatitis B surface antigen (HBsAg) antibody to HB, Ag, and antibody to the hepatitis B core antigen revealed evidence of hepatitis B virus infection in three. None of the three, however, developed overt clinical hepatitis or the chronic HBsAg carrier state. These data suggest that the immunologic defects seen in the Wiskott-Aldrich syndrome permit adequate immune responses to the hepatitis B virus and do not predispose to the chronic HBsAg carrier state.

The effect of Mycobacterium bovis (Bacillus Calmette-Guérin) on macrophage random migration, chemotaxis, and pinocytosis.

Macrophage random migration, chemotactic responsiveness, and pinocytosis were studied in the guinea pig after Bacillus Calmette-Guérin (BCG) administration. Oil-induced peritoneal exudate cells were evaluated for random migration and chemotaxis in modified Boyden chambers. Pinocytosis was measured by the in vitro uptake of colloidal 198Au.

Reversible dementia temporally associated with intraventricular therapy with methotrexate in a child with acute myelogenous leukemia.

During maintenance therapy with intraventricular methotrexate, progressive dementia developed in a child with meningeal leukemia. Cerebrospinal fluid levels of MTX were in the nontoxic range and neurologic evaluation failed to demonstrate anatomic obstruction, infection, or folate depletion. The patient's symptoms gradually resolved when the methotrexate was discontinued, suggesting that methotrexate neurotoxicity may occur in the absence of an elevated CSF concentration of MTX.

Candida arthritis treated with amphotericin B.

This report describes a patient with acute lymphoblastic leukemia who developed arthritis of the knee caused by Candida tropicalis. Systemic therapy with amphotericin B apparently suppressed but did not eliminate the infection. Resolution of the arthritis occurred only after three intra-articular injections of amphotericin B.

A clinical trial of chemotherapy and RAJI immunotherapy in advanced acute lymphatic leukemia.

Patients in remission with advanced acute lymphatic leukemia were randomly assigned to receive chemotherapy alone or chemotherapy plus immunotherapy with a Burkitt lymphoma tissue culture cell line (RAJI). Remission duration in both groups were identical. Complement-dependent cytotoxic antibody was seen in 5 of 8 immunized patients and 0 of 8 controls.

Lipid peroxidation in the killing of phagocytized pneumococci.

To directly examine the role of hydrogen peroxide in the killing of bacteria after ingestion by granulocytes, we have studied some of the events of phagocytosis of a mutant strain of pneumococci which is relatively deficient in peroxide production. The hydrogen peroxide-deficient pneumococci and the otherwise identical wild type were grown with [(14)C]arachidonic and [(3)H]palmitic acid labels to label their lipids with unsaturated and saturated fatty acids, respectively. They were then incubated with both normal and chronic granulomatous disease granulocytes.