Leukemic blasts with markers of four cell lineages in Down's syndrome ("megakaryoblastic leukemia").

Among 16 patients with Down's syndrome (DS) and acute leukemia admitted to our department during a ten year period, 6 were diagnosed as acute megakaryoblastic leukemia (AMkL). The diagnosis was based on clinical and hematologic criteria, confirmed in three patients with the use of monoclonal antibodies (MoAb) specific for megakaryocytic antigens. In these three, and in a fourth patient, the leukemic blasts were positive for other myeloid, lymphoid and erythroid markers in MoAb testing. We suggest that AMkL in DS is a mixed lineage leukemia with blasts presenting a variety of cell surface antigens, indicating origin from an early progenitor cell with the capability of megakaryocytic differentiation. Of the 6 patients with AMkL, 4 treated with standard AML protocols are in complete continuing remission (CCR) with observation periods from 57+ to 148+ months.

[Dystrophy caused by upper airway obstruction]. / Dystrofi forårsaket av øvre luftveisobstruksjon.

We describe three infants whose main symptoms were poor weight gain, delayed motor development and recurrent respiratory infections. Obstructive sleep apnea was diagnosed, and all three improved after adenotomy or adenotonsillectomy. Obstructive sleep apnea is an important differential diagnosis in infants showing retarded development and failure to thrive.

Serum immunoreactive erythropoietin in children with acute leukaemia at various stages of disease--and the effects of treatment.

Most children with leukaemia are anaemic at diagnosis and at various times during treatment. Serum erythropoietin (EPO) was estimated in 27 children with acute leukaemia (n = 26) or lymphoma (n = 1) at diagnosis (n = 16), in relation to treatment with high-dose methotrexate (MTX, n = 11) or cytosine arabinoside (Ara-C, n = 8), and during oral maintenance therapy (n = 10). At diagnosis, in children with anaemia serum EPO was increased, and was inversely related to haemoglobin (Hb). After treatment with high-dose MTX, in some children serum EPO increased where Hb was unchanged or increased. After treatment with high-dose Ara-C, Hb declined, and serum EPO increased markedly in everyone. During oral maintenance therapy without significant anaemia, serum EPO was slightly increased in some children. In conclusion, children with leukaemia respond to anaemia with increased serum EPO concentration, but in relation to treatment with high-dose MTX and Ara-C, additional mechanisms may influence the EPO concentration.

High-dose retinol in children with acute myelogenous leukemia in remission.

In a single-institution study, 23 consecutive children with acute myeloid leukemia (AML) have been treated with a protocol including doxorubicin, cytarabine and 6-thioguanine as induction therapy, followed by four courses of high-dose cytarabine as consolidation. Total duration of chemotherapy was 6-8 months from diagnosis. 21 out of the 23 children achieved complete remission. During remission, the children received 52 mumol (50,000 I.U.) retinol as retinyl palmitate per square meter daily. 14 of the 21 children are still in their first remission with a mean observation time of 36 months. In our study retinyl ester given in doses up to 30 times the recommended daily allowances has not caused any clinical or biochemical side effect for up to 4 yr of therapy.

Comparison of PGE2, 6-keto PGF1 alpha and renin release from dog kidneys.

Several renal cell types synthesize prostaglandin E2 (PGE2) and prostacyclin (PGI2). To examine whether the release of these prostaglandins varies in proportion, prostaglandin synthesis was stimulated in anaesthetized dogs by renal arterial constriction, ureteral occlusion, intrarenal angiotensin II infusion and infusion of arachidonic acid, the precursor of PG synthesis. PGI2 was measured as its stable hydrolysed product, 6-keto PGF1 alpha. The two former procedures raised PGE2 release to 13 +/- 2 pmol min-1, 6-keto PGF1 alpha release to 5 +/- 2 pmol min-1 and renin release to 23 +/- 5 micrograms AI min-1. Angiotensin II infusion, reducing the renal blood flow by 30%, increased PGE2 and 6-keto PGF1 alpha release only half as much as ureteral and renal arterial constriction, and exerted no significant effect on renin release. By increasing the infusion rate of angiotensin II up to 10 times, the renal blood flow remained unaltered in four dogs and fell to 50% of control in two dogs, but PGE2 and 6-keto PGF1 alpha release did not increase further in any of the experiments. Arachidonic acid, infused at 40 and 160 micrograms kg-1 min-1, increased prostaglandin release in proportion to the infusion rate. At the highest infusion rate, PGE2 release averaged 166 +/- 37 pmol min-1 and 6-keto PGF1 alpha release 98 +/- 28 pmol min-1. All procedures increased PGE2 and 6-keto PGF1 alpha release in a fixed proportion of about 2.5:1, whereas renin release increased only during autoregulatory vasodilation.

C-reactive protein as an indicator of infection in the immunosuppressed child.

C-reactive protein (CRP) concentrations were determined in a prospective fashion in 50 children with malignant disease. In 35 children with active and aggressive disease, but without signs of infection, no significant increase in CRP was detected. Neither did aggressive cytostatic therapy (70 courses) in non-infected children result in an increase. In bacteriologically proven, and in clinical sepsis-suspected cases, CRP values increased in all cases to levels above 100 mg/l (normal values less than 5 mg/l). Effective antibiotic therapy resulted in a prompt decline in CRP. Viral infections resulted in a much smaller increase. We conclude that serial measurements of CRP in these immunosuppressed children are of great help in monitoring infections and defining the group that needs antibiotic therapy. The measurement is also a good indicator of the effectiveness of the antibiotic therapy chosen.

Vaccination of children with malignant disease against varicella.

Nineteen seronegative children and one young adult with malignant disease in remission and on maintenance chemotherapy were immunized with the Oka-strain live attenuated varicella vaccine (Varilrix). Side effects were moderate and a rash was seen in 50% of the patients after vaccination. Humoral immune response to the vaccine was tested by the fluorescent antibody to membrane antigen (FAMA) test, a simpler indirect immunofluorescence test (IFT), and an enzyme-linked immunosorbent assay (ELISA). The seroconversion rate after immunization varied according to the method used. Seven out of 8 responded by FAMA, 15 out of 20 by IFT, and 12 out of 20 by ELISA. A decline in post-vaccination varicella-zoster virus (VZV) antibodies was seen in some responders. In 2 children, detectable levels of passively transferred VZV antibodies at the time of vaccination, due to varicella-zoster immune globulin, may have interfered with or modified the response to the vaccine. Cross-reacting antibodies to herpes simplex virus may have possibly interfered with vaccine response in a third child. Six out of 8 children receiving a second vaccine dose showed a good serological response. Specific cell-mediated immune response to the vaccine, measured by lymphocyte proliferation tests, corresponded well with the humoral response in the initial study of 8 patients. Two children who had responded to the vaccine were exposed to varicella in their families without contracting the clinical disease.

Vitamin A and/or high-dose Ara-C in the maintenance of remission in acute myelogenous leukaemia in children?

8 children with acute myelogenous leukaemia were brought into remission with a induction regimen containing cytosin arabinoside (Ara-C), 6-thioguanine and adriamycin given as the DNA complex. After remissions were obtained, the children were consolidated with high-dose Ara-C (2 g/m2 every 12 h for 6 doses) and were given 50 000 IU of vitamin A daily as an inducer of differentiation. All children are in continuous relapse-free survival for periods of 5 to 29 months (mean 14 months).