[Bone necrosis as a sequela of chemotherapy in hematologically malignant disorders].
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Biomedical subjects
Publications and source records attributed to A J Veerman.
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Echocardiograms of 47 children treated with doxorubicin in combination with other cytostatic agents in the period 1979-1984 were reviewed. The authors compared the first and the last echocardiographic registration of every individual patient, analysing the left ventricular dimensions and the shortening fraction which is the indicator of myocardial contractility. Statistical analysis revealed a significant dilation of the left ventricle with a decrease of contractility in the whole group of patients during the therapy. Seven out of 9 patients who had an abnormal shortening fraction at the last measurement died of malignancy. Three children, all in remission of their malignancy, developed a dilated cardiomyopathy that was fatal in two. The possibilities for prevention of this serious complication by means of serial echocardiography during treatment with anthracycline derivatives are discussed.
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Two patients are described with X-linked agammaglobulinaemia (XLA). After a period of gammaglobulin infusions endogenous IgG production appeared to resume and gammaglobulin therapy was gradually stopped. However, bacterial respiratory tract infections recurred. Immunological evaluation showed normal levels of serum IgG with mono/oligoclonal IgG m-bands, while B lymphocytes and plasma cells were absent from the peripheral blood and bone marrow. Endogenous IgG was synthesized in plasma cells in the submucosa of the gastrointestinal tract. Renewed high doses of exogenous gammaglobulin led to the reduction of infections and the disappearance of mono/oligoclonal m-bands in the serum. We suggest that as a rare complication of XLA some pre-B-cells may escape the blockade to B-cell maturation and produce mono/oligoclonal IgG, possibly due to chronic infectious stimulation.
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A girl is described with the thrombocytopenia and absent radii (TAR) syndrome. The literature concerning this rare, autosomal recessive inherited syndrome is discussed. The main characteristics are bilateral radius aplasia in which the thumbs are present in combination with a a- or hypomegakaryocytic thrombocytopenia. Many other anomalies and associated disorders are described in the literature, especially in the haematological, skeletal, cardiac and intestinal fields. The treatment is mainly directed to the haemorrhagic diathesis and the orthopaedic problems. It is suggested that the mortality-rate--mainly a consequence of haemorrhage--which used to be 30-40%, has diminished thanks to the evolution of platelet transfusion therapy.
The reduction of the tetrazolium salt MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) to a blue-black formazan product by living but not by dead cells can be used to measure chemosensitivity of tumor cells. The main advantages of the MTT assay are its simplicity, rapidity, and the fact that the results are read automatically with a microplate spectrophotometer. Several reports on the use of the MTT assay in chemosensitivity testing have been published, but all these studies dealt with established cell lines and not with specimens obtained directly from patients. Here we present a study in which the MTT assay has been adapted to assess the effect of antineoplastic drugs on lymphoblasts of children with leukemia.
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Purine nucleotides become available for a cell by two routes, namely purine de novo synthesis and the purine salvage pathway. 5'Nucleotidase is a purine pathway enzyme and is present in two forms. Cytoplasmic 5'nucleotidase (cyto 5'NT) catalyzes the intracellular degradation of purine nucleotides into their corresponding nucleosides. The plasma membrane bound form (ecto 5'NT) has its active site facing the external medium. Its function is the extracellular dephosphorylation of nucleotides, to which cells are generally impermeable, into nucleosides and the transport of these nucleosides through the cell membrane. Lymphoblastic 5'NT activity varies between different children with common-ALL. 5'NT positive cases have a higher relapse rate and thus a poorer prognosis than 5'NT negative cases. This can be explained by two hypotheses which are not mutually exclusive: 1. Rescue hypothesis. When purine de novo synthesis is blocked by methotrexate (MTX) and/or 6-mercaptopurine (6-MP), the malignant cell has to rely on the purine salvage pathway. This pathway depends on the ecto-5'NT activity. So, leukemic cells might be resistant to MTX and/or 6-MP because of ecto-5'NT activity. 2. Breakdown hypothesis. Leukemic cells are resistant to 6-MP because of the breakdown of the toxic nucleotide form of 6-MP into the nucleoside form by cyto-5'NT.
Bone marrow infarction is known to occur in childhood leukaemia. Although it may be suspected on clinical grounds, radiographic evidence is infrequent. We present three cases in which magnetic resonance imaging demonstrated unexpectedly extensive bone marrow lesions and discuss the evidence that these lesions were due to bone marrow infarction.
Between December, 1984, and May, 1986, 98 CSF samples were sent to a central laboratory by postal express. The samples could be kept in a medium for up to 24 hours after the lumbar puncture. The quality of the cells proved to be good. Excluded were 5 samples delayed in delivery and 13 samples contaminated with blood, defined as the macroscopical presence of blood. The microscopical presence of erythrocytes in the cytocentrifuge preparation can make interpretation of the results difficult. Especially when leukemic blasts are present in the blood, extreme caution is necessary. A total of 71 samples could be studied by cytomorphology as well as by TdT-IF. When cytomorphological leukemic blasts were present, this was confirmed by TdT-IF positivity in all cases. But in 6 of 71 samples, TdT-IF was positive without the presence of cytomorphological leukemic blasts. Follow-up of these patients will show whether the therapeutic regimen has to be changed.
Bone marrow samples from 8 children treated for acute lymphoblastic leukemia (ALL) were investigated at cessation of cytostatic treatment and during 18 months thereafter. The course of the percentage of lymphoid cells and characterization of these cells by means of monoclonal antibodies, peanut agglutinin (PNA) binding and S-phase determination are shown. The percentage of lymphocytes rises in the first 1.5 months, followed by a non-significant decline. The percentage of cells in S-phase is higher at 0 months than at 6, 15 and 18 months. The percentage of T-cells does not change significantly. In the first 1.5 months a sudden rise in the percentage of common-ALL-antigen (cALLA)-positive lymphocytes occurs. The number of B-cells rises to a peak at 6 months. PNA positively increases to a maximum at 3 months and is correlated with positivity for markers of the B-cell lineage. The percentages of B-cells, cALLA-positive, and PNA-positive lymphocytes do not change significantly after they reach their maximum values and are still high at 18 months. Our results show that after cessation of chemotherapy for ALL a lymphoid cell regeneration occurs in the bone marrow consisting of cells of the B-cell lineage; many of these are cALLA-positive, but are discernible from their malignant counterparts by PNA-positivity.
A survey was made of the contribution to the scientific research of the different pediatric departments at the universities in The Netherlands. The evaluation was based on quantitative and qualitative output of scientific papers over the period 1981-1985. It was possible to indicate the better research-groups at the universities. This information should form a solid base for future research policy with respect to pediatrics in The Netherlands.
In most cases, a diagnosis of acute leukemia is easily made. Some less frequently occurring signs and symptoms in children with acute leukemia are discussed, as well as some possibilities in the differential diagnosis.
Children with leukemia have to undergo many times painful procedures like bone-marrow aspiration and lumbar puncture. For reduction of anxiety and pain sensation good psychological support can be an important help. Often sedative drugs are used, or even general anaesthesia may be necessary. There is a need of a safe, short-acting and effective medication. Among the different possibilities the intravenous or rectal administration of midazolam seems to be very promising.
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In 25 patients under treatment or during follow-up for acute lymphoblastic leukemia magnetic resonance imaging (MRI) of both knees was compared to history and physical examination to detect osteonecrosis. Results of MRI were classified as: O, normal bone marrow (BM); 1, diffuse decrease in signal intensity; 2, circumscript lesions. Patients clinically suspected of osteonecrosis had a statistically significant increased incidence of Type 2 lesions. Three patients with a BM relapse also showed Type 2 lesions. Circumscript lesions of the epiphyses were seen exclusively in the four patients with clinical suspicion of osteonecrosis during BM remission and this may be a MR finding strongly indicative of osteonecrosis. Patients with Type 2 lesions during BM remission had received systemic chemotherapy for a statistically significant longer period than the other patients. Using MRI findings we suspect that at least four patients suffered osteonecrosis due to chemotherapy. MRI is a promising means of detecting this disorder.