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Biomedical subjects

G E Janka

Publications and source records attributed to G E Janka.

At least 19 recordsLinked to original sources
PubMed2001

Bone marrow transplantation in hemophagocytic lymphohistiocytosis.

Two important syndromes of hemophagocytic lymphohistiocytosis (HLH) have to be considered in infants and young children with recurrent fever, organomegaly and cytopenias. Familial hemophagocytic lymphohistiocytosis (FHLH) is a genetically heterogeneous autosomal recessive disease with histiocytic and lymphocytic infiltrations in multiple organs and is currently curable only by bone marrow transplantation (BMT). Secondary HLH most commonly results from viral infections and some patients may be cured by treating the causative organism, others will need chemotherapy and immunosuppression. Since infections can also trigger disease episodes in FHLH, making the correct diagnosis can prove difficult. The published experience of BMT in HLH is reviewed. Taken together, cure of the majority of patients with HLH by matched related BMT, unrelated or haploidentical BMT is possible. Incomplete resolution of disease activity does not necessarily impede a successful outcome. Central nervous system involvement will eventually develop in many HLH patients and may cause considerable morbidity. Appropriate early treatment and a timely BMT will hopefully decrease mortality rates and improve neurodevelopmental outcome in this disease.

Bone Marrow Transplantation↗
PubMed1999

Assessment of iron stores in children with transfusion siderosis by biomagnetic liver susceptometry.

To investigate the applicability of noninvasive Superconducting Quantum Interference Device (SQUID) biomagnetic liver susceptometry and its limitations in thalassemic children, 23 patients with beta-thalassemia major and other iron loading anemias (age: 4-16 years) and 16 age-related normal children were studied. Liver iron concentrations ranged from 600 to 11,000 microg/g(liver) for thalassemic patients and from 60 to 340 microg/g(liver) for normal patients. Measuring the respective organ volumes by sonography, liver and spleen iron stores, accounting for 80% of total body iron stores, were estimated. Nonliver contributions from the lung or intestine to the measured SQUID signals in the small-sized patients were not observed. Moreover, livers in thalassemia were found to be enlarged by 18% per 1,000 microg/g (r = 0.75, P < 10(-3)). Serum ferritin values correlate significantly with iron stores (r = 0.64, P < 10(-3)), but predict iron stores only within large error intervals of 4,000 microg/g(liver). Analyzing the experimental data from biomagnetometry and from related transfusion and chelation treatment data within the framework of a two-compartment model, we were able to derive additional information on total body iron elimination and chelation therapy efficacy. The exponential decline of iron stores allows forecast of steady-state conditions of the final iron load for a particular transfusion and chelation therapy regimen.

Adolescent↗
PubMed1999

Improved outcome in haemophagocytic lymphohistiocytosis after bone marrow transplantation from related and unrelated donors: a single-centre experience of 12 patients.

Haemophagocytic lymphohistiocytosis (HLH) is an autosomal recessive disease with histiocytic and lymphocytic infiltrations in multiple organs. Cure seems possible only by allogeneic bone marrow transplantation (BMT), but matched sibling donors (MSD) are restricted and high mortality rates are associated with BMT from unrelated donors (URD). We report on 12 consecutive HLH patients with an improved outcome following URD transplants. Eight patients received BMT from URD, four from MSD. Five patients had signs of active HLH at the time of BMT. The conditioning regimen consisted of 20 mg/kg busulphan, 60 mg/kg VP-16 and 120 mg/kg cyclophosphamide and, in case of URD, 90 mg/kg antithymocyte globulin. The doses of busulphan and VP-16 were reduced during the programme to 16 mg/kg and 30 mg/kg, respectively. Using a fivefold graft-versus-host disease (GVHD) prophylaxis, GVHD was absent or mild in 10, and moderate or severe in two patients undergoing unrelated transplants. One patient with URD experienced graft failure and was retransplanted on day 37. Major toxicities were hepatic veno-occlusive disease in five, capillary leak syndrome in two, pneumonia in three, sepsis in one, severe mucositis in one and seizures in two patients. All patients are alive without HLH after a median follow-up of 24.5 months. One patient has chronic GVHD, another patient has severe retardation. Three patients show slight to moderate development delay. These results indicate that in HLH, BMT from matched unrelated donors should be performed. Incomplete resolution of disease activity need not impede a successful outcome.

Adolescent↗
PubMed1995

Liver iron stores in patients with secondary haemosiderosis under iron chelation therapy with deferoxamine or deferiprone.

Total body iron stores including liver and spleen iron were assessed by non-invasive SQUID biomagnetometry. The liver iron concentration was measured in groups of patients with beta-thalassaemia major or other posttransfusional siderosis under treatment with the oral iron chelator deferiprone (n = 19) and/or with parenteral deferoxamine (n = 33). An interquartile range for liver iron concentrations of 1680-4470 micrograms/g liver was found in these patients. In both groups a poor correlation between liver iron and serum ferritin values was observed. Repeated measurements of liver and spleen iron concentrations as well as determination of liver and spleen volume by sonography were performed in six patients under continuous deferiprone treatment for 3-15 months. In this group detailed information was obtained on the whole body iron store (5-36g) and the iron excretion rates (14-34 mg/d) for each patient. As indicated by decreasing liver iron concentrations, five out of six subjects showed a negative iron balance (2-13 mg/d). Conventional measurements of both serum ferritin and urine iron excretion gave fluctuating results, thus being only of limited use in the control of iron depletion therapy. The non-invasive biomagnetic liver iron quantification is a precise and clinically verified technique which offers more direct information on the long-term efficacy of an iron depletion therapy than the hitherto used methods. This technique may be of use in the clinical evaluation of new oral iron chelators.

Adult↗
PubMed1984

In vivo production of childhood acute lymphoblastic leukemia cells in relation to ploidy and immunological subtype.

Eighteen pretreatment cases of acute lymphoblastic leukemia (ALL) in children were investigated by quantitative autoradiography in order to determine the labeling index (LI) as well as the DNA synthesis time (ts). The ploidy of the leukemic blasts was evaluated by Feulgen-microphotometry. The group consisted of 12 cases expressing the common ALL (CALL) antigen only, while 6 showed varying degrees of development along the T-cell axis. The latter subgroup was taken together and termed T-ALL for the sake of simplicity. By dividing LI by ts the fractional birth rate (FBR) was derived representing the percentage of the total leukemic cell mass newly formed per unit of time. The present study confirms a previous investigation in which a higher LI was detected in association with hyperdiploidy. It shows that ts is simultaneously prolonged, while the DNA synthesis rate remains unchanged. This proves that in hyperdiploid cases the longer ts is caused by a larger amount of DNA to be synthesized. The FBR is the same for eu- and hyperdiploid, as well as for CALL and T-ALL cases, and there is no correlation between the FBR and the white blood cell count. So far, ALL is the only type of leukemia in which a prolongation of ts has been demonstrated in comparison to normal human lymphatic cells. This prolongation is not caused primarily by differences in ploidy. The type of growth is accumulative, since the relative rate of cell production is lower than normal. As a finding of practical importance, the labeling index is shown to correlate quite closely with the FBR. In this cell system the LI can thus be used as a parameter reflecting the rate of relative cell production.

Adolescent↗
PubMed1984

Prolonged methotrexate infusions in children with acute leukemia in relapse and in remission and with medulloblastoma. Pharmacokinetics, toxicity and clinical results.

In 86 children with acute lymphocytic leukemia (ALL) and in 6 children with medulloblastoma 253 24-hour methotrexate (MTX) infusions with 150, 500, and 700 mg/m2 were performed. MTX concentrations in plasma and cerebrospinal fluid (CSF) were measured with a specific radioimmunoassay. In 131 infusions with 500 mg/m2 given to patients with ALL in remission, the MTX plasma concentration 24 h after the end of infusion did not exceed 7 X 10(-7) mol/1. Mild hematologic toxicity occurred in 22% of the treatment cycles. In contrast 8/45 infusions given to patients with ALL in relapse were associated with delayed MTX elimination followed by severe toxicity. The CSF: plasma ratio of MTX measured during 58 infusions did not exceed 11% in patients with ALL in remission, but was above this value in 13/34 infusions in patients with leukemia of the central nervous system (CNS). 24-hour MTX infusions with 500 mg/m2 were as hepatotoxic as 4- to 6-hour infusions with 3-8.5 g/m2. With MTX as single agent no remissions were achieved in 8 patients with ALL in relapse. The addition of asparaginase in 10 patients resulted in 3 complete and 2 partial remissions. In patients with ALL in first remission clinical results confirmed the value of intensive MTX therapy for disease-free survival.

Actuarial Analysis↗
PubMed1982

[Improved prognosis in Wilms' tumor due to adjuvant combination drug therapy].

78 children with Wilms' tumor stage I--IV diagnosed since 1960 are presented. There were two groups of patients: one group consisting of 35 patients which received adjuvant chemotherapy for 1 year, the other group consisting of 43 patients which received no chemotherapy. Surgical excision and irradiation was identical in both groups. The prognosis was greatly improved by adjuvant chemotherapy: 4-year survival rates increased from 25 to 69%. Late side effects from radiation and chemotherapy were noted: 15/78 patients suffered from scoliosis and all patients treated by chemotherapy had a decreased lymphotoxin activity over years. The following factors appear to be related to prognosis: the extent of disease in patients determined by better techniques, histopathology of the tumor, and the nature of treatment.

Age Factors↗
PubMed1981

Familial lymphohistiocytosis.

Familial lymphohistiocytosis is a genetically transmitted disease affecting infants and very young children with usually a fatal outcome. Cardinal symptoms are fever, hepatosplenomegaly, and pancytopenia. Histologic examination shows infiltration of all organs with phagocytosing histiocytes and lymphocytes as well as atrophy of the normal lymphoid tissue. The distinction from other histiocytic disorders, i.e., Letterer-Siwe disease or malignant histiocytosis, may be difficult. However, the familial occurrence and characteristic findings in the coagulation system and lipid pattern make familial lymphohistiocytosis a sufficiently distinct clinical entity. This report review 79 cases fron the literature and adds four of own observations.

Blood Coagulation↗
PubMed1981

Intravenous and subcutaneous desferrioxamine therapy in children with severe iron overload.

Ten children with transfusion dependent anemias (thalassemia, sideroblastic anemia, congenital pure red cell aplasia) received either intravenous desferrioxamine (DF) in increasing doses up to 450 mg/kg at the time of transfusion or daily subcutaneous DF up to 110 mg/kg on an outpatient basis. No patient on intravenous DF reached a negative iron balance. All children with a subcutaneous DF dose of more than 60 mg/kg obtained a negative iron balance with a net iron excretion (transfusion iron already substracted) between 206 to 810 mg (mean 496 mg) monthly. The effectiveness of regular subcutaneous DF on liver storage iron could be confirmed in 4 patients by liver biopsy, showing a decrease between 40-60% iron after 12-14 months of chelation therapy. So far the daily iron excretion has remained constant with a given dose of DF over a period up to 15 months. Even if poor compliance in some patients is taken into account, it is possible with this method of treatment to prevent further accumulation of iron in chronically transfused children.

Adolescent↗
PubMed1980

Wolman's disease: clinical, biochemical and ultrastructural studies in an unusual case without striking adrenal calcification.

A case of Wolman's disease is described in a German infant who died at the age of 4 months. Hepatosplenomegaly, abdominal distention, gastrointestinal symptoms, dyserythropoietic changes in the bone marrow, but not adrenal calcification on X-ray were present. Stored lipid material could be demonstrated in liver, spleen, intestine, adrenals, thymus, kidneys, blood cells, but not in the central nervous system. Cholesterylesters and triglycerides were markedly increased in liver and spleen. Lysosomal acid lipase was found to be decreased in leucocytes and liver to less than 10% of normal, when measured with synthetic and natural substrates.

Adrenal Glands↗
PubMed1979

[High-dose methotrexate therapy in osteogenic sarcoma: plasma pharmakokinetics to predict toxicity (author's transl)].

In 22 patients with osteogenic sarcoma, treated with 103 high-dose methotrexate infusions (6-8.5 g/m2 in 4-6 h) plasma methotrexate levels were measured with a specific and rapid radioimmunoassay. Nontoxic infusions were associated with methotrexate concentrations below 8.0 X 10(-6) mol/l at 24 h, 8.0 X 10(-7) mol/l at 48 h and 4.25 X 10(-7)/mol/1 at 72 h. All patients with 48 h methotrexate levels above 1 X 10-6 mol/l manifested severe toxicity with myelosuppression and stomatitis due to delayed methotrexate excretion. Rise of serum creatinine was not reliable to predict oxicity. Determination of 48- and 72-h methotrexate concentrations proved to be a valuable method for identifying patients at high risk for toxic side effects. Additional citrovorum factor may thus be given in time.

Adolescent↗