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Biomedical subjects

A Gratwohl

Publications and source records attributed to A Gratwohl.

At least 307 records · Page 17Linked to original sources

Treatment of thrombocytosis in myeloproliferative disorders with interferon alpha-2a.

In an open prospective pilot trial, we tested the effect of recombinant interferon alpha-2 a (rIFN alpha-2 a) on thrombocytosis in myeloproliferative disorders (MPD). Since October 1986, 13 patients with MPD (4 with chronic granulocytic leukemia, 4 with polycythemia vera, 3 with essential thrombocythemia and 2 with myeloid metaplasia) were treated with rIFN alpha-2 a. Platelet counts decreased in all treated patients within 2 to 10 weeks from a median value of 1,050 x 10(9)/l (range 610-1,940 x 10(9)/l) to 340 x 10(9)/l (range 230-495 x 10(9)/l). The response was dose-dependent. In 11 patients we observed a simultaneous reduction of the white blood cell count. Six patients still continue the IFN alpha-2 a therapy. In 7 treatment was discontinued, because of chronic side effects in 3, and because of noncompliance in one. In these patients, thrombocytosis recurred after discontinuation of the therapy. These results show that rIFN alpha-2 a is effective in controlling thrombocytosis in MPD. However, the long-term benefit of interferon in these disorders remains to be established.

Adult↗

Treatment of acute myelogenous leukemia. An EBMT-EORTC retrospective analysis of chemotherapy versus allogeneic or autologous bone marrow transplantation.

In a retrospective analysis, patients with acute myelogenous leukemia (AML), treated in first complete remission (CR) with chemotherapy or with allogeneic or autologous bone marrow transplantation were compared with respect to their leukemia-free survival from CR. Two hundred and thirty-six patients treated with chemotherapy according to the EORTC AML-5 and AML-6 trials were included. The data of the transplanted patients were taken from two EBMT registries; 453 with an allogeneic and 182 with an autologous BMT. The very different sources of the data (trials and registries) forced us to be cautious in our conclusions. However, for the patient cohorts analyzed in the present study, BMT patients tended to have a better leukemia-free survival than chemotherapy patients. This was especially the case for the allogeneic BMT after 6 months of transplant.

Adolescent↗

Complete recovery of marrow function after treatment with anti-lymphocyte globulin is associated with high, whereas early failure and development of paroxysmal nocturnal haemoglobinuria are associated with low endogenous G-CSA-release.

24 patients who were treated with antilymphocyte globulin (ALG) for severe aplastic anaemia (SAA) were tested for endogenous release of granulocyte colony stimulating activity (G-CSA) prior to, and at various intervals after treatment. CSA-production in vitro was induced with autologous serum as a source of 'releaser' activity, avoiding the use of plant mitogens. Before treatment, G-CSA-release was highly variable. Though mean values were higher in the 17 patients who subsequently responded to ALG treatment than in the six non-responders, this difference was not statistically significant. In the 17 responders, G-CSA-release strongly increased prior to improvement of peripheral blood counts. In one responder patient tested-before, and at regular intervals after ALG, CSA-release was high before, abnormally low at 7 d and increased again to high values before the onset of bone marrow reconstitution. In six patients who did not respond to ALG-treatment, G-CSA release decreased after treatment, and a second course of ALG was ineffective when given during this low CSA-phase. Five of the 24 patients developed paroxysmal nocturnal haemoglobinuria (PNH) at 9 months to 3 years after ALG-treatment. In all, the onset of PNH was associated with very low G-CSA-release, whether it had been high or low before treatment. We conclude that low-CSA-release after ALG treatment is a poor prognostic sign. It either indicates progression of marrow failure or heralds PNH. Such patients may be candidates for early bone marrow transplantation or treatment with G-CSF or GM-CSF.

Adolescent↗

Allogeneic bone marrow transplantation in patients with multiple myeloma.

50 patients with a median age of 41 years (range 29-54) underwent allogenic bone marrow transplantation for multiple myeloma. 35 patients were on second-line treatment, and 15 on first-line treatment. 24 patients were considered refractory to previous treatment. 45 patients received marrow from HLA-matched sibling donors (3 of these from twin donors), and 5 from unrelated or related non-sibling donors. 21 patients entered complete remission, while 15 had persistent disease following repopulation of the marrow. 14 patients were not evaluable for remission status because of early transplantation-related death. The overall median survival from bone marrow transplantation was 27 months, with a projected long-term survival of 34%. Patients who were 40 yr of age or older had a survival that was not different from that of patients between 29 and 40 yr of age. The median disease-free survival of patients who entered complete remissions was 41 months. These patients tended to have a longer survival than patients with persistent disease following repopulation of the marrow. Allogeneic bone marrow transplantation appears to be a promising method for treatment of certain patients with multiple myeloma.

Adult↗

Accidental overdose of multiple chemotherapeutic agents.

A 35-year-old man with refractory low grade diffuse centroblastic centrocytic non-Hodgkin's lymphoma was treated accidentally with an overdose of multiple chemotherapeutic agents. He was given adriamycin 50 mg/m2 and cyclophosphamide 350 mg/m2 for 6 days followed by 4 days of vincristine 1 mg/m2 and bleomycin 10 mg/m2. He was transferred when he developed pancytopenia, fever, severe mucositis, ileus and peripheral neuropathy. He was treated with broad spectrum antibiotics, red cell and single donor platelet transfusions and strict parenteral nutrition. In addition, he was given a continuous infusion of 400 micrograms daily human recombinant granulocyte macrophage-colony stimulating factor (rh GM-CSF) for 17 days. Intractable severe bleeding from his oral mucositis necessitated treatment with a continuous infusion of 8-ornithine-vasopressin for 8 days. He recovered and could be discharged home after 36 days of hospitalization with normal blood counts and without severe sequelae.

Adult↗

Bone marrow transplantation for leukaemia in Europe.

The European Bone Marrow Transplant Leukaemia Registry has collected data from 52 European centers between 1979 and 1986. More than 2,000 transplants performed for a haematological malignancy were reported. The present analysis shows that the most important factor influencing leukaemia free survival, transplant related mortality and relapse incidence is the stage of the disease at the time of the transplant. Outcome is highly better when the transplant is performed for acute myeloid and acute lymphocytic leukaemia in first complete remission and for chronic myelocytic leukaemia in first chronic phase. Additional prognostic factors are age, the method for graft-versus-host disease prevention and the donor recipient sex combination. Results are better for younger patients, for patients given cyclosporine for prevention of graft-versus-host disease and are worse for male patients receiving a female donor bone marrow. The results are not influenced by the year of the transplant per se and by the center size.

Adolescent↗

[Serum immunoglobulin concentrations in patients following bone marrow transplantation and preventive administration of high-dose nonspecific or normal-dose CMV-specific immunoglobulin].

Ten consecutive bone marrow transplant recipients were assigned alternatively to receive either a high dose polyspecific intravenous immunglobulin (HDIVIG) 0.5 g/kg weekly X 14, or a conventional dose of a CMV specific intravenous immunglobulin (CMVIG) 0.1 g/kg every three weeks. Before and after each application we determined the levels of total IgG, IgG subclasses, IgG 1, IgG 2, IgG 3, IgG 4, total IgA and IgM and of specific IgG and IgM antibody concentrations against endotoxin, lipid A, streptococcus A, hemophilus, EBV and CMV. In the HDIVIG, total IgG rose from 11 (median, range 2-11) g/l to 25 (22-32) g/l by day 89, in the CMVIG group, IgG dropped from 11 (10-15) g/l to 9 (6-12) g/l. In the same period the mean levels of IgG subclasses expressed as % of normal plasma pool increased in the HDIVIG group in all subclasses, not in the CMVIG group. The differences were significant, however, only for IgG 1 and IgG 2. IgG-antibodies against CMV, EBV, endotoxin, streptococcus and hemophilus did increase significantly in the HDIVIG group, but not in the CMVIG group. No increase was seen in both groups in lipid A antibodies and in specific IgM antibodies. Each application of CMVIG induced a transient increase of anti-CMV antibodies. We conclude that HDIVIG induces reproducibly an increase of specific and non-specific IgG antibodies. No attempt was made to assess clinical outcome. However, these results provide a rational basis for further therapeutic studies.

Adult↗

Bone marrow transplantation in Basel: single center experience from 1973 to 1989.

Bone marrow transplantation with a small to medium-sized single hospital team is feasible. It leads to results similar to those observed at large centers and with the same major risk factors: age, stage of the disease at the time of transplant, degree of histocompatibility, graft-versus-host disease prevention method, and selection. A single small to medium-sized center cannot conduct prospective randomized studies but it can pioneer new concepts. Bone marrow transplantation today offers a good choice for patients suffering from otherwise lethal bone marrow diseases. These include severe aplastic anemia, acute leukemias, chronic myeloid and chronic lymphoid leukemia, myelodysplastic syndrome, and congenital disorders. Changes in outcome are due to innovative steps, such as the introduction of CsA for GvHD prevention. In addition they are certainly influenced by unrecognized changes in the patient selection process.

Anemia, Aplastic↗

Kinetics of cytomegalovirus IgG antibody following infusion of a hyperimmune globulin preparation in allogeneic marrow transplant recipients.

We investigated prospectively cytomegalovirus (CMV) IgG antibody kinetics following infusion of a CMV hyperimmune globulin preparation in 19 consecutive patients undergoing allogeneic bone marrow transplantation (BMT). CMV IgG against late antigen was measured by enzyme-linked immunosorbent assay. On a prophylactic hyperimmune globulin regimen (100 mg/kg body weight every 20 days), the mean half-life (t1/2) +/- SD of CMV IgG in seronegative patients with seronegative marrow donors was 19.7 +/- 7.9 days after the first infusion on day -7 before BMT, 24.9 +/- 12.5 days after the second infusion on day +13 after BMT, and 19.4 +/- 6.9 days after the third infusion on day +33. The t1/2 in individual patients showed a wide variation ranging from 10.9 to 47.6 days. A therapeutic high-dose hyperimmune globulin regimen (200-400 mg/kg body weight at 4-day intervals) given to five patients resulted in high serum levels of CMV IgG, which were maintained throughout therapy, even in two patients with severe intestinal graft-versus-host disease. The variation of CMV IgG kinetics between individual BMT recipients may contribute to the lack of protection from active CMV infection observed in some patients.

Adolescent↗

[Comparative study on in vitro lymphocytotoxicity and mitogenicity of different antilymphocyte globulin (ALG) preparations].

The lymphocytotoxicity and mitogenicity between six different ALG preparations on the clinical use world wide were compared. No significant difference in the lympholytic activity was observed between preparations and 100% cell lysis was achieved at a concentration of 50 micrograms/ml in the presence of complement. On the other hand, four preparations now in use in European countries and USA showed variable mitogenic activities on lymphocytes in the absence of complement, whereas two ALGs used in Japan did not. As the stimulatory effects of ALG on lymphocytes may contribute to the clinical outcome in the treatment of severe aplastic anemia (Kawano et al, 1988), these date can explain the poor clinical results of ALG therapy with those two preparations in Japan. Careful measures should be paid in the construction of treatment protocol and selection of ALG preparations to yield the best results.

Antilymphocyte Serum↗