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Biomedical subjects

A Gratwohl

Publications and source records attributed to A Gratwohl.

At least 397 records · Page 22Linked to original sources
PubMed1983

Bone marrow cell dose and kinetics of recovery following allogeneic marrow transplantation in man.

In 50 patients transplanted for acute or chronic leukemia we studied the correlation between the number of infused bone marrow cells/kg recipient body weight and the time needed for engraftment. Engraftment was arbitrarily defined as the first day of 1 X 10(9) leukocytes/l and of 20 X 10(9) reticulocytes/l after the posttransplantation nadir. There is a negative non-linear correlation between the duration of leukopenia following marrow transplantation and the amount of transfused nucleated cells (p = 0.01). Since the incidence of infectious or hemorrhagic complications depends directly on the duration of aplasia it is justifiable to give a maximal cell dose.

Acute Disease↗
PubMed1983

Cyclosporine in human bone marrow transplantation. Serum concentration, graft-versus-host disease, and nephrotoxicity.

Serum concentrations of cyclosporine were studied in 42 patients given cyclosporine for the prevention of graft-versus-host-disease (GVHD) following allogeneic bone marrow transplantation (BMT). Serum trough levels for cyclosporine were determined in each patient at least once weekly during the first 3 months and were compared with the occurrence of GVHD and with nephrotoxicity. Cyclosporine was given as 20 mg/kg i.m. or as a 24-hr infusion for the first 5-7 days. This was followed by a single daily oral dose of 12.5 mg/kg for 6 months. Cyclosporine was then gradually reduced and stopped after one year. After a median observation period of 2 years 25 of the 42 patients (59%) are alive. Twenty six patients (62%) developed GVHD, which was stage II or more in 11 (26%) and fatal in 2 patients (5%). Five patients developed GVHD 6-8 weeks after withdrawal of cyclosporine one year after BMT. All patients improved after restarting cyclosporine. No correlation between cyclosporine serum concentration and GVHD was observed, but patients with GVHD had greater fluctuations of their serum trough levels. Serum creatinine increased in all patients soon after BMT and was correlated with cyclosporine serum concentration during the first month. Serum creatinine, however, rose further despite lower cyclosporine concentrations in the second month. These results show that cyclosporine effectively reduces the severity, but not the incidence, of GVHD suggesting that there is a subset of cells resistant to cyclosporine. The therapeutic range, however, between high doses (which are often associated with nephrotoxicity) and the minimal effective dose of cyclosporine, has yet to be defined.

Adolescent↗
PubMed1983

Immunologic reactivity in marrow graft recipients receiving cyclosporine to prevent graft-versus-host disease.

In vitro and in vivo immunologic parameters were determined in 26 patients treated continuously with cyclosporine to prevent graft-versus-host-disease (GVHD) after allogeneic bone marrow transplantation (BMT) for acute and chronic leukemia and for aplastic anemia. A group of 18 patients was tested 6 months after BMT and another group of 10 patients was tested after one year. At 6 months after BMT, 94% of the patients had normal serum IgG and IgM levels, whereas at one year 29% of them had low IgA levels. The proportion of patients with normal lymphocyte responses in vitro at 6 months after BMT was 69% and 76% for the responses to concanavalin A and to soluble antigens; 75% and 53% for the responses to allogeneic cells and pokeweed mitogen, respectively; and 89% for the response to phytohemagglutinin. All but one were able to generate suppressor cells upon con A stimulation. At one year after the graft, only one patient had demonstrable multiple abnormalities in in vitro tests. Skin test reactivity at one year was comparable to pre-graft reactivity. After BMT a lymphopenia persisted for 6 months. The rate of infectious complications was high during the first 3 months after BMT, and it diminished progressively as immune functions returned to normal. Infection was the cause of death in two cases (one disseminated cytomegalovirus infection and one septicemia). GHVD occurred in 12 patients; in nine of them the disease was transient and mild, only 1 patient developed severe chronic GVHD. Acute GVHD did not influence the tempo of immunologic reconstitution. In comparison to other studies, it seems that cyclosporine does not delay immune restoration, or increase morbidity from infection, while preventing GVHD and its complications efficiently.

Anemia, Aplastic↗
PubMed1983

Bone marrow graft versus ALG in patients with aplastic anaemia.

Eighty-six successive patients with severe aplastic anaemia were admitted to this hospital between January 1976 and October 1982. They were treated and evaluated in a prospective study according to one protocol. 26 patients with an HLA identical sibling underwent bone marrow transplantation. Overall survival calculated according to Kaplan and Meier in this group is 47%, 60 patients without an HLA identical sibling were given antilymphocyte globulin with or without an infusion of HLA-haploidentical marrow. All these 60 patients received low dose androgens after the procedure. In this study the marrow infusion did not significantly improve the results and overall survival was 74% compared to 70% in patients receiving only antilymphocyte globulin and androgens. In a current pilot study combining ALG and high dose prednisone we were able to further increase remission rates. Between HLA-identical siblings we improved the results of marrow transplants significantly by the use of cyclosporin-A instead of methotrexate for prophylaxis against GvHD.

Adolescent↗
PubMed1982

Cyclosporin A: correlation between HPLC and RIA serum levels.

Serum levels of cyclosporin A were analysed in parallel with an HPLC and a RIA method for six patients who received repeated intramuscular and oral doses of this immunosuppressive drug after bone marrow transplantation. A good correlation was found between both methods with a similar time course of the serum curves. Due to cross-reacting metabolites, the values from the RIA assay were on average 30 to 100% higher than with the HPLC assay which is specific for the parent drug.

Administration, Oral↗
PubMed1982

Allogeneic marrow transplantation for chronic granulocytic leukemia.

Six patients with Philadelphia-chromosome (Ph' +)-positive chronic granulocytic leukemia were transplanted from their HLA-identical siblings after conditioning with cyclophosphamide and 1'000 rad total body irradiation. All received cyclosporin-A for prophylaxis of Graft-versus-Host disease. All patients showed prompt engraftment and all are cytogenetically and clinically in complete remission. Two patients had transient mild signs of Graft-versus-Host-disease and one patient had unilateral facial nerve paresis of unknown origin. All are ambulatory and well 6-18 months (median 10 months) after transplantation.

Adolescent↗
PubMed1982

Histoincompatible skin and marrow grafts in rabbits on cyclosporin A.

Cyclosporin A (Cy A; 15 mg/kg s.c.) allows allogeneic histoincompatible skin graft survival in 10 of 10 rabbits as long as the drug is given. The same dose of Cy A does not affect acute graft-versus-host disease (GVHD) and increase survival of rabbits after allogeneic bone marrow transplantation between the same two strains, when two groups of 15 animals are tested. Median survival of 14 engrafted animals without Cy A was 23 days, of 12 engrafted animals with Cy A 22 days (not significant). Cryopreservation of bone marrow delays the onset of GVHD and increases survival of engrafted animals. Median survival of 5 engrafted animals without Cy A was 33 days, of 14 engrafted animals with Cy A 35 days. Our hypothesis is that one part of early GVHD as well as of early graft rejection is mediated by a subclass of cells which is resistant to Cy A. This hypothesis is supported by the finding that most transplanted skins show a self-limited period of infiltration and induration. Skin grafts survive this period of infiltration. If the same potentially self-limited process occurs in the liver or the intestine during acute GVHD, animals die. this hypothesis could explain why Cy A allows skin graft survival but does not affect acute GVHD.

Animals↗
PubMed1982

[Marrow transplantation in leukemia-recent trends].

Due to progress in conventional chemotherapy 50-60% of children with acute leukemia can be cured today. Despite these good results, however, 40-50% eventually will relapse and die. Other therapeutic modalities are therefore needed. Transplantation of bone marrow from an HLA-identical sibling offers this possibility. Initiated a decade ago as last therapy for end stage disease patients marrow transplantation is a well tolerated therapy today with well defined risks. In adults, marrow transplantation is clearly superior to conventional chemotherapy if performed early. The incidence of severe Graft-versus-Host-Disease, the major complication of marrow transplantation is much less after early transplantation and Cyclosporin-A, a new immunosuppressive agent further reduces severity of Graft-versus-Host-Disease. Since all complications are less in younger patients marrow transplantation is the therapy of choice for a child with leukemia having an HLA-identical sibling donor.

Acute Disease↗
PubMed1981

[New development in clinical bone marrow transplantation in leukemia].

39 clinical bone marrow transplants (BMT) for leukemia are described. In a historical control series of 18 patients in whom BMT was performed after all chemotherapeutic resources had been exhausted, there is only 1 long-term survivor (5.5%), 8 patients died from GvH reaction, 6 from interstitial pneumonia and 3 from recurrent leukemia. Since 1979 an attempt has been made to transplant patients under optimal conditions (1st complete remission) and cyclosporin-A (CyA) has been used for prophylaxis of GvH reaction instead of MTX. 11 patients were transplanted according to our original proposal (AML and ALL in first remission, CML in chronic phase): 10 have survived without evidence of leukemia (91%), 1 AML died in relapse. 10 patients were grafted in second or later remissions or early relapse: 5 have leukemia-free survival (50%), 1 is living with a relapse. In this group 3 deaths were due to recurrent leukemia and 1 to CMV-infection. In our experience BMT under optimal circumstances does not involve a risk of early mortality and the chances of recurrent leukemia are reduced. Severe or chronic GvH reaction is not seen under CyA. BMT is the treatment of choice for patients with histocompatible sibling donors.

Bone Marrow Transplantation↗
PubMed1981

[Treatment of severe aplastic anemia].

58 patients with severe aplastic anemia (SAA) were treated and evaluated in a prospective study either by bone marrow transplantation (BMT) or by antilymphocyte globulin (ALG). 19 patients were treated with BMT; 9 are still alive 6 months to 5 years after BMT (47%). 39 patients were treated with ALG; 28 are alive 5 months to 5 years after ALG (72%). 24 of these 28 are self-sustaining and in remission. The results show that treatment with ALG is probably superior to treatment with BMT, and also demonstrate that most patients with SAA have a pool of hematopoietic stem cells able to repopulate the marrow after this type of treatment.

Adolescent↗
PubMed1981

Treatment of severe aplastic anaemia with antilymphocyte globulin or bone-marrow transplantation.

Fifty-three patients with severe aplastic anaemia were admitted to this hospital between January 1976 and June 1980, of whom three arrived in terminal condition and died before treatment for their basic disease could be given. Thus 50 patients were treated and evaluated in a prospective study according to one protocol. Eighteen patients with an HLA-identical sibling underwent bone-marrow transplantation with the aim of achieving haematopoietic chimerism. Thirty-two patients without an HLA-identical sibling were given antilymphocyte globulin with or without an infusion of HLA-haplotype-identical marrow. All these 32 patients received low-dose androgens after the procedure. In the first group eight patients (44%) survived. In the two other groups, 22 patients survived (69%), of whom 20 were completely self-sustaining (63%). Engraftment and graft-versus-host disease did not occur in the group who received antilymphocyte globulin and haploidentical marrow, and the haematopoietic reconstitutions in these patients were all autologous. These results confirm the efficacy of antilymphocyte globulin in the treatment of severe aplastic anaemia and show that such treatment is at least as good as bone-marrow transplantation. Its mechanism of action remains unknown, but most patients with aplastic anaemia have a pool of haematopoietic stem cells able to repopulate the marrow after this type of treatment.

Adolescent↗
PubMed1981

[Thrombotic thrombocytopenic purpura: report on 5 cases and current therapy concepts].

Report on 5 patients with thrombotic thrombocytopenic purpura. Four of the five survived. The following forms of treatment have been used: up to 1976, splenectomy and corticosteroids; since 1976, antiplatelet agents and exchange transfusions, and since 1978, antiplatelet agents and fresh plasma or plasma exchange. The author's experience is identical to that in the more recent case reports: early treatment with antiplatelet agents and fresh plasma-in case of failure with plasma exchange - appears to improve the hitherto fatal prognosis.

Adult↗