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Biomedical subjects

A Gratwohl

Publications and source records attributed to A Gratwohl.

At least 379 records · Page 21Linked to original sources
PubMed1985

Heterogeneity of Ia antigen expression on myeloblastic leukaemias: correlation with stage of maturation defined by cytochemical markers.

The expression of Ia-like antigen (Ia) has been studied in 55 cases of acute myeloid leukaemia (AML) in correlation with the expression of both Sudan Black (SB) and naphthol AS-D chloroacetate esterase (NCAE) stains. Operationally the AML cases were divided into three groups using only NCAE expression on the leukaemic cells: the first group with early maturation stage (MS1) consisted of 30 cases with less than 10% NCAE positive cells (SB: 15-100%): the MS2 group of 14 cases with 10-70% NCAE positive cells (SB: 65-100%) and the MS3 group of 11 cases with 70-100% NCAE positive cells (SB: 89-100%). Ia expression was determined by complement-dependent cytotoxicity, immunofluorescence and immunoperoxidase methods. A similar high percentage (80%) of patients from both group MS1 and MS2 expressed Ia on the surface of 32-100% of the cells. Furthermore, individual comparison of all cases from these two groups showed no correlation between Ia, NCAE and SB expression. Only in the 11 cases from the MS3 group, which included nine cases of promyelocytic leukaemias, was there a correlation between very low expression of Ia antigen with the high NCAE expression. Thus, for AML with a low degree of differentiation the expression of Ia seems to be independent of conventional cytochemical markers of cell maturation.

Antigens, Surface↗
PubMed1985

Multiple cotton wool spots following bone marrow transplantation for treatment of acute lymphatic leukaemia.

Three patients with acute lymphatic leukaemia developed visual impairment due to occlusion of small retinal vessels with multiple cotton wool spots after treatment which included whole body and skull irradiation followed by bone marrow transplantation and cyclosporin A. Withdrawal of cyclosporin A and treatment with corticosteroids was followed by recovery of visual acuity. This retinopathy and the retinal changes seen in the immunodeficiency syndrome are thought to be closely related. The possible role of cyclosporin A is discussed, though cotton wool spots and retinal haemorrhages have never been described in renal transplant patients during treatment with this drug. Withdrawal of cyclosporin A, which is highly effective in preventing graft-versus-host disease, can be fatal. Irradiation of the skull prior to bone marrow transplantation and intrathecal administration of methotrexate may be the most important factors causing the retinal ischaemic signs described here. The inclusion of an ophthalmologist in the team monitoring transplant patients would lead to increased documentation and a better understanding of this disease.

Adult↗
PubMed1985

The effect of cytomegalovirus infection on T lymphocytes after allogeneic bone marrow transplantation.

The influence of cytomegalovirus (CMV) infection on peripheral T lymphocyte repopulation was studied in 59 bone marrow transplant (BMT) recipients who received either cyclosporin A (CyA) or methotrexate (MTX) as prophylaxis for acute graft-versus-host disease. We used monoclonal antibodies and single- or double-marker immunofluorescence for the quantitation of T4+, T8+ and HNK1+ T cell subpopulations. CMV infection was serologically diagnosed by an enzyme-linked immunosorbent assay (ELISA), and by viral cultures and histological studies. Among the 52 patients who were evaluable for CMV infection, one had a primary infection and 24 had CMV reactivation/reinfection after BMT. In the latter patients, increases to supranormal levels were observed in T8+ T cells and HNK1+ T cells, both in patients on CyA and in patients on MTX. Double-marker immunofluorescence revealed that the two markers were largely expressed by the same cells, which therefore had the T8+ HNK1+ phenotype. In addition, the very small subset of T4+ HNK+ T cells was slightly, but consistently, increased in the patients with CMV reactivation/reinfection. CMV infection did not influence the numbers of T4+ HNK1- and T8+ HNK1- T cells. The long-lasting presence of large numbers of T8+ HNK1+ T cells in patients who had CMV reactivation/reinfection suggests a continuing interaction between the virus and the immune system of its host.

Adolescent↗
PubMed1985

Cyclosporin-A in allogeneic bone marrow transplantation for leukemia: Basle experience 1979 to 1984.

Since July 1979 all patients transplanted in Basle have been treated with Cyclosporin-A (CyA) as prophylaxis against Graft-versus-Host-Disease (GvHD). Currently CyA is given as a continuous infusion for 3-4 weeks, followed by an oral once-daily-therapy for one year. The daily dose is adjusted depending on the serum creatinine. Patients with acute GvHD during CyA therapy are treated with high dose bolus-steroid therapy. 83 patients with leukemia were treated in these 5 years. All were conditioned with 2 X 60 mg/kg Cyclophosphamide and 10 Gy total body irradiation. 78 had an HLA-identical, 5 an HLA-haploidentical family donor. The median age is 28 years (5-42 y). 20 patients had AML in 1. CR, 9 patients AML not in 1. CR (2nd, 3rd CR or relapse), 11 ALL in 1. CR, 19 not in 1. CR, 20 CML in chronic and 4 CML in accelerated phase. 40 patients are actually alive, well and without any signs of their disease; 9 are living in relapse. Major cause of death is relapse and GvHD. CyA does not reduce the incidence, it does reduce the severity of GvHD. The only long-term side-effects of bone marrow transplantation seen are cataracts and sterility. The major factors influencing outcome is the time of transplant. 31/51 patients transplanted in 1. CR or in chronic phase of CML are alive compared to only 9/32 transplanted in later stages. We conclude that bone marrow transplantation should be performed early in the disease and that CyA eases the procedure.

Adolescent↗
PubMed1984

[Current status of allogenic bone marrow transplantation in chronic myelocytic leukemia].

Bone marrow transplants were carried out in 18 patients with chronic myelogenous leukemia (CML) in the chronic phase (CP). 12 (67%) are still alive, 11 without evidence of leukemia after a mean observation period of 24 (3-44) months, 1 relapsed and 6 died. The most frequent cause of death was GvHD and interstitial pneumonia (5). 1 patient died of septicemia. 2 grafts were performed in patients with CML in the accelerated phase (AP); both died, one from leukemic relapse and one from GvHD. The authors also participated in an international study in which 117 patients were evaluated. In CP there was a survival plateau at 63%, in AP at 36% and in blastic crisis at 12%. In CP mortality was primarily age-dependent and relapses occurred in only 7%. It is concluded that bone marrow transplantation (BMT) is a highly successful treatment for CML, with the CP the optimum moment for grafting. Longlasting cytogenetic and clinical remissions with potential for cure are possible in a high percentage of patients. The incidence of transplant-related mortality is acceptable. The incidence of leukemic relapse is low in CP. Patients under age 40 with HLA-identical siblings should be transplanted in CP. At present BMT is the only treatment with curative potential for CML.

Adolescent↗
PubMed1984

Acute myelogenous leukaemia: maintenance chemotherapy after early consolidation treatment does not prolong survival.

To investigate the value of maintenance chemotherapy after early consolidation treatment, an attempt was made to induce remission in 162 previously untreated patients, age-range 7-65 years (median 43). The 74 patients who were still in remission after early consolidation treatment (given for 3-5 months) were assigned to either maintenance chemotherapy every 8 weeks for 2 years or to observation only. After a median observation period of 44 months there was no difference between the groups in duration of remission or survival. Surprisingly, patients above 40 survived longer after early consolidation (median 4 years) than did patients aged 40 and below (median 1.6 years, p = 0.0002).

Adolescent↗
PubMed1984

[Acyclovir in the therapy of herpesvirus infections].

Intravenous acyclovir was tested both prophylactically and therapeutically in herpes infections in 48 patients undergoing bone marrow transplantation. Pretransplant prophylaxis only partly eliminated reactivated infections. Treatment of established mucocutaneous infections was usually successful, also in relapsing cases, when initiated within hours of the appearance of lesions. Extensive lesions, superinfections and dissemination could thus be prevented in this group of severely immunocompromised patients.

Acyclovir↗
PubMed1984

Experimental immunologically mediated aplastic anemia (AA) in mice: cyclosporin A fails to protect against AA.

Immunologically mediated aplastic anemia (AA) in mice was induced by the i.v. injection of 10(7) lymph node cells (LNC) from H-2k identical but Mls mismatched CBA/J donor mice into previously irradiated (600 rad total body gamma) C3H/HeJ mice. Cyclosporin A (CsA), 25 mg/kg, was administered subcutaneously from day -1 to day 30. Control mice included C3H/HeJ mice which received 600 rad alone, C3H/HeJ mice which received 600 rad plus CsA as above, and C3H/HeJ mice which received 600 rad total body irradiation followed by 10(7) LNC from CBA/J donors. CsA failed to prevent lethal AA. These results suggest that the pathogenetic mechanisms operating in immunologically mediated AA differ from the mechanisms operating in rodents transplanted with allogeneically mismatched marrow or spleen cells which develop graft-versus-host disease. The results are consistent with a non-T cell-dependent mechanism causing the AA.

Anemia, Aplastic↗
PubMed1984

Neopterin as a new biochemical marker in the clinical monitoring of bone marrow transplant recipients.

In previous reports we demonstrated that increased amounts of the pyrazinopyrimidine compound neopterin are released in the context of T lymphocyte activation. The aim of this investigation was twofold: (1) to define the contribution of hemopoetic cells to neopterin excretion, and (2) to search for the clinical utility of this biochemical marker in the monitoring of such patients. Thirteen patients were grafted with allogeneic, 1 with syngeneic, and 2 with autologous marrow. Urinary neopterin excretion was measured daily by means of high-performance liquid chromatography from the time before transplantation until the patients' discharge from the isolation unit. In all patients bone marrow aplasia was associated with depressed, and engraftment with increased, neopterin values. Rising neopterin levels invariably preceded the cytological definition of "take," on the average by seven days. After hematological reconstitution, neopterin excretion continuously declined in all 5 patients lacking infectious complications and/o-graft-versus-host disease (GVHD). A transitory increase of urinary neopterin followed by normalization was observed in 5 further patients. At the time of increased neopterin excretion, 4 experienced either herpetic infection or GVHD, both of which resolved promptly under the appropriate treatment. Neopterin values remained elevated after engraftment in 6 patients who suffered from persistent GVHD. Results of this pilot study suggest that (1) bone marrow derived cells are crucially involved in production of neopterin in vivo and (2) evaluation of neopterin excretion patterns after hemopoietic reconstitution enables one to discriminate between patients with and without an increased risk of developing GVHD or viral disease.

Biopterins↗
PubMed1984

Functional and morphological suppressor T cell deficit in acute GVHD.

Bone marrow transplantation (BMT) is currently used to treat patients with severe haematological disorders. One of its major complications is acute graft versus host disease (aGVHD). In this report we show that, during the early stages of lymphoid cell repopulation, an excess of suppressor T cell activity and a deficit of helper T cell activity are easily demonstrated by functional studies in healthy BMT recipients. On the contrary, in patients with active signs of aGVHD, a loss of suppressor T cells, as assessed by coculturing recipient T cells with donor B cells in an in vitro pokeweed mitogen (PWM) dependent Ig secreting assay, is detected. The loss of suppressor T cells in these patients is revealed also by the analysis of peripheral blood lymphocytes with the OKT5 suppressor cytotoxic monoclonal antibody (MoAb) but not with the OKT8 suppressor cytotoxic MoAb. Our data demonstrate that in several BMT recipients, during active aGVHD, a suppressor T cell deficit can be demonstrated both functionally and phenotypically.

Acute Disease↗
PubMed1983

[Bone marrow transplantation in acute lymphatic leukemia during the first remission].

9 patients with acute lymphoblastic leukaemia (ALL) were transplanted in first remission. There were no leukaemic relapses and 6 patients became longterm survivors. Causes of death were GvHD in 2 and interstitial pneumonia in 1. 14 patients with ALL were grafted in later stages of the disease. 10 had a leukaemic relapse. One attained longlasting remission with chemotherapy, while 9 died. One patient died of CMV infection. Cotton wool lesions and haemorrhages in the retina posed a problem in patients with previous cranial irradiation. We recommend transplantation of ALL in first remission if a syngeneic or HLA-identical sibling is available, particularly if the patient has poor risk factors for chemotherapy. Prophylactic cranial irradiation should be replaced by intrathecal methotrexate and/or cytosin arabinoside in these patients.

Adolescent↗
PubMed1983

[Bone marrow transplants--quo vadis?].

Early bone marrow transplantation (BMT) in leukaemia has enormously improved the results. Leukaemic relapse is rare, as is transplant-related mortality from interstitial pneumonia and severe graft-versus-host disease (GvHD). In aplastic anaemia the most important development is that treatment with ALG offers a real alternative to BMT which is of crucial importance for all patients without a histo-compatible family donor. The main problems of BMT are the lack of histocompatible donors and GvHD. In leukaemia, relapse is still an additional problem. The new immunosuppressive agent cyclosporin-A (CyA) has made an important contribution to the prophylaxis of severe GvHD. In future the results with CyA are potentially improvable by combination with other immunosuppressive agents. It is important that the use of HLA-semicompatible family donors, unrelated donors or alternative stem cell sources should become feasible. The value of autologous BMT is difficult to judge because in most instances it has been performed in patients with endstage disease. In several congenital diseases there are alternatives to BMT, such as genetic engineering. Although many problems of BMT still have to be solved, this procedure has an important place in modern medicine.

Bone Marrow Transplantation↗
PubMed1983

[Bone marrow transplantation in leukemia and aplastic anemia].

In a review of allogeneic bone marrow transplantation (BMT) for leukemia the following points proved to be of crucial importance: (1) combination of cyclophosphamide (Cy) and total body irradiation (TBI) for conditioning, (2) early BMT for acute leukemia (AL) in first remission and for chronic granulocytic leukemia (CGL) in chronic phase, (3) prophylaxis of graft-versus-host disease (GvHD) with cyclosporin-A (CyA). 50 successive BMT for leukemia performed in Basel between July 1979 and September 1982 are analyzed. 7 of 13 acute myelogenous leukemias (AML) and 8 of 9 acute lymphatic leukemias (ALL) grafted in first remission, and 7 of 10 CGL, are alive without signs of leukemia and without chronic problems. Of the patients grafted for AL in second remission or later, 3 of 6 AML and 6 of 12 ALL are alive. Severe GvHD was seen in 5 of 43 BMT between HLD identical siblings, in three of them combined with interstitial pneumonia. Thus the incidence of these two serious complications of allogeneic BMT has been drastically reduced with CyA compared to our previous experience with prophylactic methotrexate (MTX). 4 grafts were performed between HLA-haploidentical siblings. 3 of the 4 patients developed fatal GvHD. This implies that in this histocompatibility setting CyA alone is not sufficient. No problems were encountered in 3 syngeneic BMT. 12 leukemic relapses were observed. Relapse never occurred in ALL in first remission and never in CGL. 4 recurrences were seen in AML in first remission. All other relapses were in patients with AL grafted in stages other than first remission. In 86 successive patients with severe aplastic anemia (SAA) the following important advances were made: (1) it was shown that the majority of patients have sufficient hemopoietic stem cells and that after treatment with antilymphocyte globulin (ALG) over 70% have long-lasting remissions, (2) the combined treatment with ALG and high dose prednisone increases the remission rates to 90% and in addition shortens the supportive care period significantly. These developments are of crucial importance for patients without an HLA-identical sibling, (3) success rates of marrow transplants between HLA-identical siblings could be increased from 36% with prophylactic MTX to 67% using CyA.

Anemia, Aplastic↗