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Biomedical subjects

J Szer

Publications and source records attributed to J Szer.

At least 127 records · Page 7Linked to original sources
PubMed1991

Ocular surface and lacrimal disturbances in chronic graft-versus-host disease: the role of conjunctival biopsy.

Forty-four patients (21 male, 23 female) were studied following bone marrow transplantation (BMT): 40 after allogeneic, one after syngeneic and three after autologous transplantation. Diffuse punctate conjunctival and corneal epitheliopathy was seen in 27 (61%), reduced or disordered tear film in 26 (59%), acquired lacrimal outflow obstruction in three (7%) and posterior subcapsular lens opacities in five (12%) patients. Conjunctival histology showed abnormal features, including those of graft-versus-host disease (GVHD) in 41 patients. Of these, 28 (64%) had clinical and laboratory features of GVHD and six patients with no systemic evidence of GVHD had conjunctival histology specific for GVHD. We conclude that after BMT, subclinical changes of GVHD are very common in the periocular tissues and may be universal in long-term survivors following allogeneic BMT. Some minor conjunctival changes are more likely to be due to the primary disease or the transplant conditioning regimen. Conjunctival biopsy is useful in demonstrating low-grade GVHD or GVHD confined to the ocular structures and may be diagnostic in some cases.

Adolescent↗
PubMed1991

Chronic myeloid leukaemia treated by allogeneic bone marrow transplantation from histocompatible sibling donors--an invariably fatal malignancy rendered highly curable.

Twenty-eight patients aged 16-50 years with chronic myeloid leukaemia (CML) underwent allogeneic bone marrow transplantation (BMT) using human leukocyte antigen (HLA)-identical sibling donors. Of the 28 patients, 21 were in chronic phase, five were in accelerated phase and two were in blast phase at the time of BMT. Twenty-three of the patients survived more than 63-2187 days after BMT, 21 in continuous complete remission and two with haematologic relapse of CML. Two patients died of interstitial pneumonitis and one died of relapsed CML, cerebral aspergillosis and cytomegalovirus enterocolitis. The overall probability of survival at six years was 78% +/- 9% (mean +/- standard error) and of disease free survival 66 +/- 11%. For patients transplanted in chronic phase, the survival probability was 90 +/- 6%, while all of the patients undergoing BMT in chronic phase within the first year after diagnosis were alive with a relapse-free survival of 88 +/- 12%. The actuarial probability of occurrence of acute graft-versus-host disease (GVHD) was 57 +/- 9%, while for Grades II and III GVHD it was 28 +/- 9%. Chronic GVHD occurred in 18 of 25 patients at risk. The majority of patients had a Karnofsky performance score at latest follow-up of at least 90% (range 50-100). We conclude that allogeneic BMT is effective, curative therapy for CML and that BMT performed earlier in the natural history of the disease is associated with the best outcome.

Adolescent↗
PubMed1991

GM-CSF after allogeneic bone marrow transplantation: accelerated recovery of neutrophils, monocytes and lymphocytes.

Ten patients given HLA-identical sibling marrow transplants for lymphoid malignancy received recombinant human granulocyte macrophage-colony stimulating factor (GM-CSF) from day 7 to day 13 inclusive post transplant. Patients were prepared for transplantation with busulphan 16 mg/kg and cyclophosphamide 120 mg/kg. Immunosuppression to minimise the risk of graft-versus-host disease (GVHD) was cyclosporin/short methotrexate. Results were compared with a historical control group of patients (n = 16) given matched sibling transplants for acute leukaemia and receiving the same immune suppressive regime but not given GM-CSF. Recovery of total white cells, neutrophils, monocytes and lymphocytes was more rapid in the GM-CSF recipients (p less than 0.02). There was a suggestion of a decrease in non-viral infections in the first 30 days in the GM-CSF recipients (p = 0.09). There was, however, no significant difference in the severity of oropharyngeal mucositis nor in the duration of the transplant hospitalisation. Surprisingly, the severity of acute GVHD was higher in the GM-CSF recipients with six of eight evaluable patients having grade II-IV acute GVHD (p = 0.003). Two GM-CSF recipients developed a fluid retention/capillary leak syndrome. These findings indicate a need for caution in the use of GM-CSF after allogeneic marrow transplantation.

Adolescent↗
PubMed1991

Transfusion associated graft-versus-host disease after cardiac surgery: response to antithymocyte-globulin and corticosteroid therapy.

A 63-year-old patient developed graft-versus-host disease (GVHD) after the transfusion of stored, random donor red cell concentrates with coronary artery surgery. The disease was characterised by skin rash, fever, diarrhoea, hepatic dysfunction, pancytopenia and the acquisition of cells bearing human leukocyte antigens of a blood donor. Clinical and histologic improvements were noted with antithymocyte-globulin and corticosteroid therapy, as seen in some patients with acute GVHD following allogeneic bone marrow transplantation, but the pancytopenia failed to resolve prior to a fatal cerebral haemorrhage. Early aggressive immunosuppressive therapy may be beneficial for transfusion-associated GVHD but strategies for its prevention by limitation of the use of homologous blood need to be addressed.

Antilymphocyte Serum↗
PubMed1990

Loss of natural killer activity as an indicator of relapse in acute leukaemia.

A role for naturally occurring cytotoxic cells in immunosurveillance against malignancy has been presumed in several studies. The natural killer activity (NKA) of peripheral blood mononuclear cells was therefore measured at regular intervals in patients with acute leukaemia and expressed specific cytotoxicity. Sixty controls had a median NKA of 33.6% (range 15.4-71). Seventy-three patients with acute lymphoblastic leukaemia (ALL) and acute non-lymphoblastic leukaemia (ANLL) with untreated or relapsed disease had a median activity of 2.4% (range 0-13.4) (P less than 0.001), while 57 patients who had achieved complete remission had a median activity of 22.7% (range 9.5-64.4). In 15 patients, reductions of NKA were seen prior to 16 episodes of relapse. In ten of these (nine with ANLL and one with ALL), 11 relapses were preceded within 10 weeks by drops in NKA to less than 30% of remission levels. The median NKA of the group prior to the drop in activity was 25.5% and the median first low value was 6.0%. Five patients who relapsed after allogeneic bone marrow transplantation had significant, sustained drops in NKA, 5-9 weeks earlier. The median NKA prior to the drop was 25.6% and the median first low value was 8.0%. We therefore conclude that there was a marked reduction in NKA in patients with active acute leukaemia when compared with healthy blood donors and that this activity substantially improved in complete remission. All patients who relapsed had significantly reduced NKA which in some, significantly preceded the time of relapse. These data suggest that the regular assessment of NKA in patients with acute leukaemia may be a useful diagnostic tool.

Adolescent↗
PubMed1990

Lymphokine-activated killer cytotoxicity against leukaemic blast cells.

While the sensitivity of cell lines and solid tumours to lymphokine-activated killer (LAK) cell cytotoxicity is extensively reported, the ability of these generated cytotoxic cells to lyse leukaemic blast cells is controversial. This study reports the successful generation of LAK cells with specificity for leukaemic blast cells. Control donors, patients in remission and patients with active leukaemia were capable of lysing allogeneic leukaemic blast cells. One patient was also capable of lysing autologous leukaemic blast cells. Successful LAK generation was achieved by the use of high dose recombinant interleukin-2 (rIL-2) while combinations of lymphokines did not improve LAK specificity or efficacy. These findings suggest that LAK immunotherapy may be considered for the treatment of patients with acute leukaemia.

Adolescent↗
PubMed1988

Transient platelet and HLA antibody formation in multitransfused patients with malignancy.

Fifty-nine patients receiving platelet transfusions for bone marrow failure secondary to malignancy were screened at regular intervals for the presence of antibodies to human leucocyte (HLA) and platelet specific antigens. HLA antibodies occurred in 19 patients, 10 of whom also developed platelet specific antibodies. The HLA antibodies disappeared in 10 of 15 patients followed for periods of 2-14 months. In two patients this occurred whilst still receiving platelet transfusions. Antibody reappeared in only two of six patients subsequently transfused. Antibodies to platelet specific antigens were detected in 28 patients. They were transient, often appeared in association with infection, and in 50% of cases tested demonstrated autoantibody activity. There was no association with antibiotic drug therapy, or PFA/EDTA-dependent cryptantigens. Platelet recovery at 1 h or 20 h post transfusion was not significantly reduced in the presence of platelet specific antibodies. These findings have important implications for the selection of platelet donors for alloimmunized recipients.

Antibodies↗
PubMed1987

Two monoclonal antibodies recognizing subpopulations of canine T lymphocytes with or without suppressor/cytotoxic functions.

Two monoclonal antibodies (mAb) were studied in regards to their ability to differentiate functionally distinct subsets of canine lymphocytes. MAb DT-2 (IgG2a) reacts with 33-55% of canine peripheral blood mononuclear cells (PBMC), which are also surface immunoglobulin (SIg) negative. Cytolytic treatment with DT-2 eliminates the ability of PBMC to respond to allogeneic cells and mitogens but does not affect alloantigen-primed cytotoxic or suppressor cells. MAb E11 (IgG3) reacts with 15-40% of PBMC which are also SIg negative. Cytolytic treatment with E11 affects responses of PBMC to allogeneic cells or mitogens to a lesser extent than DT-2 but eliminates cytotoxic and suppressor cells among alloantigen-primed lymphocytes. Thus, canine helper cells appear to be Thy 1+, 7.2+, DT-2+, DLy 6+, DLy 1+, E11-, SIg-, and cytotoxic/suppressor cells Thy 1+, 7.2+, E11+, DT-2+, DLy 6-, DLy 1-, SIg-.

Animals↗
PubMed1985

DLA-D-specific suppressor cells characterized by monoclonal antibodies.

Canine lymphocytes alloantigen-primed in mixed leukocyte culture (MLC) were tested for their ability to suppress MLC reactivity. These cells were added to fresh responder cells in MLC at ratios of 1:50 and 1:20 and suppressed reactivity 90 +/- 7% (mean +/- 1 SD) and 91 +/- 3% respectively. At lower ratios no suppression was observed. Monoclonal antibody E11 (IgG3) recognized a subset of canine Thy1+ T cells, and with complement treatment was capable of depleting suppressor cells from bulk MLC (11 +/- 6% of control suppression), but DT-2 (IgG2a), another canine T-cell antibody, had no such effect (84 +/- 11%) (P = 0.028). Antibody A5 (IgG2b), reactive with all T and most non-T cells, also eliminated suppression. Positively selected E11+ bulk-MLC cells suppressed (91%) and E11- bulk-MLC cells did not (4%). At the ratios described, suppression was specific for the DLA-D phenotype of the stimulator cells. In tests with the original stimulators, suppression was 91 +/- 7%; in tests with DLA-D identical stimulators it was 92 +/- 5%; and for DLA-D nonidentical stimulators it was 38 +/- 25% (P = 0.005). Nonspecific suppression increased with increasing numbers of suppressor cells. At ratios of 1:10 and 1:5 nonspecific suppression was 72 +/- 13% and 92 +/- 8%, respectively. These studies show that under appropriate conditions, Thy1+, E11+, A5+, DT-2- alloantigen-activated canine T lymphocytes function as DLA-D-specific suppressor cells and DT-2+ cells do not.

Animals↗
PubMed1985

Monoclonal antibody to human cytotoxic-suppressor T-lymphocytes cross-reacts with canine lymphocytes and inhibits cell-mediated lympholysis of canine cells.

Of 19 murine antihuman Tp32 (T8) monoclonal antibodies tested, only antibody T811 showed cross-reactivity with canine lymphoid cells. It recognized an antigen expressed on 19%-27% of peripheral blood mononuclear cells (PBMC), 20%-30% of peripheral Thy 1+ T-lymphocytes, 40% of puppy thymocytes, 35%-45% of alloantigen-activated peripheral lymphocytes, and 100% of PBMC from a dog with acute T-cell leukemia. The antigen was not expressed on peripheral Thy 1- cells, bronchoalveolar cells, or null-type acute leukemia cells. The antibody inhibited cell-mediated lympholysis in the absence of complement, while antibody F3-20-7 directed at the canine Thy 1 antigen did not. It was not possible to precipitate a corresponding cell surface antigen on canine cells using standard 125I radioimmunoprecipitation techniques nor did the antibody cause antigenic modulation. Our data suggest that monoclonal antibody T811 reacts with a functional subset of canine T-lymphocytes similar to that of human cells; however, significant differences may exist between the antigens recognized on these cells in the two species.

Animals↗
PubMed1985

Failure of autologous marrow reconstitution after cytolytic treatment of marrow with anti-Ia monoclonal antibody.

Hematopoietic stem cell toxicity of the murine monoclonal antibody 7.2, recognizing Ia-like antigens on canine cells, was tested in an autologous bone marrow transplantation model. Dogs were given 9.2 Gy of total body irradiation followed by the infusion of autologous marrow treated by one of two methods to remove Ia+ cells. In six dogs, the marrow cells were pelleted, treated with antibody 7.2 (1:1,000) and rabbit complement (1:4), resuspended in culture medium, and infused. All six dogs had prompt and sustained engraftment surviving greater than 26 days. Indirect immunofluorescence showed, however, that the depletion of Ia+ cells was incomplete. Four dogs received marrow cells first separated by density gradient centrifugation and then treated with an excess of antibody 7.2 and two cycles of undiluted rabbit complement. None of these dogs, surviving 17 to 22 days, had sustained engraftment. With antibody 7.2 used as the marker, only one dog had detectable residual Ia+ cells (0.9%) after treatment. Dogs receiving marrow cells obtained by density gradient centrifugation without additional manipulation, or with subsequent treatment with complement only or with complement and an antibody (DT-2) directed at a subpopulation of T cells, engrafted promptly and completely. We conclude that Ia+ bone marrow cells are essential for the successful engraftment of transplanted marrow in dogs.

Animals↗
PubMed1984

Long-term survival after marrow transplantation for paroxysmal nocturnal hemoglobinuria with aplastic anemia.

Four patients with paroxysmal nocturnal hemoglobinuria and severe marrow aplasia were given marrow grafts either from allogeneic human-leukocyte-antigen-identical siblings (three patients) or from a syngeneic donor (one patient). The patients with allogeneic grafts were conditioned with regimens that included cyclophosphamide and had sustained and complete marrow engraftment; subsequent tests were negative for paroxysmal nocturnal hemoglobinuria. One patient developed chronic graft-versus-host disease that resolved over 4 years. The patient receiving a syngeneic graft received marrow infusion without preceding immunosuppression. He had prompt engraftment, and hematologic variables returned to normal. A Ham's test done at 3 years was negative, but a complement lysis sensitivity test done 10 years after grafting was positive; the patient, however, remains asymptomatic. All four patients are alive and well 4, 9, 10, and 12 years after transplantation. Paroxysmal nocturnal hemoglobinuria apparently can be treated successfully by allogeneic or syngeneic marrow transplantation without subsequent maintenance therapy.

Adolescent↗