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Biomedical subjects

R Powles

Publications and source records attributed to R Powles.

At least 163 records · Page 9Linked to original sources
PubMed1989

Simultaneous application of immunolabelling and in situ hybridization to detect the origin of B and T lymphocytes in a case of acute lymphocytic leukaemia after bone marrow transplantation.

Previous cytogenetic studies, using selective mitogens, on a patient with B cell acute lymphocytic leukaemia during the 6 years of remission after bone marrow transplantation from an HLA-identical sister indicated persistence of recipient B lymphocytes in the peripheral blood. Such studies are necessarily limited to dividing cells at metaphase, which represent only a small proportion of the total cell population. We have now combined the techniques of immunolabelling and in situ hybridization on the patient's peripheral blood lymphocytes in order to define accurately their individual lineage and gender. A clear difference in the proportion of the persisting recipient lymphocytes was found between B and T lymphocyte lineages.

Adolescent↗
PubMed1988

HLA-DR expression in epidermal keratinocytes after allogeneic bone marrow transplantation. Relationship to histology, rash, marrow purging, and systemic graft-versus-host disease.

HLA-DR expression on epidermal keratinocytes was studied in leukemic recipients of allogeneic marrow in order to clarify its relationship to GVHD, investigate its diagnostic value, and gain insight into the pathogenetic mechanisms. Using frozen-section immunohistological techniques, positive keratinocytes were encountered in a small minority of normal donors and in a few recipients prior to transplantation. In patients receiving marrow unpurged of T lymphocytes, keratinocyte HLA-DR staining was found in the majority of patients with, and in about one third of those without, histological evidence of GVHD. Positivity was strongly related to the presence of a rash and was more likely to be found if the interval between the onset of the rash and biopsy exceeded 24 hr. There was a strong association between the presence of positive cells and the subsequent development of systemic GVHD, indicating that staining for HLA-DR on keratinocytes may be a useful adjunct to conventional morphological analysis in the interpretation of post-transplant skin biopsies. Positivity was not observed in patients who received marrow depleted of T lymphocytes, indicating a crucial role for these cells in stimulating keratinocyte HLA-DR expression. Sequential studies, however, showed that keratinocyte positivity preceded lymphocytic infiltration of the epidermis.

Bone Marrow Transplantation↗
PubMed1987

The histological diagnosis of cutaneous graft versus host disease: relationship of skin changes to marrow purging and other clinical variables.

Punch biopsies of skin were taken from allogeneic marrow recipients routinely before transplantation, at 14-22 and 90-107 d after grafting and in the event of a clinical rash. Three histological appearances were encountered: graft versus host disease (GvHD), epidermal abnormalities, and normal. Graft versus host disease was characterized by epidermal basal vacuolation, spongiosis and individual cell necrosis associated with mononuclear cell infiltration of the upper dermis and lower epidermis, while epidermal abnormalities were identical to GvHD but without the mononuclear cell infiltrate. Graft versus host disease occurred only in patients receiving marrow unpurged of T-cells while epidermal abnormalities occurred with equal frequency in recipients of purged and unpurged marrow and were also noted in a high proportion of pre-transplant biopsies. Patients whose skin biopsies exhibited epidermal abnormalities showed no greater incidence of subsequent clinical or histological GvHD than those with normal biopsies. For these reasons, we conclude that epidermal abnormalities cannot be regarded as a minor manifestation of GvHD as has often been previously assumed. We also conclude that they cannot be regarded as the cause of a rash as, unlike GvHD, the incidence was not significantly different in patients with and without rashes. The cause of epidermal abnormalities is not entirely clear; cytotoxic drugs and irradiation appear to play a part but their occurrence in patients with previously normal post-transplant biopsies suggests that other factors may also be important. Some patients with strong clinical evidence of GvHD had negative biopsies; these should be regarded with caution especially within the first 24 h after the onset of a rash as the diagnostic histological picture may take time to develop. In some cases, GvHD was confined to pilosebaceous units; this seems to represent a minor form of the disease with only a limited capacity for progression. Dysplastic epidermal changes which have previously been attributed to the use of cyclosporin A were found with equal frequency in patients who did not receive this drug and must therefore have some other cause.

Antibodies, Monoclonal↗
PubMed1987

Molecular lesion in chronic granulocytic leukemia is highly conserved despite ethnic and geographical variation.

Leukemic cell DNA from patients with Philadelphia chromosome positive chronic granulocytic leukemia in the United Kingdom, Taiwan, and South Africa and of diverse ethnic origins all have identifiable molecular rearrangements of the breakpoint cluster region on chromosome 22 band q11 when screened with an appropriate DNA probe. This result reinforces the highly conserved nature of the molecular lesion in chronic granulocytic leukemia and its suitability as a diagnostic marker for the disease. Since the assay can be performed by sample referral on relatively small numbers of nondividing frozen or dead cells, it is ideally suited for large scale epidemiological and clinical studies, particularly in developing countries where karyotyping services are not readily available.

Chromosome Mapping↗
PubMed1987

Mediastinal emphysema in marrow transplant recipients.

Six of 146 patients at our institution developed mediastinal emphysema following marrow transplantation. Five patients were the recipients of marrow from their HLA fully matched sibling donors and one patient had an autologous marrow transplant. Features common to all included single-dose total body irradiation and high-dose systemic adrenocorticosteroids. Five of the patients had clinical and radiological evidence of recent or active interstitial pneumonitis. The clinical implications and possible aetiologies of mediastinal emphysema developing in the post-transplant patient are discussed.

Adult↗
PubMed1986

Epstein-Barr virus infection and immunity in bone marrow transplant recipients.

Studies on patients for up to one year following allogeneic, HLA-matched bone marrow transplants have shown no increased incidence of salivary Epstein-Barr (EB) virus secretion and no significant rise in EB-virus-specific antibody titers. EB-virus-specific cytotoxic T cells could be detected in the peripheral blood of all patients by six months posttransplant. For up to one year posttransplantation in vitro EB virus infection of peripheral blood B lymphocytes from the majority of patients leads to an abortive infection followed by cell death, and without the establishment of continuously growing cell lines. This abnormality appeared to be due to patients' monocytes, which formed a defective feeder cell layer in culture, and it could be circumvented by culturing the EB-virus-infected B cells from patients on a feeder layer of x-irradiated adherent cells from normal peripheral blood. These findings may explain the relative lack of EB-virus-associated lymphoma seen in bone marrow transplant recipients when compared with other groups of transplant patients.

Adolescent↗
PubMed1986

Hodgkin's disease in an adult with acute lymphoblastic leukaemia.

A 53 year old woman with common acute lymphoblastic leukaemia (ALL) developed Hodgkin's disease 20 months after the initial diagnosis of ALL. This is by far the oldest case of Hodgkin's disease complicating ALL. The unusual presentation and the aetiology of Hodgkin's disease in ALL are discussed.

Female↗
PubMed1986

Marrow transplantation for non-Hodgkin's lymphoma: a multi-centre study from the European Co-operative Bone Marrow Transplant Group.

Twenty-five patients with intermediate- or high-grade non-Hodgkin's lymphoma (NHL) were treated by allogeneic bone marrow transplantation. For the nine patients transplanted in first complete remission the disease-free survival was 100%; of the nine patients transplanted in subsequent remissions four (44%) achieved long-term disease-free survival but two died of relapsed lymphoma. For the seven patients transplanted at a time when they had active disease, the initial complete remission rate was high but four died of progressive lymphoma and no patient achieved long-term disease-free survival. The incidence of complications associated with allogeneic bone marrow transplantation was similar to that observed in other series of patients transplanted for haematological malignancy and was related to the status of the disease at the time of transplant. Thus allogeneic bone marrow transplantation is a radical but effective treatment for patients with NHL who have 'minimal residual disease'. Efforts to define further the subset of patients who can most successfully be treated by transplantation may improve the overall results.

Adolescent↗
PubMed1985

Demonstration of a leukemia-associated antigen (CAMAL) in peripheral blood leucocytes of bone marrow transplant patients prior to relapse.

We have previously described a monoclonal antibody (CAMAL-1) that reacts in an indirect immunoperoxidase slide test at high frequency with cells of patients with acute nonlymphoblastic leukemia (ANLL), both at presentation and in remission (1). This article reports on a 12-month blind study carried out on peripheral blood leukocytes (PBL) of patients who had received bone marrow transplants for acute leukemias. PBL of patients attending the Royal Marsden Hospital were sent as cytospins to the University of British Columbia for staining and screening. Results of this study showed the following: of the 15 patients who remained in remission during the period of the study, 13 showed no abnormal increase in reactivity with CAMAL-1 (2 patients did show increased levels of reactivity over time); of the four patients relapsing but surviving within this period with ANLL, all showed elevated numbers of cells reactive with CAMAL-1 as long as 3 months prior to relapse (the two relapsing patients who had acute undifferentiated leukemia and acute lymphoblastic leukemia did not show elevations of CAMAL-1-reactive cells); of the 14 patients dying during this time of causes other than leukemia, none had elevated levels of CAMAL-1-reactive cells--and, of 4 patients dying in relapse, all had extremely elevated levels of CAMAL-1-reactive cells as long as 4 months prior to relapse. The implications of these observations are discussed.

Acute Disease↗
PubMed1983

T cell regeneration after allogeneic bone marrow transplantation.

Various T cell subsets were characterized by double immunofluorescent staining using monoclonal antibodies (MoAb) in blood, bone marrow (BM) and tissues of 29 patients after allogeneic BM transplantation (BMT). In an attempt to prevent graft versus host disease (GvHD), 15 patients received cyclosporin A (Cy A). In the remaining 14 patients the BM was pre-incubated with a MoAb, OKT3. The regeneration of T4+ subset was delayed and the level of T8+ cells was abnormally high even 1 year after engraftment. This did not have any predictive value for the appearance of complications such as GvHD or severe viral infections. The number of T8+ cells was lower in the group of patients who received Cy A than in the OKT3 group (0.7 +/- 0.2 vs 1.5 +/- 0.3 X 10(9)/1 at day 90). In contrast to normal individuals, the T4/T8 ratio in both blood and regenerating BM of BMT patients was less than 1. A sizeable subset of circulating T cells expressed the phenotype T8+, T10+, HNK-1+, DR+. Circulating cells of this phenotype were transiently very high (up to 50%) in patients with active GvHD or suffering from severe viral infection. This subpopulation of lymphocytes was not found in the epidermal infiltrate that accompanied GvHD where the predominant phenotype was T8+, T1-, T10-, HNK-1-, DR-. We conclude therefore that after BMT the number and phenotype of circulating T cells reflects the T cell distribution seen in the regenerating BM.

Adolescent↗