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Biomedical subjects

R L Powles

Publications and source records attributed to R L Powles.

At least 127 records · Page 7Linked to original sources

Histopathological changes in the liver after allogeneic bone marrow transplantation.

Postmortem and surgical specimens of liver from 20 patients who had undergone allogeneic bone marrow transplantation for a variety of disorders were examined. The lesions fell into five major categories: bile duct atypia often associated with portal tract fibrosis (8 cases), veno-occlusive disease (2 cases), small foci of non-zonal hepatocyte necrosis (3 cases), opportunistic infections (3 cases), and a miscellaneous group of non-specific abnormalities. Our findings, in conjunction with those in experimental animals, point strongly to the bile duct lesion being a specific manifestation of graft versus host disease (GvHD). Veno-occlusive disease has also been reported recently as a possible manifestation of a graft versus host reaction and, although both our patients with this lesion had evidence of GvHD in the skin and gastrointestinal tract, both had also received irradiation and 6-thioguanine, and these may have been responsible. The foci of hepatocyte necrosis could not be attributed to GvHD with any confidence as the lesion was of only minor severity, infrequent, highly non-specific in appearance and, furthermore, did not correlate well with the presence of bile duct lesions. The absence of specific clinical and biochemical findings in human hepatic GvHD stresses the need for biopsy to make a firm diagnosis. However, the patchy distribution of the bile duct lesion and its absence from the needle biopsies examined in this study suggest possible sampling problems, and further study is necessary to assess its value.

Adolescent↗

Parenteral acyclovir therapy for herpesvirus infections in man.

Acyclovir is a new antiviral agent which is highly active against herpesviruses in vitro and in laboratory animals. Twenty-three cancer patients with cutaneous and/or systemic herpes zoster or herpes simplex infections were treated with parenteral acyclovir. All had received previous specific treatment for their malignant disease and ten had undergone bone-marrow transplantation. The drug seemed to arrest the progress of the infections and was most effective when given early. Although two patients showed transient increases in blood-urea, possibly the result of acyclovir, the drug was remarkably non-toxic in the doses used.

Adolescent↗

The nature of remission in acute myeloblastic leukaemia.

15 patients with acute myeloblastic leukaemia (AML) in remission were given immunotherapy and 17 similar patients were given immunotherapy plus chemotherapy with the drugs used to induce remission. Median remission length was 245 days for both groups and median survival was 465 days for patients given chemoimmunotherapy and 476 days for patients given only immunotherapy. The failure of remission chemotherapy in AML cannot be attributed to induced resistance because the same drugs induced a second remission in 60% of the patients. From laboratory studies with human AML cells it is suggested that in AML the residual leukaemic cells mature after induction chemotherapy and are then refractory to further drug treatment. Relapse occurs when the leukaemic population proliferates and the environment permits dedifferentiation into frank blast cells.

Adolescent↗

Limited activity of ICRF-159 in advanced acute leukemia.

Twenty-eight patients with advanced acute nonlymphocytic leukemia, 16 with acute lymphoblastic leukemia, and two with acute undifferentiated leukemia were treated with ICRF-159. No patient achieved a complete remission and only three patients (6%) achieved a partial bone marrow remission. The only significant toxic effect was myelosuppression which probably contributed to the death of six patients. Five patients with acute nonlymphocytic leukemia and one with acute lymphoblastic leukemia received a combination of ICRF-159 and low-dose cytosine arabinoside. There were no remissions in this group and the toxic effects were more marked than with ICRF-159 alone. This study confirms the limited activity of ICRF-159 as a single agent in acute leukemia demonstrated in smaller series, and shows that, when used in combination with low-dose cytosine arabinoside, it was ineffective and resulted in increased toxicity. ICRF-159 alone or in combination with cytosine arabinoside has very limited activity in advanced adult acute leukemia.

Clinical Trials as Topic↗

Total body irradiation and marrow transplantation for acute leukaemia. The Royal Marsden Hospital experience.

The experience with total body irradiation at the Royal Marsden Hospital is described for an elective program of transplantation in patients with acute myeloid leukaemia (AML) in first remission. Dose rate appears to be a critical factor in the reduction of radiation-associated damage and careful monitoring of the actual dose distribution and dose received is mandatory.

Adolescent↗

The relationship between serum viscosity, hypervolaemia and clinical manifestations associated with circulating paraprotein.

In 44 of 56 patients with malignant paraproteinaemia the relationship of serum viscosity, plasma volume (PV), estimated blood volume (BV) and clinical findings was investigated and in the remaining 12 patients one or more of these parameters was studied. There was a correlation between increased PV and serum viscosity (r = 0.66, P less than 0.001). The retinopathy characteristic of the hyperviscosity syndrome (HVS) was always associated with serum viscosity greater than or equal to 3.8 and with hypervolaemia. The evidence that the retinal changes were related more closely to serum hyperviscosity than to hypervolaemia is twofold. First, there was a considerable overlap in the degree of BV expansion, but not serum hyperviscosity, in patients with and without retinopathy. Second, the retinopathy in a patient with Waldenström's macroglobulinaemia (WM) improved after plasma exchange with little change in BV. While bleeding was often associated with retinopathy seven patients with multiple myeloma (MM) had no retinopathy, viscosities greater than or equal to 4.3 and BV in the same range as patients with no clinical signs. Haemorrhage in such patients may thus be unrelated to the property of the paraprotein responsible for hyperviscosity. Measurements of PV in a patient with WM having repeated plasma exchanges for bleeding suggested that hypervolaemia may contribute to haemorrhage in some patients. It is suggested that the term 'HVS' should be restricted to patients with retinopathy and that hypervolaemia should be considered a characteristic feature of this syndrome.

Blood Viscosity↗

Maintenance of remission in acute myelogenous leukaemia by a mixture of B.C.G. and irradiated leukaemia cells.

Thirty patients with acute myelogenous leukaemia (A.M.L.) in full haematological remission were allocated alternately to two groups of fifteen patients each. All patients received immunotherapy, given weekly as intradermal and subcutaneous injections of killed allogeneic A.M.L. cells, plus Glaxo B.C.G. given by Heaf gun at a separate site. One group also received a mixture of A.M.L. cells and B.C.G. on 4 occasions early in remission. Four patients in this group have remained in remission for 92 to 134 weeks, whereas all patients in the other group had relapsed by 68 weeks. The findings suggest that cells mixed with B.C.G. may be effective in prolonging remission.

Adolescent↗

Immunotherapy for acute myelogenous leukaemia: a controlled clinical study 2 1/2 years after entry of the last patient.

One hundred and thirty-nine untreated patients with acute myelogenous leukaemia (AML) were admitted between August 1970 and December 1973 and allocated into two remission treatment regimens: one to receive chemotherapy alone and the other chemotherapy with immunotherapy. Of the patients who attained remission. 22 were in the chemotherapy group and in September 1975 2 remained alive, the median survival time being 270 days and after relapse 75 days. Twenty-eight patients received immunotherapy during remission, and 5 remained alive; the median survival time of the group being 510 days and after relapse 165 days. Ongoing acturial analysis precisely predicted early in the study the median survival of the two groups, but it took a 2-year follow-up after entry of the last patient before it became clear that there were very few long-term survivors. The increase in survival time produced by the immunotherapy is apparently made up of two components: prolongation of the first remission and length of survival after the first relapse. It must be notted that the chemotherapy for this study was devised 6 years ago and the results of the control arm (chemotherapy alone) may be poorer than those obtained in contemporary studies.

Adolescent↗

Further evidence of response by leukaemia patients in remission to antigen(s) related to acute myelogenous leukaemia.

Fifteen patients with acute myelogenous leukaemia were studied to determine if their remission blood leucocytes could be stimulated into taking up [3H] thymidine after in vitro culture with their own cryo-preserved irradiated AML leukaemia cells. In 6/15 patients it was possible to show autologous recognition and equal recognition of their stored leukaemia cells, even when they had previously been maintained in in vitro proliferative cultures in liquid suspension and undergoing myeloid maturation for one week. After in vitro proliferative culture, 4 populations of leukaemia cells produced material in the supernatant media between 3 and 7 days capable of inducing [3H] thymidine uptake in autologous (2 pts, 5 supernatants) and allogeneic (2 pts, 2 supernatants) AML remission lymphocytes, but not in normal donor lymphocytes. The relevance of these observations to tumour-associated AML antigen is discussed.

Antigens, Neoplasm↗

Colony-forming ability of marrow from patients receiving immunotherapy during chemotherapy-induced remission in acute myeloid leukaemia.

An in vivo culture system, the agar diffusion chamber technique, has been used to measure the population of colony-forming precursor cells in the bone marrow of patients receiving immunotherapy during acute myeloid leukaemia in remission. The results of these assays indicate that (1) the level of committed granulocytic stem cells usually remains below the range found in normal marrow throughout remission, and (2) the maintenance of adequate cell counts in the blood may be due to increased cell production by these early granulocytic precursor cells. The relevance of these findings to the possible protective effect of immunotherapy against cytotoxic chemotherapy is discussed.

Adolescent↗