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Biomedical subjects

R L Powles

Publications and source records attributed to R L Powles.

At least 109 records · Page 6Linked to original sources
PubMed1983

Lung function after bone marrow grafting.

Results of a prospective lung function study are presented for 48 patients with acute myeloid leukemia (AML) treated with total body irradiation (TBI) and bone marrow transplantation (BMT) at the Royal Marsden Hospital between 1978 and 1980. Patients with active disease or who were in remission following cytoreductive chemotherapy had mildly impaired gas exchange prior to grafting. After TBI and BMT all patients studied developed progressive deterioration of lung function during the first 100 days, although these changes were subclinical. Infection and graft-versus-host disease (GvHD) were associated with further worsening of restrictive ventilatory defects and diffusing capacity (DLCO). Beyond 100 days, ventilatory ability returned to normal and gas transfer improved, although it failed to reach pre-transplant levels. There was no evidence of progressive pulmonary fibrosis during the first year after grafting.

Adolescent↗
PubMed1983

Interstitial pneumonitis following bone marrow transplantation after low dose rate total body irradiation.

Idiopathic and infective interstitial pneumonitis (IPn) is a common complication after bone marrow transplantation (BMT) in many centers and carries a high mortality. We report here a series of 107 patients with acute leukemia grafted at the Royal Marsden Hospital in which only 11 (10.3%) developed IPn and only 5 died (5%). Only one case of idiopathic IPn was seen. Factors which may account for this low incidence are discussed. Sixty of 107 patients were transplanted in first remission of acute myeloid leukemia (AML) and were therefore in good general condition. Lung radiation doses were carefully monitored and doses of 10.5 Gy were not exceeded except in a group of 16 patients in whom a study of escalating doses of TBI (up to 13 Gy) was undertaken. The dose rate used for total body irradiation (TBI) was lower than that used in other centers and as demonstrated elsewhere by ourselves and others, reduction of dose rate to less than 0.05 Gy/min may be expected to lead to substantial reduction in lung damage. Threshold doses of approximately 8 Gy for IPn have been reported, but within the dose range of 8 to 10.5 Gy we suggest that dose rate may significantly affect the incidence. Data so far available suggest a true improvement in therapeutic ratio for low dose rate single fraction TBI compared with high dose rate.

Acute Disease↗
PubMed1983

Infections after bone marrow transplantation using cyclosporine.

The incidence of infection in 86 consecutive patients having bone marrow transplantation for acute or chronic myeloid leukemia, in a protocol in which cyclosporine was the main immunosuppressant, was low. Severe bacterial infections were infrequent and mostly caused by gram-positive cocci but early bacterial infection was often associated with severe graft-versus-host disease. Fungal infections were prevented by nystatin and amphotericin thus avoiding the difficult combination of cyclosporine and ketaconazole. Viral infections were no more common than in other series but, in patients with mismatched grafts, they tended to be associated with neurological complications clinically diagnosed as encephalitis.

Adolescent↗
PubMed1983

Histopathology of the lung after bone marrow transplantation.

The histopathological changes in the lungs of 32 patients who died after bone marrow transplantation for leukaemia have been studied and compared with those found in 21 patients treated by conventional chemotherapy. The transplanted patients exhibited a higher incidence of interstitial pneumonitis, vascular lesions and viral infections, particularly cytomegalovirus (CMV), although bacterial and fungal diseases were commoner in the non-grafted subjects. The pathogenesis of interstitial pneumonitis is discussed with specific reference to the possible roles of irradiation, chemotherapy, viruses and the immunosuppressive drug cyclosporin A. Ten patients died of a syndrome characterised clinically by fever, skin rash, fluid retention, uraemia, low serum albumin concentrations, low central venous pressure and acute pulmonary oedema. These patients exhibited intra-alveolar haemorrhagic fibrinous exudation with or without interstitial changes. The aetiology of this syndrome is not known but it occurs more frequently in recipients of mismatched grafts and evidence is presented suggesting that viruses may play a significant causative role. No lesion was identified that could be directly attributed to Graft-versus-Host disease.

Adolescent↗
PubMed1982

Changes in serum amylase and its isoenzymes after whole body irradiation.

A study was carried out to assess the effect of total body irradiation on pancreatic and parotid isoenzymes of amylase in patients about to undergo bone-marrow transplantation who had received high-dose cyclophosphamide. Twelve patients were studied, enzyme activity being measured before and at various times after total body irradiation. Serum total amylase activity rose rapidly within 12 hours of irradiation to a maximum at 36 hours, returning to normal by six days; most of the increase was derived from salivary damage, with a much smaller pancreatic component. These results confirm that radiation produces acute changes in amylase activity, which may be of use in assessing radiation-induced damage.

Amylases↗
PubMed1982

Liver disease after bone marrow transplantation.

Liver dysfunction occurs after bone marrow transplantation but the relative importance of graft versus host disease and other factors, such as infection, radiation, and drugs, has not been clearly established. We have studied liver status before and after bone marrow transplantation in 43 consecutive patients and have related this to survival and factors that are recognised to cause liver injury. Minor abnormalities of liver tests occurred in 21% of patients before grafting but this did not influence survival or the development of liver disease after transplantation. During the first 50 days after grafting, 83% of patients had abnormal liver tests which were more severe in patients who subsequently died. Alanine transaminase was significantly higher in non-survivors and appeared to predict survival early after transplantation. Only non-survivors developed clinical signs of liver disease. Severe liver disease was always associated with graft versus host disease and atypia of the small bile ducts was the most useful histological marker of hepatic involvement with this disease. Two of the patients with hepatic graft versus host disease also has hepatic veno-occlusive disease and three fatalities had opportunistic infection of the liver, although, in the latter, death was not due primarily to liver dysfunction. Previous hepatitis and androgen therapy could not be implicated as important causes of hepatic damage but chemotherapy for acute leukaemia and conditioning regimens for bone marrow transplantation appear to be the most important factors in the development of hepatic veno-occlusive disease.

Adolescent↗
PubMed1982

Ratio of blood and marrow-derived cells in bone marrow transplantation.

The content of the cell suspensions used in bone marrow transplantation can vary by at least twelvefold in the ratio of bone marrow-derived to blood-derived cells. The ratio is somewhat higher in young donors but is similar for male and female donors and is not closely correlated with the incidence of graft v host reactions.

Adolescent↗
PubMed1981

Acute myeloid leukaemia: comparison of support required during initial induction of remission and marrow transplantation in first remission.

Two groups of patients with acute myeloid leukaemia (AML), treated concurrently, were compared to assess the support required during bone-marrow hypoplasia. One group of patients received drugs to induce initial remission; patients in the other group (in first remission) each received a bone-marrow transplant from a matched allogeneic sib. The patients who received marrow transplants required less time in hospital, were febrile on fewer days, received less therapeutic antibiotic treatment, and had fewer bacterial infections. They also required half as many units of platelets and blood per 100 days. The mean weight-loss per patient was the same in each group, and no patient required intravenous feeding. Transplantation for AML in first remission requires less supportive care than initial remission induction.

Adolescent↗
PubMed1980

The place of bone-marrow transplantation in acute myelogenous leukaemia.

28 patients with acute myeloid leukaemia (AML) in first remission were maintained on chemotherapy, consisting of courses of cytosine arabinoside and daunorubicin, and immunotherapy with irradiated AML cells and BCG. The relapse rate and survival rate of these patients were compared with those of a simultaneously treated group of 22 patients in first remission who received sibling bone-marrow transplants after cyclophosphamide (60 mg/kg) given for 2 days and followed by a single dose of 1000 rads total body irradiation. Substantially fewer transplanted patients (4 out of 22) than chemo-immunotherapy patients (19 out of 28) relapsed (p less than 0.005) and 14 (64%) transplanted patients remain alive, well, and disease-free. Survival curves of the two groups of patients show that the transplanted patients never fared worse than the chemo-immunotherapy patients. We suggest that when possible young AML patients in remission should be offered transplantation as an alternative form of treatment.

Adolescent↗
PubMed1980

Cyclosporin A to prevent graft-versus-host disease in man after allogeneic bone-marrow transplantation.

Cyclosporin A has been used in conjunction with allogeneic bone-marrow transplantation in the treatment of 23 patients--21 with acute leukaemia, 1 with chronic granulocytic leukaemia, and 1 with aplastic anaemia. The drug was given twice daily from the day before transplant. At the start of the study cyclosporin prophylaxis was stopped in 3 patients within 44 days of transplantation because of non-specific rashes and/or deteriorating renal function. All 3 patients had acute graft-versus-host disease (GVHD) and died. Thereafter the drug was not stopped because of possible toxic manifestations, and 20 patients have been studied (median follow-up 7 months; maximum 13 months). 2 patients have acquired GVHD; 1 patient died of acute GVHD and 1 has chronic mild disease. 3 other patients have died, 2 of recurrent leukaemia and a third of staphylococcal pneumonia with renal failure. Of the remaining patients, 1 has recurrent leukaemia and 1 has moderately severe renal failure. Several toxic effects of cyclosporin A have been observed but they are mostly reversible and no second malignant neoplasm has developed.

Adolescent↗