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Biomedical subjects

R L Powles

Publications and source records attributed to R L Powles.

At least 19 recordsLinked to original sources
PubMed1992

Colony-stimulating activity in the serum of patients with hemopoietic malignancies after intensive chemotherapy/radiotherapy: its augmentation by GM-CSF in vivo and interleukin 4 in vitro.

Colony-stimulating activity (CSA) in the serum of patients with hematological malignancies increased substantially after intensive therapy with cyclophosphamide/busulfan, cyclophosphamide/total body irradiation, or melphalan/total body irradiation. This was not dependent on patients receiving allogeneic bone marrow transplantation (ABMT) or autologous bone marrow rescue (ABMR). In 44 of 62 patients CSA was maximum approximately 7 days after chemotherapy/radiotherapy, whereas in 18 of 62 patients CSA was maximum between 9 and 20 days after therapy and decreased thereafter. The time course of CSA was not dependent on disease and was not affected by recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) given as a continuous infusion for 14 days after therapy; however, serum from patients receiving rhGM-CSF produced significantly more colonies from donor bone marrow than serum from patients who did not receive the cytokine (p = 0.013). Despite the early peak in CSA in the majority of patients, there was no correlation between the time at which CSA was maximum and the return of patients' neutrophils to 500/microliters. Recombinant human interleukin 4 (IL-4) increased the number of granulocyte-macrophage colony-forming unit colonies, principally granulocyte colony-forming unit colonies, from normal bone marrow exposed to patients' serum after intensive therapy and antibody to GM-CSF reduced colony numbers. The results suggest that after intensive therapy granulocyte colony-stimulating factor (G-CSF) as well as GM-CSF is released into the serum and, in addition to acting directly with G-CSF, IL-4 may stimulate mononuclear cells to produce and/or release G-CSF.

Bone Marrow Cells↗
PubMed1991

Acute myeloblastic leukaemia--a model for assessing value for money for new treatment programmes.

OBJECTIVE: To measure the effects of changes in treatment of acute myeloblastic leukaemia that may give better value for money. DESIGN: Retrospective analysis of patients' notes to identify items of management costing money; prospective costing of these items. The Medical Research Council acute myeloblastic leukaemia 9 trial was used to identify the amount and distribution of these costs when either one or two courses of induction treatment were required to obtain complete remission. These findings were then extrapolated to four published international controlled trials using similarly intense treatment and in which the number of courses of treatment required for complete remission was stated, to compare British costs for treatment with idarubicin and daunorubicin, both in combination with cytarabine. SETTING: Leukaemia unit, Royal Marsden Hospital, London. SUBJECTS: Data on 10 patients receiving intensive induction treatment for acute myeloblastic leukaemia were used to identify 160 items of cost in four broad groups: general (including accommodation), diagnostic, supportive treatment, and cytotoxic chemotherapy. One newly treated patient was prospectively assessed over one month, including a time and motion study, to cost these items; then costs for 268 patients from the MRC trial receiving moderate induction chemotherapy including daunorubicin were assessed, and costs for treatment of 522 patients in the four international studies comparing daunorubicin with idarubicin were analysed. MAIN OUTCOME MEASURES: Cost effectiveness was measured as the overall cost to obtain complete remission in untreated patients with acute myeloblastic leukaemia after treatment with idarubicin or daunorubicin. RESULTS: The 160 costed items were measured for their sensitivity in varying the total cost of treatment, this being assessed within Britain in other district general and private hospitals to measure the extremes of cost of these items. Overall, idarubicin, although more expensive, showed a substantial saving (1477 pounds per patient) in total hospital costs, more than offsetting the increased cost (607 pounds) of the new treatment, an overall savings of 870 pounds per patient (5%). CONCLUSION: Approaches modelling cost effectiveness may be an essential part of planning new programmes of treatment in the future. This method can be used to estimate the cost effectiveness of the treatments in different environments and countries where costs may vary widely.

Adolescent↗
PubMed1991

The prophylaxis of fungal infections.

With the increase in use of immunosuppressive therapies, solid organ and bone marrow transplantation and the recognition of the acquired immune deficiency syndrome (AIDS) an increased incidence and awareness of fungal infection has occurred in almost all disciplines of medicine. The problem of being unable to identify such infections accurately before serious morbidity or mortality occurs indicates a continued need for a prophylactic approach to these infections. Fortunately, the development of new, safer antifungal agents appears to be occurring. Novel approaches with amphotericin B and the use of bone marrow growth factors merit attention. Specific recommendations for antifungal prophylaxis depend on a number of factors pertinent to the individual treatment centre.

Animals↗
PubMed1991

Antagonism of the inhibitory effects of transforming growth factor-beta on colony formation of mouse bone marrow cells in vitro by increasing concentrations of growth factors.

Low concentrations of TGF-beta inhibited the clonal proliferation of three different preparations of mouse bone marrow progenitor cells in vitro. Normal marrow cells responsive to CSF-1; two-day post-fluorouracil cells responsive to CSF-1 plus IL-3 and IL-1 alpha; and regenerating seven-day post-fluorouracil cells responsive to CSF-1 plus IL-3, IL-1 alpha and IL-6 were all severely inhibited by TGF-beta 1; and the inhibitory effects were antagonized by increasing the concentrations of the relevant growth factors.

Animals↗
PubMed1991

High dose melphalan and total body irradiation with autologous marrow rescue in childhood acute lymphoblastic leukaemia after relapse.

High dose melphalan (HDM 110-140 mg/m2) and total body irradiation (TBI, 10.5 Gy, single fraction) followed by infusion of autologous bone marrow (ABMT) was evaluated for toxicity and efficacy in 24 children with acute lymphoblastic leukaemia (ALL) in second (CR2) or third remission (CR3). Marrow was purged with Campath 1 in six children (four were children in CR3). All children had engraftment with a median of 30 days (range 18-70 days) to neutrophil count greater than 0.5 x 10(9)/l. Four children (16%) died from toxicity 1-4 months after autograft, two from pneumonitis, one from an intracerebral haemorrhage and one from sepsis. Apart from fever and mucositis the procedure was well tolerated. Nine of 17 children treated in CR2 remain in complete remission 6-72 months after ABMT (median 25 months). Seven of these have a follow-up of greater than 12 months. Three of the seven children treated in CR3 are alive 17, 22 and 29 months post ABMT. Seven children relapsed within 10 months (median 4 months) of the autograft. Only one relapse has occurred beyond 10 months. HDM and TBI followed by ABMT is a relatively well tolerated regimen and may contribute to survival in children with relapsed ALL.

Adolescent↗
PubMed1990

Bone-marrow transplant from father to son and subsequent graft from son to father.

An 11-year-old boy with acute myeloblastic leukaemia in first remission received an allogeneic mismatched bone-marrow transplant (BMT) from his father in 1979; subsequent HLA typing showed that his haemopoietic system had been repopulated by the donor cells. In 1986 hypereosinophilic syndrome, secondary to a T-cell lymphocytic lymphoma, developed in the father, then aged 45 years. A full haematological remission was obtained by means of standard acute lymphoblastic leukaemia treatment. He then received melphalan, total body irradiation, and a BMT from his son. Graft-versus-host disease was transient in both patients, and father and son remain well and disease-free 20 months and 10 years, respectively, after BMT.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Thrombocytopenia after bone marrow transplantation for leukaemia: changes in megakaryocyte growth and growth-promoting activity.

Megakaryocyte growth-promoting activity (MK-GPA) was scored on a scale of 0-3 in the serum of 23 patients up to 120 d following bone marrow transplantation (BMT) for leukaemia. Nine of 19 allografts and two of four autografts had thrombocytopenia requiring platelet transfusion more than 30 d after BMT. There was a close correlation between MK-GPA and platelet count. MK-GPA reached a maximum before day 30 after BMT but remained elevated in patients with persisting thrombocytopenia secondary to poor engraftment, graft-versus-host disease (GVHD) or relapse. Recent platelet transfusion did not suppress serum MK-GPA. Two of four patients undergoing autologous BMT for acute myeloid leukaemia (AML) showed delayed platelet recovery and persistence of MK-GPA in the serum. Seven further AML remission marrows were tested for megakaryocyte production before or after autologous BMT, using pooled sera with known MK-GPA activity. Megakaryocyte generation was reduced before BMT and absent in post transplant samples. This failure of MK production was not corrected by T-cell depletion or by the presence of adherent cells from normal marrow. We conclude that thrombocytopenia after BMT is associated with an appropriate increase in MK-GPA levels in response to a reduction in the megakaryocyte pool rather than the platelet pool, and that persisting thrombocytopenia after autologous BMT is due to decreased numbers of available megakaryocyte precursors.

Adolescent↗
PubMed1990

Cyclosporine-induced graft-versus-host disease following autologous bone marrow transplantation in acute myeloid leukaemia.

Cyclosporine was used to induce graft-versus-host disease (GVHD) in patients with acute myeloid leukaemia (AML) receiving autologous bone marrow transplantation (ABMT). Nine consecutive patients with AML in remission were conditioned with either busulphan and cyclophosphamide or melphalan and total body irradiation (TBI) followed by ABMT. Cyclosporine, 1 mg/kg daily from days 1-28 was administered intravenously in four patients and orally in five. Acute GVHD of the skin, confirmed by histological and immunological criteria occurred in three patients, 4-28 days after ABMT and lasted 8-18 days. Incidence and severity of GVHD were independent of cyclosporine levels. Three patients subsequently relapsed, of whom two had had evidence of GVHD. All of these patients were in second remission at time of graft, and therefore poor risk. The potential of cyclosporine to induce GVHD in the AML autograft setting is demonstrated, although the significance of this observation in terms of an antileukaemia effect needs clarification.

Adult↗
PubMed1979

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↗
PubMed1979

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↗
PubMed1979

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↗
PubMed1979

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↗
PubMed1978

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↗
PubMed1977

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↗