PubMed Health⌕ Search

Biomedical subjects

R L Powles

Publications and source records attributed to R L Powles.

At least 55 records · Page 3Linked to original sources
PubMed1994

Neutralising antibodies in patients with multiple myeloma receiving maintenance therapy with interferon alpha 2b.

In a study of 29 patients who were receiving or had received interferon alpha 2b (IFN-alpha 2b) as maintenance therapy for multiple myeloma, antibodies were detected in 58% (17/29) of patients measured by a solid-phase enzyme-linked immunosorbent assay (ELISA). Only 7/17 patients who were positive for antibody in the ELISA had neutralising antibody to IFN-alpha 2b, measured by virus growth inhibition. These patients comprised six who were receiving IFN-alpha 2b at the time of assessment and one who had finished treatment. Among patients who were receiving the cytokine, four had progressive disease, one was in complete remission and one in partial remission. Neutralising activity was also detected to natural human leucocyte IFN-alpha in the same patients. Two patients who were positive for neutralising antibody remain in remission and are continuing to receive IFN-alpha 2b. These two patients have since lost their neutralising titre. No neutralising antibody to IFN-alpha 2b or natural human leucocyte IFN-alpha was detected in serum from six normal donors. The data suggest that neutralising antibody formation in patients with multiple myeloma is not responsible for relapse in patients receiving IFN-alpha 2b. The transient nature of neutralising antibody production in patients who remain in remission suggests that this response to IFN-alpha 2b is not associated with memory B cells.

Antibodies, Neoplasm↗
PubMed1994

Cimetidine-induced myelosuppression after bone marrow transplantation.

A strong temporal correlation was observed between cessation of cimetidine and a sustained increase in blood counts in two marrow transplant recipients. Both were receiving cimetidine from the day of transplantation for prophylaxis of stress ulceration and gastritis. The blood counts of both patients were not increasing satisfactorily 5-6 weeks after marrow transplantation without any obvious cause of marrow suppression. A similar observation has been made with the use of ranitidine after marrow transplantation suggesting that histamine H2-receptor antagonists should be used very cautiously, if at all, in the setting of bone marrow transplantation.

Adolescent↗
PubMed1994

TGF beta 1 and IL-4 have opposing effects on the proliferation of chronic phase chronic myeloid leukaemic cells stimulated by G-CSF in vitro.

The effects of transforming growth factor beta 1 (TGF beta 1) have been studied in vitro on the clonogenicity of haemopoietic progenitor cells (CFU-CML) from 14 patients with chronic myeloid leukaemia (CML) in chronic phase and 13 normal donors. In 14/14 patients with CML, 5 ng of TGF beta 1/dish decreased CFU-CML-formation in cultures stimulated with 15 ng of granulocyte colony-stimulating factor (G-CSF)/dish (p < 0.0005) and in 13/14 patients TGF beta 1 reduced CFU-CML-formation induced by G-CSF in combination with 5 ng of recombinant human interleukin-4 (rhIL-4)/dish (p < 0.005). In 10/14 samples the number of CFU-CML were reduced to levels lower than in cultures containing G-CSF alone (p < 0.01). In contrast, TGF beta 1 had no significant inhibitory effect on the G-CSF-directed proliferation of normal donor mononuclear cells (MNC) either alone or in combination with rhIL-4. RhIL-4 increased G-CSF-induced colony formation in 13/14 CML samples (p < 0.001), but did not have the same effect in the normal donor samples. The in vitro clonogenicity of CML peripheral blood MNC stimulated with 15 ng of G-CSF could not be correlated with the white cell count or the percentage of CD34+ cells at diagnosis.

Antigens, CD↗
PubMed1994

Fatal pneumococcal infections following allogeneic bone marrow transplant.

Six cases of fatal pneumococcal sepsis are described, occurring in the post-allograft setting, between 3 and 39 months after transplantation. Five of the six patients were suffering from chronic graft-versus-host disease and were receiving immunosuppressive therapy. Most were receiving prophylactic antibiotic therapy. This represents approximately 2% of the allograft population treated during the study period who survived for > 3 months after transplant. Pneumococcal sepsis is thus still a significant cause of death after allogeneic BMT and approaches to minimise its occurrence are discussed.

Acute Disease↗
PubMed1994

Selective inhibition of primary acute myeloid leukaemia cell growth by simvastatin.

Primary human acute myeloid leukaemic (AML) cells from bone marrow (BM) and peripheral (PB), the human myeloblastic leukaemia cell line (HL60) and normal human BM mononuclear cells were cultured in serum-free medium. The survival of progenitor cells from normal BM, HL60 and AML cell populations was reduced over a range of concentrations of simvastatin. This dose response relationship was more pronounced in HL60 and AML cell cultures, indicating greater sensitivity of AML progenitor cells compared with normal BM progenitors. Short-term exposure (18 h) to a range of concentrations of simvastatin showed the same differential response between leukaemic and normal BM cells in terms of clonogenicity. At a concentration of 10 micrograms/ml progenitor cell survival remained above 65% for normal BM while at this concentration leukaemia progenitor cell survival fell below 25% of the untreated values. The differential effect of simvastatin on normal and leukaemic progenitor cells may have value in the clinical management of AML. The possible use of simvastatin, or related drugs, as adjuvants to conventional chemotherapy including in vitro BM purging, merits consideration.

Acute Disease↗
PubMed1994

Graft failure after bone marrow transplantation from unrelated donors using busulphan and cyclophosphamide for conditioning.

Five patients received bone marrow allografts for leukaemia from serologically fully matched unrelated donors. The conditioning regimen was busulphan 16 mg/kg and cyclophosphamide (CY) 120 mg/kg. Engraftment was achieved in only two patients, with primary graft failure occurring in three patients. Two of the three patients with no evidence of myeloid engraftment on day 28 received GM-CSF without response. Both these patients required rescue with cryopreserved autologous material. Three patients remain alive, one died of relapse after a successful allograft and one died with pancytopenia. Although the number of patients is small, we conclude that the BuCY2 regimen with 120 mg/kg CY, while adequate for sibling allografts, may not be sufficiently immunosuppressive to permit consistent engraftment of bone marrow from unrelated donors.

Adult↗
PubMed1994

Selective inhibition of primary acute myeloid leukaemia cell growth by lovastatin.

Primary human acute myeloid leukaemic (AML) cells from bone marrow (BM) and peripheral blood (PB), the human myeloblastic leukaemia cell line (HL60) and normal human BM mononuclear cells were cultured in serum-free medium. The survival of progenitor cells from normal BM, HL60 and AML cell populations was reduced over a range of concentrations of lovastatin. This dose response relationship was more pronounced in HL60 and AML cell cultures, indicating greater sensitivity of AML progenitor cells compared with normal BM progenitors. Short-term exposure (18 h) to a range of concentrations of lovastatin showed the same differential response between leukaemic and normal BM cells in terms of clonogenicity. At a concentration of 10 micrograms/ml progenitor cell survival remained above 65% for normal BM while at this concentration leukaemia progenitor cell survival fell below 25% of the untreated values. The differential effect of lovastatin on normal and leukaemic progenitor cells may have value in the clinical management of AML. The possible use of lovastatin, or related drugs, as adjuvants to conventional chemotherapy including in vitro BM purging, merits consideration.

Adult↗
PubMed1994

Systemic fungal infections: major problems in cancer patients.

Over the last decade, with increasing use of aggressive chemotherapy and bone marrow transplantation in the treatment of cancer, fungi have emerged as a major pathogen. The prognosis of established systemic fungal infections remains poor, but newer antifungal drugs such as fluconazole are changing the outlook of therapy and prophylaxis considerably.

Antifungal Agents↗
PubMed1993

Methotrexate, cyclosporine, or both to prevent graft-versus-host disease after HLA-identical sibling bone marrow transplants for early leukemia?

Optimal prophylaxis of graft-versus-host disease (GVHD) is controversial. We compared efficacy of three posttransplant immune suppressive regimens in 2,286 recipients of HLA-identical sibling bone marrow transplants for acute lymphoblastic leukemia (ALL) in first remission, acute myelogenous leukemia (AML) in first remission, or chronic myelogenous leukemia (CML) in first chronic phase. Six hundred forty received methotrexate, 977 received cyclosporine, and 669 received combined cyclosporine and methotrexate. In children, the three regimens resulted in similar outcomes. In adults, cyclosporine and methotrexate had comparable risks of acute and chronic GVHD. Compared with methotrexate, cyclosporine was associated with less interstitial pneumonia (relative risk [RR] = 0.6; P < .001), less treatment-related mortality (RR = 0.6; P < .001), more relapses (RR = 1.6; P < .05), and less treatment failure (relapse or death from any cause; RR = 0.7; P < .001). Different effects were observed in different leukemias. In ALL, the rate of leukemia relapse was increased with cyclosporine versus methotrexate, with no effect on other outcomes. In AML and CML, interstitial pneumonia, treatment-related mortality, and treatment failures were decreased with cyclosporine, with no increase in relapse. Similar analyses comparing cyclosporine plus methotrexate with cyclosporine alone showed that adults receiving the combination had less acute GVHD (RR = 0.5; P < .001), less chronic GVHD (RR = 0.7; P < .01), and less interstitial pneumonia (RR = 0.7; P < .001). Treatment failure (RR = 0.8; P < .05) was marginally reduced. Separate analyses in ALL and AML showed less acute GVHD with combined therapy, but no significant effect on other outcomes. In CML, acute GVHD, interstitial pneumonia, treatment-related mortality, and treatment failure were decreased with combined therapy.

Adolescent↗
PubMed1993

Cytokine gene expression in skin and lymphoid organs in graft versus host disease.

AIM: To determine if human graft versus host disease (GvHD) is associated with any detectable change in cytokine gene expression in the skin and lymphoid organs. METHODS: Reverse transcriptase and the polymerase chain reaction were used to amplify mRNA for interleukins-1 (IL-1), -2 (IL-2), -4 (IL-4) and -6 (IL-6), IL-2 receptor (IL-2R), tumour necrosis factors alpha (TNF-alpha) and beta (TNF-beta), gamma interferon (IFN gamma) and granulocyte macrophage colony stimulating factor (GM-CSF) in frozen punch biopsy specimens of skin and necropsy samples of skin, lymph node, and spleen. RESULTS: No cytokine mRNA was detected in the punch biopsy specimens except weak signals for IL-6 and IL-1 and GM-CSF in two normal donors and IL2-R in one patient with GvHD. In samples of skin taken at necropsy, however, significant quantities of mRNA for TNF-alpha, TNF-beta, and IL-4 were detected in patients who had or had had GvHD in contrast to those without the disease whose skin lacked mRNA for these products but contained detectable quantities of IL-1, IL2-R, IL-6 and GM-CSF. There seemed to be a reciprocal relation between TNF-alpha and IL-4. In necropsy samples of lymph node and spleen a pattern of cytokine production similar to that in the skin was observed with a preponderance of TNF-alpha, TNF-beta and IL-4 in patients with GvHD and GM-CSF and IL-6 in those without the disease. CONCLUSIONS: The local synthesis of these molecules would explain many of the morphological and immunohistological features of GvHD. The failure to detect TNF-alpha, TNF-beta, and IL-4 in skin biopsy specimens exhibiting GvHD is probably due to their small size but further investigations are required.

Adolescent↗
PubMed1993

Transplantation of autologous peripheral blood stem cells mobilized using GM-CSF for acute leukemia with myelofibrosis.

A patient with acute mixed lineage leukemia had marked marrow fibrosis at presentation. The fibrosis persisted despite achievement of complete remission. Because the marrow was inaspirable, granulocyte-monocyte colony-stimulating factor (GM-CSF) was used to mobilize stem cells into the peripheral blood which were used for autologous transplantation. Myeloid engraftment was rapid. The extent of the fibrosis decreased after transplantation. GM-CSF-mobilized peripheral blood stem cells may be used for autologous transplantation in patients with fibrotic marrows who are not candidates for allografting.

Acute Disease↗
PubMed1993

Idarubicin for remission induction of acute myeloid leukemia: United Kingdom multicenter experience.

Ninety-eight adult patients with acute myeloid leukemia were given variable remission induction/consolidation regimens containing idarubicin. Sixty-nine (70%) were new cases (median age, 56 years) and 29 (30%) were in relapse (n = 24) or had primary refractory disease (n = 5) (median age, 46 years). Complete remission (CR) rates were 57% (39 of 69 patients) of the newly diagnosed patients, with no difference for those below or above 55 years of age (56% v 59%) or for patients exhibiting white blood cell counts of less or more than 50 x 10(9)/L (52% v 69%; P = .8). Of the 39 patients who achieved CR, 26 (67%, 38% of the total number of patients) remain in CR with a median follow-up of 3 months (range, 0 to 61 months). Forty-two percent of the relapsed cases (10 of 24 patients) and 60% of the primary refractory disease cases (three of five patients) achieved CR. Of these 13 responders, six are alive (three continuing in CR and three relapsed) with a median follow-up of 3 months (range, 1 to 20 months), and seven have died with a median survival of 7 months (range, 0 to 12 months). Of the 52 patients who have achieved CR, 84% did so with one course of treatment and 16% with two courses. The presence of normal cytogenetic analysis or favorable chromosomal aberrations significantly improved overall CR rates. The patients in this study had significantly more unfavorable cytogenetic abnormalities than the historic controls. Reported toxicity was hepatic in 13%, cardiac in 9%, and renal in 7% of all cases. These data suggest a comparable efficacy of idarubicin to other anthracyclines in remission induction of acute myeloid leukemia, with a promising role in relapsed/refractory disease.

Acute Disease↗
PubMed1993

Human Philadelphia chromosome-positive chronic myeloid leukemia: a potential model for antisense therapy.

We have developed an in vivo model of human chronic myeloid leukemia (CML). A peripheral blood (PB) sample of Philadelphia (Ph) chromosome-positive CML cells in lymphoid blast crisis was transplanted intravenously (IV) into sublethally irradiated severe combined immunodeficient (SCID) mice, and this resulted in engraftment with systemic proliferation. Growth of leukemia was monitored by PB cell morphology and by flow cytometric analysis of murine PB cells labelled with an anti-human leukocyte antigen (HLA) monoclonal antibody. Human cells were first detected in the PB at 4 weeks and comprised a mean of 57% of the total nucleated cells in the PB of these mice by 15 weeks. The Ph chromosome was retained and the population has been successfully passaged. BCR/ABL fusion gene expression was detected in a subsequent passage. Experiments are underway to use this in vivo model to assess the antileukemic activity of BCR/ABL antisense oligonucleotides.

Animals↗
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↗