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Biomedical subjects

R Powles

Publications and source records attributed to R Powles.

At least 145 records · Page 8Linked to original sources
PubMed1991

Human recombinant GM-CSF in allogeneic bone marrow transplantation for leukaemia: double-blind placebo controlled trial.

A double-blind randomised trial compared 20 patients with leukaemia receiving human recombinant granulocyte macrophage colony stimulating factor (GM CSF), with 20 patients receiving placebo for 14 days after allogeneic matched sibling bone marrow transplantation. The median neutrophil count at 14 days was significantly higher in the GM CSF group (1.90 vs. 0.46 x 10(9)/l). The duration of hospital stay, the number of antibiotic days, and the number of fever days was the same for both patient groups. The lymphocyte count was significantly higher in the GM-CSF group than in the placebo group between days 10 and 15 after transplantation. The GM-CSF group had lower haemoglobin concentrations and platelets counts, and higher plasma urea creatinine and bilirubin, than the placebo group. There was no evidence that GM CSF was associated with a greater incidence of leukaemic relapse.

Bone Marrow Transplantation↗
PubMed1991

Growth of primary human acute leukemia in severe combined immunodeficient mice.

Seven populations of human leukaemic cells were implanted i.v. into sublethally irradiated severe combined immunodeficient (scid) mice. Growth of leukaemia was monitored by labelling murine peripheral blood (PB) cells with an anti-HLA monoclonal antibody and flow cytometric analysis. Two of the populations transplanted were fresh acute lymphoblastic leukaemia (ALL) bone marrow (BM) cells which both caused sustained proliferative growth in scid mice. Human cells accounted for up to a mean of 87% of the total nucleated cells (TNC) in the PB of these mice between weeks 12-15. One of these populations was passaged into fresh mice and frank leukaemia was again established. Three populations of cryopreserved acute myeloblastic leukaemia (AML) cells (2 obtained from PB and 1 from BM) and one population of cryopreserved biphenotypic acute leukaemia BM cells, only grew to a maximum of 4% within the 15 week period of the experiment. A cell population from an AML cell line (HL60), however, did engraft and proliferate resulting in a rapid deterioration of these mice between weeks 3-6 when the proportion of human cells accounted for 9% of the TNC in the PB.

Acute Disease↗
PubMed1990

Human recombinant GM-CSF in allogeneic bone-marrow transplantation for leukaemia: double-blind, placebo-controlled trial.

In a randomised, double-blind trial 20 patients with leukaemia received human recombinant granulocyte macrophage colony-stimulating factor (GM-CSF) and 20 received placebo, for 14 days after allogeneic, matched sibling, bone-marrow transplantation. The neutrophil count recovered to 0.5 x 10(9)/l 3 days earlier in the GM-CSF group than in the placebo group (not significant), and the median neutrophil count at 14 days was significantly higher in the GM-CSF group (1.90 vs 0.46 x 10(9)/l). The lymphocyte count was significantly higher in the GM-CSF than in the placebo group between days 10 and 15 after transplantation, but this difference was not associated with a higher incidence of graft-versus-host disease. There was no evidence that GM-CSF was associated with a greater incidence of leukaemic relapse. The GM-CSF group had lower haemoglobin concentrations and platelet counts and higher plasma urea, creatinine, and bilirubin than the placebo group. The duration of hospital stay was the same for both patient groups. Further studies are now indicated to assess the overall effect of GM-CSF on outcome after allogeneic bone-marrow transplantation.

Adolescent↗
PubMed1990

Cytogenetic studies of leukemic recurrence in recipients of bone marrow allografts.

Cytogenetic studies were made in 20 leukemic patients who relapsed after treatment by allogeneic bone marrow transplantation (BMT). Seven of the eight patients in whom no chromosomal abnormalities were detected in leukemic cells before BMT developed clonal abnormalities after BMT, and in two of these patients two independent clones were observed. Most patients in whom clones were detected before BMT showed evidence of clonal evolution after BMT. Nonclonal abnormalities were also observed in clonal cells. These additional abnormalities, both clonal and nonclonal, were attributed to the effects of total body irradiation received by the patient before BMT. There was no evidence of recurrence of leukemia in donor cells among these patients. We concluded that the cells found in leukemic recurrence were derived from the original leukemic clone.

Adolescent↗
PubMed1990

High-dose cytosine arabinoside plus etoposide as initial treatment for acute myeloid leukaemia: a single centre study.

In a single centre, 52 newly diagnosed patients with acute myeloid leukemia (AML) under the age of 56 years received induction chemotherapy commencing with high-dose cytosine arabinoside (Ara-C) and etoposide (Protocol BF11), followed by Ara-C, 6 thioguanine (6TG). A total of 67% of patients entered remission using these drugs. An anthracycline was added for those patients not in remission. The overall remission rate (CR) was 86.5% (45/52), with a minimum follow-up of 90 days. Patients are hospitalised for relatively short periods, and consequently require less blood product and antibiotic support. Patients in continuing first remission following induction with Ara-C and etoposide are similar in number to those in continuing first remission who initially received an anthracycline. This would imply that the efficiency of Ara-C and etoposide in inducing long-term disease-term survival is comparable with anthracycline-containing regimens. We conclude that high-dose Ara-C and etoposide used in the first induction cycle for treating AML have good antileukaemic effect with acceptable toxicity.

Adolescent↗
PubMed1990

Teicoplanin compared to flucloxacillin for antibiotic treatment of neutropenic patients.

Ninety-eight neutropenic patients were randomized to receive piperacillin and gentamicin in combination with either teicoplanin or flucloxacillin. Sixty-seven of these patients, most of whom had myeloma, were given this combination as prophylaxis 5 d after high dose chemotherapy, 35 receiving flucloxacillin and 32 receiving teicoplanin. Of 31 patients with leukaemia who were febrile and neutropenic following induction chemotherapy or bone marrow transplantation, 18 received flucloxacillin and 13 received teicoplanin. For those given flucloxacillin, the mean number of days to change of antibiotics was 7.8 in the prophylaxis group and 5.1 in the treatment group. In the teicoplanin arm, the mean number of days to change antibiotics was 6.8 in the prophylaxis group and 6.1 in the treatment group. Two patients in the flucloxacillin arm developed drug rashes. Four patients developed rigors after teicoplanin administration and one asthmatic became wheezy. One patient had a progressive rise in creatinine, but overall the patients having teicoplanin did not have any appreciable increase of renal toxicity compared to the flucloxacillin arm. Blood cultures were positive prior to commencement in the treatment group in nine patients, and during treatment in six patients. Organisms grown were Gram-positive in 14 patients. Teicoplanin appears to be as effective as flucloxacillin when each is used in combination with piperacillin and gentamicin in the treatment of neutropenic patients, with similar rates of toxicity.

Anti-Bacterial Agents↗
PubMed1990

Bone marrow transplantation--the Marsden experience.

Leukemic relapse remains a major problem after both autologous and allogeneic transplantation. In the single-arm ALL autograft study our results were very encouraging and suggest that Melph/TBI can produce disease-free survival results at least as good as with other conditioning regimens. The role of postautograft maintenance remains unclear, but we feel our results are sufficiently encouraging to justify a randomized study, particularly as we studied a group of patients with relatively poor prognoses. In our study comparing Cy and TBI with Melph and TBI in AML, we have shown a significant increase in antileukemic activity after transplantation following the latter conditioning regimen. The retrospective study of Melph/TBI in autologous versus allogenic transplantation suggested that in AML this antileukemic effect may derive from increased GvHD and is not present in the autologous setting. We hope that by increasing the intensity of our GvHD prophylaxis we can reduce the toxicity of Melph/TBI and preserve its antileukemia effect. Our experience with GM-CSF has been a little disappointing: despite facilitating neutrophil recovery, we were unable to demonstrate a clinical benefit in the treatment arm. We hope to further investigate the use of cytokine combinations in the transplant setting.

Acute Disease↗
PubMed1990

Successful pregnancy following bone marrow transplantation for leukaemia.

We report three pregnancies with successful outcomes in two women following allogeneic bone marrow transplantation (BMT) for acute leukaemia using high dose melphalan alone as conditioning therapy. The increasing application and success of BMT together with the instigation of conditioning regimens that do not include total body irradiation should increase such cases. These and previous cases document that a normal outcome of pregnancy is likely in these patients.

Adult↗
PubMed1990

Delayed engraftment associated with splenomegaly in patients undergoing bone marrow transplantation for chronic myeloid leukaemia.

There is no general agreement about the effect of an enlarged spleen on the outcome after bone marrow transplantation (BMT) for chronic myeloid leukaemia (CML). In this retrospective analysis, we compared rate of engraftment, haematological recovery and survival in 42 CML BMT recipients, 19 with splenomegaly and 23 without. Other variables analysed included interval from diagnosis to BMT, disease status at BMT, conditioning regimen, additional splenic irradiation, marrow cell dose, donor recipient ABO match and graft-versus-host disease. In multivariate analysis, the only significant variable was the presence or absence of splenomegaly. Splenomegaly was significantly correlated with delayed engraftment and graft failure. Patients with delayed engraftment experienced higher mortality, largely due to sepsis. These results emphasize the adverse impact of splenomegaly upon BMT survival in CML, and suggest that splenic irradiation does not favourably affect the early outcome after BMT.

Adolescent↗
PubMed1989

Consequences and treatment of ovarian failure after total body irradiation for leukaemia.

OBJECTIVE: To assess the incidence and severity of physical and psychosexual symptoms in young women due to ovarian failure caused by total body irradiation for leukaemia and the women's response to hormone treatment. DESIGN: Postal questionnaire and interview. SETTING: Leukaemia unit of oncology hospital. PATIENTS: Consecutive series of 46 English speaking women who had developed ovarian failure after total body irradiation and bone marrow transplantation as treatment for leukaemia. RESULTS: Of the 36 responders, 33 reported some symptoms, vaginal dryness being the most common (29). This profoundly affected sexual function. Although 22 women had had sexual intercourse within six months after treatment, 16 were less interested in and 18 experienced difficulties with sexual intercourse. Anxieties about sterility, femininity, and appearance were common and reduced self confidence. Almost half reported that they had changed their social habits and restricted their social activities. Treatment seemed effective in abolishing symptoms in 24 women, but vaginal dryness remained a problem in three. Two women failed to respond and intercourse remained impossible. CONCLUSIONS: Such patients are vulnerable and access to gynaecologists and endocrinologists soon after treatment would be valuable. The optimal treatment regimen and the long term benefits of treatment have yet to be established.

Adolescent↗
PubMed1989

Treatment of relapsed and refractory acute leukaemia with high-dose cytosine arabinoside and etoposide.

A total of 65 patients under the age of 55 with acute leukaemia received high-dose cytosine arabinoside (Ara-C) in combination with high-dose etoposide without an anthracycline. Complete remission rates for patients with relapsed or refractory acute myelogenous leukaemia (AML) were 15/25 (60%) and 11/16 (69%), respectively. The complete remission rate for patients with refractory or relapsed acute lymphoblastic leukaemia (ALL) was 10/18 (56%). The treatment-related mortality was 17%. Nine patients whose leukaemia relapsed after matched allogeneic, sibling bone-marrow transplantation (BMT) were also treated in this way; the treatment-related mortality in this group was high (7/9) and the duration of remission in the two patients who responded, too short to justify this intensive treatment in such patients. Similarly, patients who underwent BMT after achieving a complete remission with high-dose Ara-C and etoposide did very poorly, only one patient surviving well and disease-free at 8 months. The important finding in this study was the high complete remission rate rapidly obtained in patients with relapsed or refractory AML without using an anthracycline.

Adult↗
PubMed1989

Cytomegalovirus pneumonia: the use of ganciclovir in marrow transplant recipients.

Sixteen bone marrow transplant recipients with cytomegalovirus pneumonia diagnosed by rapid, non-invasive methods were treated with ganciclovir. Seven patients survived the acute infection and there were five long term survivors. Excellent in-vivo suppression of cytomegalovirus was observed. Marrow toxicity was noted in four patients but was rapidly reversible and not life threatening. Clinical features common to surviving patients included good clinical condition, insidious development of infection and evidence of normal alveolar gas exchange. The fulminant onset of symptoms, radiographic abnormalities and hypoxaemia were characteristic of non-survivors. These results offer some encouragement towards further study of ganciclovir for the early treatment of cytomegalovirus pneumonia. To identify such patients, the use of rapid diagnostic methods and aggressive viral surveillance is recommended. Convincing evidence for the efficacy of this drug will only emerge from randomized prospective studies.

Acyclovir↗