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Biomedical subjects

R Powles

Publications and source records attributed to R Powles.

At least 19 recordsLinked to original sources
PubMed1992

Results of a double blind placebo controlled study of ondansetron as an antiemetic during total body irradiation in patients undergoing bone marrow transplantation.

Total body irradiation (TBI) is a highly emetogenic component of the majority of conditioning regimens in use for bone marrow transplantation. Conventional antiemetic therapy fails to control nausea and vomiting induced by single fraction TBI in as many as 50% of patients. In a double blind study of 20 patients undergoing marrow transplantation, a single 8 mg ondansetron dose was compared with placebo given immediately prior to TBI. Our routine premedication of phenobarbitone and corticosteroid was also administered to all patients. All patients had received high dose melphalan the previous evening. Only 1 of the 10 patients in the ondansetron group experienced an emetic event compared with 5 of the 10 in the comparison group (p = 0.029). No significant adverse events were observed. Ondansetron appears to have extremely useful antiemetic activity during single fraction low dose rate TBI.

Adult↗
PubMed1992

Tumour lysis following hydrocortisone prior to a blood product transfusion in T-cell acute lymphoblastic leukaemia.

The acute tumour lysis syndrome is a well recognised complication of chemotherapy for lymphoid malignancies. There are few reports, however, of this complication after corticosteroid therapy alone. We report a case of T-cell acute lymphoblastic leukaemia who developed the biochemical picture of tumour lysis after two doses of hydrocortisone given prior to platelet transfusion. Prophylactic corticosteroids prior to blood product infusion should be reserved for patients who have experienced febrile or allergic reactions in the past and it is suggested that they should only be administered to patients with active lymphoid malignancies with due caution.

Adolescent↗
PubMed1992

Bone marrow transplantation for acute myeloid leukemia: the EBMT experience. A prospective analysis from HLA-typing. The EMBT Leukemia Working Party.

In 1990, 4,234 BMT were performed in Europe; 2,097 autologous BMT (388 AML) and 2,137 allogeneic BMT (494 AML). Although an established therapy with leukemia free survival (LFS) at five years of 41% +/- 5% (EBMT results) its value compared to alternative therapies remains controversial. During the year 1985, the EBMT conducted a prospective evaluation study. In 12 centres 168 patients with AML were registered at the time of HLA-typing. Basic patient data and treatment intention were recorded. 79 patients were HLA-typed at diagnosis. 68 patients in 1st CR and 21 at other stages. Follow-up of these patients was obtained as of January 1, 1991. Three-year LFS is 44% for patients with an HLA-identical donor and 21% for those without (p = 0.02). Of the 68 patients HLA-typed in first CR, 40 had an HLA-identical donor and 28 no donor. Three-year LFS is 42% and 35%. resp. (n.s.). The difference in results between patients typed at diagnosis and first CR patients illustrates the problem of selection. We conclude that patient registration early in the disease can give insight into the process of selection. Allogeneic BMT incorporated prospectively at diagnosis into therapy offers a survival advantage for patients in this age category compared to alternative therapies.

Acute Disease↗
PubMed1992

No increase in relapse in patients with myeloid leukaemias receiving rhGM-CSF after allogeneic bone marrow transplantation.

Twenty patients with leukaemia received recombinant human GM-CSF (rhGM-CSF) after allogeneic bone marrow transplantation (BMT) in a double blind controlled trial, with a significant promotion of granulopoiesis when compared with 20 control patients. The follow-up in survivors is now sufficiently long to assess the potential for promotion of relapse in the patients with myeloid leukaemias. Six patients with myeloid leukaemias are alive 22-38 months after transplantation. Eight other patients with myeloid leukaemias died within 12 weeks of transplantation without active active disease. None of these 14 patients with myeloid leukaemias have relapsed. This study supports the view that rhGM-CSF does not increase the probability of relapse after allogeneic BMT in patients with myeloid leukaemia.

Bone Marrow Transplantation↗
PubMed1991

Successful treatment of acute myeloid leukemia beyond first remission with autologous bone marrow transplantation using busulfan/cyclophosphamide and unpurged marrow: the British autograft group experience.

The results in 34 adult patients with acute myeloid leukemia (AML) who have undergone autologous bone marrow transplantation (ABMT) using busulfan and cyclophosphamide (Bu/Cy) in 12 United Kingdom (UK) centers have been analyzed. There were 19 females and 15 males; median age was 40 years (range, 21 to 62 years). Nine patients were in first relapse; 25 were in second remission. The median time of first remission for the whole group was 11.5 months (range, 1 to 56 months). All the patients in first relapse and six patients in second remission received first remission marrow. The leukemia-free survival (LFS) for the patients in first relapse was 33%, with a median follow-up of 20 months. The LFS for the patients in second remission was 48% with a median follow-up of 26 months. The length of second remission exceeds the length of first remission in 14 patients. Considerable toxicity with hemorrhagic cystitis (four patients; none fatal), venoocclusive disease (four patients; one fatal), pneumonitis (four patients; one fatal), intracranial hemorrhage (two patients; two fatal) has occurred. There have been four procedure-related deaths (12%). Hematologic recovery was satisfactory for neutrophils (median time to 0.5 x 10(9)/L, 22 days [range, 11 to 101 days]), but very slow for platelets (median time to 50 x 10(9)/L, 62 days [range, 15 to 1,080 days]). This study suggests that the use of Bu/Cy with ABMT for patients beyond first remission in AML compares favorably with chemotherapy, and although the procedure-related mortality is acceptable, it is associated with protracted platelet recovery.

Acute Disease↗
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↗