PubMed Health⌕ Search

Biomedical subjects

K Atkinson

Publications and source records attributed to K Atkinson.

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

Lack of efficacy of a short ex vivo incubation of human allogeneic donor marrow with recombinant human GM-CSF prior to its infusion into the recipient.

Ten patients with haematological malignancy receiving allogeneic transplants from donors other than HLA-identical siblings were prepared for marrow transplantation with antithymocyte globulin, cyclophosphamide 120 mg/kg and fractionated total body irradiation 12 Gy, and were given cyclosporin, methotrexate and prednisolone as prophylaxis against graft-versus-host disease post-transplant. The harvested T replete donor marrow was incubated with recombinant human (rh) GM-CSF 10 micrograms/ml (supersaturating concentration) for 1 h at 37 degrees C on a gently shaking rocker platform. After incubation the marrow was washed twice in 5% human serum albumin/normal saline and infused into the recipient. Before and after incubation, there was no significant difference in cell viability, the nucleated cell count, the CFU-GM content nor the proportion of cells in S phase of the cell cycle. Compared with a preceding cohort of 16 patients treated on the same protocol but in whom the marrow was not incubated with GM-CSF, there was no difference in the incidence of graft failure or rate of neutrophil recovery.

Adult↗
PubMed1994

Bone marrow transplantation in Australia during 1992. Australian Bone Marrow Transplant Recipient Data Registry.

Australia has a population of 17.5 million people distributed in six states and two territories. The first allogeneic transplants were performed in the early 1970s. There are now 19 hospitals registered with the Australian Bone Marrow Transplant Recipient Data Registry. In 1992 a total of 478 transplant procedures were carried out, of which 228 were allografts and 250 were autografts. The principal indications for allografting were acute leukaemia and chronic myeloid leukaemia; the principal indications for autografting were non-Hodgkin's lymphoma, acute myeloid leukaemia and myeloma. In general the patterns of indications and donor use do not differ from those seen in most European countries and North America.

Acute Disease↗
PubMed1993

Choice of pretransplant treatment and timing of transplants for chronic myelogenous leukemia in chronic phase.

We analyzed the outcome of 450 HLA-identical sibling bone marrow transplants for chronic myelogenous leukemia (CML) in chronic phase performed between 1985 and 1990 and reported to the International Bone Marrow Transplant Registry (IBMTR). All patients received either hydroxyurea (n = 292) or busulfan (n = 158) to treat their CML before transplant. The median interval between diagnosis and transplant was 10 months (range, 1 to 191). Patients treated with hydroxyurea had a higher probability (95% confidence interval) of leukemia-free survival (LFS) at 3 years than those treated with busulfan (61% [51% to 70%] v 45% [36% to 55%], P < .0003). Probability of LFS was also higher in patients transplanted within 1 year of diagnosis (61% [53 to 68%] v 47% [38% to 57%], P < .001). After adjustment for patient and transplant covariables in a multivariate analysis, prior chemotherapy and duration of disease pretransplant were independently associated with LFS. These data support the use of hydroxyurea rather than busulfan and transplant within 1 year of diagnosis for patients with CML and an HLA-identical sibling.

Actuarial Analysis↗
PubMed1993

The role of duplex ultrasound arterial imaging in patients with penetrating extremity trauma.

OBJECTIVE: To investigate the role of color-flow duplex ultrasound vascular imaging in screening patients for potential arterial injuries following penetrating trauma of the extremities. DESIGN: In this prospective study, patients with penetrating trauma in proximity to major peripheral vessels but without signs of arterial injury underwent color-flow duplex imaging. Patients with abnormal color-flow duplex examination results were then studied with angiography, and the results of the two studies were compared. In patients who presented with signs of arterial injury, immediate operative exploration and/or angiography was performed. SETTING: An urban trauma center. PATIENTS: Patients entering the trauma center with penetrating trauma between April 1991 and December 1992. RESULTS: Seventy-seven patients with 86 extremity injuries were initially screened with color-flow duplex imaging. Four patients had positive study results, and all injuries were confirmed with angiography (100% true positive). No missed arterial injuries were detected in clinical follow-up. CONCLUSIONS: Color-flow duplex imaging reliably detects occult arterial injuries and may also have a role in following up minor injuries treated without surgery.

Adolescent↗
PubMed1993

A quantitative polymerase chain reaction assay for interleukin 5 messenger RNA.

The quantitation of low abundance messenger (m)RNA species such as that for interleukin 5 (IL-5) cannot be achieved by Northern blotting. Polymerase chain reaction (PCR) technology can be used to overcome this paucity of target molecules, but in its standard format it is semiquantitative. We describe the synthesis, purification, and use of a synthetic IL-5 mRNA (cRNA) molecule which, when included in the PCR reaction, enabled the amplification of IL-5 mRNA molecules from clinical samples to be made quantitative. A stringent protocol involving analysis of the purified transcript by PCR (to ensure its freedom from template molecules) is required. Preliminary experiments indicate that IL-5 mRNA levels are elevated in asthmatics.

Base Sequence↗
PubMed1993

Changing results of HLA-identical sibling bone marrow transplantation in patients with haematological malignancy during the period 1981-1990.

During the years 1981-90 inclusive 227 patients with haematological malignancy received an HLA-identical sibling first transplant at St Vincent's Hospital, Sydney. Recipients with acute leukaemia in first remission or chronic myeloid leukaemia in first chronic phase were analysed as good risk, and those beyond these stages, as poor risk patients. Good risk patients transplanted in the years 1986-90 (n = 52) showed improved actuarial survival (74%) compared to those (n = 58) transplanted during 1981-85 (37%, p = 0.01). There was a suggestion that leukaemia-free survival was also improved in those transplanted during the later time period (62% versus 36%, p = 0.07). In contrast, poor risk patients transplanted during 1986-90 (n = 55) appeared to have worse leukaemia-free survival (15%) compared to those transplanted during 1981-85 (n = 62) (22%, p = 0.09). The incidence of acute graft-versus-host disease (GVHD) grades I-IV in all patients was 94% in those transplanted during 1981-85 (n = 120) and 86% in those transplanted during 1986-90 (n = 107) (p = 0.002). The incidence of acute GVHD grades II-IV was 37% during 1981-83, 20% during 1984-86, and 28% during 1987-90 (p = 0.1). The decrease in incidence and severity of acute GVHD correlated with the introduction of the cyclosporin/short methotrexate regimen in our practice. The incidence of cytomegalovirus (CMV) pneumonitis was 18% in 1981-85, and 11% in 1986-90 (p = 0.09). In 1989 and 1990 no cases of CMV pneumonitis occurred.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1993

Unrelated volunteer bone marrow transplantation: initial experience at St Vincent's Hospital, Sydney.

BACKGROUND: Only 30% of patients with leukaemia have an HLA-compatible family member able to act as a marrow donor. The recent development of volunteer bone marrow donor registries has supplied HLA-matched donors for a number of such individuals. AIMS: To define the problem and outcome of the first cohort of patients given HLA-matched unrelated volunteer bone marrow transplants at St Vincent's Hospital, Sydney. METHODS: Post transplant outcome of patients with advanced leukaemia given HLA-identical unrelated donor marrow transplants was compared to that of patients transplanted concurrently from HLA-identical sibling donors, in terms of survival, leukaemia-free survival, incidence and severity of acute graft-versus-host disease (GVHD), duration of neutropenia, incidence of infection and duration of transplant hospitalisation. RESULTS: Sixteen patients with advanced leukaemia and without a histocompatible family member donor received unrelated donor bone marrow transplants. Actuarial survival at two years post transplant was 30%. Actuarial survival of 23 recipients of HLA-identical sibling bone marrow transplants with advanced leukaemia transplanted during the same time period was 17% (not significant). Actuarial disease free survival at two years was 30% and 13% respectively. Three of five long term survivors of the unrelated transplants had chronic myeloid leukaemia in blastic transformation at the time of transplant; thus blastic transformation should not preclude consideration of unrelated marrow transplantation. Recipients of unrelated allografts had a higher incidence of acute GVHD which occurred earlier and with greater severity than in recipients of sibling allografts, a longer duration of post transplant neutropenia (24 days to reach 0.5 x 10(9)/L versus 19.5, p = 0.07), a higher frequency of infection in the first 100 days post transplant (p = 0.0004) and a longer duration of transplant hospitalisation (p = 0.04). Transplant-related complications were the commonest cause of death in the unrelated donor recipients, while leukaemic recurrence was the commonest single cause of death in the HLA-identical sibling recipients. Improvements are needed in prophylaxis of infection and in prevention and treatment of acute GVHD in recipients of unrelated donor transplants. Nevertheless, this modality provides curative treatment for patients with otherwise incurable haematological malignancies and should no longer be considered experimental.

Adult↗
PubMed1993

Treatment of chronic myelogenous leukemia with allogeneic bone marrow transplantation after preparation with busulfan and cyclophosphamide (BuCy2): an update.

Allogeneic bone marrow transplantation (BMT) has been shown to result in long-term disease-free survival in patients with leukemia. However, the utility of this treatment approach is limited by treatment-related morbidity and mortality. We present an update of a study in which a BMT preparative regimen consisting of a 4-day course of busulfan and a 2-day course of cyclophosphamide (BuCy2) was used in patients with chronic myelogenous leukemia. Patient survival depended on disease stage, with a 58% survival rate for patients in first chronic phase, 41% for those in accelerated phase, and 25% for those in the blast transformation stage. There was a significant difference in patient survival between those who received transplants within 1 year of diagnosis and those who received transplants more than 1 year after diagnosis (70% v 40%). This difference appeared to be due to the extent of previous exposure to busulfan. The overall mortality rate in this study was 46%. We conclude that the BuCy2 preparative regimen is similar in effectiveness to regimens that include total body irradiation and results in comparable levels of transplant-related mortality. Our results strongly indicate that patients with chronic myelogenous leukemia who receive BMT within the first year after diagnosis have a significantly better clinical outcome than those who receive BMT later in the course of the disease.

Adolescent↗
PubMed1993

Apparent cure of rheumatoid arthritis by bone marrow transplantation.

We describe the induction of sustained remissions and possible cure of severe erosive rheumatoid arthritis (RA) by bone marrow transplantation (BMT) in 2 patients. BMT was used to treat severe aplastic anemia which was caused by gold in one case and D-penicillamine in the other. In the 8 and 6 years since the transplants (representing 8 and 4 years since cessation of all immunosuppressive therapy, respectively), the RA in each case has been completely quiescent. Although short term remission of severe RA following BMT has been reported, these are the first cases for which prolonged followup has been available. This experience raises the question of the role of BMT itself as a therapeutic option for patients with uncontrolled destructive synovitis.

Adult↗
PubMed1993

Production of a functional single-chain Fv fragment from the pan-leukocyte antibody WM65 using splicing by asymmetric PCR.

A method of assembly of a single-chain Fv fragment is described, whereby asymmetric polymerase chain reactions (APCR) and primer extension were used to join immunoglobulin heavy and light chain variable region genes via a linker sequence. In this procedure heavy and light chain genes, together with a linker gene containing complementary sequences, were amplified by APCR to generate single-stranded products. The single stranded heavy or light chain genes were hybridized to the relevant single-stranded link product, and extended to produce double-stranded heavy-link and link-light genes. These genes then underwent another round of APCR, resulting in two single-stranded genes (heavy-link and link-light) containing extensive overlapping sequences. Hybridization and extension of these two single-stranded products allowed the formation of the complete heavy chain-link-light chain double-stranded product. Using this method, a functional single-chain Fv fragment based on the pan-leukocyte antibody WM65 was expressed and purified from E. coli. This method of immunoglobulin gene assembly by polymerase chain reaction (PCR) offers an alternative to the current methods of the genetic engineering of antibody fragments.

Antibodies↗
PubMed1992

Bone marrow transplantation.

Over the last 20 years allogeneic bone marrow transplantation from an HLA-identical sibling donor has become the treatment of choice for a number of human haematological malignancies, severe aplastic anaemia, some congenital diseases of the immune and haemopoietic systems, and some inborn errors of metabolism. Recently, the successful introduction of HLA-matched unrelated donor transplants, convenient T cell depletion technology, combination immunosuppressive therapy to minimise graft-versus-host disease, blood products that are seronegative for cytomegalovirus, effective antiviral agents, and cloned haemopoietic and immune system growth factors have markedly increased the scope of bone marrow transplantation. Additionally, autologous transplantation appears to have promise especially in lymphoma and breast cancer.

Bone Marrow Transplantation↗
PubMed1992

Treatment of chronic myeloid leukemia with allogeneic bone marrow transplantation after preparation with BuCy2.

One hundred fifteen patients with chronic myelocytic leukemia (CML) were administered busulphan 4 mg/kg for 4 days and cyclophosphamide 60 mg/kg on each of 2 days (BuCy2) followed by allogeneic bone marrow transplantation from histocompatible sibling donors. For 62 patients in chronic phase, 26 in accelerated phase, and 27 in blast transformation, the actuarial survival at 3 years was 58%, 41%, and 25%, respectively. Actuarial probability of relapse was 3%, 12%, and 27%, respectively. Only two patients in chronic phase showed a transient cytogenetic relapse and one of these died from subsequent transplant-related complications, whereas the other remains cytogenetically normal 697 days posttransplant. Patients who were transplanted within 1 year of diagnosis in chronic phase had a survival of 70% compared with 40% when transplanted beyond 1 year from diagnosis. This significant difference in survival was due to transplant-related complications and was correlated with previous exposure to high doses of busulphan. This study indicates that BuCy2 is a useful conditioning regimen for marrow transplantation in patients with CML and results in similar survival statistics and transplant-related mortality as would be expected with conditioning regimens containing total body irradiation. It is possible that relapse after BuCy2 may be lower than expected with regimens containing total body irradiation, but larger analyses are required.

Adolescent↗
PubMed1992

Bone marrow transplants may cure patients with acute leukemia never achieving remission with chemotherapy.

About 30% of adults with acute lymphoblastic leukemia (ALL) and 20% to 40% of children and adults with acute myelogenous leukemia (AML) never achieve remission, even with intensive chemotherapy. Most die of resistant leukemia, often within 6 months or less. In this study of 126 patients with resistant ALL or AML, allogeneic bone marrow transplants from HLA-identical siblings produced remissions in 113 of 115 (98%) evaluable patients. The 3-year probability of leukemia-free survival was 21% (95% confidence interval, 15% to 29%). Leukemia-free survival was similar in ALL (23%, 12% to 40%) and AML (21%, 14% to 31%). Only 3 of 27 patients at risk relapsed more than 2 years posttransplant.

Adolescent↗
PubMed1992

Bone marrow transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia.

Philadelphia chromosome (Ph1)-positive acute lymphoblastic leukemia (ALL) has a poor prognosis when treated with conventional chemotherapy. We analyzed the outcome of 67 HLA-identical sibling bone marrow transplants (BMTs) for Ph1-positive ALL reported to the International Bone Marrow Transplant Registry (IBMTR). Twenty-one of 67 (31%) transplant recipients survived in continuous complete remission more than 2 years after transplant. Two-year actuarial probabilities (95% confidence interval) of leukemia-free survival were 38% (23% to 55%) for 33 patients transplanted in first remission, 41% (23% to 61%) for 22 patients transplanted after relapse, and 25% (9% to 53%) for 12 patients failing to achieve remission with conventional chemotherapy. These data indicate that transplants are effective treatment for Ph1-positive ALL.

Adolescent↗
PubMed1992

Lung dose rate and interstitial pneumonitis in total body irradiation for bone marrow transplantation.

The effect of dose rate to the lungs and development of interstitial pneumonitis (IP) was evaluated in 114 bone marrow transplant patients receiving fractionated total body irradiation (TBI) (1200 rads TD in 6 fractions twice daily over 3 days) as part of their pre-conditioning regimen. The tumour dose (TD) was calculated as the mean lung dose as previously described (1). A 6MV linear accelerator at a mid-line dose rate of 7.5 rads/minute was used between March 1981 and June 1985 and a Co-60 source at 5 rads/minute thereafter. This resulted in a range of dose rates to the lung of between 6.9 and 8.9 rads/minute and 2.9 and 6.5 rads/minute respectively. In the majority of patients the aetiology of IP was investigated by lung biopsy with histology and culture. There was no statistically significant difference in the incidence of IP over the two sets of dose rates. Our study suggest that the incidence of IP using fractionated TBI is not influenced by dose rates below 8.9 rads per minute.

Adolescent↗
PubMed1992

Fungal Pseudoallescheria boydii lung infiltrates unresponsive to amphotericin B in leukaemic patients.

The management of patients with acute leukaemia is often complicated by serious fungal infections, especially of the lungs. The outcome of therapy has historically depended on the early use, efficacy and toxicity of amphotericin B. Pseudoallescheria boydii is an uncommon cause of such infections but as it is more often resistant to amphotericin B early identification may enable the prompt use of alternative and newer antifungal agents. Here we report our experience and review the literature in three cases of P. boydii infection in patients with leukemia, showing unique features such as childhood and central nervous system disease, positive blood cultures and response to itraconazole.

Adolescent↗
PubMed1992

Radiation-free preparation for allogeneic bone marrow transplantation in adults with acute lymphoblastic leukemia.

PURPOSE: The study was undertaken to investigate the effectiveness of allogeneic bone marrow transplantation from HLA-identical siblings after preparation with busulfan and cyclophosphamide in adults with acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: Thirty-nine patients aged 15 to 42 years underwent transplantation at three different centers from November 1984 through November 1990. All patients received 16 mg/kg busulfan and 120 mg/kg cyclophosphamide as preparative therapy. Cyclosporine plus methotrexate or cyclosporine plus corticosteroids with or without methotrexate were given for prevention of graft-versus-host disease (GVHD). RESULTS: Twelve patients died of treatment-related complications, 12 patients relapsed, and 15 patients are leukemia-free survivors. For 27 patients in group 1 (first remission, second remission, first relapse), the estimated leukemia-free survival (LFS) rate is 42.3% (95% confidence interval [CI], 22.9% to 71.7%) at 3 years. For 12 patients with more advanced disease (group 2), the 1-year LFS rate is 13.5% (95% CI, 0% to 37.1%). Chronic GVHD occurred at an estimated incidence of 63.3% and developed significantly more frequently among patients who received corticosteroids for prevention of acute GVHD. Chronic GVHD was associated with a significantly lower incidence of relapse and with improved LFS rates. CONCLUSION: LFS rate in this study is comparable to that obtained with radiation-containing regimens; however, the effectiveness of this preparative regimen in ALL requires further study.

Actuarial Analysis↗