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Biomedical subjects

K Atkinson

Publications and source records attributed to K Atkinson.

At least 37 records · Page 2Linked to original sources
PubMed1991

Chemotherapy compared with bone marrow transplantation for adults with acute lymphoblastic leukemia in first remission.

OBJECTIVE: To compare efficacy of intensive postremission chemotherapy with allogeneic bone marrow transplantation in adults with acute lymphoblastic leukemia (ALL) in first remission. DESIGN: Retrospective comparison of two cohorts of patients. SETTING: Chemotherapy recipients were treated in 44 hospitals in West Germany in two cooperative group trials; transplants were done in 98 hospitals worldwide. PATIENTS: Patients (484) receiving intensive postremission chemotherapy and 251 recipients of HLA-identical sibling bone marrow transplants for ALL in first remission. Patients ranged from 15 to 45 years of age and were treated between 1980 and 1987. MAIN RESULTS: Similar prognostic factors predicted treatment failure (non-T-cell phenotype, high leukocyte count at diagnosis, and 8 or more weeks to achieve first remission) of both therapies. After statistical adjustments were made for differences in disease characteristics and time-to-treatment, survival was similar in the chemotherapy and transplant cohorts: Five-year leukemia-free survival probability was 38% (95% CI, 33% to 43%) with chemotherapy and 44% (CI, 37% to 52%) with transplant. No specific prognostic group had a significantly better outcome with one treatment compared with the other (6% for the difference; CI, -3% to 15%). Causes of treatment failure differed: With chemotherapy, 268 (96%) failures were from relapse and 11 (4%) were treatment-related; with transplants, 43 (32%) failures were from relapse and 92 (68%) were treatment-related. CONCLUSIONS: These results suggest that bone marrow transplants currently offer no special advantage over chemotherapy for adults with acute lymphoblastic leukemia in first remission.

Adolescent↗
PubMed1991

In vivo administration of granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage CSF, interleukin-1 (IL-1), and IL-4, alone and in combination, after allogeneic murine hematopoietic stem cell transplantation.

BALB/c mice (H-2d) given 10 Gy total body irradiation (TBI) followed by 10(7) bone marrow (BM) and 10(6) spleen cells from C57BL/6 (H-2b) donor mice received recombinant cytokines intraperitoneally (IP) twice daily. The effect on neutrophil recovery rate, graft-v-host disease (GVHD), and survival was assessed. Four reagents were used: granulocyte-colony-stimulating factor (G-CSF), granulocyte-macrophage CSF (GM-CSF), interleukin-1 (IL-1) and IL-4, both alone and in combination. The most effective combination for increasing the circulating absolute neutrophil account (ANC) above the control value at day 7 posttransplant was the combination of G-CSF and IL-1 (mean ANC 2.4 +/- 1.6 x 10(9)/L as compared with control value of 0.07 +/- 0.05, P less than .02), followed by G-CSF alone (mean ANC 1.1 +/- 0.2, P less than .0001), the combination of GM-CSF plus IL-1 (mean ANC 0.8 +/- 0.3, P less than .002), and the combination of G-CSF plus GM-CSF (mean ANC 0.8 +/- 0.3, p less than .005). At day 10 posttransplant, the most effective combination in raising the ANC was the combination of G-CSF plus GM-CSF (mean ANC 7.5 +/- 2.3 as compared with control value of 3.5 +/- 1.1, P less than .01), followed by G-CSF alone (mean ANC 6.9 +/- 2.1, P less than .02). At the doses used, neither G-CSF nor GM-CSF had a deleterious effect on the incidence or severity of GVHD; indeed, GM-CSF was associated with improved survival. In contrast, IL-1 at doses greater than or equal to 100 ng twice daily caused marked early mortality, and there was a suggestion that IL-4 at doses of 500 ng twice daily resulted in increased late mortality, possibly owing to exacerbation of GVHD. This model appears to be of value for exploring the use of hematopoietic growth factors before they are used clinically in marrow allograft recipients.

Animals↗
PubMed1991

Non-animal alternative toxicity tests for detergents: genuine replacements or mere prescreens?

Non-animal toxicity tests and testing strategies for use in identifying the potential toxic hazard of chemicals and products, and in providing information for use in risk and safety assessment, are in the course of development, validation and evaluation. Possible replacement alternatives to the rabbit Draize eye irritancy test are discussed, and results obtained for two in-vitro tests developed by FRAME (the kenacid blue test and the neutral red release test), applied to 19 surfactants and 32 formulations, are discussed. It is concluded that there are now legal and moral requirements that relevant and reliable non-animal tests should be developed and accepted for use whenever possible.

Animal Testing Alternatives↗
PubMed1991

Percutaneous urinary diversion in gynecologic oncology.

During the 10-year period after 1979, percutaneous urinary diversion (PCUD) was performed on 35 patients whose mean age was 53.5 years (30-80 years). Twenty-one patients (60%) had Stage IIB-IV cervical cancer, 11 (31%) Stage IB-IIA cervical cancer, 2 (6%) Stage IB-II endometrial cancer, and 1 (3%) Stage IB vaginal cancer. All had radiological evidence of ureteric obstruction and 8 patients also had urinary tract fistulae. Serum creatinine levels were elevated in 24. Following diversion there was a significant fall in mean pretreatment creatinine levels from 482 mumol/liter (range, 70-1703 mumol/liter) to 131 mumol/liter (range, 60-290 mumol/liter; P less than 0.0001); those patients with normal creatinine levels prior to diversion also had a reduction in their levels. A significant fall in mean serum urea levels from 22.0 mmol/liter pre- to 11.9 mmol/liter post-PCUD (P less than 0.001) was also noted. Minor complications occurred and included hemorrhage, replacement/reinsertion, infection, and blockage. Median survival of the 35 patients after PCUD was 6 months (mean, 16.5 months). For the 11 with normal pretreatment renal function median survival was 16 months (mean, 41 months) compared to 2.5 months (mean, 5.1 months) for those with elevated pretreatment serum creatinine levels. Median survival with untreated malignancy was 7 months (mean, 19.6 months) and 6 months (mean, 12.3 months) in patients with previously treated cancer. PCUD is indicated in previously untreated patients with gynecologic cancer so that primary therapy can be instituted. The role of urinary diversion in patients with previously treated cancer must be individualized. Palliative diversion is appropriate in selected patients where additional therapy is expected to prolong life, where symptom control is needed, or to allow the patient to return home for a significant proportion of the remainder of life.

Adult↗
PubMed1991

Costs of bone marrow transplants using unrelated donors.

Bone marrow transplantation is an expensive treatment, rationed primarily by the availability of donors. Recruiting potential unrelated bone marrow donors to a register would add not only to the cost, but also to the volume, of transplantation. Proposals to establish such registries have thus been subject to rigorous financial scrutiny. In Australia, 3 alternative estimates suggest that approximately 200 patients, otherwise suitable for bone marrow transplantation, do not receive transplants because they have no suitable related donor. The population of Australia is approximately 16 million. The alternatives for these patients are thus chemotherapy or unrelated bone marrow transplantation. The costs of chemotherapy and transplantation have been directly compared in 1 trial of treatment for acute nonlymphoblastic leukaemia. The cost per year of life saved was approximately the same for the 2 treatments, with better patient survival from transplantation. The estimated cost difference in both the United States and Australia, between the policy extremes of no patients transplanted, and all transplanted, was between 1.3-2.4% of the total costs of managing these patients. The cost of searching existing registers for unrelated donors for Australian patients, averages A$24,000-28,000 to the point of a successful donor procedure. The cost of establishing and maintaining an Australian Register of a size predicted to find donors for half of the potential recipients, has been estimated at A$ 10,000 per donor procedure. The decision to proceed with unrelated bone marrow transplantation commits resources that are currently used by the alternative therapies. It is thus important to monitor both the costs and effects of the new approach.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Agents↗
PubMed1991

Prophylactic use of ganciclovir in allogeneic bone marrow transplantation: absence of clinical cytomegalovirus infection.

Ganciclovir was given prophylactically to 25 patients receiving allogeneic bone marrow transplants for haematological malignancy. Patients who were seropositive for cytomegalovirus (CMV) pre-transplant were given ganciclovir both pre- and post-transplant. Those who were CMV seronegative, but who received marrow from a CMV seropositive donor, received ganciclovir post-transplant. No nonhaemopoietic toxicity was observed. Toxicity was restricted to late reversible haematological toxicity in four of the 19 evaluable patients (one thrombocytopenia, one pancytopenia, two leucopenia). No CMV interstitial pneumonitis (IP) was observed, nor were any other clinically manifest CMV infections detected. Sixteen patients remain alive at greater than 84 to greater than 518 d post-transplant. In a retrospective comparison of 152 recipients of allogeneic transplants for haematological malignancy not given prophylactic ganciclovir, and in whom either the recipient or the donor or both were CMV seropositive, the incidence of all clinically manifest CMV infections was 23% (P = 0.02) and that of CMV IP 17% (P = 0.05). If only patients in the study group and the control group receiving the same cyclosporin/short methotrexate prophylactic immune suppressive regimen, the same prophylactic acyclovir regimen and the same CMV and leucocyte-filtered blood product transfusion strategy were considered, the incidence of all clinically manifest CMV infections in the control group was 24% (P = 0.01) and that of CMV IP 13% (P = 0.07). Ganciclovir appears to reduce the incidence of CMV infections in allogeneic marrow transplant recipients even in those given immune suppressive regimens associated with adequate control of acute graft-versus-host disease.

Acute Disease↗
PubMed1991

The toxicity of busulphan and cyclophosphamide as the preparative regimen for bone marrow transplantation.

The toxicity of the conditioning regimen of high dose busulphan (Bu) (16 mg/kg) and cyclophosphamide (Cy) (120 mg/kg) has been compared to cyclophosphamide (Cy) (120 mg/kg) and fractionated total body irradiation (TBI) 12-14 Gy. Since 1985, 67 patients have received conditioning of Bu and Cy for HLA-identical sibling bone marrow transplants. 166 patients have received Cy and TBI since 1981. Veno-occlusive disease of the liver occurred in 19% in the Bu-Cy group and was fatal in 1/12 cases, but only in 1.3% of Cy-TBI group (P less than 0.0005) and was fatal in 1/2. 30% of evaluable patients developed haemorrhagic cystitis in the Bu-Cy group and 14% in the Cy-TBI group (P = 0.008). A multiple logistic regression analysis demonstrated the preparative regimen as the only significant risk factor for the development of veno-occlusive disease or haemorrhagic cystitis. Interstitial pneumonia was diagnosed in 12/56 evaluable patients (21%) in the Bu-Cy group and was fatal in 75%. It occurred in 39/137 evaluable patients (28%) in the Cy-TBI group with a 54% case mortality. Within the Bu-Cy group, the incidence of veno-occlusive disease and haemorrhagic cystitis was similar in chronic myeloid leukaemia (CML) and acute leukaemia (AL) groups, but there was a significant (P = 0.003) incidence of interstitial pneumonia in the CML group 36% as compared to 7% in the AL group. Preparative regimen and age were significant risk factors in the development of interstitial pneumonia in patients with CML. A flexural and acral rash ranging from pigmentation to severe erosion was noted in the Bu-Cy group, but not in the Cy-TBI group. Thus, veno-occlusive disease, haemorrhagic cystitis and cutaneous changes were more common in patients receiving Bu-Cy. Interstitial pneumonia was more common in patients receiving Bu-Cy for CML than for AL.

Adolescent↗
PubMed1991

GM-CSF after allogeneic bone marrow transplantation: accelerated recovery of neutrophils, monocytes and lymphocytes.

Ten patients given HLA-identical sibling marrow transplants for lymphoid malignancy received recombinant human granulocyte macrophage-colony stimulating factor (GM-CSF) from day 7 to day 13 inclusive post transplant. Patients were prepared for transplantation with busulphan 16 mg/kg and cyclophosphamide 120 mg/kg. Immunosuppression to minimise the risk of graft-versus-host disease (GVHD) was cyclosporin/short methotrexate. Results were compared with a historical control group of patients (n = 16) given matched sibling transplants for acute leukaemia and receiving the same immune suppressive regime but not given GM-CSF. Recovery of total white cells, neutrophils, monocytes and lymphocytes was more rapid in the GM-CSF recipients (p less than 0.02). There was a suggestion of a decrease in non-viral infections in the first 30 days in the GM-CSF recipients (p = 0.09). There was, however, no significant difference in the severity of oropharyngeal mucositis nor in the duration of the transplant hospitalisation. Surprisingly, the severity of acute GVHD was higher in the GM-CSF recipients with six of eight evaluable patients having grade II-IV acute GVHD (p = 0.003). Two GM-CSF recipients developed a fluid retention/capillary leak syndrome. These findings indicate a need for caution in the use of GM-CSF after allogeneic marrow transplantation.

Adolescent↗
PubMed1991

A prospective randomised trial of cyclosporin and methotrexate versus cyclosporin, methotrexate and prednisolone for prevention of graft-versus-host disease after HLA-identical sibling marrow transplantation for haematological malignancy.

A prospective randomised trial was performed in patients given HLA-identical sibling bone marrow transplants for haematological malignancy comparing the combination of cyclosporin and methotrexate (CM) (n = 20) with the combination of cyclosporin, methotrexate and prednisolone (CMP) (n = 21) as prophylaxis for graft-versus-host disease (GVHD). There was no significant differences between the two arms for the incidence of acute GVHD grades I-IV, acute GVHD grades II-IV, chronic GVHD, interstitial pneumonitis, relapse, survival and disease-free survival. The actuarial incidence of acute GVHD grades II-IV in the CMP group was 10% and in the CM group 15% (ns). The incidence of leukaemic relapse in good risk patients was 42% in the CMP group and 40% in the CM group (ns), although the majority of these relapses were cytogenetic relapses only in patients with chronic myeloid leukaemia. The incidence of acute GVHD grades II-IV in both arms of the current trial was significantly lower than in our previous trial comparing cyclosporin and methotrexate as single agents. Leukaemic relapse is now the principal cause of treatment failure in this patient population. We conclude that prednisolone should not be included as part of the prophylactic GVHD regime and that further improvement in therapeutic outcome is dependent upon better control of the underlying malignancy.

Actuarial Analysis↗
PubMed1991

An acute pulmonary syndrome possibly representing acute graft-versus-host disease involving the lung interstitium.

An acute pulmonary syndrome possibly representing acute graft-versus-host disease (GVHD) involving lung interstitium occurred in a patient given an allogeneic bone marrow transplant for haematological malignancy. He presented at day 34 with acute GVHD of skin and bowel, and this was associated with cough, dyspnoea and an asymmetrical change on chest X-ray. Lung biopsy demonstrated an interstitial and peribronchial lymphocytic infiltrate and acute bronchial epithelial degeneration. He responded symptomatically to high dose intravenous methylprednisolone. The radiological change resolved completely. This case, thought to represent GVHD involving lung interstitium, emphasizes the need for tissue procurement in the management of non-bacterial lung disease after marrow transplantation.

Acute Disease↗
PubMed1991

Bladder irrigation does not prevent haemorrhagic cystitis in bone marrow transplant recipients.

Thirty-four patients receiving allogeneic bone marrow transplants as treatment for haematological malignancy were prospectively randomized to receive or not to receive bladder irrigation by indwelling urinary catheter during preparation for transplant. Twenty-two patients received busulphan and cyclophosphamide, four received busulphan, cyclophosphamide and irradiation, and eight received cyclophosphamide and total body irradiation. The actuarial incidence of haemorrhagic cystitis in those randomized to receive bladder irrigation was 48% for the whole group and 52% in those receiving busulphan and cyclophosphamide only. In those randomized not to receive bladder irrigation the incidence of haemorrhagic cystitis was 29% for the overall group and 38% in those receiving busulphan and cyclophosphamide. There was no statistically significant difference between the two groups. We conclude that bladder irrigation does not minimize the risk of haemorrhagic cystitis in this patient population.

Adolescent↗
PubMed1990

Risk factors for chronic graft-versus-host disease after HLA-identical sibling bone marrow transplantation.

Chronic graft-versus-host disease (GVHD) is an important complication of bone marrow transplantation. We analyzed risk factors for chronic GVHD in 2,534 recipients of HLA-identical sibling transplants surviving at least 90 days after transplantation. The actuarial probability of developing chronic GVHD within three years posttransplant was 46% +/- 3% (95% confidence interval). The most important risk factor for chronic GVHD was acute GVHD. The 3-year probabilities of chronic GVHD were 28% +/- 3%, 49% +/- 5%, 59% +/- 6%, 80% +/- 9%, and 85% +/- 15% for persons with grades 0, I, II, III, and IV acute GVHD, respectively (P less than .0001). Among patients with no or grade I acute GVHD, recipient age greater than 20 years, use of non-T-cell depleted bone marrow, and alloimmune female donors for male recipients predicted a higher risk of chronic GVHD. When all three adverse risk factors were present, the probability of chronic GVHD was 62% among persons with no prior acute GVHD and 85% among those with grade I acute GVHD. Among patients with grade II through IV acute GVHD, no other risk factor predicted chronic GVHD. These data identify individuals who might benefit from treatment strategies aimed at changing the incidence of chronic GVHD.

Acute Disease↗
PubMed1990

Serum erythropoietin changes in autologous and allogeneic bone marrow transplant patients.

Sequential changes in serum erythropoietin (sEPO) levels were measured by radioimmunoassay in six patients receiving autologous rescue (AR) and 11 patients receiving an allogeneic bone marrow transplant (BMT) for malignant disease. Longitudinal studies showed an inverse relationship between sEPO and haemoglobin levels in the autologous rescue and allogeneic transplant patients throughout the 130 d post-transplant study period. Early post-conditioning EPO responses were normal for the haemoglobin level in both groups, but after day 14 post-transplant, erythropoietin production in response to anaemia became impaired in one autologous rescue patient and eight of the 11 allogeneic transplant patients. There was no clear association between late impairment of sEPO production and conditioning therapy, infection, graft-versus-host disease, immunosuppressive therapy or serum creatinine. Blood transfusion requirements were similar for both groups in the first month after transplantation, but from days 31 to 90 post-transplant, BMT patients required an average of 5.5 units per patient compared with 1 unit per patient for the autologous group. Marrow transplant procedures do not affect early EPO responses but may diminish late responses. The potential value of exogenous rHuEPO in hastening engraftment and decreasing transfusion requirements, particularly for those patients who appear to have impaired EPO responses, remains to be shown by clinical trials.

Adolescent↗
PubMed1990

A novel human leucocyte surface membrane antigen defined by murine monoclonal antibody.

A murine monoclonal antibody has been produced which identifies a novel human leucocyte differentiation antigen. The antibody, designated WM-66, of IgM subclass, was cytolytic with human complement. WM-66 was shown to react with virtually all normal T and B lymphocytes from peripheral blood and lymphoid tissues, as well as blood monocytes and approximately 40% of bone marrow mononuclear cells. The antibody also bound to the majority of cases of chronic B-cell malignancies, including chronic lymphatic leukaemia and non-Hodgkin's lymphoma, but not to cases of acute leukaemia or to the majority of leukaemic and lymphoblastoid cell lines. WM-66 also reacted with epithelium of bronchus and salivary gland ducts. A single band of relative molecular mass 65,000 Daltons was immunoprecipitated from membrane extracts of normal lymphocytes and the B-cell line Daudi. Treatment of a number of WM-66-negative B-cell lines with neuraminidase resulted in WM-66 binding, indicating that the antigen exists in a covert form masked by sialic acid residues on a wider spectrum of cell types than was initially apparent. The reactivity pattern of WM-66 indicates that it recognises a previously undescribed surface membrane molecule with broad non-lineage-specific distribution on leucocytes. This has recently been confirmed at the Fourth International Workshop on Human Leucocyte Differentiation Antigens. Although the biological function of the molecule recognised by WM-66 is unknown, the lytic properties of the antibody suggest a possible in vivo therapeutic role as an immunosuppressant or for treatment of lymphoid malignancy.

Animals↗