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Biomedical subjects

H E Kay

Publications and source records attributed to H E Kay.

At least 19 recordsLinked to original sources

Risk factors for acute graft-versus-host disease.

Acute graft-versus-host disease (GvHD) is an important complication of bone marrow transplantation in humans. Risk factors are imprecisely defined and controversial. We analysed data from 2036 recipients of HLA-identical sibling transplants for leukaemia or aplastic anaemia to identify risk factors for GvHD. Analyses indicate that grading of GvHD can be reproducibly divided into absent or mild versus moderate to severe; 2-year actuarial probability was 54% (95% confidence interval 52-56%) for absent or mild and 46% (44-48%) for moderate to severe. Factors predictive of development of moderate to severe GvHD include donor/recipient sex-match (female----male greater than others, relative risk 2.0, P less than 0.001). This risk was markedly increased if female donors for male recipients were previously pregnant or transfused (relative risk 2.9, P less than 0.0001). Older patients were at increased risk of GvHD (relative risk 1.6, P less than 0.001), but the age gradient was modest, even the youngest patients had a substantial risk of GvHD and, if parous or transfused female----male transplants were excluded, age was not a significant risk factor. Cyclosporine or methotrexate were equally effective at preventing GvHD and were superior to no prophylaxis (relative risk 2.3, P less than 0.01). These data should be useful in estimating the risk of acute GvHD in an individual patient and in designing clinical trials to investigate methods to modify or prevent GvHD.

Acute Disease

Interstitial pneumonitis after bone marrow transplantation. Assessment of risk factors.

Data from 932 patients with leukemia who received bone marrow transplants were analyzed to determine factors associated with an increased risk of developing interstitial pneumonitis. Interstitial pneumonitis developed in 268 patients for a 2-year actuarial incidence of 35 +/- 4% (SD) and with a mortality rate of 24%. Six factors were associated with an increased risk: use of methotrexate rather than cyclosporine after transplantation (relative risk, 2.3; p less than 0.0002); older age (relative risk, 2.1; p less than 0.0001); presence of severe graft-versus-host disease (relative risk, 1.9; p less than 0.003); long interval from diagnosis to transplantation (relative risk, 1.6; p less than 0.002); performance ratings before transplantation of less than 100% (relative risk, 2.1; p less than 0.0001); and high dose-rates of irradiation in patients given methotrexate after transplantation (relative risk, 3.2; p less than 0.03). The risk of developing interstitial pneumonitis ranged from 8% in patients with none of these adverse risk factors to 94% in patients with all six. These findings may help to identify patients at high risk for this complication.

Adolescent

Mismatched family donors for bone-marrow transplantation as treatment for acute leukaemia.

35 patients were treated for acute myeloid leukaemia or acute lymphoblastic leukaemia with allogeneic bone-marrow grafts from a parent, child, or sibling who was mismatched at the major histocompatibility complex (MHC). 11 of these patients are alive at least 6 months after grafting, 5 of them after more than 2 years. Of the 15 patients aged under 20 at the time of the graft, 8 are alive and well 6 months to 3 years later. Cyclosporin A was given to all patients after grafting. 1 patient died of acute graft-versus-host disease and in 2 other cases this was a major factor in their death. Graft failure caused the death of 2 patients. 4 patients died of recurrent leukaemia. A fatal complication in 12 patients was pulmonary oedema, often associated with convulsions, intravascular haemolysis, and renal failure. Some of these patients had viral or bacterial infections, but in the majority the syndrome was not associated with demonstrable infection. This syndrome, in which the essential lesion appears to be vascular, was much more common in recipients of mismatched than matched grafts. 3 others died from lung disease in which infection was a factor.

Acute Disease

Bone marrow transplantation for acute myelogenous leukemia. Factors associated with early mortality.

Comprehensive data were reported to the International Bone Marrow Transplant Registry, Milwaukee, regarding 156 patients with acute myelogenous leukemia who were treated with allogeneic bone marrow transplantation between 1978 and 1980. The minimum observation period was 15 months after transplant and most deaths occurred within the first six months. Prognostic factors were evaluated for associations with early mortality or life-threatening complications. Most early deaths were due to infections, interstitial pneumonitis, and graft-v-host disease (GVHD). Multivariate analyses disclosed five factors with significant associations with early death or a major cause of early death: (1) disease status; (2) dose-rate of irradiation; (3) drug used to prevent GVHD; (4) severity of GVHD; and (5) dose of marrow cells. It is emphasized that several of the important prognostic factors are within the control of the referring physician or the transplant team.

Adolescent

Infections after bone marrow transplantation using cyclosporine.

The incidence of infection in 86 consecutive patients having bone marrow transplantation for acute or chronic myeloid leukemia, in a protocol in which cyclosporine was the main immunosuppressant, was low. Severe bacterial infections were infrequent and mostly caused by gram-positive cocci but early bacterial infection was often associated with severe graft-versus-host disease. Fungal infections were prevented by nystatin and amphotericin thus avoiding the difficult combination of cyclosporine and ketaconazole. Viral infections were no more common than in other series but, in patients with mismatched grafts, they tended to be associated with neurological complications clinically diagnosed as encephalitis.

Adolescent

Bone-marrow transplantation for acute leukaemia in first remission.

Between 1978 and 1980 133 patients with acute myelogenous leukaemia were given allogeneic bone-marrow transplants from an HLA-identical sibling and were followed up for at least a year. Pre-transplant preparation consisted of high-dose chemotherapy and/or radiation and post-transplant immune suppression consisted of methotrexate or cyclosporin-A. Data for 76 patients transplanted in first transplanted in either second to fourth remission, partial remission, or relapse. The 2-year actuarial survival-rate was 48% (95% CI, 36-60%) for patients transplanted in first remission and 30% 95% CI, 17-43%) for patients with more advanced disease (p = 0.037). Disease status at the time of transplantation was related to the probability of survival (p less than 0.02). The 2-year actuarial leukaemia recurrence-rate was 32% for patients transplanted in first remission and 50% for patients with more advanced disease (p = 0.0017). The probability of remaining in remission also was associated with disease status at time of transplantation (p less than 0.01). The incidence of graft-vs-host disease and interstitial pneumonitis was similar for patients transplanted in first remission and those transplanted later, and methotrexate and cyclosporin A were equally effective in modifying acute GVHD. These data indicate that prolonged survival can be achieved in approximately one-half of patients with acute myelogenous leukaemia given transplants of bone marrow from an HLA-identical sibling during their first complete remission.

Adolescent

Factors associated with interstitial pneumonitis after bone-marrow transplantation for acute leukaemia.

Data from 176 patients with acute leukaemia given allogeneic marrow transplants between Jan. 1, 1977, and Dec. 31, 1980, and reported to the International Bone Marrow Transplant Registry were analysed retrospectively for prognostic factors associated with the development of interstitial pneumonitis (IPn). The overall incidence of IPn was 20% (36/176), and the disease was fatal in 21 of the 36 cases (58%). Three of more than thirty prognostic factors studied seemed to be associated with a low risk of IPn--pretransplant total body irradiation at a dose-rate less than or equal to 5.7 cGy/min, when compared with higher dose-rates (p less than 0.001); post-transplant immunosuppression with cyclosporin-A, when compared with methotrexate (p less than 0.0003); and transplantation of cells from female donors into female recipients (p less than 0.0005). The low dose-rate of total body irradiation and the use of cyclosporin-A were considered as independent variables, but were confounded to the extent that it was not possible to determine if one or both factors were associated with a decreased incidence of IPn.

Blood Grouping and Crossmatching