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Biomedical subjects

K Atkinson

Publications and source records attributed to K Atkinson.

At least 109 records · Page 6Linked to original sources

T cell subpopulations defined by monoclonal antibodies after HLA-identical sibling marrow transplantation. II. Activated and functional subsets of helper-inducer and cytotoxic-suppressor subpopulations defined by two-colour fluorescence flow cytometry.

Two-colour fluorescence flow cytometry was utilized to define subsets within the Leu-3+ (T4+) helper-inducer and the Leu-2+ (T8+) cytotoxic-suppressor T cell subpopulations in recipients of unmanipulated HLA-identical sibling bone marrow transplants. The absolute number of activated cytotoxic-suppressor T cells expressing the HLA-DR and OKT10 activation antigens was increased. The proportion (or relative number) of cells bearing each of these activation antigens was also elevated in both the Leu-2+ and the Leu-3+ subpopulations, with up to 60% of Leu-2+ cells and up to 40% of Leu-3+ cells expressing them. Interestingly, absolute numbers of cells expressing two other activation-associated antigens, the interleukin-2 (IL-2) and transferrin receptors, were not increased in either major T cell subpopulation, although the relative number of Leu-3+ cells expressing both these surface structures was increased early post-transplant. Three putative functional subsets were also enumerated: the Leu-3+, Leu-8+ suppressor-inducer subset was depressed in absolute and relative numbers at most time points post-transplant. The Leu-4+, Leu-15+ suppressor-effector subset subpopulation was normal at all time points posttransplant, while the Leu-2+, 9.3+ cytotoxic precursor subset showed low relative and absolute numbers both early and late post-transplant. None of the abnormalities demonstrated in the present study was correlated with presence or absence of graft-versus-host disease. The study further demonstrates the heterogeneity of the abnormalities in the immune system after human marrow transplantation and lays the basis for functional studies involving these cell populations.

Adult

Second marrow transplants for recurrence of haematological malignancy.

Nine patients with haematological malignancy relapsed 3-32 months after receiving cyclophosphamide 120 mg/kg, 12-14 Gy fractionated total body irradiation and an HLA-identical sibling bone marrow transplant. They were reconditioned with melphalan 180-220 mg/m2 and retransplanted using the same donor and the same cyclosporin regimen as prophylaxis for graft-versus-host disease (GVHD). Three of the nine remain alive greater than 81, greater than 33, and greater than 36 months after second transplant. While the rate of marrow engraftment, the incidence of acute GVHD and the incidence of interstitial pneumonitis were similar after first and second transplants, the use of melphalan before second transplant was associated with increased nephrotoxicity and oropharyngeal mucositis. The present study shows that second narrow transplants are feasible, can produce prolonged remission of haematological malignancies and should be considered in appropriate patients who relapse after first marrow transplant.

Actuarial Analysis

PUVA therapy for drug-resistant graft-versus-host disease.

Ultraviolet irradiation is known to diminish the functional capacity of cells of the immune system. We have used ultraviolet A irradiation in combination with psoralen (PUVA) to treat three patients with drug-resistant graft-versus-host disease (GVHD) of the skin or mouth. Each of the three patients had received an HLA-identical sibling bone marrow transplant for haematological malignancy or severe aplastic anaemia. One patient developed acute GVHD of skin and mouth and two patients developed chronic GVHD of the mouth, which did not respond to conventional immunosuppressive drugs including cyclosporin and methyl prednisolone (all three patients) and anti-thymocyte globulin (two patients). PUVA irradiation to the skin was given at a dose of 0.75-1.25 J (joules) daily for four days per week and that to the mouth at 0.75 J daily four days per week. Before each treatment, 8-methoxypsoralen (0.6 mg/kg) was given orally as a photosensitizer. Each patient improved considerably and in each case the dosage of conventional immunosuppression was reduced. No flare was noted in the two patients with chronic GVHD of the mouth at 1 month after the end of treatment. PUVA irradiation is a useful therapeutic adjunct in GVHD affecting skin and mouth and appears to confer a steroid or cyclosporin sparing effect.

Acute Disease

Lack of correlation between nucleated bone marrow cell dose, marrow CFU-GM dose or marrow CFU-E dose and the rate of HLA-identical sibling marrow engraftment.

There was no correlation between the rate of marrow engraftment and the number of nucleated bone marrow cells infused into 50 HLA-identical sibling marrow graft recipients with haematological malignancy conditioned with cyclophosphamide and fractionated total body irradiation, and immunosuppressed with either cyclosporin (42 patients) or methotrexate (eight patients). Similarly, there was no correlation between the number of marrow CFU-GM or CFU-e infused into recipients immunosuppressed with cyclosporin. The data show that recipients of HLA-identical sibling marrow allografts conditioned with cyclophosphamide and total body irradiation require less than 3 X 10(8) nucleated bone marrow cells/kg recipient weight to ensure engraftment, and throw doubt on the relevance of measuring committed progenitor cells in the donor marrow to assess the likelihood of subsequent haemopoietic reconstitution after matched sibling transplantation.

Body Weight