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Biomedical subjects

K Atkinson

Publications and source records attributed to K Atkinson.

At least 91 records · Page 5Linked to original sources
PubMed1987

Avascular necrosis of the femoral head secondary to corticosteroid therapy for graft-versus-host disease after marrow transplantation: effective therapy with hip arthroplasty.

Of 50 patients surviving 2 years or longer after HLA-identical sibling bone marrow transplantation for haematological malignancy or severe aplastic anaemia, five developed avascular necrosis of the femoral head. All had previously received corticosteroid therapy post-transplant for graft-versus-host disease. Median day of onset of symptoms was 545 days post-transplant (range 249-731). Clinical, radiological and radionuclide findings were typical of osteonecrosis. One patient has had bilateral hemiarthroplasties and one total hip replacements performed, both with excellent results. Bilateral arthroplasties are planned for a third patient but, interestingly, the disease process in the other two patients has been relatively mild with no progression over a period of greater than 256 and greater than 825 days, respectively. Since one patient had as little as 14 days treatment with prednisone, this complication should be borne in mind when designing prophylactic regimens for minimisation of GVHD that include corticosteroids.

Adrenal Cortex Hormones↗
PubMed1987

Late onset transfusion-dependent anaemia with thrombocytopenia secondary to marrow fibrosis and hypoplasia associated with chronic graft-versus-host disease.

Late onset transfusion-dependent anaemia is very rare in the presence of sustained engraftment after HLA-identical sibling bone marrow transplantation. The only previously described consistent cause is pyridoxine-responsive sideroblastic anaemia. We describe here a second cause, marrow hypoplasia and fibrosis, occurring in association with extensive chronic graft-versus-host disease (GVHD). A 20-year-old Caucasian male who received cyclophosphamide and fractionated total body irradiation followed by an unmanipulated HLA-identical sibling marrow transplant from his sister for acute nonlymphoblastic leukaemia in first remission developed chronic GVHD of the skin and mouth at day 101 post-transplant. At day 689 post-transplant, he developed leuco-erythroblastic anaemia with thrombocytopenia, due to patchy marrow hypoplasia and fibrosis. Between days 689 and 1987 post-transplant he received 71 units of packed red cells, requiring transfusion approximately monthly. He remains well although still on prednisone for chronic GVHD of skin and is receiving desferrioxamine 4 g five nights/week i.v. as prophylaxis for iron overload.

Adult↗
PubMed1986

Hemopoietic progenitor cell function after HLA-identical sibling bone marrow transplantation: influence of chronic graft-versus-host disease.

We examined hemopoietic reconstitution during the first 12 months post-transplant in 31 patients given high-dose cyclophosphamide, total body irradiation and an HLA-identical sibling marrow transplant for hematological malignancy. Unexpectedly, we found marrow CFU-gm and marrow CFU-e cells to be denser than normal throughout the first year post-transplant. While functionally adequate neutrophil and platelet counts were achieved in the first six weeks post-transplant, there were defects in hemopoietic progenitor cell function during the first year post-transplant. Although we could detect no influence from acute graft-versus-host disease (GVHD), chronic GVHD adversely affected the growth of both myeloid and erythroid blood progenitor cells.

Bone Marrow Cells↗
PubMed1986

Mononuclear cell subpopulations in the skin defined by monoclonal antibodies after HLA-identical sibling marrow transplantation.

Mononuclear cell subpopulations present in the skin of 36 recipients of HLA-identical sibling marrow transplants were defined by immunoperoxidase using a battery of monoclonal antibodies to cell surface differentiation antigens. The T4-positive (T4+) (helper-inducer T cells), T8+ (cytotoxic-suppressor T cells) and the T6+ (Langerhans cells) decreased in number early post transplant and returned towards normal numbers from day 42 onwards. There was no evidence that either the T4+ or the T8+ subset was involved in cell-to-cell contact damage in acute graft-versus-host disease (GVHD). The paucity of lymphoid cell infiltration of the epidermis in acute GVHD suggested the possibility of a soluble factor being responsible for basal layer damage. In patients with chronic GVHD there was no evidence of T4+ lymphocyte involvement, but T8+ lymphocytes were present in increased numbers, suggesting a role for the T8+ population in the skin lesions of chronic GVHD, or possibly a reflection of the pattern of T4+ and T8+ cell reconstitution in the blood post-transplant. Finally, our study provided no evidence that BI+ (B cells), Leu 7+ (natural killer cells), OKMI+ (histiocytes) or OKT1O+ cells were involved in cell-to-cell contact damage in either acute or chronic GVHD.

Bone Marrow Transplantation↗
PubMed1986

Female marrow donors increase the risk of acute graft-versus-host disease: effect of donor age and parity and analysis of cell subpopulations in the donor marrow inoculum.

We evaluated 27 factors for their influence on acute graft-versus-host disease (GVHD) in 40 recipients of HLA-identical sibling marrow transplants. These factors included the doses of mononuclear cell subpopulations present in the donor marrow inoculum quantitated using a panel of monoclonal antibodies. Female donors were associated with increased severity of acute GVHD, and the older the female donor the greater this effect. Increasing donor parity was also associated with an increased risk of acute GVHD. The number of T cells, T cells subsets, natural killer cells and monocytes infused did not influence the incidence or severity of acute GVHD in this study, and we could not explain the influence of female donors and of female donor age on acute GVHD by the cellular content of their marrow inocula. We postulate that non-HLA histocompatibility antigen disparity is a more important determinant for acute GVHD than the number of infused donor T cells, especially when female donors are used. The association between acute GVHD and increasing parity suggests that some female marrow donors have been pre-sensitized to their respective recipients by preceding pregnancies.

Acute Disease↗
PubMed1986

Ph1 negative haematological chimaerism after marrow transplantation in Ph1 positive chronic granulocytic leukaemia.

A 17-year-old girl with Philadelphia chromosome (Ph1) positive chronic granulocytic leukaemia (CGL) who has undergone two bone marrow transplants from her HLA identical brother is described. Following the second transplant, cytogenetic analysis of her bone marrow cells showed haematological chimaerism with equal numbers of normal male cells and Ph1 negative female cells indicating the probable eradication of the Ph1 positive clones with the retention of normal host stem cells.

Adolescent↗
PubMed1986

The impact of leukemia status at the time of HLA-identical sibling marrow transplantation on subsequent complication rate and survival of adults with acute leukemia.

Between March 1981 and March 1985, 76 patients with acute leukemia were treated with cyclophosphamide (120 mg/kg), 12 or 14 Gy total body irradiation, and an HLA-identical sibling marrow transplant. Forty-seven patients had acute non-lymphoblastic leukemia (ANLL) and 29 had acute lymphoblastic leukemia (ALL). Forty-one were transplanted during first remission and 28 during or after first relapse of their disease. An additional six patients were transplanted because their leukemia was refractory to conventional cytotoxic chemotherapy, and one was transplanted as initial therapy. Actuarial 42 month survival for those transplanted during first remission was 47% and for those transplanted in first relapse or later it was 22% (p = 0.02). There was no difference in either group between those with ANLL and those with ALL. Two of the six patients with refractory leukemia are alive more than 22 and more than 15 months after the transplant. The incidence of acute graft-versus-host disease and interstitial pneumonitis was 90% and 39%, respectively, for the first remission group, and 96% and 37% for those transplanted in first relapse or later. There was no significant difference in transplant-related mortality between the two groups (29% and 43%, respectively). The leukemia recurrence rate, however, was 13% for those transplanted in first remission and 67% for those transplanted in first relapse or later (p = 0.0003). Thus, the major factor determining the incidence of leukemia recurrence and survival after transplant was the status of the leukemia at the time of transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗
PubMed1986

Aplastic anemia: analysis of two methods of treatment.

Between 1981 and 1985, 27 patients with aplastic anemia have been treated by immunosuppression with antilymphocyte globulin and prednisolone or allogeneic bone marrow transplantation. Fifteen have undergone bone marrow transplantation and have an actuarial survival at 54 months of 65% +/- 12% (95% confidence limits). There have been four deaths from graft rejection, septicemia (two), and graft-versus-host disease. Twelve have received antilymphocyte globulin and have an actuarial survival at 56 months of 67% +/- 21%. Five of these now have a normal blood count and two have had good partial responses and are self supporting. Of the five non-responders, three survived, two with persistent aplasia and one after allogeneic bone marrow transplantation. Two are dead, one of hemorrhage and one after mismatched bone marrow transplantation. In this study antilymphocyte globulin produced survival equivalent to bone marrow transplantation although only 58% of patients had a response to the antilymphocyte globulin. The advantages and disadvantages of these two methods of treatment are discussed.

Adolescent↗
PubMed1986

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↗
PubMed1986

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↗
PubMed1986

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↗