Infection complicating bone marrow transplantation: what are the risks and can they be reduced?
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Biomedical subjects
Publications and source records attributed to T R Rogers.
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Twenty patients have undergone bone marrow transplantation for acute lymphoblastic leukaemia (ALL). Eighteen patients were in complete remission and two had less than 10% leukaemic blasts in the marrow aspirate in the week prior to transplantation. Eighteen patients were grafted from HLA/MLC compatible siblings. One identical twin and one fully compatible parent were also used as donors. Two patients died of graft-versus-host disease and one of radiation-induced pneumonitis. Four have subsequently relapsed. Thirteen patients remain well and in remission from 202 to 1126 d post transplantation. These results show that morbidity and mortality from the bone marrow transplantation procedure is low. However, the major obstacle to permanent success in marrow transplantation of patients with ALL is recurrence of the disease (35% actuarial disease free survival at 1126 d).
A one-year-old boy with type I H mucopolysaccharidosis (Hurler's disease) was given a bone-marrow transplant (BMT) from his mother in an attempt to replace the deficient enzyme, alpha-L-iduronidase (iduronidase). These is definite evidence of engraftment, the enzyme activity of the recipient's leucocytes reaching heterozygote levels within 37 days of the BMT. Graft-versus-host disease (GVHD) developed but was partially controlled by steroids. From 3-4 months after graft until the present (13 months after the graft) iduronidase activity has been present in the serum and the urine and there has been evidence of considerable degradation of glycosaminoglycans excreted in the urine. The hepatosplenomegaly has disappeared, corneal clouding has cleared, and deterioration in the child's development seems to have been arrested.
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High dose methyl prednisolone (HDMP) was used to treat 25 episodes of graft versus host disease (GVHD) in 13 patients after bone marrow transplantation for aplastic anaemia or acute leukemia. All patients showed rapid improvement of GVHD following HDMP with resolutions of gut and skin manifestations over several days, but liver GVHD was less responsive to treatment. The major complication of treatment was infection and four patients died from infection following HDMP. The mode of action of HDMP may be a nonspecific anti-inflammatory effect but it appears to be rapidly effective in controlling GVH reactions.
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A 15-year-old boy with Fanconi's anaemia, who required four units of blood each month, received a bone marrow graft from his 9-year-old brother, who has HLA identical and compatible on mixed lymphocyte reaction. Considerable immunosuppression was used and bacterial infection was prevented by vigorous decontamination in a Vickers-Trexler isolator. After the graft the patient's blood counts remained satisfactory for nine months, but it took six months before qualitative immune function was normal.
Four children, 5 months to 15 years of age, underwent bone marrow transplantation in Vickers-Trexler isolator tents. Two grafts were elective. During 170 days of isolation no clinical infections due to exogenous micro-organisms developed despite severe immunodeficiency. The decontamination regimen and sterile procedures used, as well as the microbiological results, are described. This form of isolation in paediatric practice was found to be highly acceptable to both patients and staff.
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A glycoprotein with an apparent molecular weight of 93 kDa was purified from a water-soluble extract of Aspergillus fumigatus NCPF 2109 by single step affinity chromatography using the mannose-specific snowdrop (Galanthus nivalis) lectin coupled to agarose. The carbohydrate moiety contained only mannose and galactose. Partial sequencing of cyanogen bromide fragments of the antigen yielded two sequences, KQNKP and GEIPMKF?PQL, with no homology to any reported proteins. In a preliminary evaluation of its diagnostic potential the 93 kDa antigen was recognized by the sera of four patients with allergic bronchopulmonary aspergillosis, in addition to a monoclonal antibody raised against a partially purified fraction of the A. fumigatus water-soluble extract.