Trichosporon cutaneum (syn. T. beigelii), a saprophytic fungal organism normally found in the soil, is increasingly being recognized as a cause of life-threatening systemic illness in ...immunosuppressed patients. Of 42 cases reported in the literature, 27 (64%) have died, including all four occurring after bone marrow transplantation. We report here a 44-year-old man who developed an invasive pulmonary infection and fungemia with T. cutaneum following bone marrow transplantation. The infection was manifest by severe respiratory distress and hypoxemia despite a clear chest X-ray, and was diagnosed by the identification of fungal hyphae on a percutaneous lung aspirate and by culture of the organism from the blood. Despite the previous reports indicating that there is a high mortality rate in this situation, the patient recovered following treatment with amphotericin B, miconazole and ketoconazole. T. cutaneum needs to be recognized as a potentially serious but treatable pathogen in severely immunosuppressed patients, including bone marrow transplant recipients.
We tested the hypothesis that chronic graft-versus-host disease (GVHD) is due to inadequate thymic function by examining pretransplant serum levels of facteur thymique serique (FTS). Four of five ...patients with no detectable FTS activity developed chronic GVHD, while one of four with some FTS activity did. Further patient numbers are needed to confirm or reject this hypothesis. We further postulated that chronic GVHD, whatever its cause, involves thymic epithelium as a target organ. When tested 11 mo or more posttransplant, patients with chronic GVHD had lower absolute FTS levels (p < 0.02) and lower age-corrected levels (p = 0.05) than patients without chronic GHVD. Low values in chronic GVHD were associated with the disease itself and not its therapy. These findings show that thymic epithelial secretory function is impaired in chronic GVHD, and this may in part be responsible for the immunodeficiency characteristic of these patients.
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.
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.
Previous studies in dogs given 1200 R and a hemopoietic graft from DLA-identical littermates have shown that marrow graft rejection generally does not occur when the recipient is untransfused (58 of ...59 achieved sustained engraftment) but is seen after a single transfusion of blood from the marrow donor on day -10 (13 of 18 rejected) and even after multiple transfusions of random blood (3 of 11 rejected). This study extends those initial observations by determining the incidence of rejection of DLA-identical littermate marrow grafts following administration of different cells from the marrow donor on days -24. -17. and -10 prior to transplantation. Using this protocol, the following results and conclusions were established. (1) All 19 dogs given transfusions of whole blood rejected their grafts. This 100% incidence of rejection after three transfusions indicates that more than one minor histocompatibility system outside of DLA is involved in transfusion-induced sensitization and subsequent marrow graft rejection. (2) Six dogs given subcutaneous injections of cultured skin epithelial cells rejected their subsequent marrow grafts. Hence, antigens mediating rejection are not restricted to hemopoietic cells but are also expressed on at least one other tissue. (3) Seven of 15 dogs given transfusions of platelet concentrates (“free” of white and red blood cells) rejected the marrow graft, while 8 showed sustained engraftment. (4) Five of 14 dogs given transfusions of red blood cells (free of white blood cells and platelets) rejected the marrow graft, while 9 had sustained engraftment. This suggests that only some (and perhaps none) of the non-DLA antigens responsible for rejection reside on platelets and red blood cells. To definitively answer this question, the current blood cell separation techniques must be improved further to provide pure red blood cells and platelets for transfusion studies. Assays of lymphocytotoxic antibodies, mixed leukocyte culture reactivity, and survival of donor platelets in the recipient did not predict the fate of the subsequent marrow graft. These findings in DLA-identical canine marrow graft recipients are of potential practical importance for planning platelet and red blood cell support of human marrow graft candidates.
Strong evidence has been obtained that the funnel-web spider venom inhibitor, previously found to occur naturally in the blood of rats, is at least partly immunoglobulin in composition. However, the ...results of chromatographic and immunological studies, including the use of specific antisera, indicate that this inhibitor is not a single chemical entity and apparently resides within more than one immunoglobulin class. In addition, it was observed that challenge of rats with Atrax venom substantially increased the venom-inhibiting powers of their blood and that these powers were located in the same plasma fractions as in unchallenged rats.
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