Analysis of late infections in 89 long-term survivors of bone marrow transplantation

Abstract

Eighty-nine patients with aplastic anemia or acute leukemia treated by either syngeneic (1 3 patients) or allogeneic (76 patients) marrow transplantation who had survived for more than 6 mo were surveyed to determine the incidence of late infections. Most patients (72 % ) had either no infection or very few late infections, and only a minority (28 % ) had three or more infections. Eight patients (9 % ) died from infection. Bacterial infections of lung, respiratory tract, skin. and blood represented more than half of the 1 52 infections encountered. Gram-positive cocci represented one-third of the documented infecting organisms. Varicella-zoster (VZ) infections were seen in 22 % of all patients. Each affected patient had only a single episode of VZ infection. Fungal infections and interstitial pneumonia were uncommon. By the use of a proportional hazards regression model we attempted to identify clinical and immunologic factors predictive of and predisposing to late infections. Only one factor was significantly associated with late non-VZ infectons: chronic graftversus-host disease (C-GVHD). Other factons analyzed, e.g.. underlying disease. conditioning regimen, type of transplant. inability to respond to cutaneous dinitrochlorobenzene (DNCB). age, and sex. did not show significant associations. In contrast. VZ infections were not associated with C-GVHD. Negative DNCB skin test reactivity appeared to be the only factor correlating with VZ infections. The recurrent (and occasionally fatal) infections seen in a minority of long-term survivors after syngeneic and allogeneic marrow transplantation are most likely the result of deficits of humoral and cellular immunity. which in turn are most often associated with C-GVHD. I NCREASING NUMBERS of bone marrow transplants from HLA-identical siblings (allogeneic grafts) and monozygous twins (syngeneic grafts) are being carried out for the treatment of aplastic anemia (AA) and acute leukemia (AL).’7 In preparation for the transplant the patients’ own hemopoietic and immunologic systems are destroyed by therapy with high-dosage cyclophosphamide (CY) and/or total body irradiation (TBI). Subsequent recovery of hemopoiesis and immune function is dependent on proliferation of cells of donor marrow origin. Granulocyte counts are low during the first 2-4 wk after transplantation. This period is characterized by frequent bacterial and fungal infections.78 Immunologic function is most severely depressed during the first 4 mo.912 In this period interstitial pneumonias, presumably related to the state of immunodeficiency, are a major