LYMPHOCYTES AND LMYPHOKINES IN APLASTIC ANEMIA

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Clinical studies have focused the development of more specific and standard therapy for patients with aplastic anemia. A study of cyclosporine has demonstrated that patients with refractory aplastic anemia can improve hematologically with this form of T- cell directed immunosuppression. Cyclosporin A resulted in approximately 35% hematologic response rate. The addition of prednisone and the maintenance of adequate blood levels of cyclosporine appeared to be important for success of this regimen. Studies of hematopoietic growth factors in aplastic anemia have begun with the treatment of three patients with severe disease, including severe neutropenia and frequent bacterial infections using recombinant human GM-CSF. In laboratory studies, monocytes from patients with aplastic anemia have been shown to be very poor producers of interleukin 1 (Il-1), a principle regulator of immune and possibly also of hematopoietic cell proliferation. Il.1 activity in monocyte cultures was correlated to the degree of neutropenia and improved with successful therapy of aplastic anemia. The ability of hematopoietic growth factors to overcome the negative effects on hematopoietic cell proliferation of gamma interferon have been investigated. G-CSF had no effect on gamma interferon suppression of colony formation. GM-CSF could overcome gamma interferon's negative effect on myelopoiesis, and Il-3 its effect on erythropoiesis, consistent with the relative activity of these factors on CFU-GM and BFU-E- derived colony formation.