A B S T R A C T The marrow cells of a patient with pure red cell aplasia markedly increased their rate of heme synthesis when they were freed from the host environment and were incubated in vitro. When the red cell aplasia was treated with cyclophosphamide and prednisone, marrow cell incorporation of 'Fe into heme in vitro increased several weeks before a reticulocytosis was apparent, and was the earliest effect noted. The plasma 'YG-globulins of this patient inhibited heme synthesis by normal marrow cells or the patient's own marrow cells obtained after remission of the disease.Since the inhibition of heme synthesis could be the result of damage to erythroblasts, the patient's posttreatment marrow cells or normal marrow cells were labeled with '9Fe and were then incubated with the patient's pretreatment, treatment, and posttreatment ,YG-globulins as well as normal YG-globulins. At the end of this incubation the supernatant and cells were separated and counted. Heme was extracted and also was counted. Treatment of the cells with the patient's pretreatment YG-globulins resulted in a release of 40% of the radioactive heme from the cells. This represented the loss of radioactive hemoglobin and was an index of erythroblast cytotoxicity. A progressive disappearance of the cytotoxic factor in the YG-globulins occurred in the 3 wk period preceding the onset of reticulocytes in the patient's blood. Posttreatment and normal yG-globulins did not produce this effect and increased injury of red cells and lymphocytes was not produced by the patient's pretreatment yG-globulins. These studies demonstrate a method for measuring erythroblast cytoxicity and show that red cell aplasia is associated with YG-globulins that This study was presented in part at
Thirty-one patients with hairy-cell leukemia were treated with 2'-deoxycoformycin (DCF) in a National Cancer Institute of Canada multicenter trial. The DCF was administered in a cycle (4 mg/m2 iv weekly X 3), which was repeated every 8 weeks. Following a complete remission, consolidation was done with two further cycles of DCF. Of 28 patients evaluable for response, 25 obtained a complete remission; 3 had a partial response. To date there has been only one relapse; the median time with no therapy was 429.5 days (range 99-743 days). Toxicity was moderate and included nausea and vomiting, lethargy, and skin rash; with the first cycle of treatment, neutropenia and an increased incidence of fever or infection were also observed. We conclude that low-dose DCF is highly effective in treating hairy-cell leukemia.
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