Interferon‐induced aplasia: Evidence for t‐cell‐mediated suppression of hematopoiesis and recovery after treatment with horse antihuman thymocyte globulin

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Abstract
A severe and persistent pancytopenia occurred in a 42‐year‐old woman with a non Hodgkin's lymphoma following a 10‐day course of intramuscular human leukocyte alpha interferon (IFN, 9.0 IU/day). Within 2 weeks of IFN, marrow nucleated myeloid and erythroid precursor cells and megakaryocytes were nearly absent and marrow progenitor cells (CFU‐E, BFU‐E, CFU‐GM) were undetectable. Analysis of marrow lymphocytes revealed that nearly 50% of the cells were E‐rosette +, Tγ+, OKT8 + (suppressor/cytotoxic) T‐and/or Leu 7 + natural killer (NK) lymphocytes and 50% were IgM Kappa, B1 +, B‐lymphocytes. In vitro erythroid culture studies were consistent with T‐cell‐mediated suppression of erythropoiesis. After 2 months without improvement on corticosteroid/androgen therapy, a 10‐day course of intravenous antithymocyte globulin (ATG) was administered. This was followed by a prompt reticulocytosis and a rise in blood neutrophils. After ATG therapy, there was a sixfold reduction in marrow suppressor cells, loss of in vitro suppressor effects on erythroid progenitor cells, and complete reversal of blood and marrow OKT4/OKT8 (helper/suppressor) ratios. These studies suggest that interferon may suppress hematopoiesis in some patients by activating marrow suppressor T‐ and/or NK cells. Treatment aimed at reduction of marrow suppressor cells may aid in hematologic recovery without eliminating the infiltrating lymphoma.