Interferon-induced aplasia: evidence for T-cell-mediated suppression of hematopoiesis and recovery after treatment with horse antihuman thymocyte globulin.
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+, T gamma+, 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.
K F
KF
Mangan
B
B
Zidar
R K
RK
Shadduck
Z
Z
Zeigler
A
A
Winkelstein
D000328:Adult; D000741:Anemia, Aplastic / Q000139:chemically induced* / Q000628:therapy; D000818:Animals; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D005260:Female; D006410:Hematopoiesis / Q000187:drug effects*; D006736:Horses / Q000276:immunology; D006801:Humans; D007372:Interferons / Q000009:adverse effects*; D007958:Leukocyte Count; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology*
D000961:Antilymphocyte Serum; D007372:Interferons