Myeloblastic leukemic cells causing suppression of granulopoiesis and excessive binding of colony-stimulating activity. The effect of antithymocyte globulin.

The three and a half year course of an adult woman (65 years) with myeloblastic leukemia, the leukemic clone being trisomic for chromosome #8, was characterized by suppressed granulopoiesis despite a small mass of leukemic tissue relative to cytogenetically normal marrow precursors. The leukemic tissue was shown to be productive of mature neutrophilic granulocytes with hypersegmented nuclei and increased alkaline phosphatase content. These granulocytes showed active phagocytosis but diminished fungicidal capacity. The leukemic tissue inhibited granulocyte-monocyte colony formation in soft agar with colony-stimulating activity from human and murine sources when co-cultured with normal, chronic myelocytic leukemia, Philadelphia chromosome positive (CML Ph¹⁽⁺⁾) human and C57 black (BL) murine marrow. This inhibition was associated with binding of colony-stimulating activity at sites on the leukemic cells which failed to elicit colony formation by leukemia colony-forming units, culture (CFUc). Pretreatment of the leukemic tissue with antithymocyte globulin (ATG) before co-culture removed the inhibitory effect of the leukemic tissue and promoted colony formation by leukemic CFUc. This effect of ATG involved competitive binding of colony-stimulating activity and ATG by leukemic cells since the consumption of colony-stimulating activity by leukemic cells was blocked by prior treatment of leukemic cells with ATG. Infusion of autochthonous cytogenetically normal marrow after two years of cryopreservation was ineffective in altering the neutropenic state. Bacteremia (Klebsiella pneumoniae) at a time when the marrow contained mostly leukemic precursors was associated with transient neutrophilic granulocytosis involving mature leukemic progeny. ATG given to the patient in a preterminal state was associated with a simitar leukocytosis as well as colony formation in vitro by the leukemic marrow tissue.