The chronic leukemias: a review of disease manifestations and the aims of therapy.

Certain aspects of the chronic leukemias that may influence future therapeutic trials are reviewed. In chronic lymphocytic leukemia (CLL), there is minimal mitotic activity in lymphoid tissues; indolent, long-lived lymphocytes, unresponsive to antigenic or phytohemagglutinin (PHA) stimulation accumulate. In many patients, erythroid precursors fail to proliferate despite the stimulus of a severe anemia, but a proliferative response can be initiated by prednisone. We need to know how the normal proliferative responses of these cells are modified, because the correction of these abnormalities would relieve most of the disease manifestations. CLL may not be a neoplastic disorder. In chronic myelogenous leukemia (CML), the leukocyte doubling time shortens as the disease duration lengthens; a significant correlation between this time and survival is demonstrated. Before therapy designed to eliminate the Ph(1)-positive (Philadelphia chromosome) stem cell is tried, we need to know whether a normal hematopoietic stem cell exists in Ph(1)-positive CML.