HEMATOLOGIC SIDE-EFFECTS OF RADIOLABELED IMMUNOGLOBULIN THERAPY

Radiolabeled immunoglobulin therapy (RIT) is a new cancer treatment th at is more selective than its predecessors. Its dose-limiting normal t issue side effect is bone marrow toxicity, and hematopoietic stem cell damage appears to be its most significant mechanism. Platelet consump tion in irradiated normal liver tissues and apoptosis of circulating p eripheral blood lymphocytes are other, less important, hematologic sid e effects. I-131 and Y-90 are the radioisotopes most commonly used for RIT; in addition, animal toxicology and initial clinical studies of c helate immunoglobulins radiolabeled with In-111 (for diagnosis) or Y-9 0 (for therapy) are reviewed. The bone-seeking properties of free Y-90 are not considered to be a major component of the hematologic damage caused by yttrium-labeled immunoglobulins. The microenvironment of the bone marrow system is not significantly damaged by current RIT protoc ols. Moreover, granulocyte colony-stimulating factor (G-CSF) can open the blood-marrow barrier. Bone marrow toxicity after RIT can be correc ted by bone marrow transplantation, growth factors, blood products, or fractionation of RIT. Selection of the appropriate corrective regimen depends on the severity of the bone marrow damage and will further en hance the therapeutic ratio of RIT.