OVERVIEW OF RADIATION MYELOTOXICITY SECONDARY TO RADIOIMMUNOTHERAPY USING I-131 LYM-1 AS A MODEL

The radiation dose-limiting toxicity from radioimmunotherapy has been myelotoxicity in the absence of bone marrow reconstitution (transplant ation). Myelotoxicity can be assessed directly by biopsy examination o f the bone marrow and indirectly by peripheral blood counts. In patien ts with B-cell malignancies, thrombocytopenia has been the initial and most severe manifestation of (131)-I-Lym-1 radiation toxicity from tr eatment. Manifestations of myelotoxicity varied greatly among the pati ents and from one treatment dose to another in the same patient, sugge sting that additional factors were present. There was an increased lik elihood of Grade 3-4 hematopoietic toxicity after I-131-Lym-1 treatmen t if the patient had peripheral blood cell abnormalities before underg oing I-131-Lym-1 treatment. Fractionation of the total I-131-Lym-1 dos e was associated with less toxicity. In many patients, myelotoxicity c ould not be explained by marrow radiation dose (0.36 +/- 0.13 rads per administered mCi) from I-131-Lym-1 in the blood and body alone. Bone marrow examination and I-131-Lym-1 imaging usually provided evidence f or additional marrow radiation from I-131-Lym-1-targeting of marrow ma lignancy and also for residual toxic effects from prior treatment in t hese patients. Immunohistologic and imaging examination of the bone ma rrow performed with the intended treatment antibody allowed assessment of extent of marrow malignancy and prediction of degree of myelotoxic ity from subsequent treatment.