MARROW TOXICITY AND RADIATION ABSORBED DOSE ESTIMATES FROM RHENIUM-186-LABELED MONOCLONAL-ANTIBODY

Estimates of radiation absorbed dose to the red marrow (RM) would be v aluable in treatment planning for radioimmunotherapy if they could sho w a correlation with clinical toxicity. In this study, a correlation a nalysis was performed to determine whether estimates of radiation abso rbed dose to the bone marrow could accurately predict marrow toxicity in patients who had received Re-186-labeled monoclonal antibody. Metho ds: White blood cell and platelet count data from 25 patients who rece ived Re-186-NR-LU-10 during Phase I radioimmunotherapy trials were ana lyzed, and the toxicity grade, the fraction of the baseline counts at the nadir (percentage baseline) and the actual nadir were used as the indicators of marrow toxicity. Toxicity was correlated with various pr edictors of toxicity. These predictors included the absorbed dose to R M, the absorbed dose to whole body (WB) and the total radioactivity ad ministered. Results: Percentage baseline and grade of white blood cell s and platelets all showed a moderate correlation with absorbed dose a nd radioactivity administered (normalized for body size). The percenta ge baseline platelet count was the indicator of toxicity that achieved the highest correlation with the various predictors of toxicity (r = 0.73-0.79). The estimated RM absorbed dose was not a better predictor of toxicity than either the WE dose or the total radioactivity adminis tered. There was substantial variation in the blood count response of the patients who were administered similar radioactivity doses and who had similar absorbed dose estimates. Conclusion: Although there was a moderately good correlation of toxicity with dose, the value of the d ose estimates in predicting toxicity is limited by the patient-to-pati ent variability in response to internally administered radioactivity. In this analysis of patients receiving Re-186-labeled monoclonal antib ody, a moderate correlation of toxicity with dose was observed but mar row dose was of limited use in predicting toxicity for individual pati ents.