PROGNOSTIC FACTORS IN PURGED MARROW FROM PATIENTS WITH NEUROBLASTOMA RECEIVING MYELOABLATIVE TREATMENT - TUMOR-CELL NUMBER, N-MYC PROTEIN, N-MYC GENE AMPLIFICATION AND RATE OF HEMATOLOGIC RECOVERY

Abstract

We have previously reported on a study of a small number of patients with advanced neuroblastoma (NBL) receiving myeloablative treatment and autologous marrow rescue in which occult NBL cells were found in the marrow of almost every transplanted patient. In addition, we have shown that the incidence of later relapse correlated better with the N-myc protein level in the harvested marrow than with the presence of N-myc gene amplification. We have now analyzed the characteristics of marrow harvested from 60 patients in remission and correlated survival time with the following variables: number of NBL cells, expression of N-myc and c-myc protein, N-myc gene amplification, expression of MDR-1, DNA index, and rate of the patients' engraftment after myeloablation. The results of this retrospective study indicate a marginally significant association between survival time and the level of N-myc protein (p=0.053) or N-myc gene amplification (p=0.063). On the other hand, the number of NBL cells recovered from the purged marrow was significantly associated with survival time (p=0.019). Similarly, the number of nucleated cells reinfused into the patients (p=0.003), and their rate of engraftment (p=0.008) were strongly associated with survival time. The expression of c-myc protein and perhaps of MDR-1 protein, and the DNA index were not associated with survival, in this particular group of patients. Prospective studies will be needed to substantiate the results of this retrospective study. Detailed evaluation of marrow purgates harvested from NBL patients undergoing myeloablative treatment and bone marrow rescue can potentially provide valuable information on the biology of the disease and may eventually help in the improvement of treatment.