SEVERE ATYPICAL NEUROPATHY ASSOCIATED WITH ADMINISTRATION OF HEMATOPOIETIC COLONY-STIMULATING FACTORS AND VINCRISTINE

Purpose: We have observed a severe atypical neuropathy (SAN) in patien ts with small non-cleaved-cell (SNCL) and large-cell lymphoma (LCL) tr eated with intensive chemotherapy and hematopoietic colony-stimulating factors (CSFs). The present analysis was undertaken in an attempt to identify factors associated with the development of this syndrome. Pat ients and Methods: Fifty-four adult and pediatric patients consecutive ly treated according to the same chemotherapy protocol were included i n the analysis. Low-risk patients received three cycles of cyclophosph amide, vincristine, doxorubicin, and high-dose methotrexate (CODOX-M) while in high-risk patients this drug combination was alternated with high-dose cytarabine (ara-C), etoposide, and ifosfamide (IVAC) for a t otal of four cycles, Twenty-eight patients received a CSF (granulocyte [G]- or granulocyte-macrophage [GM]-CSF), and 26 patients received no CSF, A statistical analysis, which included a logistic regression mod el, was undertaken to examine the importance of potential contributing factors to the development of SAN. Results: SAN, which consisted of e xcruciating foot pain, usually associated with marked motor weakness, was observed in 12 patients, There was a highly significant associatio n between the occurrence of this syndrome and the administration of CS Fs, and on independent association with the cumulative dose of vincris tine given in the first cycle of chemotherapy. Furthermore, the analys is suggested a synergistic effect between administration of the CSFs a nd vincristine in the genesis of this neuropathy. Conclusion: Our resu lts indicate that CSFs can precipitate SAN when given in conjunction w ith vincristine. The development of SAN was associated most strongly w ith the cumulative dose of vincristine-the size of individual doses an d the number of doses given in cycle 1 were important to the extent th at they influenced the cumulative dose.