SEVERE VINCRISTINE NEUROPATHY IN CHARCOT-MARIE-TOOTH-DISEASE TYPE-1A

BACKGROUND. A general predisposition for vincristine-related neuropath y has been observed in persons with a family history of hereditary neu ropathies. METHODS. In a retrospective case series, we investigated th e possible association between the DNA rearrangement found in patients with Charcot-Marie-Tooth Disease Type 1A (CMT1A) and susceptibility t o the neurotoxicity of vincristine. In selected patients and family me mbers, we performed electrodiagnostic studies and analyzed DNA samples for 17p11.2-12 duplication associated with CMT1A. RESULTS. We describ e three families with autosomal dominant CMT1, among whom a family mem ber with a neoplastic disease suffered rapid onset, severe neuropathy after receiving initial doses of vincristine as a part of a routine ch emotherapy protocol. All three families had at least one affected fami ly member with 17p11.2-12 duplication. CONCLUSIONS. These cases show t hat 17p11.2-12 duplication predisposes patients to severe neurotoxicit y from vincristine and that this drug should be avoided in patients wi th CMT1A. It is therefore essential to obtain a detailed family histor y for all oncology patients to screen for possible hereditary neuropat hies. In patients with unexplained or preexisting familial neuropathy, testing for 17p11.2-12 duplication should be carried out prior to ini tiating vincristine therapy, Patients with other hereditary neuropathi es may also be at risk for severe neurotoxic reactions. (C) 1996 Ameri can Cancer Society