Successful treatment of IgM paraproteinaemic neuropathy with fludarabine

Objectives-To evaluate the response of four patients with IgM paraproteinae mic neuropathy to a novel therapy-pulsed intravenous fludarabine. Background-The peripheral neuropathy associated with IgM paraproteinaemia u sually runs a chronic, slowly progressive course which may eventually cause severe disability. Treatment with conventional immunosuppressive regimens has been unsatisfactory. Fludarabine is a novel purine analogue which has r ecently been shown to be effective in low grade lymphoid malignancies. Methods-Four patients were treated with IgM paraproteinaemic neuropathy wit h intravenous pulses of fludarabine. Two of the four patients had antibodie s to MAG and characteristic widely spaced myelin on nerve biopsy and a thir d had characteristic widely spaced myelin only. The fourth had an endoneuri al lymphocytic infiltrate on nerve biopsy and a diagnosis of Waldenstrom's macroglobulinaemia. Results-In all cases subjective and objective clinical improvement occurred associated with a significant fall in the IgM paraprotein concentration in three cases. Neurophysiological parameters improved in the three patients examined. The treatment was well tolerated. All patients developed mild, re versible lymphopenia and 50% mild generalised myelosuppression, but there w ere no febrile episodes. Conclusion-Fludarabine should be considered as a possible treatment for pat ients with IgM MGUS paraproteinaemic neuropathy.