Individualized Dosing of Fludarabine (FLU) for Low Grade Lymphoproliferative Disorders Results in Administration of Less Medication with Fewer Infections and Equivalent Survival.

When used in the treatment of low-grade lymphoproliferative disorders, common practice is to administer 6 monthly cycles of FLU 25-mg/m² daily × 5. This practice is reported to cause infections (including opportunistic such as PCP and Listeria) in over 50% of patients. It has been our practice to individualize the number of monthly cycles of FLU per treatment course based on response in general administering 1 cycle of therapy when rapid and substantial response is obtained, or 1 cycle past best response. Our objective is to describe our experience with this dosing schema - incidence of infections in relation to the number of cycles of FLU administered per treatment course and overall survival. We conducted a retrospective chart review of medical records of all patients who received FLU at the Stratton VA Medical Center. We defined one treatment course as the number of five day monthly FLU doses received. Any time interval of 3 or more months between FLU was considered to indicate a new treatment course. All infectious episodes of NCI grades 3 or higher that occurred within 6 months of the last FLU treatment course were attributed to that prior treatment course. Survival was estimated by Kaplan-Meier analysis from date of diagnosis to death or last known alive. There were 15 patients treated for CLL, 9 for low-grade lymphoma, and 4 for macroglobulinemia. Three individuals treated with FLAG for ANLL were excluded. These 28 patients received a total of 44 treatment courses (each treatment course with 1 to 6 monthly cycles) of FLU. Fifty-four (54) percent of the treatment courses were with ≤2 cycles. Mean ± SD age of the patients was 65 ± 11 years.

The overall incidence of NCI grade 3 or higher infections was significantly increased with increased numbers of FLU cycles per treatment course (complex Chi-square = 0.0193). Treatment cycles with ≤2 compared with 3 or more cycles per treatment course (Chi-square with Yate’s correction = 0.0008) had significantly fewer infections. Median overall survival was 158 months with 78 ± 44 months of follow-up. Our data indicates that individualized dosing of FLU based on response results in using lower numbers of monthly cycles per treatment course, lower incidence of severe infections, and equivalent (based on historical controls) overall survival.