Purine Nucleosides

Patients treated with either cladribine or pentostatin have a disease course that resembles patients with indolent lymphoma, with prolonged responses to therapy and overall survival longer than relapse-free survival.22 Goodman et al.14 reported on 209 patients treated with cladribine and followed them for at least 7 years. Of the 207 patients evaluated, 95% had a CR and 5% a PR. The median duration of a CR was 99 months (range, 8-172 months) and that of a PR was 37 months (range, 10-116 months). Seventy six patients (37%) relapsed after the first course of treatment, with a median time to relapse of 42 months (range, 8-118 months). The risk of relapse was increased with short disease duration prior to therapy, lower hemoglobin levels, and higher white blood counts at baseline. Sixty patients in first relapse after cladribine were retreated, with a CR rate of 75% in the 59 evaluable patients and a median duration of second remission of 35 months (range, 4-92 months). Second relapses were seen in 20 patients, with 6 of 10 patients treated again achieving CR. When survival was evaluated for all patients, only six patients (3%), all complete responders, had died. However, only one of these patients died from causes related to disease. The overall survival rate in this series was 97% at 108 months.

Flinn et al.23 reported a 9-year follow-up of a large intergroup study of HCL patients treated with pento-statin. A total of 241 patients were treated with pento-statin initially or after interferon failure. There were 40 deaths, with only 2 deaths due to HCL. And 201 patients were followed for a median of 9.3 years, with a Kaplan-Meier estimate of survival of 90% at 5 years and 81% at ten years. The 173 patients (71%) who achieved a confirmed CR had an overall relapse-free survival of 85% at 5 years and 67% at 10 years. There was no comment on retreatment after relapse.

Kraut et al.24 reported 24 patients followed after pentostatin therapy for a median of 82 months (range, 54-104 months). Out of 24 patients 23 were alive, with one dying of refractory/recurrent disease. Twelve patients remained in remission and 11 patients relapsed. Seven patients were retreated, with 5 achieving a second complete remission. The overall survival from treatment initiation of this group was 93 months (range, 63-116 months). There have been only two documented deaths in this group, and neither related to disease.

In summary, patients treated with purine nucleo-sides have a dramatic increase in their survival, and few responding patients have died due to their disease. The development of other therapies for resistant disease, such as rituximab25 or anti-CD-22 recombinant immunotoxin (BL 22),26 and the potential benefit of splenectomy or interferon in treatment failures, may further extend survival.

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