Relapses After Primary Purine Nucleoside Analogue Therapy

In the Intergroup study, four of the nine HCL patients (44 percent) who relapsed following primary dCF therapy achieved a complete response to a second induction therapy with dCF.81 Of five patients resistant (three patients) or intolerant (two patients) to dCF who were treated with 2-CdA, four patients achieved a complete response, which suggests a possible lack of cross-resistance in HCL between these two agents despite structural and mechanistic similarities.103 The National Cancer Institute Group C protocol treated 68 patients with 2-CdA who had relapsed following dCF therapy; the overall response rate was 79 percent.93

In the Scripps Clinic series of 53 evaluable patients treated with second courses of cladribine at first relapse, 33 (62 percent) achieved complete responses and 14 (26 percent) had partial responses, which suggests that patients who relapse can be successfully retreated with 2-CdA.90 2'-Deoxycoformycin may represent a reasonable therapeutic alternative for HCL patients who relapse after 2-CdA therapy, but response rate and duration data in substantial numbers of patients are lacking. Of three patients who relapsed following treatment with 2-CdA, two responded to interferon but then progressed within months of interferon discontinuation.104 For selected HCL patients refractory to purine analogues, splenectomy remains an option.

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