Long‐term survivors of acute lymphoblastic leukemia — risk of relapse after cessation of therapy

The results of cessation of therapy (COT) in 64 long-term survivors (disease-free survival of five years or more) of acute lymphoblastic leukemia (ALL) were analyzed to determine the incidence of relapse off therapy. Thirty-seven of the patients had intermittent central nervous system (CNS) prophylaxis. Total follow-up from diagnosis varied from 5.75 to 27.75 years. The median time off therapy was three years (range, 8 months to 26 years). Eighty-six percent (55/64) of the patients continue in their initial remission. Eight patients had relapse, and one patient had a morphologically different leukemia at recurrence. All the relapses occurred between five to eight years from diagnosis and the cumulative rate of relapse for the period was 0.14. There was no significant difference in the rate of relapse for those receiving CNS prophylaxis (0.08) versus those not receiving CNS prophylaxis (0.19). The difference in the relapse rates for boys (0.24) versus girls (0.04) was statistically significant (P = 0.04). Isolated testicular relapse (ITR) was not seen in any of the 34 boys. The present study confirms the earlier observations by others that relapse is uncommon in ALL patients remaining in remission longer than seven to eight years. ALL patients treated with intermittent CNS prophylaxis administered throughout the period of maintenance chemotherapy appear to be at no greater risk for relapse off therapy than those treated with high-dose initial cranial irradiation and intrathecal methotrexate. The longer duration of therapy and the use of a repetitive reinduction regimen for maintenance seem to be associated with a decreased risk of ITR after discontinuation of therapy for boys and men. There appears to be a small but definite risk of "second" leukemia in the long-term survivors of leukemia.