A stratification system for evaluating and selecting therapies in patients with relapsed or primary refractory acute myelogenous leukemia letter

Several characteristics have been predictive of outcome of therapy for relapsed or "primary refractory" acute myelogenous leukemia (AML).'-4Among these are duration of first complete remission (CR) and the number of, and response to, prior salvage regimens.Using these covariates, we have developed a system that stratifies patients by probability of response to previous salvage agents.This system may be useful when comparing new salvage regimens and when considering which patients might be candidates for phase I studies.The system is based on analysis of outcome (CR or not) in 206 patients (median age, 56 years) who received chemotherapy without transplantation for relapsed or primary refractory AML, excluding acute promyelocytic leukemia (APL), at M.D. Anderson between 1991 and 1994.For first salvage, 68% of the patients received conventional regimens (principally high-dose ara-C-based), and the remaining 32% received investigational regimens (usually single agents such as topotecan, 2 CDA, CI 973, or taxol).The overall CR rate was 23%.Ninety-three of the 206 patients received a second salvage attempt either at second relapse or after failing to respond to the first attempt.Forty-three percent of the 93 received conventional and 57% received investigational regimens; the overall CR rate was 1 I %.Forty patients received a third and 17 patients received a fourth salvage regimen, with CR rates of 10% and 6%, respectively.The system recognizes four groups: (1) patients with an initial CR duration in excess of 2 years who are receiving their first salvage attempt (15 patients; CR rate, 73%; 95% confidence interval CI, 45% to 92%); (2) patients with an initial CR duration of 1 to 2 years who are receiving their first salvage attempt (30 patients; CR rate, 47%; 95% CI, 28% to 66%); (3) patients with a first CR lasting less than 1 year, or with no initial CR, who are receiving their initial salvage attempt (160 patients; CR rate, 14%; 95% CI, 8% to 21%); and (4) patients with an initial CR under 1 year, or with no initial CR, who are receiving a second or subsequent (up to and including a fourth) salvage regimen, having not responded to a first salvage attempt (58 patients; 96 salvage attempts; CR rate, 0%; 95% CI, 0% to 4%).Other patients, eg, those who responded on a first salvage attempt and who proceed to a second salvage regimen, are excluded from consideration because of small numbers, although there are suggestions that patients who respond to the first regimen may be relatively responsive to the second (3/7 CRs if first CR duration was I to 2 years; 2/13 if it was shorter).The system was similarly effective in stratifying the 137 patients who received both initial and salvage therapy at M.D. Anderson and the 69 patients who were referred in relapse (49% of whom had received 2 1 regimen for relapse before referral), with CR rates of 8 of 1 I , 1 1 of 24, 11 of 102, and 0 of 80, and 3 of 4, 3 of 6 , 12 of 58, and 0 of 18 for the 4 groups in the M.D. Anderson and referred categories, respectively.Considering only patients who received conventional (eg, HDAC,