Abstract
Allogeneic stem cell transplant (alloSCT) is often recommended therapy for patients with acute myeloid leukemia (AML) who either achieve a second complete remission (CR2), or who fail to do so, following salvage chemotherapy; however, there are few comparisons of transplant and continued chemotherapy without transplant in patients in CR2 or who fail to enter CR2. We thus performed such comparisons with our database consisting of all 490 patients followed after 1st salvage chemotherapy (54% of which contained cytarabine) given here from 1995 through 2004. Median age was 59, median first complete remission (CR1) duration was 22 weeks, and poor risk cytogenetics (CG) (-5 or -7 deletions, complex karyotype) were present in 59%. The CR2 rate after receiving a first salvage regimen was 23% (N=113) while 77% (N=377) did not achieve a second complete remission (failed CR2). Overall survival was compared between patients who underwent allogeneic transplant (N=130, 27%) and those who did not (N=360, 73%) for both the CR2 and failed CR2 cohorts. As shown in the accompanying figure, survival for alloSCT patients was superior in both subgroups (CR2: 11.7 months versus 5.6 months, p<0.0001; failed CR2: 5.1 months versus 2.3 months, p=0.004). While the transplant and non-transplant groups showed similar baseline renal and hepatic function at the time of first salvage therapy, alloSCT patients had longer mean CR1 duration (41.4 weeks vs. 31.1 weeks, P=0.004), less unfavorable CG (50.8% vs. 62.2%, P=0.03), and were younger (44.4 years vs. 59.5 years, P<0.0001). Because of these strong associations between treatment and prognostic factors, a multivariate analysis including treatment and these factors failed to yield a stable model. Thus we divided the cohort into subgroups defined by age, cytogenetics, and CR1 duration. The first subgroup analysis created 8 subgroups divided by age (< or ≥50), CG (intermediate vs. unfavorable) and CR2 status. AlloSCT produced superior survival in the subgroup of patients <50 regardless of CG or remission status. No survival advantage was observed for transplant among patients ≥50 who achieved a CR2; however, a slight survival benefit (intermediate CG: 6.3 months vs. 2.7 months, P=0.006; adverse CG: 2.6 months vs. 2.0 months, P=0.09) favoring alloSCT was noted in patients ≥50 who failed to achieve a CR2. A second subgroup analysis created 6 groups divided according to age (< or ≥50) and CR1 duration (≥36 weeks, <36 weeks, and primary refractory). AlloSCT was again superior to chemotherapy in patients <50 regardless of CR1 duration; however, in the ≥50 cohort the benefit was only significant for patients with a short CR1 (CR1 <36 weeks: 2.7 months vs. 2.5 months, P=0.05). Bearing in mind that, although our results may have been influenced by selection biases, a randomized trial is unlikely to be done. These results suggest that all patients <50 in CR2 or who do not enter CR2 benefit from alloSCT as do patients ≥50 with a CR1 duration of 1–36 weeks.
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