Prognostic factors and outcomes of adult patients with acute myeloid leukemia after first relapse

Abstract

Background: Patients with acute myeloid leukemia who are treated with conventional chemotherapy still have a substantial risk of relapse; the prognostic factors and optimal treatments after relapse have not been fully established. We, therefore, retrospectively analyzed data from patients with acute myeloid leukemia who had achieved first complete remission to assess their prognosis after first relapse.

Design and methods: Clinical data were collected from 70 institutions across the country on adult patients who were diagnosed with acute myeloid leukemia and who had achieved a first complete remission after one or two courses of induction chemotherapy.

Results: Among the 1,535 patients who were treated with chemotherapy alone, 1,015 relapsed. Half of them subsequently achieved a second complete remission. The overall survival was 30% at 3 years after relapse. Multivariate analysis showed that achievement of second complete remission, salvage allogeneic hematopoietic cell transplantation, and a relapse-free interval of 1 year or longer were independent prognostic factors. The outcome after allogeneic transplantation in second complete remission was comparable to that after transplantation in first complete remission. Patients with acute myeloid leukemia and cytogenetic risk factors other than inv(16) or t(8;21) had a significantly worse outcome when they did not undergo salvage transplantation even when they achieved second complete remission.

Conclusions: We found that both the achievement of second complete remission and the application of salvage transplantation were crucial for improving the prognosis of patients with acute myeloid leukemia in first relapse. Our results indicate that the optimal treatment strategy after first relapse may differ according to the cytogenetic risk.

Figure 1.

In first complete remission, 494 patients underwent allogeneic hematopoietic cell transplantation (allo-HCT). The remaining 1,535 patients were treated with conventional chemotherapy, and 1,015 of them subsequently relapsed. Of 931 patients for whom detailed information was available, 463 achieved second complete remission, and 305 of them underwent salvage allogeneic transplantation. Among 468 patients who did not achieve second complete remission, 189 underwent salvage allogeneic transplantation.

Figure 2.

Overall survival after first relapse (A) for the total population, and according to (B) age, (C) relapse-free interval from first complete remission, (D) the number of courses of remission induction chemotherapy to achieve first complete remission, (E) cytogenetic risk according to the SWOG criteria, and (F) application of salvage allogeneic hematopoietic cell transplantation.

Figure 3.

(A) Overall survival from first complete remission is compared between patients who underwent allogeneic transplantation in first complete remission and those who underwent transplantation after first relapse. (B) Overall survival after salvage allogeneic transplantation compared in relation to the disease status at transplantation: patients who underwent transplantation in second complete remission are represent by the black line, those who achieved second complete remission but subsequently relapsed before the salvage transplantation are represented by the green line, and those who never achieved remission after relapse are represented by the gray line. Overall survival from the date of transplantation (C) and from first complete remission (D) is compared between patients who underwent transplantation in first complete remission and those who underwent transplantation in second complete remission. Cumulative incidence of non-relapse mortality (E) and cumulative incidence of relapse (F) from the date of transplantation are compared between patients who underwent transplantation in first complete remission and those who underwent transplantation in second complete remission.

Figure 4.

Overall survival after first relapse is shown according to treatment after relapse: allogeneic hematopoietic cell transplantation in second complete remission (HCT in CR2, indicated by red line), no allogeneic transplantation after achievement of second complete remission (CR2/no HCT, black line), allogeneic transplantation in a disease status other than second complete remission (HCT in non-CR2, green line), and no achievement of second complete remission without salvage allogeneic transplantation (NR/no HCT, gray line). P values among each of the cytogenetics groups are in the following order: (i) HCT in CR2 vs. CR2/no HCT, (ii) HCT in CR2 vs. HCT in non-CR2, (iii) HCT in CR2 vs. NR/no HCT, (iv) CR2/no HCT vs. HCT in non-CR2, (v) CR2/no HCT vs. NR/no HCT, (vi) HCT in non-CR2 vs. NR/no HCT. (A) inv(16): 3-year overall survival from relapse: HCT in CR2, n=31, 70%; CR2/no HCT, n=14, 78%; HCT in non-CR2, n=13, 50%; NR/no HCT, n=3, 0%; P values, (i) 0.415, (ii) 0.280, (iii)<0.001, (iv) 0.130, (v)<0.001, (vi) 0.003. (B) t(8;21): HCT in CR2, n=46, 64%; CR2/no HCT, n=18, 53%; HCT in non-CR2, n=50, 32%; NR/no HCT, n=25, 0%; P values, (i) 0.600, (ii) 0.012, (iii) <0.001, (iv) 0.163, (v) <0.001, (vi) <0.001. (C) intermediate-risk acute myeloid leukemia: HCT in CR2, n=109, 58%; CR2/no HCT, n=82, 19%; HCT in non-CR2, 31%, n=129; NR/no HCT, n=149, 2%; P values, (i) <0.001, (ii) <0.001, (iii) <0.001, (iv) 0.814, (v)<0.001, (vi)<0.001 (D) unfavorable-risk acute myeloid leukemia: HCT in CR2, n=27, 67%; CR2/no HCT, n=18, 35%; HCT in non-CR2, n=61, 13%; NR/no HCT, n=71, 0%; P values, (i) 0.005, (ii) <0.001, (iii)<0.001, (iv) 0.288, (v) <0.001, (vi) <0.001.