The myth of the second remission of acute leukemia in the adult

Abstract

Although the majority of adult patients with both acute lymphoblastic leukemia and acute myelogenous leukemia achieve remission with upfront chemotherapy, many patients still suffer relapse. Often, the strategy is proposed of treating patients with relapsed leukemia into a second remission (CR2) and then proceeding to allogeneic transplantation as the definitive curative approach. However, the long-term outcomes of such a strategy are poor: the 5-year overall survival from first relapse for patients with acute leukemia is only approximately 10%. This Perspective highlights the fact that most patients do not achieve CR2 and therefore never really have an opportunity for a potential curative therapy. Although patients who undergo transplantation after relapse may be cured, those who do not achieve CR2 are rarely candidates for transplantation; therefore, the overall outcome for patients who relapse is dismal. There is therefore an urgent need not only for more effective upfront therapy to prevent relapse, but also for the development of therapies that can serve as effective bridging treatments between relapse and transplantation. We suggest that more optimal use of minimal residual disease detection during first remission may also improve the chances for successful transplantation therapy via earlier reinduction therapy, allowing transplantation before overt relapse.

Figure 1

Acute leukemia OS after CR2 transplantation. Probability of survival after allogeneic hematopoietic stem cell transplantation with myeloablative conditioning for AML (A) or ALL (B) in CR2 in adults 18-50 years of age in the United States, 2005-2007. Used with permission from the CIBMTR.

Figure 2

Probability of survival from first relapse. (A) OS in years from date of first relapse based on sex. (B) Survival postrelapse stratified according to therapy given in relapse. Patients who died within 100 days of relapse and those who were transplanted in CR1 were excluded from this analysis for better comparison of the different therapeutic modalities. MUD indicates matched unrelated donor. Used with permission from Fielding et al.

Figure 3

OS for AML after first relapse. Data are from 8 consecutive ECOG studies for newly diagnosed AML patients. Used with permission from Rowe et al.²¹

Figure 4

OS for Patients with AML after first relapse based on previous transplantation. SCT refers to both autologous and allogeneic hematopoietic stem cell transplantation. OS for the No SCT group is 12% and for the previous SCT group is 5%. Used with permission from Breems et al.

Figure 5

Time to clinical relapse. The probability of relapse-free survival after initiation of blinatumomab treatment in all 20 evaluable patients is shown in blue. Median follow-up for relapse-free survival is 405 days (range, 78-655). The probability of relapse-free survival after initiation of blinatumomab treatment in all 12 evaluable patients who have not undergone allogeneic transplantation after completion of blinatumomab treatment is shown in yellow. Median follow-up for relapse-free survival is 276 days (range, 78-655). HSCT indicates hematopoietic stem cell transplantation. Used with permission from Topp et al.