Allogeneic transplantation for advanced acute myeloid leukemia: The value of complete remission

Abstract

Background Patients with AML without complete remission (CR) or in first relapse (relapse1) can have extended leukemia control and survival following allogeneic hematopoietic cell transplantation (HCT). Transplantation in relapse1 or primary induction failure (PIF) versus treatment to achieve CR2 and subsequent HCT might yield similar outcomes, but available comparative data are scarce. Methods We studied 4682 HCT recipients, analyzing survival by disease status: PIF (N=1440), relapse1 (failing ≥1 reinduction, N=1256) and CR2 (N=1986). Results Patient, disease and transplantation characteristics were similar except CR2 patients more often had performance scores of 90-100, de novo AML and longer duration of CR1. Adverse cytogenetics were more common in PIF patients. 5-year survival adjusted for performance score, cytogenetic risk and donor type for CR2 was 39% (95% CI 37-41) compared to 18% (95% CI 16-20) for HCT in relapse1 and 21% (95% CI 19-23) in PIF, p<0.0001. Conclusion Although survival is superior for HCT in CR2, transplantation for selected patients in relapse1 or PIF may still be valuable. These data can guide decision-making about additional salvage therapy versus prompt HCT for patients not in CR, but also highlight intrinsically more treatable AML who have favorable risk cytogenetics, longer CR1 duration and younger patients with better performance status.

Novel Disease Risk Model for Patients with Acute Myeloid Leukemia Receiving Allogeneic Hematopoietic Cell Transplantation

“…Despite rapid advances in understanding disease biology and development of several novel therapies, allogeneic hematopoietic cell transplantation (AHCT) remains an important curative treatment option for these patients. Survival post-transplant depends on disease and patient characteristics [2][3][4][5][6][7][8].…”

The emergence of acid ceramidase as a therapeutic target for acute myeloid leukemia

“…Consolidation therapy could consist of additional rounds of high dose chemotherapy or consideration of autologous or allogeneic stem cell transplant. There is debate as to when best to recommend transplant, but high risk patients are often considered for stem cell transplantation in first remission 14, 15 . Allogeneic hematopoietic stem cell transplantation (HSCT) provides benefit of the graft versus leukemia effect but increases the risk of graft versus host disease and other complications 11, 14-16 .…”

Favourable/Intermediate ELN-Risk Acute Myeloid Leukemia to Transplant or Not to Transplant First-Line?

“…Indeed, the actual rates of allo-SCT transplant-related mortality (TRM) are considered not acceptable for those patients whose relapse risk is below 35% to 40% with standard consolidation/intensification treatment [3]. Once these patients relapse, it is commonly thought that a 2 nd CR may be obtained in the great majority of patients and that allo-SCT may be offered at this time [4]. These indications are certainly embraceable but, at the same time, it has to be considered that the achievement of a 2 nd CR should not be assumed as certain and that a number of major complications (e.g.…”

“…Furthermore, and this is even more important, it may be questionable whether allo-SCT in 2 nd CR is as curative as in 1 st CR. Several data suggest that allo-SCT in 2 nd CR shows less potent antileukemic activity and much higher toxicity [4]. In other words, for advanced-phase diseases, if the clinical patients' conditions may be worse, the burden and the drug resistance of leukemia may be higher and negatively influence the relapse after transplant.…”