The Cutoff Leukemic Cell Burden to Influence Outcomes of Allogeneic Stem Cell Transplantation for Acute Myelogenous Leukemia In Hematological Complete Remission.

Pre-transplant disease status is considered a critical prognostic factor of patients undergoing allogeneic stem cell transplantation (SCT) for AML. The previous studies about the impact of leukemic cell burden on transplant outcomes were based on hematological complete remission (CR), which requires <5% blasts in a bone marrow aspirate. This study was performed to evaluate 2 questions: (1) Can we discriminate the impact of leukemic cell burden from CR status according to current hematological CR definition? (2) Is it possible that the poor outcomes by leukemic cell burden are overcome by the graft-versus-host disease (GVHD)-related graft-versus-leukemic (GVL) effect?

We retrospectively analyzed 363 patients with de novo AML who underwent allogeneic SCT between January 2002 and December 2008. There were 183 men and 180 women with a median age of 37 years (range 15–68).

To compare outcomes according to blast counts in patients who were in CR at bone marrow aspirate just before allogeneic SCT, we divided the patients into subgroups which had >2 - <3% blasts (n = 17), >3 - <5% blasts (n = 8) by plotting a receiver operating characteristic (ROC) curve. At a median follow-up of 37.1 months (range: 0.2–90.1) for survivors, there were significant differences in overall survival (OS) (68.3 vs 37.5, P= 0.075), event-free survival (EFS) (68.3 vs 18.8, P= 0.022), relapse (14.1 vs 64.3, P= 0.063) between two groups. In Multivariate analysis for the patients in CR status just before allogeneic SCT, <3% blasts remained a significant favorable independent variable influencing EFS after adjusting for significant pre-transplant variables in compare with the group which had >3 - <5% blasts [HR (95% CI) 4.21 (1.46-12.1), P=0.008] and the development of chronic GVHD was associated with lower relapse [HR (95% CI) 2.93 (1.7-5.06), P=<0.000], which was translated into improved OS [HR (95% CI) 2.0 (1.28-3.16), P=0.003], EFS [HR (95% CI) 2.24 (1.46-3.43), P=<0.001].

These results indicate that pre-transplant bone marrow status is an important prognostic factor for patients with AML, and even among the patients in CR, strictly more than 3% blasts is suggested as a poor prognostic factor. Therefore, the impact of leukemic cell burden on outcomes of allogeneic SCT for AML should be considered to make more defined SCT plan. Further studies for treatment strategies to enhance the GVL effect according to leukemic cell burden before transplant are needed.

No relevant conflicts of interest to declare.