General AML,   FLT3,  NPM1

Impact of hyperleukocytosis on the long-term outcome of AML patients undergoing allogeneic HSCT

Approximately 5–20% of Acute Myeloid Leukemia (AML) patients have an elevated level of White Blood Cell (WBC) count of more than 100,000/ml. Elevated WBC count, hyperleukocytosis (HL), in AML patients is associated with an increased risk of mortality during induction therapy. However, there is a paucity of studies that have examined the long-term impact of HL in AML patients undergoing Hematopoietic Stem Cell Transplantation (HSCT), hence the rationale for this study.

Jonathan Canaani from Chaim Sheba Medical Center, Tel Aviv, Israel, and colleagues, on behalf of the European Society for Blood and Transplantation (EMBT), retrospectively studied the prognostic significance of HL on the long-term outcome of AML patients undergoing HSCT. The results of the study were published in the American Journal of Hematology.

In total, 1,275 newly diagnosed AML patients who received HSCT between 2005–2014 and reported to the EMBT Acute Leukemia Working Party were included in this study. HL was defined as WBC count over 50,000/ml and thus patients were divided into three cohorts. Patients were either without HL and had a WBC < 50,000/ml (n = 918), or with HL and had WBC 50,000–100,000/ml (n = 159) or WBC ≥ 100000/ml (n = 198).

The key results of the study were:
  • Compared to patients without HL, HL patients were significantly younger (P = 0.016) and were more likely to be FLT3-ITD or NPM1 mutated
  • 3-year cumulative incidence of relapse in patients with WBC count < 50,000/ml, 50,000–100,000/ml or ≥ 100,000/ml; 22% vs 29% vs 30%, respectively, P = 0.0013
  • HL was independently associated with increased incidence of relapse; HR = 1.55, P = 0.004
  • Decreased Leukemia Free Survival (LFS) and Overall Survival (OS) were associated with HL; HR = 1.38, P = 0.01 and HR = 1.4, P = 0.013, respectively

Canaani et al. concluded by highlighting that their study is the first to show that HL indicates an “inferior clinical outcome for transplanted AML patients, independent of cytogenetic and molecular risk factors and constitutes a major determinant of long term outcome”. The authors further suggested that HL “should be implemented and considered as a major risk factor for relapse” after allogenic HSCT in AML patients.

Abstract

Up to 20% of acute myeloid leukemia (AML) patients present initially with hyperleukocytosis, placing them at increased risk for early mortality during induction. Yet, it is unknown whether hyperleukocytosis still retains prognostic value for AML patients undergoing hematopoietic stem cell transplantation (HSCT). Furthermore, it is unknown whether hyperleukocytosis holds prognostic significance when modern molecular markers such as FLT3-ITD and NPM1 are accounted for. To determine whether hyperleukocytosis is an independent prognostic factor influencing outcome in transplanted AML patients we performed a retrospective analysis using the registry of the acute leukemia working party of the EBMT. A cohort of 357 patients with hyperleukocytosis (159 patients with WBC 50K-100K, 198 patients with WBC≥100K) was compared to 918 patients without hyperleukocytosis. Patients with hyperleukocytosis were younger, had an increased rate of favorable risk cytogenetics, and more likely to be FLT3 and NPM1 mutated. In multivariate analysis, hyperleukocytosis was independently associated with increased relapse incidence (hazard ratio [HR] of 1.55, 95% confidence interval [CI], 1.14 - 2.12; p=0.004), decreased leukemia-free survival (HR of 1.38, 95% CI, 1.07 - 1.78; p=0.013), and inferior overall survival (HR of 1.4, 95% CI, 1.07 - 1.84; p=0.013). Hyperleukocytosis retains a significant prognostic role for AML patients undergoing HSCT.

References
  1. Canaani J.et al. Long term impact of hyperleukocytosis in newly diagnosed acute myeloid leukemia patients undergoing allogeneic stem cell transplantation: an analysis from the acute leukemia working party of the EBMT. Am J Hematol. 2017 Mar 28. DOI: 10.1002/ajh.24737. [Epub ahead of print].
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