General AML

The significance of CD34+/CD38- cell burden on the prognosis of AML patients receiving allogenic SCT- A German study

Leukemia Initiating Cells (LICs) are contained within the CD34+/CD34- stem cell compartment and have been proposed to survive chemotherapy as Minimal Residual Disease (MRD) and relapse in patients with Acute Myeloid Leukemia (AML). High burden of LICs at diagnosis have been shown to be associated with inferior survival outcomes and increased relapse probability in AML patients. However, the prognostic impact of high burden of LICs in patients undergoing Stem Cell Transplantation (SCT) is not yet known.

Madlen Jentzsch from the University of Leipzig, Germany, and colleagues evaluated the prognostic significance of CD34+/CD38-  cell burden at diagnosis in patients undergoing SCT.  The results of the study were published in the American Journal of Hematology.

In total, 169 adult AML patients (median age = 62) who received SCT at Complete Remission (CR) at the University of Leipzig between June 2001–July 2013 and had pretreatment Bone Marrow (BM) samples  were enrolled in this study.

The key results of the study were:
  • Using flow cytometry, BM CD34+/CD38- cell burden at diagnosis was highly variable in patients; median 0.5%, range 0–89% of all mononuclear cells
  • Compared to patients with de novo AML, secondary AML patients were more likely to have high CD34+/CD38- cell burden; P = 0.009
  • Patients with high CD34+/CD38- cell burden (n = 25) were more likely to have poor-risk cytogenetics compared to patients with low CD34+/CD38- cell burden (n = 144)
  • Patients with high CD34+/CD38- cell burden at diagnosis had a shorter Overall Survival (OS [HR = 1.86, P = 0.04]) and Relapse Free Survival (RFS [HR = 2.44, P < 0.001]) compared to patients with low CD34+/CD38- cell burden

In summary, high LICs containing cell population at diagnosis is associated with adverse outcomes in AML patients undergoing SCT at CR.

The authors concluded by suggesting that “CD34+/CD38- cell burden at AML diagnosis may help improve risk stratification, adjust disease monitoring and treatment” in patients. Additionally, Jentzsch et al. recommended that “novel therapeutic agents targeting AML LICs within the CD34+/CD38- cell population may help improve outcomes” of AML patients.

Abstract

In acute myeloid leukemia (AML), leukemia-initiating cells exist within the CD34+/CD38- cell compartment. They are assumed to be more resistant to chemotherapy, enriched in minimal residual disease cell populations, and responsible for relapse. Here we evaluated clinical and biological associations and the prognostic impact of a high diagnostic CD34+/CD38- cell burden in 169 AML patients receiving an allogeneic stem cell transplantation in complete remission. Here, the therapeutic approach is mainly based on immunological graft-versus-leukemia effects. Percentage of bone marrow CD34+/CD38- cell burden at diagnosis was measured using flow cytometry and was highly variable (median 0.5%, range 0%-89% of all mononuclear cells). A high CD34+/CD38- cell burden at diagnosis associated with worse genetic risk and secondary AML. Patients with a high CD34+/CD38- cell burden had shorter relapse-free and overall survival which may be mediated by residual leukemia-initiating cells in the CD34+/CD38- cell population, escaping the graft-versus-leukemia effect after allogeneic transplantation. Evaluating the CD34+/CD38- cell burden at diagnosis may help to identify patients at high risk of relapse after allogeneic transplantation. Further studies to understand leukemia-initiating cell biology and develop targeting therapies to improve outcomes of AML patients are needed.

References
  1. Jentzsch M. et al., Prognostic impact of the CD34+/CD38- cell burden in patients with acute myeloid leukemia receiving allogeneic stem cell transplantation. Am J Hematol. 2017 Apr; 92(4): 388–396. DOI: 10.1002/ajh.24663. Epub 2017 Feb 21.