Proportion Of Cd34+Cd38-Leukemia Stem Cell Fraction Predicts Relapse Rate After Umbilical Cord Blood Transplantation In Acute Myeloid Leukemia With Adverse Karyotype

Abstract BACKGROUND Acute myeloid leukemia (AML) contains heterogenous leukemia cells in its morphology, phenotype, genetic and epigenetic alterations. In AML, leukemia stem cells (LSCs) are at the apex of the hierarchy of these heterogeneity, and they are enriched within CD34+CD38- fraction. They are thought to initiate the disease and relapse after treatment, leading to dismal prognosis. To treat relapsed or refractory AML patients urgently with transplantation, umbilical cord blood is an advantageous donor cell source because of its accessibility. Although several groups reported that resistant LSCs contributed to relapse after chemotherapy, relapse after allogeneic hematopoietic cell transplantation (HCT) has not been discussed up to this time. We investigated the clinical impact of the proportion of CD34+CD38- fraction on relapse after umbilical cord blood transplantation (CBT) for AML patients not in remission. METHOD We retrospectively investigated the outcome of AML patients who were not in remission and underwent CBT as the first allogeneic HCT from Aug 2013 to Mar 2016, in Toranomon Hospital. Before transplantation, the proportion of CD34+CD38- fraction in leukemia cells was quantified using flow cytometry in each patient. The patients whose proportion of CD34+ fraction was less than 10% of leukemia cells were excluded. The patients who were dead within 4 weeks after transplantation were also excluded from the analysis. RESULT A total of 58 patients were studied. They included 22 of AML, not otherwise specified (AML-NOS) and 36 of AML with myelodysplasia-related changes (AML-MRC). The median proportion of CD34+ fraction was 85.7% (range, 19.3 - 99.1) and 95.8% (range, 14.8 - 99.5) in AML-NOS and AML-MRC, respectively. The proportion of CD34+CD38- fraction was significantly higher in patients with AML-MRC patients, compared to patients with AML-NOS; 44.1% (range, 1.3 - 97.4) vs. 12.1% (0.3 - 85.0) , p CONCLUSION The present study concluded that the combination of karyotype and the proportion of CD34+CD38- fraction predicted relapse after CBT for AML-MRC patients not in remission. LSCs in CD34+CD38- fraction might be resistant not only to chemothrapy but also to allogeneic HCT. Disclosures No relevant conflicts of interest to declare.