Pre-transplant bone marrow monocytic myeloid-derived suppressor cell frequency is not associated with outcome after allogeneic hematopoietic cell transplantation for acute myeloid leukemia in remission

Abstract

Outcomes in acute myeloid leukemia (AML) vary widely [1]. Current prognostic models cannot fully capture this diversity [2, 3], prompting interest in identifying additional factors to refine outcome prediction. Mounting evidence from other cancers suggests myeloid-derived suppressor cells (MDSCs) may be such a factor. Different types of MDSCs, including polymorphonuclear MDSCs (PMNMDSCs; typically characterized as CD14 negative and CD11b, CD15, or CD66b positive) and monocytic MDSCs (M-MDSCs; typically characterized as CD14 positive and HLA-DR low/negative), have been studied as modulators of the anti-cancer immune response [4]. Expansion of MDSCs has been associated with poor prognosis in some solid tumors [5]. MDSCs may also play a role in the pathogenesis and/or prognosis of hematologic malignancies. For example, M-MDSCs expansion has been associated with poor outcome in myeloma [6] while MDSC signaling modulation can improve myelodysplastic hematopoiesis in vitro [7]. Less is known about the role(s) of MDSCs in AML. Not felt to be derived from the malignant clone, MDSCs are expanded in AML vs. healthy patients possibly because of leukemia–microenvironment interactions [8]. A small study also suggested that MDSC frequencies are associated with disease burden after AML chemotherapy [9] but larger studies on the prognostic role of MDSCs in AML are lacking. We hypothesized that in AML patients undergoing hematopoietic cell transplantation (HCT), leukemia burden pre-HCT would be associated with MDSC frequency and that elevated MDSC frequency could portend poor postHCT outcomes in AML just as it portends poor prognosis in a variety of other malignancies [5–7]. Here, we used a large cohort of adults with AML (based on 2016 WHO criteria [10]) undergoing allogeneic HCT in first morphologic complete remission (CR) or CR with incomplete hematologic recovery (CRi) [1] to test this hypothesis and examine the associations between M-MDSC frequency, pretransplant measurable (“minimal”) residual disease (MRD), and post-HCT outcome. Adults ≥ 18 years of age were included if they underwent a first allograft after myeloablative or nonmyeloablative conditioning with peripheral blood or bone marrow (BM) as stem cell source from April 2006 until October 2014. We used the refined MRC/NCRI criteria to assign cytogenetic risk [11]. Secondary leukemia was defined as AML following an antecedent hematologic disorder or prior chemotherapy/radiotherapy treatment [12]. All patients were treated on Institutional Review Board (IRB)-approved protocols or standard treatment plans and gave consent in * Colin D. Godwin [email protected]