A Pilot Study of Circulating Monocyte Subsets in Patients Treated with Stem Cell Transplantation for High-Risk Hematological Malignancies.

Ida Marie Rundgren,Anita Ryningen,Elisabeth Ersvær,Øystein Bruserud,Aymen Bushra Ahmed

doi:10.3390/medicina56010036

Abstract

Background and Objectives: Autologous and allogeneic stem cell transplantation is used in the treatment of high-risk hematological malignancies, and monocytes are probably involved in hematological reconstitution as well as posttransplant immunoregulation. The aim of our study was to investigate the levels of circulating monocyte subsets in allotransplant recipients. Materials and Methods: The levels of the classical, intermediate, and nonclassical monocyte subsets were determined by flow cytometry. Sixteen patients and 18 healthy controls were included, and the levels were analyzed during pretransplant remission (n = 13), early posttransplant during cytopenia (n = 9), and early reconstitution (n = 9). Results: Most patients in remission showed a majority of classical monocytes. The patients showed severe early posttransplant monocytopenia, but the total peripheral blood monocyte counts normalized very early on, and before neutrophil and platelet counts. During the first 7–10 days posttransplant (i.e., during cytopenia) a majority of the circulating monocytes showed a nonclassical phenotype, but later (i.e., 12–28 days posttransplant) the majority showed a classical phenotype. However, the variation range of classical monocytes was wider for patients in remission and during regeneration than for healthy controls. Conclusions: The total peripheral blood monocyte levels normalize at the very early stages and before neutrophil reconstitution after stem cell transplantation, and a dominance of classical monocytes is reached within 2–4 weeks posttransplant.

Highlights

Acute myeloid (AML) and acute lymphoblastic leukemia are both aggressive malignancies characterized by the accumulation of immature malignant cells in the bone marrow [1,2]
We analyzed the monocyte subset levels after 13 different chemotherapy cycles in 11 patients (Table 1) who fulfilled the criteria of disease control/complete remission at the time of sampling, and in addition they all had peripheral blood total monocyte counts within the normal range
The monocyte subset levels showed a wider variation in the patients than in the healthy controls, but for 11 of the 13 samples, the majority of circulating monocytes

Summary

Introduction

Acute myeloid (AML) and acute lymphoblastic leukemia are both aggressive malignancies characterized by the accumulation of immature malignant cells in the bone marrow [1,2]. Several new and promising therapeutic approaches are considered and/or are available for high-risk hematological malignancies, including T-cell targeting immunotherapy [5,6], new monoclonal antibodies for the treatment of acute lymphoblastic leukemia [7], modulation of apoptotic regulation with increased proapoptotic activity, or [8] inhibition of intracellular. Medicina 2020, 56, 36 signaling, including metabolic targeting [9,10] These new therapeutic strategies may be used as a part of the initial treatment to reduce the risk of later relapse and thereby reduce the need for high-toxicity antileukemic therapy (e.g., allogeneic stem cell transplantation), or they can be used to reduce the risk of posttransplant relapse [9,11].

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