IC-02. Dynamics of cellular immunity in patients with acute myeloid and acute lymphoblastic leukemia at the stage of induction therapy as an indicator of secondary immunodeficiency
Olga V. Gerasimovich, Ihar A. Iskrou, Irina Yu. Lendina
Minsk Scientific Practical Center of Surgery, Transplantation and Hematology, Republic of Belarus
Correspondence:
Olga V. Gerasimovich; phone: +375 293 758313, e-mail: gerasimovichov@gmail.com
Summary
Acute leukemias are immune-mediated diseases, the severity of the clinical condition is largely determined by changes in the patient’s immune system caused both by the disease itself and its pathogenetic treatment. At the onset stage of hemoblastosis immune system cells deficiency develops due to cytopenia initiated by blast cells replacing normal hematopoiesis. At this stage immune defense works due to residual population of highly differentiated immunocompetent cells and antibodies produced by these cells. Changes in cellular composition of bone marrow immune pool on later stages after induction polychemotherapy directly and indirectly affect the secondary immunodeficiency development (due to the cellular component and, subsequently, humoral immunity).
Materials and methods
The study included 14 adult patients diagnosed with acute leukemia who received polychemotherapy during induction. In 9 cases therapy was given for acute myeloid leukemia (AML) according to “7+3” regimen, 1 patient with a mixed-cell leukemia with myeloid predominance received a course of FLAG-Ida, and 3 patients with acute lymphoblastic leukemia (ALL) received Hyper-CVAD/HMA (course of Hyper-CVAD-1) in 2 or CALGB in 1 case. The study cohort was recruited according to the main hematological diagnosis. All patients included were evaluated according to clinical and demographic characteristics (results of regression analysis do not suggest an effect on cellular immunodeficiency development, p=0.27). The primary result of the analysis was a decrease in CD3 + and CD19 + cells levels compared to reference interval at the stage of hematopoiesis detuning after induction (median of day +21 after the course was finished).
Results
In the studied cohort 3 patients had infectious complications at diagnosis verification stage, and 4 patients had infectious episodes during chemotherapy-induced cytopenia period. In AML subgroup the median CD3+ lymphocytes level was 0.636×109/ml, while the reference range is within 1.1-1.7×109/ml (Fig. 1). The median CD19+ lymphocytes level was 0.0025×109/ml (normal range 0.2-0.4×109/ml). The CD3+/CD19+ ratio in ALL subgroup was 0.41 to 0.036×109/ml. At the same time, there were 85.15% of CD3+ cells among lymphocytes in AML and 85.15% I ALL patients. The CD3+ / CD19+ ratio at screening and hematopoiesis detuning was 5.5:1 and 8.5:1, respectively. In the pool of CD19+ cells, the predominant class of cells was memory B-cells (CD19+ CD27+ IgD- IgM-) as seen in Fig. 2. In AML and ALL subgroups they made for 71.15% and 64.9% of total B-cell pool, respectively.
Figure 1. Main lymphocyte subpopulations (%)
Figure 2. Memory B-cells on screening and detuning
Conclusion
The absolute T-cell deficiency and absolute or relative B-cell deficiency in patients with AML and ALL after induction polychemotherapy leads to a state of secondary immunodeficiency, which is an indicator of an increased risk of infectious episodes development caused by different infectious agents. The memory B-cell predominance among CD19+ population illustrates immune system adaptation to cytopenia and newly formed elements deficiency, leading to shortage of both cellular and humoral immune system components.
Keywords
Acute leukemia, immune cells, secondary immunodeficiency, infectious episode.
