PS1187 ASSOCIATION OF CELLULAR IMMUNITY WITH MOLECULAR RESPONSE IN CHRONIC MYELOID LEUKEMIA PATIENTS ON TYROSINE KINASE INHIBITORS THERAPY
Authors: Jagurinoski M. , Stojcov M. , Vladimirova R. , Muhtarova M. , Yanitsa D. , Madzarova V. , Ivanova S. , Stoyanova Z. , Spassov B. , Balatzenko G. , Guenova M. 
Published: June 2019

Background:

Chronic myeloid leukemia (CML) is considered to be one of the cancers most sensitive to immunological manipulation. The most recent goal in CML treatment tyrosine kinase inhibitors (TKIs) is to induce a durable deep molecular response (DMR; BCR‐ABL1 ≤ 0.01%) as a prelude to successful treatment‐free remission. The lack of overt relapse in such pts has been attributed to immunological control of CML, although its precise mechanisms are as yet unclear.

Aims:

The aim of the study was to assess the relative (%) and absolute counts (AC) of major lymphocytic populations in correlation with the molecular response in a large series of patients with CML on TKI therapy.

Methods:

A total of 171 consecutive patients with CML treated with TKIs were enrolled in the study ‐ 91 men and 80 women. Immunophenotypic analysis of major T/B/NK cell populations was performed by flow cytometry at diagnosis and in the course of the disease in parallel with the monitoring of the molecular response (MR) by quantitative PCR analysis using GeneXpert fully automated platform (n = 523 tests).

Results:

At diagnosis, significant lymphocytosis was detected in all CML pts (mean 8.7 ± 4.4 x109/l), due to higher % and AC of T‐cells (mean 79.4% ± 11.6%; 7.1 ± 4.2 x109/l) with normal CD4:CD8 ratio (Th:Tc). The AC of NK and CD19+ B‐cells were within or close to the reference ranges. After therapy was given, all lymphocytic populations demonstrated a decrease of AC. However, significant differences in major lymphocytic populations were observed between pts with hematological response to TKIs who had never achieved MR compared to those with DMR in terms of higher mean values of WBC counts (p = 0.009); % and AC of CD3+ T‐cells (mean 68.4% ± 11.9% vs 67.3% ± 11.7%; mean 1.6 ± 8.3x109/l vs 1.4 ± 5.5 x109/l, p = 0.000); % and AC of CD8+ T‐cells (mean 24.8% ± 8.0% vs 22.1% ± 7.3%; mean 0.6 ± 0.4x109/l vs 0.4 ± 0.2x109/l, p = 0.000) resulting in lower Th:Tc. Further, within the group of MR4.5log/MR5log, pts with undetectable BCR‐ABL1 transcripts demonstrated lower % of CD8+ T‐cells compared to BCR‐ABL1 positive cases (mean 20.9% ± 6.7% vs 23.2 ± 7.4%, p = 0.011). Pts with optimal MR according to ELN criteria were characterized with lower % of CD8+ (mean 22.4% ± 7.2% vs 26.1 ± 9.2%, p = 0.000) and CD3+ (mean 72.1% ± 12.6% vs 76.4% ± 11.5%, p = 0.001) T‐cells; higher % of CD19+ B‐cells (mean 11.8 ± 6.1% vs 8.8 ± 4.8%, p = 0.000) and Th:Tc ratio (p = 0.006).

Summary/Conclusion:

Our data demonstrated dynamics in lymphocyte counts with treatment of CML patients as well as the differences in the lymphocytic populations, and clearly in the cytotoxic cells, depending on the depth of the therapeutic response achieved, thus supporting the idea that, in addition to the specific inhibition of the hybrid BCR‐ABL oncoprotein by TKIs in CML pts, the cellular immunity may further play role in disease control.