ASSOCIATION OF CELLULAR IMMUNITY WITH MOLECULAR RESPONSE IN CHRONIC MYELOID LEUKEMIA PATIENTS ON TYROSINE KINASE INHIBITORS THERAPY
Author(s): ,
Milan Jagurinoski
Affiliations:
Laboratory of Hematopathology & Immunology,Specialized Hospital for Active Therapy of Hematological Diseases,Sofia,Bulgaria
,
Milena Stojcov
Affiliations:
Department of Clinical Hematology,Specialized Hospital for Active Therapy of Hematological Diseases,Sofia,Bulgaria
,
Rositsa Vladimirova
Affiliations:
Laboratory of Hematopathology & Immunology,Specialized Hospital for Active Therapy of Hematological Diseases,Sofia,Bulgaria
,
Maria Muhtarova
Affiliations:
Laboratory of Hematopathology & Immunology,Specialized Hospital for Active Therapy of Hematological Diseases,Sofia,Bulgaria
,
Davidkova Yanitsa
Affiliations:
Laboratory of Hematopathology & Immunology,Specialized Hospital for Active Therapy of Hematological Diseases,Sofia,Bulgaria
,
Valentina Madzarova
Affiliations:
Laboratory of Hematopathology & Immunology,Specialized Hospital for Active Therapy of Hematological Diseases,Sofia,Bulgaria
,
Siyana Ivanova
Affiliations:
Laboratory of Cytogenetics & Molecular Biology,Specialized Hospital for Active Therapy of Hematological Diseases,Sofia,Bulgaria
,
Zhanin Stoyanova
Affiliations:
Department of Clinical Hematology,Specialized Hospital for Active Therapy of Hematological Diseases,Sofia,Bulgaria
,
Branimir Spassov
Affiliations:
Department of Clinical Hematology,Specialized Hospital for Active Therapy of Hematological Diseases,Sofia,Bulgaria
,
Gueorgui Balatzenko
Affiliations:
Laboratory of Cytogenetics & Molecular Biology,Specialized Hospital for Active Therapy of Hematological Diseases,Sofia,Bulgaria
Margarita Guenova
Affiliations:
Laboratory of Hematopathology & Immunology,Specialized Hospital for Active Therapy of Hematological Diseases,Sofia,Bulgaria
EHA Library. Jagurinoski M. Jun 15, 2019; 266804; PS1187
Dr. Milan Jagurinoski
Dr. Milan Jagurinoski
Contributions
Abstract

Abstract: PS1187

Type: Poster Presentation

Presentation during EHA24: On Saturday, June 15, 2019 from 17:30 - 19:00

Location: Poster area

Background

Chronic myeloid leukemia (CML) is considered to be one of the cancers most sensitive to immunological manipulation. Тhe 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).

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.

Session topic: 8. Chronic myeloid leukemia - Clinical

Keyword(s): Chronic myeloid leukemia, Immunology, Molecular response

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