Myeloid Derived Suppressor Cells and Chronic Myeloid Leukemia

Assiut University

Status: Unknown

Conditions: Chronic Myeloid Leukemia Patients

Treatments: Diagnostic Test: Measurement level of myeloid derived suppressor cells in CML patients treated with imatinibe 400 mg/day; Diagnostic Test: Measurement level of myeloid derived suppressor cells in CML patients treated with nilotinib 600 mg/day

Study type: Interventional

Funder types: Other

Identifiers

NCT03214718

MDCSCML

Details and patient eligibility

About

The suppression of the immune system creates a permissive environment for development and progression of cancer. One population of immunosuppressive cells that have become the focus of intense study is myeloid derived suppressor cells , immature myeloid cells able to induce immune-escape, angiogenesis, and tumor progression. Two different subpopulations have been identified and studied: granulocytic and monocytic myeloid derived suppressor cells with a different immunophenotype and immunosuppressive properties

Full description

Myeloid-derived suppressor cells utilize different mechanisms to block both innate and adaptive arms of anti-tumour immunity, mostly through inhibition of T cell activation and expansion . Human monocytic myeloid derived suppressor cells are mostly identified as CD14+ cells with negative or low expression of HLADR. And also express high levels of CD11b and CD33 antigen . Human granulocytic myeloid derived suppressor cells are usually defined as CD66b+ CD11b+ CD15+ HLADR- cells and display an intermediate expression of CD33 and a variable expression of CD11b, depending on their maturation stage .

Chronic myeloid leukemia (CML) is a hematological cancer, characterized by a reciprocal chromosomal translocation between chromosomes 9 and 22 [t(9;22)], producing the Bcr-Abl oncogene. Tyrosine kinase inhibitors represent the standard of care for CML patients and exert a dual mode of action: direct oncokinase inhibition and restoration of effector-mediated immune surveillance, which is rendered dysfunctional in CML patients at diagnosis, prior to TKI therapy. TKIs such as imatinib, and more potent second-generation nilotinib and dasatinib induce a high rate of deep molecular response (DMR, BCR-ABL1 ≤ 0.01%) in CML patients. As a result, the more recent goal of therapy in CML treatment is to induce a durable deep molecular response as a prelude to successful treatment-free remission .

Accumulation of both Gr-MDSCs and Mo-MDSCs cells has been found in the peripheral blood of chronic myeloid leukemia (CML) patients. They are part of the tumor clone showing BCR/ABL expression.

BCR-ABL tyrosine kinase inhibitors (TKI) are able to induce remission in CML patients but not to eliminate leukemia stem cells , which can regenerate leukemia on drug discontinuation .

Unfortunately, molecular relapse is observed after cessation of tyrosine kinase inhibitors in 61-66% of CML patients, previously in complete molecular response (presumably due to the reactivation of dormant CML LSCs that are resistant to TKI-induced leukemic cell ablation. Thus, current research efforts aim to develop additional therapies to target these TKI-refractory CML LSCs .

With the aim of increasing cure rates and make it possible for patients to discontinue treatment, TKI therapies are currently evaluated in combination with immune modulators .

Enrollment: 50 estimated patients

Sex: All

Ages: 18 to 60 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• All newly diagnosed chronic phase CML patients during one year in Assiut university hospital.

Exclusion criteria

• Preivously diagnosed CML patients .
• Other myeloproliferative disorders .

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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50 participants in 2 patient groups

CML patients treated with imatinib 400 mg/day

Experimental group

Description:

Measurement of the level of myeloid derived suppressor cells (MDSCs) by flowctytometry for each newly diagnosed chronic phase chronic myeloid leukemia (CML) patients treated with imatinib 400 mg/day before starting treatment and every 3 months till one year and correlate between it and level of BCR-ABL gene level and the sokal score of the patients and deep molecular response of the patients after one year .

Treatment:

Diagnostic Test: Measurement level of myeloid derived suppressor cells in CML patients treated with imatinibe 400 mg/day

CML patients treated with nilotinib 600 mg/day

Active Comparator group

Description:

Measurement of the level of myeloid derived suppressor cells (MDSCs) for each newly diagnosed chronic phase chronic myeloid leukemia ( CML) patients treated with nilotinib 600 mg/day before starting treatment and every 3 months till one year and correlate between it and level of BCR-ABL gene, the sokal score and deep molecular response of the patients after one year .

Treatment:

Diagnostic Test: Measurement level of myeloid derived suppressor cells in CML patients treated with nilotinib 600 mg/day