Cancer-associated Gene Mutations in CML Treatment With TKIs by NGS

Study Overview
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Brief Summary
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We performed targeted-capture sequencing of 127 known and putative cancer-related genes of patients who best effect to TKIs ,or intolerance to TKIs,or resistance to TKIs by next-generation sequencing (NGS) .

Official Title
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Integrative Genomic Analysis Reveals Cancer-associated Gene Mutations in Chronic Myeloid Leukemia Patients With Tyrosine Kinase Inhibitor Resistance or Intolerance

Conditions
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Different Gene Between Different TKIs Effection

Intervention / Treatment
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* Genetic: different effection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chronic myeloid leukemia-Chronic phase(CML-CP) patients treated with receiveTyrosine kinase inhibitor -TKI(including imatinib, dasatinib and nilotinib) for more than 1 years best effect to TKIs ,or intolerance to TKIs,or resistance to TKIs according to Q-pcr detected BCR/ABL(IS) in peripheral blood and hematologic response and cytogenetic response Informed consent of the patient or his legal representative Exclusion Criteria: Patients had history of CML-AP or CML-BC CML Patients who have received allogeneic hematopoietic stem cell transplantation CML Patients who have received immunotherapy (except interferon, including car-t and other cellular immunotherapy) Woman who is pregnant or nursing

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| TKI best effect group<br>TKI best effect was defined achieve complete cytogenetic response (CCyR)after 3 months of treatment and the level of BCR/ABL<10% after 3 months of treatment,the level of BCR/ABL<1% . | Genetic: different effection<br>* Analysis of the reasons for treatment<br>|
| TKI resistance group<br>TKI resistance was defined as the lack of a complete hematologic response (CHR) after 3 months of TKI treatment, the lack of any cytogenetic response after 6 months of treatment, the lack of major cytogenetic response (MCyR) (Ph-positive cells > 35%) after 12 months of treatment, an increase of white blood cell (WBC) count in at least two consecutive samplings (with a doubling of the count from the nadir to ≥ 20×109/L or an absolute increase of ≥ 50×109/L), or a relapse after a CHR or MCyR. | Genetic: different effection<br>* Analysis of the reasons for treatment<br>|
| TKI intolerance group<br>TKI intolerance was defined as at least grade 3 nonhematologic toxicity or grade 4 hematologic toxicity persisting for more than 7 days, related to TKIs at any dose. | Genetic: different effection<br>* Analysis of the reasons for treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| cancer-associated gene mutations in CML treatment with TKIs by NGS | We performed targeted-capture sequencing of 127 known and putative cancer-related genes of patients who best effect to TKIs ,or intolerance to TKIs,or resistance to TKIs by next-generation sequencing (NGS) | 1 year after TKI treatment |