System for predicting curative effect of '3+7' induced chemotherapy of acute myelogenous leukemia patient and application of system

Abstract

The invention provides a system for predicting the curative effect of '3 + 7' induced chemotherapy of an acute myelogenous leukemia patient and application of the system, and belongs to the technical field of biomedicine. The system comprises a data acquisition module, a prediction module and a prediction result acquisition module, and is used for predicting the curative effect of induced chemotherapy based on the change of the peripheral blood leukemia immunophenotype cell count: compared with the prior art, the peripheral blood leukemia immunophenotype cell count is reduced by more than or equal to 1.5 log on the fourth day of induced chemotherapy; obtaining a result that the patient is sensitive to induced chemotherapy; compared with the induction chemotherapy, the number of the peripheral blood leukemia immunophenotype cells is reduced by less than 1.5 log on the fourth day of the induction chemotherapy, and the result that the patient is insensitive to the induction chemotherapy is obtained. The invention further provides a kit, computer equipment, a computer readable storage medium and a computer program product based on the system, patients sensitive and insensitive to induced chemotherapy can be effectively recognized, and accurate treatment guidance is provided for clinic.

Description

Technical Field

[0001] This invention belongs to the field of biomedical technology, specifically relating to a system for predicting the efficacy of "3+7" induction chemotherapy in patients with acute myeloid leukemia and its application. Background Technology

[0002] Acute myeloid leukemia (AML) is a serious hematologic malignancy that typically requires induction chemotherapy. Among existing chemotherapy regimens, the "3+7" regimen is the most commonly used induction chemotherapy method, consisting of three days of idarubicin (IDA) and seven days of cytarabine (Ara-C). Currently, there is a lack of effective methods for predicting the efficacy of the "3+7" regimen. Generally, the efficacy can only be directly assessed by analyzing the primitive cell count through bone marrow morphology examination. However, this method involves bone marrow aspiration, collecting bone marrow samples, and relying on bone marrow morphology examination, significantly increasing patient suffering and being time-consuming. Therefore, addressing the lack of efficacy prediction methods for AML patients undergoing "3+7" induction chemotherapy and providing patients with a rapid and economical efficacy prediction plan has become an important issue in clinical treatment. Summary of the Invention

[0003] To address the problems existing in the prior art, the primary objective of this invention is to provide a system for predicting the efficacy of "3+7" induction chemotherapy in patients with acute myeloid leukemia. This system can be used to effectively identify patients who are sensitive to and insensitive to induction chemotherapy, thereby providing more precise treatment guidance for clinical practice and improving the treatment outcomes for patients.

[0004] A second objective of the present invention is to provide the application of the above-described system in the preparation of products for predicting the efficacy of “3+7” induction chemotherapy in patients with acute myeloid leukemia.

[0005] A third objective of the present invention is to provide reagent kits, computer devices, computer-readable storage media, and computer program products based on the above-described systems.

[0006] To achieve the above-mentioned objectives, the present invention provides the following technical solution:

[0007] This invention provides a system for predicting the efficacy of "3+7" induction chemotherapy in patients with acute myeloid leukemia, the system comprising:

[0008] (1) Data acquisition module, used to acquire cell counts with leukemia immunophenotype in peripheral blood samples of patients before induction chemotherapy and on day 4 of induction chemotherapy;

[0009] (2) A prediction module is used to provide a risk prediction model with the cell count of the leukemia immunophenotype in the peripheral blood sample obtained by the data acquisition module as input data. The risk prediction model predicts the efficacy of induction chemotherapy based on the degree of decrease in the cell count of the leukemia immunophenotype in the peripheral blood sample.

[0010] (3) Prediction result acquisition module, used to acquire the output result of the risk prediction model in the prediction module, and obtain the prediction result of the induction chemotherapy efficacy of the patient with acute myeloid leukemia to be tested;

[0011] The risk prediction model predicts the efficacy of induction chemotherapy based on the degree of decrease in the cell count of leukemia immunophenotype in peripheral blood samples as follows: if the cell count of leukemia immunophenotype in peripheral blood samples on day 4 of induction chemotherapy decreases by ≥1.5 log compared to before induction chemotherapy, the patient is considered sensitive to induction chemotherapy; if the cell count of leukemia immunophenotype in peripheral blood samples on day 4 of induction chemotherapy decreases by <1.5 log compared to before induction chemotherapy, the patient is considered insensitive to induction chemotherapy.

[0012] Preferably, the leukemia immunophenotype includes CD7, CD20, CD19, CD123, CD33, CD117, CD34, CD38, CD10, HLADR, CD36, CD13, CD64, CD11B, CD56, CD16, CD14, CD15, TDT, CD22, mCD3, cCD3, MPO, cCD79a, CD2, CD5, CD4, and CD45.

[0013] Preferably, the cell count is obtained using flow cytometry.

[0014] Preferably, the peripheral blood sample is collected using a blood collection tube containing EDTA anticoagulant.

[0015] The present invention also provides the application of the above system in the preparation of products for predicting the efficacy of “3+7” induction chemotherapy in patients with acute myeloid leukemia.

[0016] This invention also provides the application of the above system in the preparation of products that assist in predicting the efficacy of "3+7" induction chemotherapy in patients with acute myeloid leukemia.

[0017] The present invention also provides a kit for predicting the efficacy of "3+7" induction chemotherapy in patients with acute myeloid leukemia, comprising reagents for implementing the modules in the above system.

[0018] The present invention also provides a computer device for predicting the efficacy of "3+7" induction chemotherapy in patients with acute myeloid leukemia, comprising a memory, a processor, and a computer program stored in the memory and executable on the processor, wherein the processor executes the computer program to construct the system described above.

[0019] The present invention also provides a computer-readable storage medium having a computer program stored thereon, which, when executed by a processor, constructs the system described above.

[0020] The present invention also provides a computer program product, comprising a computer program that, when executed by a processor, constructs the system described above.

[0021] Compared with the prior art, the beneficial effects of the technical solution of the present invention are as follows:

[0022] This invention provides a system for predicting the efficacy of "3+7" induction chemotherapy in patients with acute myeloid leukemia (AML), addressing the lack of efficacy prediction methods for AML patients undergoing "3+7" induction chemotherapy. Through the system of this invention, the efficacy of "3+7" induction chemotherapy in AML patients can be accurately predicted by dynamically monitoring peripheral blood leukemia immunophenotypic cell counts, filling the gap in efficacy prediction methods in the field. It can effectively identify patients sensitive and insensitive to induction chemotherapy, and its results are highly consistent with the 2022 European Leukemia Network (ELN) risk stratification and bone marrow morphology, thus providing more precise treatment guidance for clinicians and improving patient outcomes. Attached Figure Description

[0023] Figure 1 Image showing the results of flow cytometry analysis of peripheral blood leukemia immunophenotype cells before (d0) induction chemotherapy in patient F001;

[0024] Figure 2 Image showing the results of flow cytometry analysis of peripheral blood leukemia immunophenotype cells on day 4 (d4) of F001 induction chemotherapy in patient;

[0025] Figure 3 The image shows the results of flow cytometry analysis of minimal residual disease (MRD) in a bone marrow sample after the completion of F001 induction chemotherapy in the patient. Detailed Implementation

[0026] This invention provides a system for predicting the efficacy of "3+7" induction chemotherapy in patients with acute myeloid leukemia. The system includes a data acquisition module, a prediction module, and a prediction result acquisition module.

[0027] In this invention, the data acquisition module is used to acquire the cell counts of leukemia immunophenotype in peripheral blood samples of patients before and on day 4 of induction chemotherapy. "Before induction chemotherapy" refers to the detection of peripheral blood leukemia immunophenotype cell counts in acute myeloid leukemia patients before receiving "3+7" induction chemotherapy (d0). "Day 4 of chemotherapy" refers to the detection of peripheral blood leukemia immunophenotype cell counts in acute myeloid leukemia patients on day 4 (d4) of receiving "3+7" induction chemotherapy.

[0028] In this invention, the prediction module is used to provide a risk prediction model with the cell counts of leukemia immunophenotypes in peripheral blood samples obtained by the data acquisition module as input data. The risk prediction model predicts the efficacy of induction chemotherapy based on the degree of decrease in the cell counts of leukemia immunophenotypes in peripheral blood samples. The risk prediction model of this invention predicts the efficacy of induction chemotherapy based on the cell counts of leukemia immunophenotypes in peripheral blood samples of patients before and on day 4 of induction chemotherapy. The degree of decrease in cell count is calculated, and the prediction criteria are: if the decrease in the cell count of leukemia immunophenotypes in peripheral blood samples on day 4 of induction chemotherapy is ≥1.5 log compared to before induction chemotherapy, the patient is considered sensitive to induction chemotherapy; if the decrease in the cell count of leukemia immunophenotypes in peripheral blood on day 4 of induction chemotherapy is <1.5 log compared to before induction chemotherapy, the patient is considered insensitive to induction chemotherapy.

[0029] In this invention, the prediction result acquisition module is used to acquire the output result of the risk prediction model in the prediction module, and obtain the prediction result of the induction chemotherapy efficacy of the patient with acute myeloid leukemia to be tested.

[0030] In this invention, the leukemia immunophenotype includes CD7, CD20, CD19, CD123, CD33, CD117, CD34, CD38, CD10, HLADR, CD36, CD13, CD64, CD11B, CD56, CD16, CD14, CD15, TDT, CD22, mCD3, cCD3, MPO, cCD79a, CD2, CD5, CD4, and CD45. This invention identifies and counts leukemia cells through specific immunophenotypic markers.

[0031] The cell counting described in this invention is preferably obtained using flow cytometry. The peripheral blood sample is preferably collected using a blood collection tube containing EDTA anticoagulant, and the collection volume is preferably 2-3 mL.

[0032] The present invention also provides the application of the above system in the preparation of products for predicting or assisting in the prediction of the efficacy of “3+7” induction chemotherapy in patients with acute myeloid leukemia.

[0033] The present invention also provides a kit for predicting the efficacy of "3+7" induction chemotherapy in patients with acute myeloid leukemia, comprising reagents for implementing the modules in the above system.

[0034] The present invention also provides a computer device for predicting the efficacy of "3+7" induction chemotherapy in patients with acute myeloid leukemia, comprising a memory, a processor, and a computer program stored in the memory and executable on the processor, wherein the processor executes the computer program to construct the system described above.

[0035] The present invention also provides a computer-readable storage medium having a computer program stored thereon, which, when executed by a processor, constructs the system described above.

[0036] The present invention also provides a computer program product, comprising a computer program that, when executed by a processor, constructs the system described above.

[0037] The technical solutions of this invention will be clearly and completely described below with reference to the embodiments thereof. Obviously, the described embodiments are only a part of the embodiments of this invention, and not all of them. All other embodiments obtained by those skilled in the art based on the embodiments of this invention without creative effort are within the scope of protection of this invention.

[0038] Unless otherwise specified, the following embodiments are all conventional methods.

[0039] Unless otherwise specified, all materials and reagents used in the following examples are commercially available.

[0040] Example 1

[0041] A system for predicting the efficacy of "3+7" induction chemotherapy in patients with acute myeloid leukemia, the system comprising:

[0042] (1) Data acquisition module, used to acquire cell counts of leukemia immunophenotype in peripheral blood samples of patients before induction chemotherapy and on day 4 of induction chemotherapy; peripheral blood samples were collected using blood collection tubes with EDTA anticoagulant, with a collection volume of 2 mL; cell counts were obtained using a flow cytometer (Beckman Coulter NAVIOS flow cytometer); specimen preparation was performed using the whole blood erythrolysis method; hemolysin was obtained from QIAGEN Sciences; cell count collected and analyzed: 50,000; gating: CD45 / SSC.

[0043] The detection antibodies were CD7, CD20, CD19, CD123, CD33, CD117, CD34, CD38, CD10, HLADR, CD36, CD13, CD64, CD11B, CD56, CD16, CD14, CD15, TDT, CD22, mCD3, cCD3, MPO, cCD79a, CD2, CD5, CD4 and CD45, purchased from Beckman Coulter and DAKO.

[0044] (2) A prediction module is used to provide a risk prediction model with the cell counts of the leukemia immunophenotype in the peripheral blood samples obtained by the data acquisition module as input data. The risk prediction model predicts the efficacy of induction chemotherapy based on the changes in the cell counts of the leukemia immunophenotype in the peripheral blood samples. The module calculates the decrease in the cell counts of the leukemia immunophenotype in the peripheral blood samples of patients before and on day 4 of induction chemotherapy. If the cell counts of the leukemia immunophenotype in the peripheral blood samples of patients on day 4 of induction chemotherapy decrease by ≥1.5 log compared to before induction chemotherapy, the patient is considered sensitive to induction chemotherapy. If the cell counts on day 4 of induction chemotherapy decrease by <1.5 log compared to before induction chemotherapy, the patient is considered insensitive to induction chemotherapy.

[0045] (3) Prediction result acquisition module, used to acquire the output results of the risk prediction model in the prediction module, and obtain the prediction results of the induction chemotherapy efficacy of the patient with acute myeloid leukemia to be tested.

[0046] Example 2

[0047] A computer device, which may be a server or a terminal, includes a processor, memory, input / output (I / O) interfaces, and a communication interface. The processor, memory, and I / O interfaces are connected via a system bus, and the communication interface is also connected to the system bus via the I / O interfaces. The processor provides computational and control capabilities. The memory includes a non-volatile storage medium and internal memory. The non-volatile storage medium stores an operating system, computer programs, and a database. The internal memory provides an environment for the operation of the operating system and computer programs in the non-volatile storage medium. The database stores data. The I / O interfaces allow the processor to exchange information with external devices. The communication interface allows communication with external terminals via a network connection. When the computer program is executed by the processor, it constructs the system of Embodiment 1 to predict the efficacy of "3+7" induction chemotherapy in patients with acute myeloid leukemia.

[0048] Example 3

[0049] A computer-readable storage medium storing a computer program that, when executed by a processor, constructs the system implementation of Embodiment 1 for predicting the efficacy of “3+7” induction chemotherapy in patients with acute myeloid leukemia.

[0050] Example 4

[0051] A computer program product includes a computer program that, when executed by a processor, constructs the system implementation of Embodiment 1 to predict the efficacy of “3+7” induction chemotherapy in patients with acute myeloid leukemia.

[0052] Experimental Example 1

[0053] 1. Predicting the efficacy of "3+7" induction chemotherapy in acute myeloid leukemia patients based on the degree of decrease in cell counts with leukemia immunophenotypes in peripheral blood samples before and on day 4 of induction chemotherapy:

[0054] Cell counts of leukemia immunophenotypes were detected in peripheral blood samples from patients with acute myeloid leukemia (AML) before induction chemotherapy (d0). Peripheral blood samples (2 mL) were collected using EDTA anticoagulant tubes. Flow cytometry was used to analyze the collected peripheral blood samples to detect cell counts of leukemia immunophenotypes (CD7, CD20, CD19, CD123, CD33, CD117, CD34, CD38, CD10, HLADR, CD36, CD13, CD64, CD11B, CD56, CD16, CD14, CD15, TDT, CD22, mCD3, cCD3, MPO, cCD79a, CD2, CD5, CD4, and CD45). Cell counting was performed using a Beckman Coulter NAVIOS flow cytometer, and specimen preparation was performed using the whole blood erythrolysis method; hemolysin was obtained from QIAGEN Sciences; cell count collected and analyzed: 50,000; gating: CD45 / SSC.

[0055] Patients with acute myeloid leukemia (AML) receiving a "3+7" induction chemotherapy regimen had their peripheral blood samples collected again on day 4 (d4) of induction chemotherapy, and the cell counting procedure described above was repeated. The changes in the number of cells with the leukemia immunophenotype in the peripheral blood samples were compared between before induction chemotherapy (d0) and day 4 (d4). The decrease in the number of cells with the leukemia immunophenotype in the peripheral blood samples was calculated. If the decrease was ≥1.5 log, the patient was considered sensitive to induction chemotherapy, and the original regimen was continued. If the decrease was <1.5 log, the patient was considered insensitive to chemotherapy, classified as intermediate- to high-risk, and additional chemotherapy drugs should be considered to enhance the anti-leukemia effect.

[0056] 2. Evaluation of the efficacy of "3+7" induction chemotherapy in patients with acute myeloid leukemia based on bone marrow morphology examination:

[0057] After completing "3+7" induction chemotherapy, bone marrow morphology examination is performed in patients with acute myeloid leukemia to assess the effectiveness of the treatment.

[0058] After chemotherapy, a bone marrow aspiration is performed to collect a bone marrow sample. The sample is then examined morphologically, and the proportion of blast cells is counted under a microscope. If all blast cells are less than 5%, it indicates that the patient has achieved morphological complete remission.

[0059] 3. Risk stratification assessment of acute myeloid leukemia patients before "3+7" induction chemotherapy based on 2022 ELN risk stratification:

[0060] According to the "2022ELN risk stratification" commonly used in this field, patients with acute myeloid leukemia were subjected to next-generation sequencing gene mutation and chromosome karyotype detection. Before induction chemotherapy, the risk stratification of patients was determined based on next-generation sequencing gene mutation and chromosome karyotype, and patients were specifically divided into low, intermediate and high risk groups.

[0061] The information and results of patients with acute myeloid leukemia predicted or assessed using the three methods mentioned above are shown in Table 1.

[0062] Table 1 Patient Information and Test Results

[0063]

[0064]

[0065] Note: IA: 3 days of idarubicin + 7 days of cytarabine; Vene: Veneclare; ELN: European Leukemia Network; CR: Complete remission; NR: No remission.

[0066] The results showed that in the low-risk group of 2022ELN patients, 100% (5 / 5) of patients had a decrease of ≥1.5 log in peripheral blood leukemia immunophenotypic cell count; in the intermediate-risk group of 2022ELN patients, 66.7% (4 / 6) of patients had a decrease of <1.5 log in peripheral blood leukemia immunophenotypic cell count; and in the high-risk group of 2022ELN patients, 100% (4 / 4) of patients had a decrease of <1.5 log in peripheral blood leukemia cell count.

[0067] Patients with a ≥1.5 log decrease in peripheral blood leukemia immunophenotypic cell count showed <5% blast cells in bone marrow morphology after completing "3+7" induction chemotherapy, indicating morphological complete remission. These results suggest that the degree of decrease in peripheral blood leukemia immunophenotypic cell count before and on day 4 of induction chemotherapy can determine the sensitivity of acute myeloid leukemia patients to the induction chemotherapy regimen. Specifically, patients with a ≥1.5 log decrease in peripheral blood leukemia immunophenotypic cell count are sensitive to the induction chemotherapy regimen; patients with a <1.5 log decrease are not sensitive to the induction chemotherapy regimen and require additional chemotherapy drugs to enhance the anti-leukemia effect. Most importantly, in the predictive results of the "3+7" induction chemotherapy efficacy for acute myeloid leukemia (AML) patients, 100% of the low-risk group (2022ELN) was sensitive to the induction chemotherapy regimen; 100% of the high-risk group was insensitive; and in the intermediate-risk group, 2 patients were sensitive to induction chemotherapy, and 4 were insensitive. After adding a third chemotherapy drug to the induction chemotherapy regimen of these 4 patients, the efficacy assessment after the completion of induction chemotherapy showed that 100% achieved complete myeloid morphological remission. This indicates that the "3+7" induction chemotherapy efficacy prediction method described in this invention can not only predict the sensitivity of AML to induction chemotherapy but also guide clinical practice, thereby avoiding chemotherapy-related toxicities caused by overtreatment.

[0068] Since there are many test results corresponding to the patient information in Table 1, we provide a test result image of one patient as an example. Figure 1 The image shows the cell count results of peripheral blood samples with leukemia immunophenotypes obtained by flow cytometry before chemotherapy (d0) for patient F001. Red represents protoblasts, blue represents granulocytes, purple-red represents monocytes, and green represents mature lymphocytes. Figure 2 The image shows the cell count results of a peripheral blood sample with a leukemia immunophenotype, obtained by flow cytometry on day 4 (d4) of chemotherapy for patient F001. Red represents problasts, blue represents granulocytes, purple-red represents monocytes, and green represents mature lymphocytes.

[0069] Figure 3 This image shows the results of flow cytometry analysis of minimal residual disease lesions in a bone marrow sample from patient F001 after chemotherapy. Figure 3 The antigens detected were CD34, CD117, CD13, CD33, CD7, CD56, CD10, CD19, CD38, HLA-DR, and CD45. 442,238 cells were acquired and analyzed. CD45 / SSC gating was used. Detection results: CD34+CD117+CD13+CD33+CD7-CD19 / CD56-CD10-CD38+HLA-DR-CD45 ± 8.8 × 10⁻⁶-5 According to the ELN guidelines for AML MRD, the proportion of residual tumor cells in this patient was <0.1% of the total number of cells detected, thus qualifying as MRD negative. This corroborates that patient F001 is indeed a low-risk patient, demonstrating the accuracy of the "3+7" induction chemotherapy efficacy prediction method described in this invention.

[0070] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A system for predicting the efficacy of "3+7" induction chemotherapy in patients with acute myeloid leukemia, characterized in that, The system includes: (1) Data acquisition module, used to acquire cell counts with leukemia immunophenotype in peripheral blood samples of patients before induction chemotherapy and on day 4 of induction chemotherapy; (2) A prediction module is used to provide a risk prediction model with the cell count of the leukemia immunophenotype in the peripheral blood sample obtained by the data acquisition module as input data. The risk prediction model predicts the efficacy of induction chemotherapy based on the degree of decrease in the cell count of the leukemia immunophenotype in the peripheral blood sample. (3) Prediction result acquisition module, used to acquire the output result of the risk prediction model in the prediction module, and obtain the prediction result of the induction chemotherapy efficacy of the patient with acute myeloid leukemia to be tested; The risk prediction model predicts the efficacy of induction chemotherapy based on the degree of decrease in the cell count of leukemia immunophenotype in peripheral blood samples as follows: if the cell count of leukemia immunophenotype in peripheral blood samples on day 4 of induction chemotherapy decreases by ≥1.5 log compared to before induction chemotherapy, the patient is considered sensitive to induction chemotherapy; if the cell count of leukemia immunophenotype in peripheral blood samples on day 4 of induction chemotherapy decreases by <1.5 log compared to before induction chemotherapy, the patient is considered insensitive to induction chemotherapy.

2. The system according to claim 1, characterized in that, The leukemia immunophenotypes include CD7, CD20, CD19, CD123, CD33, CD117, CD34, CD38, CD10, HLADR, CD36, CD13, CD64, CD11B, CD56, CD16, CD14, CD15, TDT, CD22, mCD3, cCD3, MPO, cCD79a, CD2, CD5, CD4, and CD45.

3. The system according to claim 1, characterized in that, The cell counts were obtained using flow cytometry.

4. The system according to claim 1, characterized in that, The peripheral blood samples were collected using blood collection tubes containing EDTA anticoagulant.

5. The use of the system according to any one of claims 1 to 4 in the preparation of a product for predicting the efficacy of "3+7" induction chemotherapy in patients with acute myeloid leukemia.

6. The use of the system according to any one of claims 1 to 4 in the preparation of a product for assisting in predicting the efficacy of "3+7" induction chemotherapy in patients with acute myeloid leukemia.

7. A kit for predicting the efficacy of "3+7" induction chemotherapy in patients with acute myeloid leukemia, characterized in that, The reagents include those for implementing modules in the system according to any one of claims 1 to 4.

8. A computer device for predicting the efficacy of "3+7" induction chemotherapy in patients with acute myeloid leukemia, comprising a memory, a processor, and a computer program stored in the memory and executable on the processor, characterized in that, The processor executes the computer program to construct the system according to any one of claims 1 to 4.

9. A computer-readable storage medium having a computer program stored thereon, characterized in that, When the computer program is executed by the processor, it constructs the system according to any one of claims 1 to 4.

10. A computer program product, comprising a computer program, characterized in that, When the computer program is executed by the processor, it constructs the system according to any one of claims 1 to 4.

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