System for predicting post-transplant refractory and / or recurrent cytomegalovirus infection and applications

Abstract

The application discloses a system for predicting intractable and recurrent cytomegalovirus infection after haplotype transplantation and application. The application provides a data processing device for predicting cytomegalovirus infection after haplotype transplantation of an acute leukemia patient, which is provided with a data input module, a data operation module, a threshold storage module, a data comparison module and a conclusion output module; a CMV infection incidence prediction value of a to-be-tested person is calculated according to age, a cumulative dose of prednisone before implantation, absolute values of CD34 + cells of a graft, a primary disease assignment value (acute myeloid leukemia: 0, acute lymphoblastic leukemia: 1), a gender assignment value (male: 0, female: 1); and the intractable and recurrent cytomegalovirus infection after haplotype transplantation is predicted by comparing the CMV infection incidence prediction value with a CMV incidence threshold value (0.5243). The application has very important clinical significance for predicting the occurrence of intractable and / or recurrent CMV infection after HID HSCT.

Description

Technical Field

[0001] This invention relates to the field of biomedicine, and more specifically to a data processing device, system, and application for predicting refractory and / or recurrent cytomegalovirus infection after haplotype transplantation. Background Technology

[0002] Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the most important radical treatment for acute leukemia, and haploidentical donors (HID) are currently the most important source of donors. However, infection is a common complication after haploidentical transplantation (HID-HSCT) and the leading cause of transplant-related death after HID HSCT. Cytomegalovirus (CMV) infection is the most common infectious event after HID HSCT. The cumulative incidence of CMV is approximately 60-70% in patients receiving anti-thymocyte globulin (ATG)-based conditioning regimens and 40-50% in patients receiving post-transplant cyclophosphamide (PTCy)-based conditioning regimens. Although various antiviral treatments (such as ganciclovir and foscarnet) are available, the side effects of these drugs are often amplified after HID HSCT because poor engraftment function (PGF) and conditioning-related toxicities are more common in patients receiving HID HSCT. Furthermore, even after receiving antiviral therapy, 50.6% and 30.3% of these patients presented with refractory and recurrent CMV infection, respectively, and refractory and / or recurrent CMV infection were independent risk factors for non-recurrent death (NRM) after transplantation.

[0003] Previous studies have identified a number of risk factors associated with CMV infection, such as age, use of ATG therapy, and previous or long-term use of anti-CMV drugs. Since most CMV infections occur in the early stages after HID HSCT implantation, we hypothesize that pre-implantation variables (e.g., pre-implantation glucocorticoid exposure) may also be associated with post-implantation CMV activation. However, there is currently no comprehensive model that includes patient, transplant-related, and pre-implantation characteristics to predict refractory and / or recurrent CMV infection after HID HSCT.

[0004] How to design a comprehensive predictive model to predict the occurrence of CMV infection after HID HSCT? Further research is needed. Providing a comprehensive predictive model that can simultaneously consider various risk factors such as patient characteristics, transplantation, and pre-implantation features to predict the occurrence of refractory and / or recurrent CMV infection after HID HSCT has significant clinical implications. Summary of the Invention

[0005] The purpose of this invention is to provide a data processing device, system, and application for predicting refractory and relapsed cytomegalovirus infection after haplotype transplantation. In this invention, the haplotype transplantation is haploidentical donor hematopoietic stem cell transplantation (HID-HSCT).

[0006] In a first aspect, the present invention claims a data processing device for predicting haplotype cytomegalovirus infection after transplantation in patients with acute leukemia.

[0007] The data processing apparatus claimed in this invention for predicting haplotype cytomegalovirus infection after transplantation in patients with acute leukemia includes the following modules: (A1) Data input module; the data input module is configured to input the following data of the subject: age (in years, rounded to the nearest integer), cumulative prednisone dose before implantation (mg / kg), and graft CD34. + Absolute cell count (×10) 6 / kg), primary disease value, and gender value; the primary disease value is: 0 for acute myeloid leukemia and 1 for acute lymphoblastic leukemia; the gender value is: 0 for male and 1 for female. (A2) Data processing module; the data processing module is configured to receive data sent from the data input module and calculate the predicted CMV infection rate of the subject according to formula I; Predicted CMV infection rate = Formula I; Where, Y = 0.0322 × (age value) - 0.0696 × (gender value) + 0.5492 × (primary disease value) + 0.0963 × (cumulative prednisone dose before implantation) - 0.0771 × (graft CD34) + (Absolute cell count) -1.2926; (A3) Threshold storage module; the threshold storage module is configured to store a CMV occurrence rate threshold; the CMV occurrence rate threshold is 0.5243; (A4) Data comparison module; The data comparison module is configured to receive the predicted CMV incidence rate of the subject calculated by the data processing module, and call the CMV incidence rate threshold stored in the threshold storage module, and then compare them; (A5) Conclusion Output Module; The conclusion output module is configured to receive the comparison result sent by the data comparison module, and then output the conclusion as follows: If the predicted CMV incidence rate of the subject is greater than the CMV incidence rate threshold, then the conclusion that the probability of cytomegalovirus infection after haplotype transplantation of the subject is relatively high is output. If the predicted CMV incidence rate of the subject is less than or equal to the CMV incidence rate threshold, the conclusion that the probability of cytomegalovirus infection after haplotype transplantation of the subject is relatively low is output.

[0008] In other words, subjects with a predicted CMV incidence rate greater than the CMV incidence rate threshold (0.5243) have a relatively high probability of developing cytomegalovirus infection after haplotype transplantation, while subjects with a predicted CMV incidence rate less than or equal to the CMV incidence rate threshold (0.5243) have a relatively low probability of developing cytomegalovirus infection after haplotype transplantation.

[0009] In this invention, the data processing device can be implemented by software program or by hardware that implements the functions of the corresponding modules, and this invention does not impose any restrictions on this.

[0010] In a preferred embodiment, the data processing apparatus of the present invention may further include a control module or controller, which is used to control the various modules.

[0011] In this invention, the function of the control module or controller is to control the input of data and the output of results, the transmission of data between modules, and the data processing routines of each module. Therefore, as long as the above functions can be achieved, any control device or controller, such as a central processing unit (CPU) or an industrial computer control chip, can be used.

[0012] Secondly, the present invention claims a system for predicting cytomegalovirus infection after haplotype transplantation in patients with acute leukemia.

[0013] The system claimed in this invention for predicting haplotype cytomegalovirus infection after transplantation in patients with acute leukemia may include: (B1) Reagents and / or instruments used to detect the cumulative prednisone dose (mg / kg) before implantation in the subject; (B2) Used to detect CD34 in transplanted subjects. + Absolute cell count (×10) 6 Reagents and / or instruments per kg, such as human CD34 molecular detection kits and flow cytometers; (B3) Reagents and / or instruments used for clinical diagnosis of the primary disease type of acute leukemia in the subject, such as bone marrow morphology examination, flow cytometer, etc.; wherein the primary disease type of acute leukemia is acute myeloid leukemia and acute lymphoblastic leukemia.

[0014] (B4) Control devices and output devices; The control device is configured or programmed to perform the following steps: The recipient's age (in years, rounded to the nearest integer), cumulative prednisone dose before implantation (mg / kg), and graft CD34 count were also received. + Absolute cell count (×10) 6 / kg), primary disease value, and gender value; the primary disease value is: 0 for acute myeloid leukemia and 1 for acute lymphoblastic leukemia; the gender value is: 0 for male and 1 for female. The predicted CMV infection rate of the subject was calculated according to Formula I. Predicted CMV infection rate = Formula I; Where, Y = 0.0322 × (age value) - 0.0696 × (gender value) + 0.5492 × (primary disease value) + 0.0963 × (cumulative prednisone dose before implantation) - 0.0771 × (graft CD34) + (Absolute cell count) -1.2926; The calculated predicted CMV incidence rate of the subject is compared with a CMV incidence rate threshold of 0.5243. If the predicted CMV incidence rate of the subject is greater than the CMV incidence rate threshold, the output device is controlled to output the conclusion that the probability of cytomegalovirus infection after haplotype transplantation of the subject is relatively high. If the predicted CMV incidence rate of the subject is less than or equal to the CMV incidence rate threshold, the output device is controlled to output the conclusion that the probability of cytomegalovirus infection after haplotype transplantation of the subject is relatively low.

[0015] In the above system, the control device can be any computer capable of performing the above steps, such as a personal computer (PC), an industrial control computer, or other general-purpose computer.

[0016] The system may also include an input device configured to input the subject's age (years), prednisone cumulative dose before implantation (mg / kg), and graft CD34 levels. + Absolute cell count (×10) 6 / kg), primary disease value, and gender value; the primary disease value is: 0 for acute myeloid leukemia and 1 for acute lymphoblastic leukemia; the gender value is: 0 for male and 1 for female.

[0017] In this invention, the input device can be any type of common input device used for various types of data, such as a keyboard, mouse, camera, scanner, light pen, handwriting input tablet, joystick, voice input device, etc. The output device can be any type of common output device used for various types of data, such as a monitor, printer, plotter, image output system, voice output system, magnetic recording device, etc.

[0018] Thirdly, the present invention claims protection for a method of using the system described above, which may include the following steps: obtaining the cumulative prednisone dose (mg / kg) of the subject before implantation using the reagents and / or instruments in (B1); obtaining the CD34 of the graft in the subject using the reagents and / or instruments in (B2). + Absolute cell count (×10) 6 / kg); using the reagents and / or instruments in (B3) to obtain the primary disease type of acute leukemia in the subject; then using the control device in the system described above to perform the steps to obtain a predicted result of the CMV incidence rate of the subject.

[0019] Fourthly, the present invention claims protection for a computer-readable storage medium.

[0020] The computer-readable storage medium claimed in this invention stores a computer program for performing the following steps: The recipient's age (in years, rounded to the nearest integer), cumulative prednisone dose before implantation (mg / kg), and graft CD34 count were also received. + Absolute cell count (×10) 6 / kg), primary disease value, and gender value; the primary disease value is: 0 for acute myeloid leukemia and 1 for acute lymphoblastic leukemia; the gender value is: 0 for male and 1 for female. The predicted CMV infection rate of the subject was calculated according to Formula I. Predicted CMV infection rate = Formula I; Where, Y = 0.0322 × (age value) - 0.0696 × (gender value) + 0.5492 × (primary disease value) + 0.0963 × (cumulative prednisone dose before implantation) - 0.0771 × (graft CD34) + (Absolute cell count) -1.2926; The calculated predicted CMV incidence rate of the subject is compared with a CMV incidence rate threshold of 0.5243. If the predicted CMV incidence rate of the subject is greater than the CMV incidence rate threshold, the output device is controlled to output the conclusion that the probability of cytomegalovirus infection after haplotype transplantation of the subject is relatively high. If the predicted CMV incidence rate of the subject is less than or equal to the CMV incidence rate threshold, the output device is controlled to output the conclusion that the probability of cytomegalovirus infection after haplotype transplantation of the subject is relatively low.

[0021] In the above aspects, the prediction of cytomegalovirus infection after haplotype transplantation in acute leukemia patients can specifically be any of the following situations: P1. Predict the probability of refractory and / or relapsed CMV infection in patients with acute leukemia after haplotype transplantation; P2. Predict the probability of total CMV infection after haplotype transplantation in acute leukemia patients; P3. Predict the probability of refractory and / or relapsed CMV infection in acute leukemia patients who have not developed aGVHD after haplotype transplantation. P4. Predict the probability of total CMV infection in acute leukemia patients who have not developed aGVHD after haplotype transplantation. P5. Predicting the probability of refractory and / or relapsed CMV infection in acute leukemia patients who develop aGVHD after haplotype transplantation.

[0022] The term "refractory CMV infection" refers to at least one of the following (1)-4) after at least 2 weeks of anti-CMV treatment: 1) a 10-fold increase in peripheral blood CMV DNA copy number; 2) persistently high CMV viral load; 3) worsening of signs / symptoms or progression to end-organ disease; 4) no improvement in signs / symptoms. The term "relapsed CMV infection" refers to the re-detection of CMV infection in patients with a previous record of CMV infection and at least a 4-week interval without viral detection. The term "CMV disease" refers to severe infection caused by CMV virus affecting end-organs, such as CMV pneumonia, enteritis, retinitis, encephalitis, hepatitis, etc. The term "total CMV infection" refers to positive CMV DNA testing in peripheral blood after transplantation and / or concurrent end-organ involvement, including any type of CMV infection, including the aforementioned refractory CMV infection, relapsed CMV infection, and CMV disease. All the above technical terms are well-known and recognized technical terms in the art.

[0023] Fifthly, the present invention claims the use of M1 in the preparation of a product for predicting cytomegalovirus infection after haplotype transplantation in patients with acute leukemia. M1 may include: reagents and / or instruments for detecting the cumulative prednisone dose (mg / kg) before implantation in the subject; and for detecting CD34 in the graft of the subject. + Absolute cell count (×10) 6 Reagents and / or instruments ( / kg); reagents and / or instruments for clinical diagnosis of the primary disease type of acute leukemia in subjects; and the data processing device described in the first aspect above.

[0024] Sixthly, the present invention claims the use of the system described in the second aspect above in the preparation of products for predicting cytomegalovirus infection after haplotype transplantation in patients with acute leukemia.

[0025] In both the fifth and sixth aspects, the prediction of cytomegalovirus infection after haplotype transplantation in acute leukemia patients can specifically be any of the following: P1. Predict the probability of refractory and / or relapsed CMV infection in patients with acute leukemia after haplotype transplantation; P2. Predict the probability of total CMV infection after haplotype transplantation in acute leukemia patients; P3. Predict the probability of refractory and / or relapsed CMV infection in acute leukemia patients who have not developed aGVHD after haplotype transplantation. P4. Predict the probability of total CMV infection in acute leukemia patients who have not developed aGVHD after haplotype transplantation. P5. Predicting the probability of refractory and / or relapsed CMV infection in acute leukemia patients who develop aGVHD after haplotype transplantation.

[0026] In this invention, the prediction of cytomegalovirus infection after haplotype transplantation in acute leukemia patients is the prediction of the probability of cytomegalovirus infection occurring within 100 days after haplotype transplantation in acute leukemia patients.

[0027] This invention presents a comprehensive predictive model that simultaneously considers various risk factors, including patient characteristics, transplantation, and pre-implantation features, and provides corresponding data processing devices and systems. This invention has significant clinical implications for predicting the occurrence of refractory and / or recurrent CMV infection after HID-HSCT. Attached Figure Description

[0028] Figure 1 This describes the process of establishing a mathematical model.

[0029] Figure 2ROC curves and confusion matrices were modeled in the cohort (A) and validation cohort (B) with refractory and / or relapsed CMV infection as the endpoint.

[0030] Figure 3 The cumulative incidence of refractory and / or relapsed CMV infection (A) and total CMV infection (B) at 100 days in the high-risk and low-risk groups of the overall cohort.

[0031] Figure 4 The cumulative incidence of refractory and / or recurrent CMV infection at 100 days in patients without aGVHD (A) and those with aGVHD (B).

[0032] Figure 5 A computer flowchart illustrating the prediction of cytomegalovirus infection after haplotype transplantation in patients with acute leukemia, as described in this invention. Detailed Implementation

[0033] The present invention will now be described in further detail with reference to specific embodiments. The given embodiments are merely illustrative of the invention and not intended to limit its scope. The embodiments provided below can serve as a guide for further improvements by those skilled in the art and do not constitute a limitation on the invention in any way.

[0034] Unless otherwise specified, the experimental methods used in the following examples are conventional methods, performed according to the techniques or conditions described in the literature in this field or according to the product instructions. Unless otherwise specified, the materials and reagents used in the following examples are commercially available.

[0035] Example 1: Predicting refractory and / or relapsed cytomegalovirus infection after haplotype transplantation I. Subjects and CMV infection surveillance and prevention protocols 1. This prospective study included 289 patients with acute leukemia who underwent HIDHSCT. 60% of patients (n=170) were randomly selected to form a modeling cohort for mathematical modeling, and the remaining 40% (n=119) served as a validation cohort to validate the mathematical model. The primary endpoint was refractory and / or relapsed CMV infection. Refractory CMV infection was defined as: 1) a 10-fold increase in peripheral blood CMV DNA copy number after at least 2 weeks of appropriate anti-CMV therapy; 2) persistently high CMV viral load; 3) worsening of signs / symptoms or progression to end-organ disease; and / or 4) no improvement in signs / symptoms. Relapsed CMV infection was defined as a re-detection of CMV infection in patients with a previous history of CMV infection who had been virus-free for at least 4 weeks. Refractory and / or relapsed CMV infection includes cases where, after at least 2 weeks of appropriate doses of anti-CMV therapy: 1) a 10-fold increase in peripheral blood CMV DNA copy number; 2) CMV viral load remains at the same level; 3) worsening of signs / symptoms or progression to end-organ disease; 4) no improvement in signs / symptoms; and / or 5) re-detection of CMV infection in patients with a history of previous CMV infection and no detectable virus for at least 4 weeks.

[0036] 2. CMV Infection Surveillance and Prevention Protocol: Ganciclovir 5 mg / kg / dose twice daily for 9 to 1 day before transplantation to prevent CMV activation; acyclovir (200-400 mg / dose twice daily) for prophylaxis after transplantation. Quantitative polymerase chain reaction (PCR) analysis of plasma CMV copies should be performed at least weekly until day 100. A single peripheral blood PCR test should show a result >1×10⁻⁶. 3 When CMV levels are 1 copy / mL, administer intravenous ganciclovir or intravenous foscarnet for antiviral therapy. After initiating antiviral therapy, perform PCR analysis of plasma CMV copies at least twice weekly until two negative results are obtained. For patients presenting with refractory and / or relapsed CMV infection, combination therapy with ganciclovir and foscarnet may be considered.

[0037] II. Model Establishment and Analysis Methods 1. Backward Feature Selection Strategy: This invention randomly selects 60% (n=170) of the entire population as the modeling cohort and the remaining 40% as the validation cohort (n=119). Using refractory and / or recurrent CMV infection as the research endpoint, a predictive model is constructed in the modeling cohort and validated in the validation cohort. This invention uses sensitivity, specificity, area under the ROC curve, and accuracy to evaluate the model's performance in the modeling and validation cohorts, respectively.

[0038] This invention employs feature selection techniques to choose effective predictive variables. Feature selection reduces the complexity of machine learning models while improving their generalization ability. This invention sets age and gender as mandatory variables for the machine learning model. For other variables, a backward feature selection strategy is used to select the top three most important variables. Specifically, the initial model considers all variables, including age and gender. In each iteration, except for age and gender, the variable with the lowest importance in the current model (i.e., the variable with the least significant p-value) is removed. In addition to the aforementioned variables, an extra constant variable is added to increase the robustness of feature selection. This invention is developed on the Anaconda3 platform and implements this feature selection technique using a generalized linear model with a binomial exponential family distribution from the statsmodels v0.13.0 statistical model module in Python 3.8.

[0039] 2. Model Building: The process of building a mathematical model is as follows: Figure 1 As shown. In the model building phase, this invention also uses a generalized linear model with a binomial exponential family distribution to construct the prediction model, which is equivalent to a logistic regression model. In addition to the five variables selected above, this invention adds an extra constant variable to the prediction model to increase the predictive performance of the machine learning model. This invention is based on the Anaconda3 development platform and uses Python 3.8's statsmodelsv0.13.0 to construct the prediction model, with all model parameters set to default values.

[0040] 3. Finding the Optimal Threshold: The predictive model (Logistic Regression model) outputs a value between 0 and 1, which is usually regarded as the probability of predicting a positive sample. In order to output the final predicted positive sample (1) or negative sample (0) result, this invention needs to determine the threshold based on the probability. Specifically, this invention needs to first plot the receiver operating characteristic curve on the training set, and then calculate the g-mean value corresponding to each threshold. The optimal threshold corresponds to the largest g-mean value. The g-mean value is calculated as g-mean = sqrt(tpr × (1-fpr)), where tpr represents the true positive rate under a given threshold, and fpr represents the false positive rate.

[0041] 4. Evaluation index: ROC-AUC is defined as the area under the curve formed by the true positive rate and false positive rate and the coordinate axis at each threshold from 0 to 1.

[0042] A confusion matrix is ​​a summary table of prediction results. In this paper, the confusion matrix is ​​2x2, with the values ​​on its diagonal representing the number of correct predictions and the values ​​in the remaining positions representing the number of incorrect predictions. Furthermore, this invention normalizes the number of predictions using either the number of true labels or the number of predicted labels.

[0043] III. Results and Analysis 1. Patient's condition The patient's general condition is shown in Table 1.

[0044] Table 1. General Information of Patients

[0045] Note: CR stands for complete remission; HLA stands for human leukocyte antigen; HCTCI stands for hematopoietic stem cell transplantation comorbidity index; TBI stands for total body irradiation.

[0046] Following HID HSCT, 231 (79.9%), 136 (47.1%), 29 (9.7%), and 146 (50.5%) patients developed CMV infection, refractory CMV infection, recurrent CMV infection, and refractory and / or recurrent CMV infection (19 of whom had both refractory and recurrent CMV infection). The median time to first CMV infection was 32 days (17–76). Five patients developed CMV disease (pneumonia: 2; enteritis: 2; cystitis: 1). Initial plasma CMV-DNA levels were 2.4 (1.0–100.0) × 10⁻⁶. 3 The highest plasma level of CMV-DNA was 7.23 (1.01-730.00) × 10 copies / mL. 3 copies / mL. At 100 days post-transplantation, the cumulative incidence of total CMV infection, refractory CMV infection, relapsed CMV infection, and refractory / relapsed CMV infection were 79.9% (95% CI, 75.3%-84.5%), 47.1% (95% CI, 41.3%-52.9%), 9.7% (95% CI, 6.3%-13.1%), and 50.5% (95% CI, 44.7%-56.3%), respectively.

[0047] 2. Model Construction: The mathematical model for predicting refractory and / or relapsed CMV infection is as follows: Incidence (refractory and / or recurrent CMV infection) = .

[0048] Y = 0.0322 × (age) - 0.0696 × (sex) + 0.5492 × (primary disease) + 0.0963 × (cumulative prednisone dose before implantation) - 0.0771 × (graft CD34) + (Absolute cell count) -1.2926.

[0049] Among them, age (years, rounded to the nearest integer), cumulative prednisone dose before implantation (mg / kg), and graft CD34 + Absolute cell count (×10) 6 / kg) represents a specific numerical value; primary disease is assigned values: 0: acute myeloid leukemia; 1: acute lymphoblastic leukemia. Gender is assigned values: 0: male; 1: female. The incidence threshold is 0.5243, and the g-mean is 0.635. Patients are divided into high-risk and low-risk groups based on the threshold: an incidence rate greater than the threshold is considered high-risk, and an incidence rate less than or equal to the threshold is considered low-risk.

[0050] 3. Sensitivity, specificity, area under the ROC curve, and accuracy of the modeling and validation cohorts. In the modeling queue, the model's sensitivity, specificity, area under the ROC curve, and accuracy were 0.531, 0.742, 0.654, and 0.641, respectively. Figure 2 (A)). In the validation queue, the model's sensitivity, specificity, area under the ROC curve, and accuracy were 0.446, 0.667, 0.586, and 0.546, respectively. Figure 2 (B) Therefore, the effectiveness of the model was verified in the validation queue.

[0051] 4. Occurrence of refractory and / or relapsed CMV infection in high-risk and low-risk groups in the overall cohort. In the overall cohort, the cumulative incidence of refractory and / or relapsed CMV infection at 100 days was 42.0% (95% CI, 34.7%–49.4%) in the low-risk group and 63.7% (95% CI, 54.8%–72.6%) in the high-risk group (P<0.001). Figure 3 (A)

[0052] 5. Occurrence of total CMV infection in high-risk and low-risk groups in the overall cohort. In the overall cohort, the cumulative incidence of total CMV infection over 100 days was 74.4% (95% CI, 67.9%–80.9%) in the low-risk group and 88.5% (95% CI, 82.6%–94.4%) in the high-risk group (P = 0.004). Figure 3 (B)

[0053] Total CMV infection: refers to positive CMV DNA test in peripheral blood after transplantation and / or involvement of end organs, including any type of CMV infection, such as refractory CMV infection, relapsed CMV infection, and CMV disease.

[0054] 6. Incidence of CMV disease in high-risk and low-risk groups in the overall cohort. In the overall cohort, the cumulative incidence of CMV disease over 100 days was 0.6% (0.0%-1.7%) in the low-risk group and 3.5% (0.1%-6.9%) in the high-risk group (P = 0.059).

[0055] CMV disease refers to severe infections caused by the CMV virus that affect end organs, such as CMV pneumonia, enteritis, retinitis, encephalitis, and hepatitis.

[0056] 7. In patients without aGVHD and in those with aGVHD, and in high-risk and low-risk groups, refractory and / or recurrent CMV infections. In patients who did not develop aGVHD (n = 122), the cumulative incidence of refractory and / or recurrent CMV infection at 100 days post-transplantation was 29.6% (95% CI, 18.9%–40.3%) in the low-risk group and 54.9% (95% CI, 41.0%–68.8%) in the high-risk group (P = 0.003). Figure 4 (A) Furthermore, the overall CMV infection rate was lower in the low-risk group than in the high-risk group (69.0%, [95% CI, 58.1%–79.9%] and 88.2%, [95% CI, 79.0%–97.4%], P = 0.001).

[0057] In patients who developed aGVHD (n = 167), the cumulative incidence of refractory and / or recurrent CMV infection at 100 days post-transplantation was 50.5% (95% CI, 40.9%–60.1%) in the low-risk group and 71.0% (95% CI, 59.5%–82.4%) in the high-risk group (P = 0.024). Figure 4 (B)

[0058] Figure 5 A computer flowchart illustrating the prediction of cytomegalovirus infection after haplotype transplantation in patients with acute leukemia, as described in this invention.

[0059] In step S1, the subject's age, pre-implantation cumulative prednisone dose, and graft CD34 levels are received. + The values ​​are: absolute cell count, primary disease, and gender. The primary disease is assigned as follows: 0 for acute myeloid leukemia and 1 for acute lymphoblastic leukemia. The gender is assigned as follows: 0 for male and 1 for female. In step S2, the predicted CMV infection rate of the subject is calculated according to formula I; Predicted CMV infection rate = Formula I; Where, Y = 0.0322 × (age value) - 0.0696 × (gender value) + 0.5492 × (primary disease value) + 0.0963 × (cumulative prednisone dose before implantation) - 0.0771 × (graft CD34) + (Absolute cell count) -1.2926; In step S3, the calculated predicted CMV incidence rate of the subject is compared with the CMV incidence rate threshold; the CMV incidence rate threshold is 0.5243. In step S4, based on the comparison results of S3, the following conclusions are output: if the predicted CMV incidence rate of the subject is greater than the CMV incidence rate threshold, the output device is controlled to output the conclusion that the probability of cytomegalovirus infection after haplotype transplantation of the subject is relatively high; if the predicted CMV incidence rate of the subject is less than or equal to the CMV incidence rate threshold, the output device is controlled to output the conclusion that the probability of cytomegalovirus infection after haplotype transplantation of the subject is relatively low.

[0060] The present invention has been described in detail above. For those skilled in the art, the invention can be practiced in a wide range of ways with equivalent parameters, concentrations, and conditions without departing from its spirit and scope, and without requiring unnecessary experiments. Although specific embodiments have been given, it should be understood that further modifications can be made to the invention. In summary, according to the principles of the invention, this application is intended to include any changes, uses, or improvements to the invention, including changes made using conventional techniques known in the art that depart from the scope disclosed herein. Some of the essential features can be applied within the scope of the following appended claims.

Claims

1. A data processing device for predicting haplotype cytomegalovirus infection after transplantation in patients with acute leukemia, comprising the following modules: (A1) Data input module; the data input module is configured to input the following data of the subject: age, cumulative prednisone dose before implantation, and graft CD34. + Absolute cell count, primary disease value, and gender value; the primary disease value is: 0 for acute myeloid leukemia and 1 for acute lymphoblastic leukemia; the gender value is: 0 for male and 1 for female. (A2) Data processing module; the data processing module is configured to receive data sent from the data input module and calculate the predicted value of the cytomegalovirus infection incidence rate of the subject according to formula I; Predicted incidence of cytomegalovirus infection = Formula I; in, Y = 0.0322 × (age value) - 0.0696 × (gender value) + 0.5492 × (primary disease value) + 0.0963 × (cumulative prednisone dose before implantation) - 0.0771 × (graft CD34) + (Absolute cell count) - 1.2926; (A3) Threshold storage module; the threshold storage module is configured to store a cytomegalovirus infection incidence rate threshold; the cytomegalovirus infection incidence rate threshold is 0.5243; (A4) Data comparison module; The data comparison module is configured to receive the predicted value of the cytomegalovirus infection rate of the subject calculated by the data processing module, and call the cytomegalovirus infection rate threshold stored in the threshold storage module, and then compare them; (A5) Conclusion Output Module; The conclusion output module is configured to receive the comparison result sent by the data comparison module, and then output the conclusion as follows: If the predicted incidence of cytomegalovirus infection in the subject is greater than the cytomegalovirus infection incidence threshold, then the conclusion that the probability of cytomegalovirus infection after haplotype transplantation in the subject is relatively high is output. If the predicted incidence of cytomegalovirus infection in the subject is less than or equal to the cytomegalovirus infection incidence threshold, then the conclusion that the probability of cytomegalovirus infection after haplotype transplantation in the subject is relatively low is output. The prediction of cytomegalovirus infection after haplotype transplantation in acute leukemia patients is based on any of the following conditions: P1. Predict the probability of refractory and / or relapsed cytomegalovirus infection in patients with acute leukemia after haplotype transplantation; P2. Predict the probability of total cytomegalovirus infection after haplotype transplantation in patients with acute leukemia; P3. Predict the probability of refractory and / or relapsed cytomegalovirus infection in acute leukemia patients who have not developed aGVHD after haplotype transplantation. P4. Predict the probability of total cytomegalovirus infection in acute leukemia patients who have not developed aGVHD after haplotype transplantation. P5. Predicting the probability of refractory and / or relapsed cytomegalovirus infection in acute leukemia patients who develop aGVHD after haplotype transplantation.

2. The data processing apparatus according to claim 1, characterized in that: The data processing device further includes a control module or controller; the control module or controller is used to control each module.

3. Systems for predicting haplotype-associated cytomegalovirus infection in patients with acute leukemia, including: (B1) Reagents and / or instruments used to detect the cumulative prednisone dose value before implantation in the subject; (B2) Used to detect CD34 in transplanted subjects. + Reagents and / or instruments for absolute cell counts; (B3) Reagents and / or instruments used for clinical diagnosis of the primary disease type of acute leukemia in test subjects; (B4) Control devices and output devices; The control device is configured or programmed to perform the following steps: Receiving the subject's age, cumulative prednisone dose before implantation, and graft CD34 levels. + Absolute cell count, primary disease value, and gender value; the primary disease value is: 0 for acute myeloid leukemia and 1 for acute lymphoblastic leukemia; the gender value is: 0 for male and 1 for female. The predicted incidence of cytomegalovirus infection in the subject was calculated according to Formula I. Predicted incidence of cytomegalovirus infection = Formula I; Where Y = 0.0322 × (age value) - 0.0696 × (gender value) + 0.5492 × (primary disease value) + 0.0963 × (cumulative prednisone dose before implantation) - 0.0771 × (graft CD34) + (Absolute cell count) - 1.2926; The calculated predicted incidence of cytomegalovirus (CMV) infection in the subject is compared with a CMV infection incidence threshold of 0.5243. If the predicted incidence of CMV infection in the subject is greater than the CMV infection incidence threshold, the output device is controlled to output the conclusion that the probability of CMV infection after haplotype transplantation in the subject is relatively high. If the predicted incidence of CMV infection in the subject is less than or equal to the CMV infection incidence threshold, the output device is controlled to output the conclusion that the probability of CMV infection after haplotype transplantation in the subject is relatively low. The prediction of cytomegalovirus infection after haplotype transplantation in acute leukemia patients is based on any of the following conditions: P1. Predict the probability of refractory and / or relapsed cytomegalovirus infection in patients with acute leukemia after haplotype transplantation; P2. Predict the probability of total cytomegalovirus infection after haplotype transplantation in patients with acute leukemia; P3. Predict the probability of refractory and / or relapsed cytomegalovirus infection in acute leukemia patients who have not developed aGVHD after haplotype transplantation. P4. Predict the probability of total cytomegalovirus infection in acute leukemia patients who have not developed aGVHD after haplotype transplantation. P5. Predicting the probability of refractory and / or relapsed cytomegalovirus infection in acute leukemia patients who develop aGVHD after haplotype transplantation.

4. The method of using the system of claim 3, comprising the following steps: obtaining the cumulative prednisone dose value of the subject before implantation using the reagents and / or instruments in (B1); obtaining the CD34 of the graft in the subject using the reagents and / or instruments in (B2). + Absolute cell count; obtaining the primary disease type of acute leukemia in the subject using the reagents and / or instruments in (B3); then performing the steps using the control device in the system of claim 3 to obtain a predicted result of the cytomegalovirus infection rate in the subject.

5. A computer-readable storage medium storing a computer program for performing the following steps: Receiving the subject's age, cumulative prednisone dose before implantation, and graft CD34 levels. + Absolute cell count, primary disease value, and gender value; the primary disease value is: 0 for acute myeloid leukemia and 1 for acute lymphoblastic leukemia; the gender value is: 0 for male and 1 for female. The predicted incidence of cytomegalovirus infection in the subject was calculated according to Formula I. Predicted incidence of cytomegalovirus infection = Formula I; in, Y = 0.0322 × (age value) - 0.0696 × (gender value) + 0.5492 × (primary disease value) + 0.0963 × (cumulative prednisone dose before implantation) - 0.0771 × (graft CD34) + (Absolute cell count) - 1.2926; The calculated predicted incidence of cytomegalovirus (CMV) infection in the subject is compared with a CMV infection incidence threshold of 0.5243. If the predicted incidence of CMV infection in the subject is greater than the CMV infection incidence threshold, the output device is controlled to output the conclusion that the probability of CMV infection after haplotype transplantation in the subject is relatively high. If the predicted incidence of CMV infection in the subject is less than or equal to the CMV infection incidence threshold, the output device is controlled to output the conclusion that the probability of CMV infection after haplotype transplantation in the subject is relatively low. The prediction of cytomegalovirus infection after haplotype transplantation in acute leukemia patients is based on any of the following conditions: P1. Predict the probability of refractory and / or relapsed cytomegalovirus infection in patients with acute leukemia after haplotype transplantation; P2. Predict the probability of total cytomegalovirus infection after haplotype transplantation in patients with acute leukemia; P3. Predict the probability of refractory and / or relapsed cytomegalovirus infection in acute leukemia patients who have not developed aGVHD after haplotype transplantation. P4. Predict the probability of total cytomegalovirus infection in acute leukemia patients who have not developed aGVHD after haplotype transplantation. P5. Predicting the probability of refractory and / or relapsed cytomegalovirus infection in acute leukemia patients who develop aGVHD after haplotype transplantation.

6. The use of M1 in the preparation of products for predicting haplotype-related cytomegalovirus infection in patients with acute leukemia after transplantation; wherein M1 comprises: Reagents and / or instruments used to detect the cumulative prednisone dose before implantation in a subject; Used to detect CD34 in implants in test subjects. + Reagents and / or instruments for absolute cell counts; Reagents and / or instruments used for the clinical diagnosis of the primary disease type of acute leukemia in test subjects; And the data processing apparatus according to claim 1 or 2.

7. The use of the system of claim 3 in the preparation of a product for predicting haplotype cytomegalovirus infection after transplantation in patients with acute leukemia.

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