CMV Infection and Immune Intervention After Transplantation

Study Overview
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Brief Summary
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Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective or even the only way to cure blood malignant diseases. Cytomegalovirus (CMV) infection is a serious early complication of allo-HSCT. Its high incidence and poor prognosis can cause a series of terminal organ diseases such as CMV pneumonia, encephalitis, and enteritis,which seriously affecting the prognosis of patients post allo-HSCT. Our data show that rapid reconstruction of NK cells after transplantation can reduce the incidence of CMV infection. Patients with a rapid reconstruction of NKG2C after transplantation have a low CMV infection rate, and patients with strong secretion of IFN-gamma of NK after transplantation have low CMV infection. Our previous research showed that trophoblast cells transfected with IL-21 and 4-1BBL can achieve a large number of clinical-grade expansion of NK cells (mIL-21 / 4-1BBL NK cells), and mIL-21 / 4-1BBL NK cells It is safe to treat patients with minimal residual disease (MRD) positive AML after transplantation, and can induce MRD to turn negative. Previous studies have shown that adoptive infusion of expanded NK cells after haplotype transplantation is safe and can improve the functional reconstruction of NK cells. Therefore, we hypothesized that the infusion of NK cells can improve the antiviral capacity of NK cells, thereby effectively reducing the CMV infection. Incidence.

Official Title
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CMV Infection and Immune Intervention After Haploidentical Hematopoietic Stem Cell Transplantation

Conditions
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CMV Viremia, Transplantation Infection

Intervention / Treatment
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* Biological: expanded NK cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with acute leukemia (AL) or myelodysplastic syndrome (MDS) or myeloma or lymphoma undergoing haploidentical allogeneic stem cell transplantation No CMV infection by 20 days ± 3 days after transplantation No active acute GVHD by 20 days ± 3 days after transplantation The dose of prednisolone was less than 0.5mg / kg / d within 72 hours before and after infusion of NK cells Prior to transplantation, the CMV IgG of the recipient and donor were positive, and the recipient had a suitable donor to expand NK cells. Patient age 16-65 years Donor age 16-65 years Patient Karnofsky score> 70% Estimated survival> 3 weeks Patient agrees to participate in study Exclusion Criteria: Participants in any other clinical trials within 1 month before enrollment Active infection HBV or HCV or HIV carriers With moderate to severe renal dysfunction (blood creatinine> 130umol / L) and / or liver dysfunction (total bilirubin> 34umol / L, ALT, AST> 2 times the upper limit of normal) before NK infusion Researchers do not consider it appropriate to participate in this trial.

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: adaptive NK cells infusion post transplantation<br>Adaptive donors expanded NK cells infusion at day 20±3d and 27±3d post transplantation | Biological: expanded NK cells<br>* Donor derived expanded NK cells were infused to patients at around days 20±3d, and 27±3d post transplantation.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative incidence of CMV infection post transplantation | Whether to reduce the incidence of CMV infection in patients post haploidentical transplantation | within 180 days post transplantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative incidence of refractory CMV infection post transplantation | Whether to reduce the incidence of refractory CMV infection in patients post haploidentical transplantation | within 180 days post transplantation | 
| Cumulative incidence of CMV disease post transplantation | Whether to reduce the incidence of CMV disease in patients post haploidentical transplantation | within 180 days post transplantation | 
| Enhanced anti-CMV function of reconstituted NK cells | Whether to enhance the anti-CMV function of reconstituted NK cells | within 180 days post transplantation | 
| cumulative incidence of TRM | Whether to reduce the incidence of transplantation related mortality in patients post haploidentical transplantation | within 180 days post transplantation | 
| cumulative incidence of overall survival | Whether to increase the incidence of overall survival in patients post haploidentical transplantation | within 180 days post transplantation | 
| cumulative incidence of disease free survival | Whether to increase the incidence of disease free survival in patients post haploidentical transplantation | within 180 days post transplantation |