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Although patients with acute myeloid leukemia (AML) who have relapsed after allogeneic hematopoietic stem cell transplantation (allo-HSCT) can choose demethylating drugs, chemotherapy, donor lymphocyte infusion (DLI) or a second allo-HSCT, etc.
treatment, but the prognosis is still poor
.
Anti-CD123 chimeric antigen receptor-γδT (CAR-γδT) cells are a promising approach for AML treatment and may be a new option for relapsed AML after allo-HSCT
.
The team of Professor Jiang Erlie from the Hospital of Hematology, Chinese Academy of Medical Sciences applied universal anti-CD123 CAR-γδT cells combined with DLI to a patient with AML who had relapsed after allo-HSCT, and evaluated the efficacy and safety
.
The results were selected for the poster presentation of the 48th European Society of Blood and Marrow Transplantation (EBMT) annual meeting in 2022.
The editor will organize the main contents as follows for the reference of readers
.
Methods A 43-year-old male patient with myelodysplastic syndrome-transformed AML underwent haploid HSCT in June 2019
.
Before transplantation, the percentage of primitive monocytes in the bone marrow was 22%
.
Flow cytometry showed that primitive monocytes expressed CD34, CD123 and HLA-DR
.
He underwent a myeloablative conditioning regimen and successfully underwent hematopoietic reconstitution
.
Bone marrow examination showed complete remission and minimal residual disease (MRD) negative
.
Tandem repeats (STRs) show complete donor chimerism
.
To prevent recurrence, the patient received 6 cycles of azacitidine (50mg/m2/d*5d, once a month) 4 months after haploid HSCT
.
In July 2020, the patient had a positive MRD (1.
47%) recurrence
.
One course of azacitidine combined with low-dose cytarabine (20mg/m2/d*7) and two courses of veneclax (400mg/d*28) were given successively
.
Following the above treatments, the patient developed extensive chronic graft-versus-host disease (cGVHD) involving the skin, eyes and mouth
.
Unfortunately, in December 2020, 1.
5 years after haploid HSCT, the patient experienced a hematologic relapse
.
The percentage of primitive monocytes was 9.
5%, and the STR decreased to 78.
83%
.
Universal anti-CD123 CAR-γδ T cells were prepared from third-party cord blood
.
Briefly, γδ T cells were screened using the TCRg/d+ T cell isolation kit and stimulated with anti-gd TCR antibody
.
Activated gd T cells were transduced with anti-CD123 CAR-bearing lentivirus
.
The conditioning regimen was fludarabine 50 mg/d*5 and melphalan 50 mg/d*2
.
Patients received universal anti-CD123 CAR-γδ T cells (2.
5×106/kg), and 7 days later, G-CSF mobilized and cryopreserved donor monocytes (1.
98×108/kg) were infused, including 0.
693×108 /kg CD34+ stem cells and 1.
67×107/kg CD3+ T cells
.
To prevent GVHD, sirolimus (0.
5 mg/d) was started after donor cell infusion
.
Results After pretreatment, the MRD was 3.
69%, and the STR decreased to 61.
12%
.
Universal anti-CD123 CAR-γδ T cells rapidly proliferated from day +3 to day +7, and then declined
.
The patient developed grade 1 cytokine release syndrome (CRS), including fatigue, nausea, and headache, without neurotoxic syndrome
.
Seven days after CAR-γδ T cell infusion, bone marrow testing showed negative AML-MRD and STR increased to 90.
24%, followed by infusion of donor monocytes
.
On day 17 after CAR-γδT infusion, the patient was in the agranulocytosis phase with bacteremia and received antibiotics
.
After 21 days of CAR-γδ T cell infusion, the patient achieved MRD-negative remission and full donor chimerism
.
There was no acute GVHD (aGVHD) or new-onset cGVHD, and sirolimus was discontinued 1 month after DLI
.
Furthermore, after donor cell infusion, the number of universal anti-CD123 CAR-γδ T cells increased again, probably due to CD123 antigen expressed on donor cells (Panels A,B)
.
Six months later, the patient had another hematologic relapse and received supportive care
.
A: Percentage of anti-CD123 CAR-γδT in CD3+ T lymphocyte of the patient`s peripheral bloodB: The ratio of anti-CD123 CAR DNA to genome DNA of patient`s peripheral blood Research conclusion Universal anti-CD123 CAR-γδT combined with DLI Appears to be an effective and safe treatment for patients with relapsed AML after allo-HSCT
.
Reference source: R.
Zhang, R.
Jiang, X.
Chen, et al.
UNIVERSAL ANTI-CD123 CAR-γδT CELLS COMBINED WITH DONOR LYMPHOCYTES INFUSION FOR RELAPSED ACUTE MYELOID LEUKEMIA AFTER ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION.
The 48th Annual Meeting of the EBMT .
Abstract P122.
Editor: Quinta Review: Quinta Typesetting: Quinta pokes "read the original text", we make progress together
treatment, but the prognosis is still poor
.
Anti-CD123 chimeric antigen receptor-γδT (CAR-γδT) cells are a promising approach for AML treatment and may be a new option for relapsed AML after allo-HSCT
.
The team of Professor Jiang Erlie from the Hospital of Hematology, Chinese Academy of Medical Sciences applied universal anti-CD123 CAR-γδT cells combined with DLI to a patient with AML who had relapsed after allo-HSCT, and evaluated the efficacy and safety
.
The results were selected for the poster presentation of the 48th European Society of Blood and Marrow Transplantation (EBMT) annual meeting in 2022.
The editor will organize the main contents as follows for the reference of readers
.
Methods A 43-year-old male patient with myelodysplastic syndrome-transformed AML underwent haploid HSCT in June 2019
.
Before transplantation, the percentage of primitive monocytes in the bone marrow was 22%
.
Flow cytometry showed that primitive monocytes expressed CD34, CD123 and HLA-DR
.
He underwent a myeloablative conditioning regimen and successfully underwent hematopoietic reconstitution
.
Bone marrow examination showed complete remission and minimal residual disease (MRD) negative
.
Tandem repeats (STRs) show complete donor chimerism
.
To prevent recurrence, the patient received 6 cycles of azacitidine (50mg/m2/d*5d, once a month) 4 months after haploid HSCT
.
In July 2020, the patient had a positive MRD (1.
47%) recurrence
.
One course of azacitidine combined with low-dose cytarabine (20mg/m2/d*7) and two courses of veneclax (400mg/d*28) were given successively
.
Following the above treatments, the patient developed extensive chronic graft-versus-host disease (cGVHD) involving the skin, eyes and mouth
.
Unfortunately, in December 2020, 1.
5 years after haploid HSCT, the patient experienced a hematologic relapse
.
The percentage of primitive monocytes was 9.
5%, and the STR decreased to 78.
83%
.
Universal anti-CD123 CAR-γδ T cells were prepared from third-party cord blood
.
Briefly, γδ T cells were screened using the TCRg/d+ T cell isolation kit and stimulated with anti-gd TCR antibody
.
Activated gd T cells were transduced with anti-CD123 CAR-bearing lentivirus
.
The conditioning regimen was fludarabine 50 mg/d*5 and melphalan 50 mg/d*2
.
Patients received universal anti-CD123 CAR-γδ T cells (2.
5×106/kg), and 7 days later, G-CSF mobilized and cryopreserved donor monocytes (1.
98×108/kg) were infused, including 0.
693×108 /kg CD34+ stem cells and 1.
67×107/kg CD3+ T cells
.
To prevent GVHD, sirolimus (0.
5 mg/d) was started after donor cell infusion
.
Results After pretreatment, the MRD was 3.
69%, and the STR decreased to 61.
12%
.
Universal anti-CD123 CAR-γδ T cells rapidly proliferated from day +3 to day +7, and then declined
.
The patient developed grade 1 cytokine release syndrome (CRS), including fatigue, nausea, and headache, without neurotoxic syndrome
.
Seven days after CAR-γδ T cell infusion, bone marrow testing showed negative AML-MRD and STR increased to 90.
24%, followed by infusion of donor monocytes
.
On day 17 after CAR-γδT infusion, the patient was in the agranulocytosis phase with bacteremia and received antibiotics
.
After 21 days of CAR-γδ T cell infusion, the patient achieved MRD-negative remission and full donor chimerism
.
There was no acute GVHD (aGVHD) or new-onset cGVHD, and sirolimus was discontinued 1 month after DLI
.
Furthermore, after donor cell infusion, the number of universal anti-CD123 CAR-γδ T cells increased again, probably due to CD123 antigen expressed on donor cells (Panels A,B)
.
Six months later, the patient had another hematologic relapse and received supportive care
.
A: Percentage of anti-CD123 CAR-γδT in CD3+ T lymphocyte of the patient`s peripheral bloodB: The ratio of anti-CD123 CAR DNA to genome DNA of patient`s peripheral blood Research conclusion Universal anti-CD123 CAR-γδT combined with DLI Appears to be an effective and safe treatment for patients with relapsed AML after allo-HSCT
.
Reference source: R.
Zhang, R.
Jiang, X.
Chen, et al.
UNIVERSAL ANTI-CD123 CAR-γδT CELLS COMBINED WITH DONOR LYMPHOCYTES INFUSION FOR RELAPSED ACUTE MYELOID LEUKEMIA AFTER ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION.
The 48th Annual Meeting of the EBMT .
Abstract P122.
Editor: Quinta Review: Quinta Typesetting: Quinta pokes "read the original text", we make progress together
