Contributions
Abstract: EP1269
Type: E-Poster Presentation
Session title: Stem cell transplantation - Clinical
Background
Relapse remains the main cause of failure for hematopoietic stem cell transplantation (HSCT) in acute myeloid leukemia (AML). In some cases, leukemia cells may develop HLA loss which would result in poor response to conventional immunotherapy such as donor lymphocyte infusion (DLI) and thus NK cell therapy would be appropriate treatment.
Aims
In present clinical study, the safety and efficacy of donor-derived activated NK cells in management of relapse after allogeneic HSCT in AML were examined.
Methods
Between October 2019 and January 2021, 7 AML patients with hematologic relapse or minimal residual disease (MRD) positive after allogeneic HSCT and then received donor-derived activated NK cell therapy were enrolled. The median age was 10 (3-41) years old. Seven patients were with fusion genes (MLL-AF6 in 1, MLL-PTD in 1, CBFβ-MYH11 in 1, AML1-ETO in 4). The disease status before transplant was CR1 in 2 cases, CR2 in 3 and non-remission in 2. All transplants were from haploientical donors. Conditioning regimen was busulfan/fludarabine-based. Cyclosporine, MMF and short-term MTX were employed for GVHD prophylaxis. Isolated peripheral blood mononuclear cells (PBMCs) from original donors were co-cultured with cryopreserved-thawed irradiated genetically engineered (GE)_K562 feeder cells (a gift of Alex H. Chang, Shanghai YaKe Biotechnology Ltd., China) at a ratio of 2:1 (PBMCs:GE_K562) in SCGM media, with 100ul/ml IL-2 and donor serum for 8-9 days. Escalated dosages of NK cells were infused starting with 1×105 cells/kg (recipient’s body weight) with or without IL-2 injection. The patients with hematologic relapse received NK cells 3 days later after chemotherapy. The disease status before NK cell therapy was hematologic relapse in 2 and MRD+ in 5, and 2 cases with hematologic relapse failed to chemotherapy combined with DLI before NK cell therapy.
Results
The purity of donor-derived ex-vivo activated NK cells was 80-90%. Compared with our original culture system, the modified culture system enhanced approximately 20% to 40% of the purity and 3 to 6 fold in number of NK cells by day 8-9. The median NK cells infused were 5 (1-100) ×105 cells/kg with four-week interval. No transfusion-related side effects were noted. Five cases had response to NK cell therapy. Two cases with hematologic relapse all had response (CR) to NK cell therapy. For 5 cases with MDR+, 1 case had a complete response, 2 cases had 1 log reduction in fusion gene, and 2 cases had no response. With the median follow-up192 (22-510) days, 7 cases have been survived, 5/7 cases have been survived free of diseases. Two patients relapsed.
Conclusion
Our preliminary results have demonstrated that donor-derived ex-vivo activated NK cells are safe and effective treatment in relapse after allogeneic HSCT in AML patients who even failed to chemotherapy combined with DLI. Optimal culture system with cryopreserved-thawed irradiated genetically engineered (GE)_K562 feeder cells has improved not only NK cell’s purity and number but also clinical efficacy compared with our previous study.
Keyword(s): Acute myeloid leukemia, Allogeneic hematopoietic stem cell transplant, NK cell, Relapse
Abstract: EP1269
Type: E-Poster Presentation
Session title: Stem cell transplantation - Clinical
Background
Relapse remains the main cause of failure for hematopoietic stem cell transplantation (HSCT) in acute myeloid leukemia (AML). In some cases, leukemia cells may develop HLA loss which would result in poor response to conventional immunotherapy such as donor lymphocyte infusion (DLI) and thus NK cell therapy would be appropriate treatment.
Aims
In present clinical study, the safety and efficacy of donor-derived activated NK cells in management of relapse after allogeneic HSCT in AML were examined.
Methods
Between October 2019 and January 2021, 7 AML patients with hematologic relapse or minimal residual disease (MRD) positive after allogeneic HSCT and then received donor-derived activated NK cell therapy were enrolled. The median age was 10 (3-41) years old. Seven patients were with fusion genes (MLL-AF6 in 1, MLL-PTD in 1, CBFβ-MYH11 in 1, AML1-ETO in 4). The disease status before transplant was CR1 in 2 cases, CR2 in 3 and non-remission in 2. All transplants were from haploientical donors. Conditioning regimen was busulfan/fludarabine-based. Cyclosporine, MMF and short-term MTX were employed for GVHD prophylaxis. Isolated peripheral blood mononuclear cells (PBMCs) from original donors were co-cultured with cryopreserved-thawed irradiated genetically engineered (GE)_K562 feeder cells (a gift of Alex H. Chang, Shanghai YaKe Biotechnology Ltd., China) at a ratio of 2:1 (PBMCs:GE_K562) in SCGM media, with 100ul/ml IL-2 and donor serum for 8-9 days. Escalated dosages of NK cells were infused starting with 1×105 cells/kg (recipient’s body weight) with or without IL-2 injection. The patients with hematologic relapse received NK cells 3 days later after chemotherapy. The disease status before NK cell therapy was hematologic relapse in 2 and MRD+ in 5, and 2 cases with hematologic relapse failed to chemotherapy combined with DLI before NK cell therapy.
Results
The purity of donor-derived ex-vivo activated NK cells was 80-90%. Compared with our original culture system, the modified culture system enhanced approximately 20% to 40% of the purity and 3 to 6 fold in number of NK cells by day 8-9. The median NK cells infused were 5 (1-100) ×105 cells/kg with four-week interval. No transfusion-related side effects were noted. Five cases had response to NK cell therapy. Two cases with hematologic relapse all had response (CR) to NK cell therapy. For 5 cases with MDR+, 1 case had a complete response, 2 cases had 1 log reduction in fusion gene, and 2 cases had no response. With the median follow-up192 (22-510) days, 7 cases have been survived, 5/7 cases have been survived free of diseases. Two patients relapsed.
Conclusion
Our preliminary results have demonstrated that donor-derived ex-vivo activated NK cells are safe and effective treatment in relapse after allogeneic HSCT in AML patients who even failed to chemotherapy combined with DLI. Optimal culture system with cryopreserved-thawed irradiated genetically engineered (GE)_K562 feeder cells has improved not only NK cell’s purity and number but also clinical efficacy compared with our previous study.
Keyword(s): Acute myeloid leukemia, Allogeneic hematopoietic stem cell transplant, NK cell, Relapse