Analysis of allogeneic hematopoietic stem cell transplantation with high-dose cyclophosphamide-induced immune tolerance for severe aplastic anemia

Abstract

The study was aimed to explore the efficacy and safety of allo-HSCT with high-dose cyclophosphamide-induced immune tolerance for SAA. In the present study, 20 cases (12 male, 8 female; average age = 17.8 years) received reduced-intensity conditioning allo-HSCT from August 2012 to August 2014 in the Beijing Military Region General Hospital. All were HLA mismatched and received CSA; 11 received ATG-intensive immune therapy. Donors underwent mobilization with cell colony-stimulating factor. The modified preconditioning regimen included reduced-strength fludarabine combined with Busulfex and cytarabine, cyclophosphamide. Cyclophosphamide (50 mg/kg/d) induced immune tolerance 3 days after transplantation and was combined with immunosuppressive agents, including CSA, MTX, and FK506, for GVHD prophylaxis and the management of observed toxicity, GVHD and DFS. Hematopoietic reconstitution was achieved in 17 cases and engraftment after a second transplantation in an additional three cases. The average times to engraftment were 17.4 and 21.3 days, respectively, with neutrophils ≥0.5 × 10/L and platelets ≥20 × 10/L. Engraftment was confirmed by the evidence of 100 % donor hematopoiesis; T lymphocyte subset counts also increased significantly after transplantation. During follow-up monitoring to April 2015 (median duration = 17.7 months), three patients died of complications, while the other 17 showed disease-free survival (DFS rate = 85 %; longest DFS period = 32 months). Reduced-intensity allo-HSCT with high-dose cyclophosphamide-induced immune tolerance treatment is effective for SAA and can be the key technology extensively used in clinic, but its efficacy needs to be confirmed further with prospective randomized study with increased sample size.

The consensus on indications, conditioning regimen, and donor selection of allogeneic hematopoietic cell transplantation for hematological diseases in China—recommendations from the Chinese Society of Hematology

“…A total of 99% of HID-HSCT cases followed the “Beijing Protocol”, which includes T-replete myeloablative HID-HSCT with granulocyte colony-stimulating factor (G-CSF) and anti-thymocyte globulin (ATG) [ 9 – 23 ]. The Baltimore group introduced HID-HSCT followed by the posttransplant cyclophosphamide (PT-CY) regimen, which was also implemented in China [ 24 ]. The number of HID-HSCT cases increased to approximately 2500 annually in 2016, which made it the largest source of allo-HSCT donors (37.6–51.5%) in China since 2013 [ 5 , 8 , 25 ] and take 40% of annual HID-HSCT cases worldwide.…”

Allogeneic hematopoietic stem cell transplantation for relapsed acute myeloid leukemia in ETO positive with reduced-intensity conditioning

“…The majority of these high-risk patients will eventually die from complications of chemotherapy, recurrence or progression. Allogeneic hematopoietic stem cell transplantation(allo-HSCT) is the best choice for these high-risk patients [ 3 – 4 ]. However, most patients have been treated with intensive chemotherapy for many times before the recurrence, especially for combination regimen based on high dose cytarabine and the relapsed and refractory leukemia patients normally have difficulty in accepting the allogeneic hematopoietic stem cell transplantation.…”

Expert consensus on the relevance of intestinal microecology and hematopoietic stem cell transplantation

“…By using allo-HSCT, the receiver can receive bone marrow or peripheral blood stem cells from the donor. 8 Contrary to solid organ transplantation, which only results in a one-way rejection after transplantation, GVHD following allo-HSCT affects both the host and the donor as well as the donor graft. This is because the implanted donor graft contains immunoreactive cells, including T lymphocytes and monocyte-macrophages that detect the host's own antigens and then activate, multiply, and differentiate in response.…”