Two Focuses Of Allogeneic Hematopoietic Stem Cell Transplantation

In patients with malignant hematological disease such as leukemia, and severe aplastic anemia, and some genetic hematological diseases, allogeneic hematopoietic stem cell transplantation (Allo-HSCT) is the best effective treatment. In this study, we pay close attention to two focuses of allo-HSCT. (1) The use of double-unit umbilical cord blood (UCB) HSCT (CBT) in adults with hematologic disease. The main stem cell sources were bone marrow and peripheral blood (PB) since long time. UCB is a cryopreserved HSC source that is rapidly available without the risk of donor unavailability. Perhaps more important, it needs a reduced requirement of HLA match. CBT could not be used widely in adult patients because of deficiency of stem cells. Now double-unit CBT would resolve this problem expectedly. (2) To decrease the relapse mortality of allo-HSCT, patients with a high risk for disease relapse after allo-HSCT were treated with donor lymphocyte infusion (DLI) as intervention under the guidance of monitoring minimal residual disease (MRD). In this study, we will give you the answer whether MRD monitoring has a value in the treatment of relapsed/refractory acute lymphoblastic leukemia (ALL) patients after allo-HSCT using DLI therapy. Objective: In this study, we explored the efficiency and toxicity of 38 cases of double-unit CBT in adults with hematologic disease. Methods: The tolerance; transplant related complications; survival rate and disease free survival rate were observed and analyzed. A nonmyeloablative conditioning regimen included cyclophosphamide, fludarabine and 2Gy TBI. Cyclosporine combined mycophenolate mofetil and ATG were used to prevent graft versus host disease (GVHD). Results: All these 38 patients tolerated the therapy well while two patients had graft failure. Severe acute GVHD was presented in 6 patients. Chronic GVHD was occurred in 16 patients. Fatal infection complications were occurred in 5 patients (including CMV idiopathic pneumonia in 2 patients) and 4 patients relapsed after transplantation. Neutrophil engraftment obtained on day +17 and platelet reconstitution occurred on day +42 on median. In the follow-up duration of 17 months on median, the expected 2-year relapse mortality was 17.95%; non-relapse mortality was 25.90%; overall survival was 60.80%, and disease free survival was 52.11%. Compare with 39 cases of haplo-identical HSCT in our department, significant delays in engraftment and lower severe GVHD occurred after CBT. There was no apparent difference between the risk of relapse and DFS in both groups. Conclusion: The use of double-unit CBT after reduced intensive conditioning therapy in adults with hematologic disease is an effective and safe treatment. Fatal infection and relapse are the main reasons of failure.In this study we examined the expression of NKp30, NKp46 and NKp80 in peripheral blood (PB) of patients who received double-unit CBT at different stage. PB expressions of 7 patients, 10 normal controls and 10 other stem cell source of HSCT were analyzed by flow cytometry. The high level of expression of NKp46 and NKp80 in CBT group on day +21 indicated that NK cell was probably activated early and initiated graft versus leukemia effect. While the other two groups showed no results like that; NKp46 and NKp80 not expressed until day +90 after transplant. The reason of persistently low level expression of NKp30 is unclear.Objective: In this study, we explored the efficiency and toxicity of allo-HSCT for relapsed/refractory ALL. whether MRD monitoring has a value in the treatment of relapsed/refractory ALL patients after allo-HSCT using DLI therapy. Methods: Forty-seven patients of relapsed/refractory ALL received allo-HSCT containing 19/47 cases from HLA-identical siblings donors, 18/47 cases from HLA-identical unrelated donors and 10/47 cases from haplo-identical donors of the mothers. The tolerance, transplant related complications, survival rate and disease free survival rate were observed and analyzed. A myeloablative conditioning regimen included modified TBI and cyclophosphamide(42/47) or modified busulfan and cyclophosphamide(5/47). Cyclosporine combined short term methotrexate were used to prevent GVHD. In these cases of URD-HSCT or Hi-HSCT, mycophenolate mofetil and ATG were also administered. These patients who would relapse at cytogenetics/molecular biology level received DLI. Results: All these 47 patients tolerated the therapy well. Fatal infection complications were occurred in 9 patients (including CMV idiopathic pneumonia in 3 patients). Severe acute GVHD was presented in 7 patients, and Chronic GVHD was occurred in 22 patients. 13 patients relapsed after transplantation. Hematopoietic reconstitution obtained on day +17 on median. Nineteen patients received DLI, and 6 of them had no disease progression. In the follow-up duration of 43 months on median, the expected overall survival was 49.65%, disease free survival was 46.55%. Conclusion: Allo-HSCT is an effective therapy in the treatment of relapsed/refractory ALL. Relapse after transplantation, fatal infection, and severe acute GVHD are the main reasons of failure. MRD monitoring has been demonstrated in this study that it can provide valuable data to guide ALL treatment after transplantation.