Paroxysmal nocturnal hemoglobinuria （PNH） is a consequence of nonmalignant clonal expansion of one or several hematopoietic stem cells that have acquired a somatic mutation of phosphatedalinositol glycae-class A （P...Paroxysmal nocturnal hemoglobinuria （PNH） is a consequence of nonmalignant clonal expansion of one or several hematopoietic stem cells that have acquired a somatic mutation of phosphatedalinositol glycae-class A （PIGA） gene leading to deficient glycosyl phosphatidylinositol （GPI） synthesis. The pathophysiology of PNH is an abnormality in the glycolipid-anchored proteins of the membranes of blood cells. The absence of complement control proteins, including decay accelerating factor （DAF, CD55） and membrane inhibitor of reactive lysis （MIRL, CD59）, results in intravascular lysis of the abnormal cells. Patients with PNH manifest not only clinical and laboratory signs of chronic hemolytic anemia, but also formation of cytopenia and venous thromboses.展开更多
Objective To evaluate the application of anti-T-lymphocyte globulin (ATG) based nonmyeloablative but profoundly immunosuppressive regimens followed by donor lymphocyte infusion (DLI) for the treatment of hematologic ...Objective To evaluate the application of anti-T-lymphocyte globulin (ATG) based nonmyeloablative but profoundly immunosuppressive regimens followed by donor lymphocyte infusion (DLI) for the treatment of hematologic malignancies.Methods The protocol was designed to minimize the intensity of the conditioning regimen to the range of nonmyeloablative therapies based on ATG with low-dose busulfan (Bu) and Cytoxan (CTX) (15-19.5 mg/kg, 8 mg/kg and 80 mg/kg, respectively). The patients received the first lymphocytic infusion from HLA-identical sibling donors on days 28-30 after transplant, and the first T cell dosage of 10 6/kg followed by the escalated dosage in the range of (0.5-1.5)×10 8/kg. The total number of procedures were performed at a median of 4.2 procedures (range of 2-8 procedures).Results Engraftment was documented in all six patients in the form of donor-recipient hematopoietic cells mixed chimera at early-stage posttransplant, which was converted gradually into complet chimera by DLI in four patients. Graft-versus-host disease (GVHD) developed in three of six cases, only one of which was severe. To date,four patients are disease free and alive.Conclusions Allogeneic donor stem cell engraftment into host can be achieved by nonmyeloablative conditioning regimen based on ATG. Transient mixed donor-recipient hematopoietic cell mixed with chimeras may be successfully converted into complete chimerism by DLI posttransplant. GVHD remains major clinical concern in our study.展开更多
The objectve of this investigation was to explore the use of nonmyeloablative allogeneic peripheral blood stem cell tranplantation for treatment of hematologic diseases. Six patients were included: 3 cases with acute ...The objectve of this investigation was to explore the use of nonmyeloablative allogeneic peripheral blood stem cell tranplantation for treatment of hematologic diseases. Six patients were included: 3 cases with acute leukemia in first complete remission(2 AML and 1 ALL), 2 severe aplastic anemias and 1 chronic myeloid leukemia in chronic phase. All of the 6 cases were received HLA-identical siblings donor peripheral blood stem cell transplantation after a nonmyeloablative conditioning. The donor cells were engrafted in all patients(3 cases were full engrafment of donor cells and 3 were mixed chimerism). Hematopoietic recovery was appeared in all of the cases(ANC recovered to more than 0.5×10 9/L and platelet count to more than 30×10 9/L on day 9 to day 21 and day 14 to day 28 after transplantation, respectively). Two patients developed Ⅲ or Ⅳ degree GVHD. Our preliminary results suggest that the procedure is more safe, efficient and less complications than myeloablative conditioning regimens and represents another new approach in the management of patients with hematologic diseases.展开更多
文摘Paroxysmal nocturnal hemoglobinuria （PNH） is a consequence of nonmalignant clonal expansion of one or several hematopoietic stem cells that have acquired a somatic mutation of phosphatedalinositol glycae-class A （PIGA） gene leading to deficient glycosyl phosphatidylinositol （GPI） synthesis. The pathophysiology of PNH is an abnormality in the glycolipid-anchored proteins of the membranes of blood cells. The absence of complement control proteins, including decay accelerating factor （DAF, CD55） and membrane inhibitor of reactive lysis （MIRL, CD59）, results in intravascular lysis of the abnormal cells. Patients with PNH manifest not only clinical and laboratory signs of chronic hemolytic anemia, but also formation of cytopenia and venous thromboses.
文摘Objective To evaluate the application of anti-T-lymphocyte globulin (ATG) based nonmyeloablative but profoundly immunosuppressive regimens followed by donor lymphocyte infusion (DLI) for the treatment of hematologic malignancies.Methods The protocol was designed to minimize the intensity of the conditioning regimen to the range of nonmyeloablative therapies based on ATG with low-dose busulfan (Bu) and Cytoxan (CTX) (15-19.5 mg/kg, 8 mg/kg and 80 mg/kg, respectively). The patients received the first lymphocytic infusion from HLA-identical sibling donors on days 28-30 after transplant, and the first T cell dosage of 10 6/kg followed by the escalated dosage in the range of (0.5-1.5)×10 8/kg. The total number of procedures were performed at a median of 4.2 procedures (range of 2-8 procedures).Results Engraftment was documented in all six patients in the form of donor-recipient hematopoietic cells mixed chimera at early-stage posttransplant, which was converted gradually into complet chimera by DLI in four patients. Graft-versus-host disease (GVHD) developed in three of six cases, only one of which was severe. To date,four patients are disease free and alive.Conclusions Allogeneic donor stem cell engraftment into host can be achieved by nonmyeloablative conditioning regimen based on ATG. Transient mixed donor-recipient hematopoietic cell mixed with chimeras may be successfully converted into complete chimerism by DLI posttransplant. GVHD remains major clinical concern in our study.
文摘The objectve of this investigation was to explore the use of nonmyeloablative allogeneic peripheral blood stem cell tranplantation for treatment of hematologic diseases. Six patients were included: 3 cases with acute leukemia in first complete remission(2 AML and 1 ALL), 2 severe aplastic anemias and 1 chronic myeloid leukemia in chronic phase. All of the 6 cases were received HLA-identical siblings donor peripheral blood stem cell transplantation after a nonmyeloablative conditioning. The donor cells were engrafted in all patients(3 cases were full engrafment of donor cells and 3 were mixed chimerism). Hematopoietic recovery was appeared in all of the cases(ANC recovered to more than 0.5×10 9/L and platelet count to more than 30×10 9/L on day 9 to day 21 and day 14 to day 28 after transplantation, respectively). Two patients developed Ⅲ or Ⅳ degree GVHD. Our preliminary results suggest that the procedure is more safe, efficient and less complications than myeloablative conditioning regimens and represents another new approach in the management of patients with hematologic diseases.
