Granulocyte Colony-stimulating Factor-mobilized Bone Marrow Research Articles

Efficacy and safety of haploidentical hematopoietic stem cell transplantation for 17 patients with paroxysmal nocturnal hemamoglobinuria

目的探讨单倍型造血干细胞移植治疗阵发性睡眠性血红蛋白尿症（PNH）的疗效和安全性。方法回顾性分析2013年1月至2017年9月采用亲缘单倍型移植治疗的17例PNH患者临床资料。结果17例患者中原发PNH 4例，再生障碍性贫血（AA）-PNH综合征13例。所有患者均以改良白消安+环磷酰胺联合抗胸腺细胞球蛋白（ATG）进行清髓性预处理。G-CSF动员的供者骨髓联合外周血干细胞作为移植物来源。环孢素A+吗替麦考酚酯+短程甲氨蝶呤预防移植物抗宿主病（GVHD）。移植后17例患者均获粒系及巨核系造血重建，粒细胞中位植入时间为移植后12（10~15）d，血小板中位植入时间为移植后14（11~45）d。所有患者在+30 d经植入鉴定证实为完全供者嵌合体。7例患者发生Ⅱ~Ⅳ度急性GVHD，4例发生慢性GVHD。中位随访时间为27.1（8.6~60.4）个月，17例患者中15例存活，2例死亡，死因分别为肺部重症感染和移植相关的血栓性微血管病。3年总生存率为（77.8±15.2）%。结论对于无完全相合供者的PNH患者，尝试进行单倍型造血干细胞移植有效、安全。

Cotransplantation of Allogeneic Mesenchymal and Hematopoietic Stem Cells in Children With Aplastic Anemia

We report here the preliminary results of allogeneic hematopoietic stem cell transplantation with mesenchymal stem cells (MSCs) for 6 cases of severe aplastic anemia. The patients ranged in age from 3 to 16 years, and the median time from diagnosis to transplantation was 32 months (range: 3-156 months). The conditioning regimens consisted of fludarabine, cyclophosphamide, and antithymocyte globulin with or without busulfan. Graft-versus-host disease (GvHD) was prevented by the administration of cyclosporine A, methotrexate, and mycophenolate mofetil, with or without anti-CD25 monoclonal antibody. The grafts were granulocyte colony-stimulating factor-mobilized bone marrow and peripheral blood from HLA antigen-haploidentical donors (3 cases) or peripheral blood only from unrelated HLA antigen-identical donors (3 cases). MSCs were intravenously injected at a median dose of 1.43 × 10(6)/kg (range: 0.85-2.5 × 10(6)/kg). The mean time for neutrophil and platelet recovery was 12.3 and 13.8 days, respectively. Acute GvHD grade I and II developed in 2 cases, and no chronic GvHD was documented. All patients were alive and transfusion independent at a median follow-up of 15 months (range: 6-29 months). Our report suggests that cotransplantation of allogeneic hematopoietic stem cells and MSCs might provide an opportunity for therapy for children with severe aplastic anemia.

Haploidentical hematopoietic stem cell transplantation in hematologic malignancies with G-CSF mobilized bone marrow plus peripheral blood stem cells grafts without T cell depletion: a single center report of 29 cases

Haploidentical Hematopoietic stem cell transplantation (Haplo-HSCT) has provided an alternative option since virtually all patients have an immediately available donor. Here, we report the results of Haplo-HSCT with granulocyte-colony-stimulating factor (G-CSF) mobilized bone marrow grafts plus peripheral blood stem cells as the grafts without T-cell depletion. Twenty-nine patients with the mean age of 27.27 years (ranging from 15 to 51 years) were enrolled in this study, and 10 cases were in high risk status. The patients received myeloablative preconditioning with or without total body irradiation and acute graft-versus-host disease (GVHD) prophylaxis consisting of basiliximab, cyclosporine A, methotrexate, mycophenolate mofetil and a rabbit anti-thymocyte globulin. All the patients attained successful neutrophil and platelet recovery. The mean times for neutrophil and platelet recovery were 17.1 and 20.9 days, respectively. During the follow-up at a median time of 30.69 months (ranging from 3 to 76 months), nine patients developed aGVHD grade II–IV, including two developed grade III–IV GVHD after donor lymphocyte infusion. The incidence of cGVHD was 48.3%. 13 patients died within the first two years after transplantation, and the total disease-free survival rate longer than 2 years was 55.2%. These results suggest that G-CSF-primed bone marrow plus peripheral blood stem cell grafts are an appropriate stem cell source for Haplo-HSCT and large scale investigations are needed to confirm this protocol.

Factors influencing engraftment in HLA-haploidentical/mismatch related transplantation with combined granulocyte-colony stimulating factor-mobilized peripheral blood and bone marrow for patients with leukemia

Unmanipulated HLA-haploidentical/mismatch related transplantation with combined granulocyte-colony stimulating factor-mobilized peripheral blood stem cells (G-PBSCs) and granulocyte-colony stimulating factor-mobilized bone marrow (G-BM) has been used as an alternative transplantation strategy for patients without an HLA-matched donor. In this transplantation setting, factors associated with hematopoietic recovery have not been defined completely. The aim of this study was to investigate the factors influencing the engraftment in this transplantation setting for patients with leukemia. The study group comprised 104 patients with leukemia who underwent transplantation at a single institution between 2005 and 2008. Factors correlating with neutrophil and platelet engraftment post-transplantation were analyzed retrospectively. All patients achieved an absolute neutrophil count of 500/μL with a mean time of 13.6 days (range 8–20 days) and a platelet count over 20 × 10 9/L with a mean time of 20.2 days (range 16–26 days). In univariate analysis, donor and age were associated with increased risk of neutrophil engraftment, but their significance was lost upon multivariate analysis. The sex, age, donor, CD34 + cell dose, conditioning regimen, mismatched locus, ABO mismatched and diagnosis have no effect on platelet engraftment. Our results suggest that it is an ideal approach to treat patients with leukemia with HLA-haploidentical/mismatched related transplantation with combined G-PBSCs and G-BM for a high level of stem cells without delayed engraftment.

Cost and outcome in stem cell collections in HLA-haplo identical/mismatched related transplantation with combined granulocyte-colony stimulating factor -mobilized blood and bone marrow for patients with hematologic malignancies

Unmanipulated HLA-haplo identical/mismatched related transplantation with combined granulocyte-colony stimulating factor -mobilized peripheral blood stem cells (G-PBSCs) and granulocyte-colony stimulating factor-mobilized bone marrow (G-BM) has been developed as an alternative transplantation strategy for patients without an HLA-matched related or unrelated donor. In this transplantation setting, the cost and outcome of stem cell collections have not been defined completely. The aim of this study was to compare the cost and outcome of stem cell collection in HLA-haplo identical/mismatched related transplantation with combined G-PBSCs and G-BM to the HLA-identical/matched transplantation with G-PBSCs alone for patients with hematologic malignancies. Hundred and fifty-two healthy donors received twice-daily granulocyte-colony stimulating factor (G-CSF) subcutaneously for 5 days. The PBSCs were collected on day 4 and 5 of G-CSF treatment for HLA-identical/matched transplantation from unrelated/related donors. The PBSC collections and BM harvests was performed on day 4 and 5 of G-CSF treatment for HLA-haplo identical/mismatched related transplantation from related donors, respectively. There was no difference in the major characteristics between groups. More stem cells were harvested in HLA-haplo identical/mismatched related donors than that of HLA-identical/matched donors and a lower cost was seen in the former. The HLA-haplo identical/mismatched related transplantation with combined G-PBSCs and G-BM was a feasible approach with high cell harvest and low cost of stem cell collection for patients with hematologic malignancies.