Study on graft-versus-host disease in the allogeneic peripheral blood stem cell transplantation for the treatment of leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyze the incidence and the effective prevention and treatment of graft-versus-host disease (GVHD) for the allogeneic peripheral blood stem cell transplantation (allo-PBSCT) for the treatment of leukemia.</p><p><b>METHODS</b>Fifty patients with acute leukemia (n = 29) and chronic myeloid leukemia (n = 21) were treated with allo-PBSCT. The conditioning regimens were TBI plus CTX and Vp16 or TBI plus CTX. Two regimens were used for prophylaxis of GVHD: one was the combination of low dose cyclosporine (CsA, 2 - 3 mg x kg(-1) x d(-)1 i.v. or 4 - 6 mg x kg(-1) x d(-1) p.o.) and short course methotrexate (MTX, 15 approximately 10 mg, +1, +3, +6, +11 d) (CsA/MTX group, 32 patients), the other was short course of mycophenolate mofetil (MMF, 1.0 bid, +1 - +28 d) in addition to CsA and MTX (MMF/CsA/MTX group, 18 patients).</p><p><b>RESULTS</b>All patients were successfully engrafted and the median times to ANC > 0.5 x 10(9)/L and to platelet > 20 x 10(9)/L were 14 (10 - 22) and 20 (10 - 68) days post PBSCT respectively. The incidence of acute GVHD (aGVHD) was 40% (20/50) and of grade III - IV was 12% (6/50). The chronic GVHD (cGVHD) occurred in 22 out of 33 (66.7%) evaluable patients (survived longer than 6 months post PBSCT) and extensive cGVHD in 11 out of 33 (33.3%) patients. Patients with aGVHD displayed significantly higher sIL-2R levels [(277.3 +/- 26.4) U/L] and CD(25)(+) cells [(8.1 +/- 3.4)%] than those without GVHD [(128.1 +/- 96.7) U/L and (3.6 +/- 1.7)%] (P < 0.05). The incidences of aGVHD (16.7%) and extensive cGVHD (9.1%) in MMF/CsA/MTX group were significantly lower than that in CsA/MTX group (53.1% and 45.5%, P < 0.05). The median follow-up duration was 30 (3 - 70) months and 33 patients were still alive. The relapse rate was significantly higher in GVHD negative group (47.1%) than in GVHD positive group (0, P < 0.05). The 3 year disease-free-survival (DFS) rate was 66%.</p><p><b>CONCLUSION</b>The incidence of aGVHD was low, but of cGVHD was high in allo-PBSCT. sIL-2R and CD(25)(+) cells after PBSCT may provide predictive markers for aGVHD. The MMF/CsA/MTX regimen for prevention of aGVHD in allo-PBSCT is more effective than the CsA/MTX one. There was a strong antileukemic effect of GVHD in the allo-PBSCT.</p>

Role of interleukin-18 in pathogenesis of acute graft-versus-host disease / 中国实验血液学杂志

To investigate the relationship between interleukin-18 (IL-18) and human acute graft-versus-host disease (aGVHD), 26 patients undergoing allogeneic peripheral blood stem cell transplantation (allo-PBSCT) were included in this study. IL-18 secreted by peripheral blood mononuclear cells (MNCs) was measured by enzyme-linked immunosorbent assay (ELISA) before transplantation and during aGVHD. The results showed that grade I GVHD and grades III-IV GVHD developed in 10 and 5 cases, respectively. The levels in the supernatants of MNCs from patients with aGVHD were significantly higher than those in the cases without aGVHD. The levels of IL-18 were correlated with the severity of aGVHD. It is concluded that IL-18 plays an important role in the development of aGVHD.

Fetal bone marrow stromal cells support the in vitro expansion of human hematopoietic bone marrow progenitor cells: requirement for cell-to-cell interactions and colony-stimulating factors / 第二军医大学学报

Objective： To elucidate the role of bone marrow stromal cells in cooperation with exogenous cytokines in hematopoiesis. Methods： Fetal bone marrow stromal cells (FBMSC) was combined with cytokines including SCF,IL-3,IL-6,GM-CSF in a 5-day liquid culture system of adult bone marrow mononuclear cells, then we cultured bone marrow derived CD34+-enriched cells with FBMSC+SCF+IL-3+IL-6+G-CSF+EPO for 2 weeks. Results：FBMSC were in good cooperation with above mentioned exogenous cytokines. When CD34+-enriched cells from adult bone marrow were cultured with combinations of FBMSC, SCF, IL-3, IL-6, G-CSF and EPO, total nucleated cells, CFU-GM, BFU-E and CD34+ cells were increased by 119.6±30.9, 54.6±17.4, 25.2±4.4, 11.1±4.2 folds, respectively. Conclusion：FBMSC in cooperation with exogenous cytokines support the in vitro expansion of human hematopoietic progenitor cells efficiently.

Fetal bone marrow stromal cells support the in vitro expansion of human hematopoietic bone marrow progenitor cells: requirement for cell-to-cell interactions and colony-stimulating factors / 第二军医大学学报

Objective： To elucidate the role of bone marrow stromal cells in cooperation with exogenous cytokines in hematopoiesis. Methods： Fetal bone marrow stromal cells (FBMSC) was combined with cytokines including SCF,IL-3,IL-6,GM-CSF in a 5-day liquid culture system of adult bone marrow mononuclear cells, then we cultured bone marrow derived CD34+-enriched cells with FBMSC+SCF+IL-3+IL-6+G-CSF+EPO for 2 weeks. Results：FBMSC were in good cooperation with above mentioned exogenous cytokines. When CD34+-enriched cells from adult bone marrow were cultured with combinations of FBMSC, SCF, IL-3, IL-6, G-CSF and EPO, total nucleated cells, CFU-GM, BFU-E and CD34+ cells were increased by 119.6±30.9, 54.6±17.4, 25.2±4.4, 11.1±4.2 folds, respectively. Conclusion：FBMSC in cooperation with exogenous cytokines support the in vitro expansion of human hematopoietic progenitor cells efficiently.

Study on Relation of Early Immune Reconstitution with Acute Graft-Versus-Host Disease / 中国实验血液学杂志

To analyze the relation of early immune reconstitution with acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation (all-HSCT), the changes of CD3(+), CD4(+), CD8(+), CD25(+) and CD69(+) cells in peripheral blood from 26 patients with hematologic malignancies were assayed by flow cytometry within 2 months after allo-HSCT. All patients achieved hematopoietic reconstitution, and grade I and II - IV GVHD were developed in 9 and 5 patients, respectively. CD25(+) cells were increased in patients aGVHD at week 2 after transplantation and the peak value was appeared at week 3. The increase of CD25(+) cells was preceded the occurence of clinical signs of aGVHD. The maximal levels of CD25(+) cells increase correlated significantly with the severity of aGVHD. The increase of CD25(+) cells was declined along with remission of aGVHD signs. Our results suggest that analyzing immune reconstitution after allo-HSCT could predict occurence of aGVHD, and CD25(+) cell increase prior occurence of aGVHD is predictive marker for aGVHD.