Clinical observation of mesenchymal stem cell as salvage treatment for refractory acute graft-versus-host disease / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the effect of mesenchymal stem cells (MSCs) on refractory acute graft-versus-host disease (GVHD) failed to second-line immunosuppressive therapy.</p><p><b>METHODS</b>Twenty-two patients with refractory aGVHD received the treatment of first- and/or second-line immunosuppressive agents in combination with MSCs. The MSCs from bone marrow (BM) of HLA-unrelated third-party donors, were used at the median time of 19 (11 - 49) days after aGVHD onset, at a dose of 1×10(6)/kg once with an interval of 14 days. If the symptoms of aGVHD did not improve after continuous infusion four times, MSCs would be discontinued. Meanwhile the proportion of CD3(+)CD4(+), CD3(+)CD8(+) and CD4(+)CD25(+) was detected by flow cytometry (FCM) before and 4 weeks after the MSCs infusion.</p><p><b>RESULTS</b>The median dose of MSC was 4.8 (2.5 - 6.3)×10(6) cell×kg(-1) with a median infusion of 2.5 (1 - 7) times per case. Twelve patients achieved complete response (CR), four partial response (PR) after treatment. The total effective rate was 72.7% (16/22). With a median follow-up of 246.5 (36 - 1116) days post-transplantation, 11 patients survived and 11 died. The causes of death included GVHD(n = 6), infections (n = 3), leukemia relapse (n = 1) and post-transplant lymphoproliferative diseases (n = 1), respectively. The proportion of CD3(+)CD4(+)/CD3(+)CD8(+) was significantly higher at 4th week after MSCs infusion compared to before infusion (1.58 ± 0.54 vs 0.49 ± 0.19, \%t\% = 0.628, P = 0.04). The number of CD4(+)CD25(+) Treg cells had not changed much compared to before infusion (P = 0.606).</p><p><b>CONCLUSION</b>MSCs derived from the BM of a third-party donor are effective to treat aGVHD failed to second-line immunosuppressive therapy after allo-HSCT. MSCs might play a role in aGVHD by regulating the rate of CD3(+)CD4(+)/CD3(+)CD8(+).</p>

The outcome and safety of mesenchymal stem cells from bone marrow of a third party donor in treatment of secondary poor graft function following allogeneic hematopoietic stem cell transplantation / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of bone marrow-derived mesenchymal stem cells (MSC) from a third party donor for secondary poor graft function (PGF) following allogeneic hematopoietic stem cell transplantation(allo-HSCT).</p><p><b>METHODS</b>Five patients with secondary PGF were treated with MSC at a dose of 1 x 10(6)/kg body weight at a median of 47 days (35 to 61) after secondary PGF. MSC were derived from bone marrow (BM) of HLA-disparate third party donors, cultured in vitro and infused without HSC. If absolute neutrophil cell (ANC) and platelet counts (PLT) did not reach the standardization of > 1.5 x 10(9)/L and > 50.0 x 10(9)/L, respectively, within 28-30 days after the first MSC treatment, a second MSC treatment was required.</p><p><b>RESULTS</b>MSC were infused once in one patient and twice in four patients with an interval of 28 to 30 days. All patients obtained ANC and PLT recovery at a median of 34 (25 to 49) days and 47 (26 to 54) days, respectively, without toxic side effects within follow-up periods of median 761 (204-1491) days. Three patients developed Epstein-Barr virus (EBV) reactivation at 42, 48, 108 days after MSC infusion, respectively and two of the three coverted to posttransplant lymphoproliferative disorders (PTLD).</p><p><b>CONCLUSION</b>MSC from a third party donor are effective to patients with secondary PGF following allo-HSCT, whether it might increase the risk of EBV reactivation and EBV-associated PTLD need further observation.</p>