HLA haploidentical peripheral blood stem cells transplantation for β thalassemia major / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the feasibility of HLA haploidentical peripheral blood hematopoietic stem cell transplantation (PBSCT) for patients with β thalassemia major.</p><p><b>METHODS</b>Sixteen patients with β thalassemia major received HLA haploidentical PBSCT from parents. Two conditioning regimens were used. Regimen A was adopted before December 2007, which consisted of fludarabine (total 150 mg/m²), busulfex (total 520 mg/m²), cyclophosphamide (CTX, total 100 mg/kg), antithymocyte globulin (ATG, total 10 mg/kg) and total body irradiation of 3 Gy. Regimen B was adopted after December 2007, which consisted of fludarabine (total 240 mg/m²), busulfex (total 520 mg/m²), CTX (total 100 mg/kg), and ATG (total 10 mg/kg). Combination of cyclosporin (CsA), methotrexate (MTX) and mycophenolate mofetil (MMF) were used for prophylaxis of graft-versus-host disease (GVHD).</p><p><b>RESULTS</b>Of 16 patients, 14 (87.5%) had sustained engraftment. The median days of neutrophil exceeding 0.5 × 10⁹/L and platelet exceeding 20 × 10⁹/L were 13 days (range 10 - 17 days) and 15 days (range 14 - 20 days) after PBSCT, respectively. Complete chimerism was achieved in all the 14 patients at one month after PBSCT. One patient lost his graft with autologous reconstitution 52 days after transplantation. Four patients had grade II-IV acute GVHD and one patient had chronic extensive GVHD. In the 49-month median follow-up duration, 13 of 16 patients were alive in disease-free situation.</p><p><b>CONCLUSION</b>HLA haploidentical PBSCT, which could provide stable and sustained engraftment for thalassemia major patients with no HLA identical donor, is a promising treatment strategy.</p>

Role of paternal veto cells in preventing graft-versus-host disease after HLA-haploidentical stem cell transplantation in mice / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the role of paternal veto cells in preventing graft-versus-host disease (GVHD) after related HLA- haploidentical stem cell transplantation in mice.</p><p><b>METHODS</b>MHC-haploidentical recipient B6CF1(H-2 b/d) mice pretreated with total body irradiation at 9.0 Gy for 4 h before transplantation. The recipient mice were divided into 4 groups, and in the irradiation group, only injection of 0.3 ml D-Hank's liquid was given through the tail vein; in the control group, the mice received injection through the tail vein of 4.5x10(6) bone marrow cells mixed with 3.0x10(7) spleen cells from C57BL/6 mice without the preventive measures of GVHD; the mice in the two experiment groups received cell transplantation in the same manner, and on day 4 after transplantation, 5.0x10(6) and 1.0x10(7)spleen cells from BALB/c mice were injected through tail vein, respectively. The hematopoietic recovery, engraftment and GVHD of the recipient mice were observed.</p><p><b>RESULTS</b>Without any treatment, all mice in the control group developed GVHD and died after transplantation. In the 10 mice with injection of 5.0x10(6) spleen cells, GVHD occurred in 5 mice with a 30-day survival rate of 50%; the median survival time of the mice with GVHD was 20 days, significantly longer than that of the control mice (14 days, P<0.05). In the 10 mice injected with 1.0x10(7) spleen cells, 2 developed GVHD and the 30-day survival rate was 80% (8/10) with a median survival time of 30 days, significantly longer than that of mice with injection of 5.0x10(6) spleen cells and the control mice (P<0.05).</p><p><b>CONCLUSION</b>Paternal veto cell transplantation can decrease the occurrence of GVHD after related HLA haploidentical stem cell transplantation in mice.</p>

Role of TJU103 in prevention of graft-versus-host disease after allogeneic stem cell transplantation in mice / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the role of TJU103 in preventing graft-versus-host disease (GVHD) after allogeneic stem cell transplantation in mice.</p><p><b>METHODS</b>BALB/c mouse splenic lymphocytes were collected and treated by mitomycin as the activating cells and the C57BL/6 mouse splenic lymphocytes as the reacting cells. In the experimental groups, the effect of TJU103 on the proliferative response of T cells was observed. BALB/c(H-2d) and CB6F1(H-2d/b) mice were used as the MHC-full-mismatched recipients and MHC-haplo-identical recipients, respectively, and pretreated by total body irradiation at 9.0 Gy before transplantation. For the recipients of the irradiation group, 0.3 ml D-Hank's solution was injected through the tail vein without cell transplantation, the recipients of the control group received injection of 4.5x10(6) bone marrow cells mixed with 3.0x10(7) spleen cells from C57BL/6 mice through the tail vein, and those in the experimental group received cell transplantation in the same manner with also injection via the tail vein of 25 microg/ml TJU103, which was subsequently injected intraperitoneally for 7 consecutive days at daily dose of 50 microg. The hematopoietic recovery, engraftment and GVHD of the recipients were observed.</p><p><b>RESULTS</b>TJU103 resulted in a dose-dependent inhibition of T cell proliferation in mixed lymphocyte reaction (MLR), and nearly 83% inhibition of the proliferative response was observed with the addition of 25 microg/ml of TJU103. Without any treatment, the occurrence of GVHD and death rate in the control group was both 10/10. Daily injection of TJU103 at 50 microg for the initial post-transplantation week protected the mice from GVHD. In the MHC-full-mismatched model, the incidence of GVHD and survival rate on day 30 of the experiment group was 2/10 and 8/10, showing significant difference from those in the control group (P<0.01). The median survival time (MST) was 30 days in the experimental group versus 15 days in the control group (P<0.05). In the MHC-haplo-identical model, the incidence of GVHD and the survival rate on day 30 of the experimental group was 1/10 and 9/10, which were significantly different from the control group (P<0.01). The MST was 30 days in the experimental group versus 14 days in the control group (P<0.05).</p><p><b>CONCLUSION</b>TJU103 is capable of markedly inhibiting T cell proliferative response in vitro and can decrease GVHD incidence after allogeneic stem cell transplantation in mice.</p>