Chunji Gao

Cotransplantation of haploidentical hematopoietic and umbilical cord mesenchymal stem cells for severe aplastic anemia: Successful engraftment and mild GVHD

Haploidentical hematopoietic stem-cell transplantation (haplo-HSCT) is associated with an increased risk of graft failure and severe graft-versus-host disease (GVHD). Mesenchymal stromal cells (MSCs) have been shown to support in vivo normal hematopoiesis and to display potent immunesuppressive effects. We cotransplanted the culture-expanded third-party donor-derived umbilical cord MSCs (UC-MSCs) in 21 young people with severe aplastic anemia (SAA) undergoing haplo-HSCT without T-cell-depleted. We observed that all patients had sustained hematopoietic engraftment without any adverse UC-MSC infusion-related events. Furthermore, we did not observe any increase in severe aGVHD. These data suggest that UC-MSCs, possibly thanks to their potent immunosuppressive effect on allo-reactive host T lymphocytes escaping the preparative regimen, reduce the risk of graft failure and severe GVHD in haplo-HSCT.

Unmanipulated HLA-mismatched/haploidentical peripheral blood stem cell transplantation for high-risk hematologic malignancies.

BACKGROUND: Haploidentical hematopoietic stem cell transplantation (HSCT) has been increasingly applied in high‐risk hematologic patients due to the absence of HLA‐matched donors. The aim of this study was to investigate the efficacy and safety of unmanipulated haploidentical allogeneic peripheral blood stem cells transplantation (PBSCT) for hematologic malignancies.

Reduced Intensity Conditioning, Combined Transplantation of Haploidentical Hematopoietic Stem Cells and Mesenchymal Stem Cells in Patients with Severe Aplastic Anemia

We examined if transplantation of combined haploidentical hematopoietic stem cells (HSC) and mesenchymal stem cells (MSC) affected graft failure and graft-versus-host disease (GVHD) in patients with severe aplastic anemia (SAA). Patients with SAA-I (N = 17) received haploidentical HSCT plus MSC infusion. Stem cell grafts used a combination of granulocyte colony-stimulating factor (G-CSF)-primed bone marrow and G-CSF-mobilized peripheral blood stem cells of haploidentical donors and the culture-expanded third-party donor-derived umbilical cord MSCs (UC-MSCs), respectively. Reduced intensity conditioning consisted of fludarabine (30 mg/m2·d)+cyclosphamide (500 mg/m2·d)+anti-human thymocyte IgG. Transplant recipients also received cyclosporin A, mycophenolatemofetil, and CD25 monoclonal antibody. A total of 16 patients achieved hematopoietic reconstitution. The median mononuclear cell and CD34 count was 9.3×108/kg and 4.5×106/kg. Median time to ANC was >0.5×109/L and PLT count >20×109/L were 12 and 14 days, respectively. Grade III-IV acute GVHD was seen in 23.5% of the cases, while moderate and severe chronic GVHD were seen in 14.2% of the cases. The 3-month and 6-month survival rates for all patients were 88.2% and 76.5%, respectively; mean survival time was 56.5 months. Combined transplantation of haploidentical HSCs and MSCs on SAA without an HLA-identical sibling donor was safe, effectively reduced the incidence of severe GVHD, and improved patient survival.

Efficacy of Oral Cryotherapy on Oral Mucositis Prevention in Patients with Hematological Malignancies Undergoing Hematopoietic Stem Cell Transplantation: A Meta-Analysis of Randomized Controlled Trials

Objectives Controversy exists regarding whether oral cryotherapy can prevent oral mucositis (OM) in patients with hematological malignancies undergoing hematopoietic stem cell transplantation (HSCT). The aim of the present meta-analysis was to evaluate the efficacy of oral cryotherapy for OM prevention in patients with hematological malignancies undergoing HSCT. Methods PubMed and the Cochrane Library were searched through October 2014. Randomized controlled trials (RCTs) comparing the effect of oral cryotherapy with no treatment or with other interventions for OM in patients undergoing HSCT were included. The primary outcomes were the incidence, severity, and duration of OM. The secondary outcomes included length of analgesic use, total parenteral nutrition (TPN) use, and length of hospital stay. Results Seven RCTs involving eight articles analyzing 458 patients were included. Oral cryotherapy significantly decreased the incidence of severe OM (RR = 0.52, 95% CI = 0.27 to 0.99) and OM severity (SMD = -2.07, 95% CI = -3.90 to -0.25). In addition, the duration of TPN use and the length of hospitalization were markedly reduced (SMD = -0.56, 95% CI = -0.92 to -0.19; SMD = -0.44, 95% CI = -0.76 to -0.13; respectively). However, the pooled results were uncertain for the duration of OM and analgesic use (SMD = -0.13, 95% CI = -0.41 to 0.15; SMD = -1.15, 95% CI = -2.57 to 0.27; respectively). Conclusions Oral cryotherapy is a readily applicable and cost-effective prophylaxis for OM in patients undergoing HSCT.

Efficacy and safety of thrombopoietin receptor agonists in patients with primary immune thrombocytopenia: A systematic review and meta-analysis.

Immune thrombocytopenia (ITP) is an autoimmune disease characterized by increased platelet destruction and impaired platelet production. In this study, we conducted a systematic review and meta-analysis to determine the efficacy and safety of thrombopoietin receptor agonists (TPO-RAs) in primary ITP patients. Thirteen randomized controlled trials were included in this study, the pooled results of which demonstrated that TPO-RAs significantly increased platelet response (R) and durable response (DR) rates [risk ratio (RR): 2.77, 95% confidence interval (CI): 2.01–3.82, P = 5.9 × 10−10; RR: 7.52, 95% CI: 3.94–14.35, P = 9.2 × 10−10; respectively] and that TPO-RAs significantly reduced the incidences of any or severe bleeding events (RR: 0.80, 95% CI: 0.67–0.95, P = 0.013; RR: 0.52, 95% CI: 0.27–0.99, P = 0.048; respectively). Moreover, our results indicated that there was a significant reduction in the proportion of patients needing rescue medications in the TPO-RA groups compared with the control groups (RR: 0.50, 95% CI: 0.42–0.59, P = 2.0 × 10−15) and that the rates of any or severe adverse events were similar between the TPO-RA and control regimens (RR: 1.01, 95% CI: 0.92–1.10; RR: 0.74, 95% CI: 0.54–1.01; respectively). These findings demonstrate that TPO-RAs are an effective and safe second-line treatment option for primary ITP patients.

The efficacy and safety of sirolimus‐based graft‐versus‐host disease prophylaxis in patients undergoing allogeneic hematopoietic stem cell transplantation: a meta‐analysis of randomized controlled trials

The efficacy and safety of sirolimus (SIR)‐based graft‐versus‐host disease (GVHD) prophylaxis in patients who were subjected to allogeneic hematopoietic stem cell transplantation (allo‐HSCT) remain to be clarified; this meta‐analysis was conducted to evaluate these factors.

Mesenchymal stem cells provide prophylaxis against acute graft-versus-host disease following allogeneic hematopoietic stem cell transplantation: A meta-analysis of animal models

A meta-analysis of animal models was conducted to evaluate the prophylactic effects of mesenchymal stem cells (MSCs) on acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation. A total of 50 studies involving 1848 animals were included. The pooled results showed that MSCs significantly reduced aGVHD-associated mortality (risk ratio = 0.70, 95% confidence interval 0.62 to 0.79, P = 2.73×10−9) and clinical scores (standardized mean difference = −3.60, 95% confidence interval −4.43 to −2.76, P = 3.61×10−17). In addition, MSCs conferred robust favorable prophylactic effects on aGVHD across recipient species, MSC doses, and administration times, but not MSC sources. Our meta-analysis showed that MSCs significantly prevented mortality and alleviated the clinical manifestations of aGVHD in animal models. These data support further clinical trials aimed at evaluating the efficacy of using MSCs to prevent aGVHD.

Similar incidence of severe acute GVHD and less severe chronic GVHD in PBSCT from unmanipulated, haploidentical donors compared with that from matched sibling donors for patients with haematological malignancies

The features of graft‐versus‐host disease (GVHD) were compared between patients who underwent myeloablative conditioning and received a peripheral blood stem cell transplant (PBSCT) from either a haploidentical donor (HID) or a matched sibling donor (MSD) during the same period of time. The HID group included more patients with advanced disease. Both groups received the same GVHD prophylaxis with the addition of antithymoglobulin (ATG) in HID group. Higher cumulative incidences (CI) of acute GVHD grade 2–4 (35·1% vs. 13·9%, P = 0·003), similar CI of grade 3–4 (14·5% vs. 9·8%, P = 0·595), less 3‐year CI of extensive chronic GVHD (17·1% vs. 41·5%, P = 0·017) and less severe chronic GVHD (5·8% vs. 21·2%, P = 0·049) occurred in the HID group compared with the MSD group. There was no difference in the sites of the involved organs between these two groups. Higher 3‐year CI of non‐relapse mortality (24·0% vs. 10·2%, P = 0·014), relapse (39·0% vs. 22·6%, P = 0·032) and inferior disease‐free survival (45·7% vs. 78·9%, P = 0·000) were recorded in the HID cohort compared with the MSD group. More HID patients had Karnofsky scores above 90 than those in MSD group (P = 0·016). In conclusion, ATG plays a key role in the unmanipulated HID PBSCT protocol, producing better quality of life in survivors.

The efficacy and safety of rabbit anti-thymocyte globulin vs rabbit anti-T-lymphocyte globulin in peripheral blood stem cell transplantation from unrelated donors

The comparative efficacy and safety of antithymocyte globulin (ATG) at fixed doses in patients undergoing allogeneic peripheral blood stem cell transplantation from unrelated donors (UR-PBSCT) has not been evaluated. In this study, the records of 56 patients and 54 patients who received pre-transplant ATG-Thymoglobulin (ATG-T) at a total dose of 10 mg/kg and ATG- Fresenius (ATG-F) at a total dose of 20 mg/kg, respectively, were retrospectively analyzed. ATG-F patients had a significantly lower probability of developing chronic graft-vs-host disease (cGVHD) than those treated with ATG-T (p = 0.04). ATG-F was associated with a non-significant trend towards lower relapse rates and higher survival at 3- and 5-years of follow-up compared with ATG-T. A significantly greater proportion of ATG-T patients experienced chills and high fever than ATG-F patients (p < 0.01). The current findings suggest that ATG-F may more effectively and safely prevent cGVHD without increasing relapse rates in patients undergoing UR-PBSCT.

Identification of a new HLA allele, HLA-B*13:70, in a Chinese individual

HLA-B*13:70 differs from HLA-B*13:02:01 by one nucleotide (A to G) at nucleotide position 329 in exon 2.