Mesenchymal Stem Cells Co-transplantation in Alternative Donor Transplantation of Severe Aplastic Anemia.

Related Clinical Trial
Efficacy and Safety of Hetrombopag in Non-severe Aplastic Anemia Long Term Follow-up Observational Study After Clinical Trials of AMG531 (Romiplostim) in Patients With Untreated Aplastic Anemia Efficacy and Safety of Lower-dose Decitabine in Refractory Aplastic Anemia Quantitative MRI of Bone Marrow Fat Fraction in Patients With Trepanobiopsy Avatrombopag Usage in NSAA Ibrutinib for the Treatment of COVID-19 in Patients Requiring Hospitalization Retrospective Study of Patients With Severe Aplastic Anemia Who Relapsed After Immunosuppressive Therapy Retrospective Study of Patients With Severe Aplastic Anemia Who Developed High Risk Clonal Evolution With Chromosome 7Abnormalities After Immunosuppressive Therapy REGN7257 in Adult Patients With Severe Aplastic Anemia That Is Refractory to or Relapsed on Immunosuppressive Therapy Transfer of Effector Memory T Cells (Tem) Following Allogeneic Stem Cell Transplantation Phase II Study Evaluating Busulfan and Fludarabine as Preparative Therapy in Adults With Hematopoietic Disorders Undergoing MUD SCT A Multicenter Access and Distribution Protocol for Unlicensed Cryopreserved Cord Blood Units (CBUs) Investigation of the Cylex® ImmuKnow® Assay Cytokine-Treated Veto Cells in Treating Patients With Hematologic Malignancies Following Stem Cell Transplant Umbilical Cord Blood Transplantation From Unrelated Donors Patient-Driven Transfusion Thresholds in Hematological Disorders: A Pilot Study Unrelated Umbilical Cord Blood (UBC)Transplantation New York Blood Center National Cord Blood Program Pooled Unrelated Donor Umbilical Cord Blood Transplant For Hematologic Malignancy Needing Allogeneic Stem Cell Transplant Without Related HLA-Match Bone Marrow Transplantation of Patients in Remission Using Partially Matched Relative Donor Nonmyeloablative Allo SCT for the Treatment of Hematologic Disorders Nonmyeloablative Allogeneic Stem Cell Transplantation From HLA-Matched Unrelated Donor for the Treatment of Hematologic Disorders Post Transplant Cyclophosphamide (Cytoxan) for GvHD Prophylaxis Effects of Aerobic Training and Inspiratory Muscle Training in Patients During Hematopoietic Stem Cell Transplantation A Phase II Study of Umbilical Cord Blood Transplantation Transplants With Unlicensed Preserved Cord Blood Safety Study of Cord Blood Units for Stem Cell Transplants Pharmacokinetic Study of Fludarabine in Pediatric Hematopoietic Stem Cell Transplantation Screening Gene Mutations in Myeloid Cancers by Next Generation Sequencing to Improve Treatment Results Safety Study of CD3/CD19 Depleted Haploidentical Stem Cells Trial of Two Central Venous Catheter (CVC) Flushing Schemes in Pediatric Hematology and Oncology Patients Blood Transplantation for Patients With Hematologic Malignancies or Bone Marrow Failure States Unrelated Cord Blood Transplant Plus a Haplo-Identical (Half-Matched), T-Cell Depleted Stem Transplant From a Related Donor for Subjects With High Risk Malignancies Extended Platelet Parameters as a Means to Differentiate Immune Thrombocytopenia From Hypo-proliferative Thrombocytopenias. Protection Against Benzene Toxicity Treatment of Menorrhagia in Women With Thrombocytopenia Using Platelets or Platelets and Hormones Risk Stratification Directed Conditioning Regimen for Haploidentical HSCT in SAA Etiology of Blood Dyscrasias: Analysis of the International Agranulocytosis and Aplastic Anemia Study Data Multi-Center Trial of Anti-Thymocyte Globulin in Treatment of Aplastic Anemia and Other Hematologic Disorders King’s Invasive Aspergillosis Study II Identification of Mechanism in the Erythroid Response in Patients With Myelodysplasia Undergoing Chelation Therapy Aplastic Anemia Epidemiology: Incidence and Case-control Drug Etiology of Aplastic Anemia and Related Dyscrasias hATG+CsA vs hATG+CsA+Eltrombopag for SAA Non-Myeloablative Allogeneic Stem Cell Transplantation With Matched Unrelated Donors for Treatment of Hematologic Malignancies, Renal Cell Carcinoma, and Aplastic Anemia Conditioning Regimens for Patients With Severe Aplastic Anemia Transplanted With Marrow From an Unrelated Donor Study of Allogeneic Bone Marrow and T-Cell Depleted, CD34+ Peripheral Blood Stem Cell Transplantation in Patients With Aplastic Anemia Posaconazole Prophylaxis During ATG Treatment for hMDS/AA Patients Efficacy and Safety of Thrombopoietin In Patients With Severe and Very Severe Aplastic Anemia Study of MRI Monitoring in Patients With Aplastic Anemia and Low or Int-1 Risk of MDS Complicated With Iron Overload A Pilot Study of the Thrombopoietin-Receptor Agonist Eltrombopag in Refractory Aplastic Anemia Patients Phase IIA Open Label Study to Evaluate Efficacy and Safety of BL-8040 Followed by (hATG), Cyclosporine and Methyprednisolone in Adult Subjects With Aplastic Anemia or Hypoplastic Myelodysplastic Syndrome Sirolimus and Cyclosporine for Treatment-Resistant Aplastic Anemia Flu+CPM+rATG Conditioning Regimes for Unrelated Bone Marrow Transplantation (UBMT)(or Mobilized Peripheral Blood)in Severe Aplastic Anemia (SAA) Unrelated Umbilical Cord Blood Transplantation for Severe Aplastic Anemia and Hypo-plastic MDS Using CordIn(TM), Umbilical Cord Blood-Derived Ex Vivo Expanded Stem and Progenitor Cells to Expedite Engraftment and Improve Transplant Outcome Hetrombopag or Placebo in Treatment-Naive Severe Aplastic Anemia Safety and Efficacy Study of Umbilical Cord/Placenta-Derived Mesenchymal Stem Cells to Treat Severe Aplastic Anemia Eltrombopag in Combination With Rabbit Anti-thymocyte Globulin/Cyclosporine A in Naive Aplastic Anemia (AA) Subjects Reduced-Intensity Preparative Regimen for Allogeneic Stem Cell Transplantation in Patients With Severe Aplastic Anemia Methylprednisolone, Horse Anti-Thymocyte Globulin, Cyclosporine, Filgrastim, and/or Pegfilgrastim or Pegfilgrastim Biosimilar in Treating Patients With Aplastic Anemia or Low or Intermediate-Risk Myelodysplastic Syndrome Efficacy and Safety of Eltrombopag + CSA in Patients With Moderate Aplastic Anemia (EMAA) Allogeneic Stem Cell Transplantation for Patients With Severe Aplastic Anemia Multi Center Case Control Study on Multiple Risk Factors of Aplastic Anemia NMA Haplo or MUD BMT for Newly Diagnosed Severe Aplastic Anemia Horse ATG/CsA in Aplastic Anemia Patients Unresponsive to or With a Suboptimal Response to Rabbit ATG/CsA Treatment Safety and Efficacy Study of Ex Vivo Immunotherapy for Treatment of Aplastic Anemia Phase II Study of Bone Marrow Transplantation Using Related Donors in Patients With Aplastic Anemia Early Initiation of Oral Therapy With Cyclosporine and Eltrombopag for Treatment Naive Severe Aplastic Anemia (SAA) Haploidentical Transplantation in Severe Aplastic Anemia A Description of Bacteria in the Mouths of Patients With Severe Aplastic Anemia Efficacy and Safety of Eltrombopag + Tacrolimus in Chinese Refractory or Relapsed Aplastic Anemia Patients A Study to Evaluate the Safety and Efficacy of Hetrombopag Olamine in Severe Aplastic Anemia (SAA) Patient Haploidentical Bone Marrow Transplant With Post-Transplant Cyclophosphamide for Patients With Severe Aplastic Anemia Cyclophosphamide and Anti-thymocyte Globulin Followed By Methotrexate and Cyclosporine in Preventing Chronic Graft-Versus-Host Disease in Patients With Severe Aplastic Anemia Undergoing Donor Bone Marrow Transplant Peripheral Blood Allogenic Stem Cell Transplantation Using Non-anti Thymocyte Globulin Regimens in Severe Aplastic Anemia Patients A Phase 2 Study to Evaluate the Efficacy and Safety of AMG531 in Aplastic Anemia Sirolimus (Rapamune ) for Relapse Prevention in People With Severe Aplastic Anemia Responsive to Immunosuppressive Therapy Phase III Randomized Study of Cyclophosphamide With or Without Antithymocyte Globulin Before Bone Marrow Transplantation in Patients With Aplastic Anemia Anti-thymocyte Globulin and Cyclosporine as First-Line Therapy in Treating Patients With Severe Aplastic Anemia Cyclophosphamide, Antithymocyte Globulin, and Total-Body Irradiation in Treating Patients With Severe Aplastic Anemia Undergoing Umbilical Cord Blood Transplant Purified CD34+ Hematopoietic Stem Cell Transplantation From Alternate Donors for Patients With Severe Aplastic Anemia Stem Cell Factor Medication for Aplastic Anemia Thymoglobulin and Cyclosporine in Patients With Aplastic Anemia or Myelodysplastic Syndrome Extended Dosing With Eltrombopag for Severe Aplastic Anemia Randomized Study In Severe Aplastic Anemia Patients Receiving Atg, Cyclosporin A, With Or Without G-CSF (SAA-G-CSF) Umbilical Cord Derived Mesenchymal Stem Cells Therapy in Aplastic Anemia Stem Cell Mobilization Potential in Patients With Aplastic Anemia in Remission A Phase II Dose-escalation Study Characterizing the PK of Eltrombopag in Pediatric Patients With Previously Untreated or Relapsed Severe Aplastic Anemia or Recurrent Aplastic Anemia Eltrombopag With Standard Immunosuppression for Severe Aplastic Anemia Mycophenolate Mofetil and Cyclosporine to Treat Relapsing Aplastic Anemia Human Leukocyte Antigen (HLA)-Haploidentical Hematopoietic Stem Cell Transplantation for Patients With Aplastic Anemia Collection of Blood and Bone Marrow From Patients With Aplastic Anemia for Analysis of Adhesion Molecules, Chemokines and Their Receptors Purine Analog-Based Conditioning in Patients With Severe Aplastic Anemia Alefacept in Patients With Relapsed/Refractory Aplastic Anemia Oral Manifestations of Aplastic Anemia The Efficacy of Immunosuppressive Therapy Combined With Cord Blood Transfusion in Treatment of Severe Aplastic Anemia Clinical Study of Non Severe Aplastic Anemia Treated With Cyclosporine, Androgen and Levamisole Mesenchymal Stem Cells Transplantation to Patients With Relapsed/Refractory Aplastic Anemia. Safety and Efficacy of Exjade in the Treatment of Transfusion-dependent Iron Overload in Aplastic Anemia Patients Cyclophosphamide Plus Cyclosporine in Treatment-Naive Severe Aplastic Anemia Neuropsychological Effects of Immunosuppressive Treatment in Subjects With Aplastic Anemia Unrelated Donor Transplant Versus Immune Therapy in Pediatric Severe Aplastic Anemia Reduced Toxicity Fludarabine (Flu) + Cyclophosphamide (CPM) + Rabbit Antithymocyte Globulin (rATG) Conditioning Regimen for Unrelated Donor Transplantation in Severe Aplastic Anemia (SAA) ATG Combined With Cyclophosphamide And Cord Blood Transfusion in Treating Patients With Severe Aplastic Anemia A Novel TBI Free Conditioning Protocol for Haploidentical Transplant in Acquired Aplastic Anemia: Combination Therapy of Severe Aplastic Anemia Comparing Therapies for the Treatment of Severe Aplastic Anemia Mesenchymal Stem Cells Co-transplantation in Alternative Donor Transplantation of Severe Aplastic Anemia. Study of AMG531(Romiplostim) in Patients With Aplastic Anemia Bone Marrow Transplant Trial for Patients With Refractory Severe Aplastic Anemia Study of AMG531 (Romiplostim) in Patients With Aplastic Anemia Improving Immunosuppressive Treatment for Patients With Severe Aplastic Anemia Study of Romiplostim(AMG531) in Subjects With Aplastic Anemia A Single-Arm Phase 2 Study With Optimized Standard Protocol for Severe Aplastic Anemia Rabbit Antithymocyte Globulin (Thymoglobuline) With Ciclosporin for Patients With Acquired Aplastic Anaemia Efficacy and Safety of Eltrombopag In Patients With Severe and Very Severe Aplastic Anemia A Study to Assess Efficacy and Safety of PF-06462700 in Japanese Participants With Aplastic Anemia Alemtuzumab and Rituximab in Aplastic Anemia Allogeneic Stem Cell Transplant for Patients With Severe Aplastic Anemia Comparison of Two Different Doses of Rabbit ATG-Fresenius With Cyclosporin in the Treatment of Acquired Aplastic Anaemia Mesenchymal Stem Cells in the Treatment of Relapsed/Refractory Severe Acquired Aplastic Anemia Study of Fludarabine + Cyclophosphamide + TBI Conditioning Regimen for Double Units Cord Blood Transplantation(CBT)in Severe Aplastic Anemia(SAA) Safety and Efficacy of Patient’s Own AD-MSC and AD-HSC Transplantation in Patients With Severe Aplastic Anemia Ambispective Observational Study to Evaluate the Incidence and Management of Aplastic Anemia in Spain Moderate-dose Cyclophosphamide for Childhood Acquired Aplastic Anemia

Brief Title

Mesenchymal Stem Cells Co-transplantation in Alternative Donor Transplantation of Severe Aplastic Anemia.

Official Title

PhaseⅡTrial of Co-transplantation With Bone Marrow Derived Mesenchymal Stem Cells From Related Donors in Alternative Donor Transplantation of Severe Aplastic Anemia.

Brief Summary

      The study is a phase II trial designed to evaluate the efficacy and safety of
      co-transplantation with bone marrow derived mesenchymal stem cells from related donors in
      alternative donor transplantation of severe aplastic anemia.

Detailed Description

      Aplastic anemia (AA) is an autoimmune hematologic stem cell disease mediated by activated
      T-lymphocytes that leads to bone marrow dysfunction. In the presence of an empty marrow,
      pancytopenia, and transfusion dependence, the severity of the disease is based on neutrophil
      (PMN) count: nonsevere AA (nSAA; PMN > 0.5 × 109/L), severe AA (SAA;PMN 0.2- 0.5 × 109/L),
      and very severe AA (vSAA; PMN< 0.2 × 109/L).

      Allogeneic BMT from an HLA-identical sibling donor or matched-alternative donor is the
      treatment of choice for patients with aplastic anaemia.Transplantation for patients with
      severe aplastic anaemia from an HLA identical sibling donor is now very successful with a
      75-90% chance of long term cure and with overall survival of between 65% and 73% at 5 years
      for matched-alternative donor transplantation. However, these two approachs are limited by
      the availability of HLA-matched donors.

      Patients without HLA-identical sibling donor or matched-alternative donor can be offered
      immunosuppressive treatment (IST) involving injections of Anti-thymocyte globulin (ATG) in
      combination with cyclosporine (CsA). The treatment response with ATG is at best between
      60-80%, 30%-40% patients relapse following an initial response to treatment. Moreover, a
      recent study has shown that on multivariate analysis of response at 6 months, only younger
      age, absolute reticulocyte count (ARC) and absolute lymphocyte count (ALC), correlate with
      response to ATG. Patients with SAA or vSAA, with much lower ARC and ALC, were poor response
      to IST and have high risks of dying of infection and bleeding.

      Nowadays, with advances in transplant technology, HLA-mismatched related donors and unrelated
      donors transplantation has achieved good clinical results. Data from the XJ Huang indicated
      that patients with HLA-mismatched related donors achieved 100% donor myeloid engraftment and
      have a survival rate of 64.6±12.4%. Retrospectively analyzed results for 154 patients with
      acquired SAA who received BMT from unrelated donors identified through the Japan Marrow Donor
      Program showed the probability of OS at 5 years was 56% (95% confidence interval, 34%-78%).

      Compared with malignant disease, mismatched related donor or unrelated donor HSCT for SAA
      involves distinct challenges mainly associated with high graft failure and high GVHD. So, if
      we can find a way to promote implantation meanwhile prevent or reduce GVHD , the efficacy of
      HLA-mismatched related donors transplantation can improve.

      Mesenchymal stem cells (MSCs) are multi-potent non-hematopoietic progenitors mainly found in
      BM, cord blood, and adipose tissue. MSCs are attractive because of the ease with which they
      can be isolated and expanded ex vivo, their ability to undergo multilineage differentiation,
      and their lack of immunogenicity. These cells were shown to provide support for the growth
      and differentiation of hematopoietic progenitor cells in BM micro-environments. In additon,
      preliminary studies have shown clinical effectiveness of allogeneic MSC in the treatment of
      refractory graft-versus-host disease and an improvement in or resolution of severe aGVHD when
      co-transplantation with MSCs. Due to these properties, MSCs have become an interesting
      candidate for use in cellular therapy and are considered "theoretically perfect cells" for
      potential clinical use against AA mismatched related donors transplantation.

Study Phase

Phase 2

Study Type


Primary Outcome

survival rate

Secondary Outcome

 acute GVHD


Severe Aplastic Anemia


mesenchymal stem cells

Study Arms / Comparison Groups

 Mesenchymal stem cells
Description:  Intravenous bone marrow derived mesenchymal stem cells infusion from related donor to patients with severe aplastic anemia.


* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status


Estimated Enrollment


Start Date

February 2013

Completion Date

February 2018

Primary Completion Date

February 2017

Eligibility Criteria

        Inclusion Criteria:

          1. In line with the 2009 Edition (United Kingdom) aplastic anemia diagnostic criteria for
             SAA or VSAA;

          2. Age less than 50 years old,willing to transplant;

          3. No HLA-identical sibling donor;

          4. Have HLA-mismatched related donors or unrelated donors ( ≥5/10 HLA matched loci in
             related donors; ≥8/10 HLA matched loci in unrelated donors )

          5. No serious infection or acute hemorrhage;

          6. Cardiac ultrasound examination showed left ventricular ejection fraction is greater
             than 50%;

          7. Both transaminase and serum creatinine level are no more than twice times the upper
             limit of normal value (ULN);

          8. No acute infectious disease;

          9. Ability to understand and the willingness to sign a written informed consent document.

         10. ECOG score of 0-2 points.

        Exclusion Criteria:

          1. Patients with severe infection or active bleeding;

          2. With severe cardiac insufficiency, left ventricular ejection fraction <50%;

          3. With severe liver dysfunction, liver function (ALT and the TBIL) is higher than the
             ULN 3 times;

          4. With severe renal insufficiency, renal function (Cr) is twice higher than the ULN; or
             24-hour urine creatinine clearance rate (Ccr) lower than 50ml/min;

          5. Active tuberculosis, severe acute hepatitis and other infectious diseases in active

          6. ECOG score more than 3 points;

          7. Accompanied by malignant tumors and other clonal disease;

          8. Poor compliance and the researchers considered unsuitable for MSC infusion.




14 Years - 50 Years

Accepts Healthy Volunteers



Yang Xiao, MD, , 

Location Countries


Location Countries


Administrative Informations



Organization ID

MSC-alternative donor SCT-SAA

Responsible Party

Principal Investigator

Study Sponsor

Guangzhou General Hospital of Guangzhou Military Command


 Guangzhou First People's Hospital

Study Sponsor

Yang Xiao, MD, Study Chair, Guangzhou General Hospital of Guangzhou Military Command

Verification Date

September 2014