Last updated on April 2019

Haplo-identical Transplantation for Severe Aplastic Anemia and Hypo-plastic MDS Using Peripheral Blood Stem Cells and Post-Transplant Cyclophosphamide for GVHD Prophylaxis

Brief description of study


  • Severe aplastic anemia (SAA) and myelodysplastic syndrome (MD) cause serious blood problems. Stem cell transplants using bone marrow or blood plus chemotherapy can help. Researchers want to see if using peripheral blood stem cells (PBSCs) rather than bone marrow cells works too. PBSCs are easier to collect and have more cells that help transplants.


  • To see how safely and effectively SAA and MD are treated using peripheral blood hematopoietic stem cells from a family member plus chemotherapy.


  • Recipients ages 4 55 with SAA or MD and their relative donors ages 4 75


  • Recipients will have:
    • Blood, urine, heart, and lung tests
    • Scans
    • Bone marrow sample
  • Recipients will need a caregiver for several months. They may make fertility plans and a power of attorney.
  • Donors will have blood and tissue tests, then injections to boost stem cells for 5 7 days.
  • Donors will have blood collected from a tube in an arm or leg vein. A machine will separate stem cells and maybe white blood cells. The rest of the blood will be returned into the other arm or leg.
  • In the hospital for about 1 month, recipients will have:
    • Central line inserted in the neck or chest
    • Medicines for side effects
    • Chemotherapy over 8 days and radiation 1 time
    • Stem cell transplant over 4 hours
  • Up to 6 months after transplant, recipients will stay near NIH for weekly physical exams and blood tests.
  • At day 180, recipients will go home. They will have tests at their doctor s office and NIH several times over 5 years.


Detailed Study Description

Severe aplastic anemia (SAA) and myelodysplastic syndrome (MDS) are life-threatening bone marrow disorders. For SAA patients, long term survival can be achieved with immunosuppressive treatment. However, of those patients treated with immunosuppressive therapy, one quarter to one third will not respond, and about 50% of responders will relapse.

Although allogeneic stem cell transplantation (allo-SCT) offers the opportunity of cure, HLA-matched donors are available for only half the patients needing a transplant. Combined haplo-cord transplantation has recently been shown to be a viable transplant option for those patients lacking an HLA matched donor. In our ongoing protocol 08-H-0046, we have utilized this approach in 29 patients with SAA, and SAA evolving to MDS with 27/29 patients having sustained engraftment and achieving transfusion independence. However, engraftment patterns have varied substantially and in some patients, cord engraftment was profoundly delayed or never occurred.

Haploidentical peripheral blood stem cell transplantation (haplo-SCT) has the advantage over cord transplantation of immediate allograft availability, higher stem cell doses, and the feasibility of repeating cell collections if necessary for collecting CD34+ cells for stem cells boosts or lymphocytes to treat or prevent disease relapse or infection. Recently, the use of post-transplant cyclophosphamide (Cy) has been shown to be an effective strategy to prevent GVHD in recipients of haploidentical HSCT, but most reports have focused on patients with hematological malignancies. At present, few data exist on the use of haploidentical transplantation using post-transplant cyclophosphamide for patients with aplastic anemia that have ATG-refractory disease and are heavily-transfused and HLA-alloimmunized. These patients are at an exceedingly high-risk for graft rejection compared to other patient populations.

This research protocol is therefore designed to evaluate the safety and effectiveness of using an unmanipulated G- CSF mobilized peripheral stem cell allograft from a haploidentical donor and post-transplant cyclophosphamide for patients with SAA or SAA evolving to MDS that has proven to be refractory to conventional immunosuppressive therapy (IST) in patients who lack an HLA-matched donor (sibling/ or matched unrelated donor) and who do not have access to a good quality umbilical cord product that meets criteria for expansion (due to insufficient numbers of TNC and/or CD 34+ cells and/or inadequate HLA match) on NHLBI protocol number No. 17-H-0091.

The primary endpoint of the study is chronic GVHD-free survival (defined as the percentage of patients who are alive with no evidence of moderate or severe chronic GVHD at 1 year post-transplant).

Secondary endpoints will include engraftment, 100 day and 200-day treatment related mortality (TRM), and standard transplant outcome variables such as non-hematologic toxicity, incidence and severity of acute and chronic GVHD, and relapse of disease. Health related quality of life will also be assessed as secondary outcome measure.


Clinical Study Identifier: TX218211

Find a site near you

Start Over

Recruitment Status: Open

Brief Description Eligibility Contact Research Team

Volunteer Sign-up

Sign up for our FREE service to receive email notifications when clinical trials are posted in the medical category of interest to you.