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

Updated on 22 December 2020
myelodysplastic syndromes
myelodysplastic syndrome (mds)
anemia studies
aplastic anemia



  • 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.



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.


Condition Aplastic Anemia, Aplastic Anemia, Anemia; Non-Small-Cell Lung Cancer, Myelodysplastic Syndromes (MDS), Severe Aplastic Anemia (SAA) Hypo-Plastic Myelodysplastic Syndrome (MDS)
Clinical Study IdentifierTX218211
Last Modified on22 December 2020


Yes No Not Sure

Inclusion Criteria

HLA mismatched family donor (greater than or equal to 5/10 and less than or equal to 8/10 HLA match (HLA-A, B, C, DR, and DQ loci)) who is available to donate cells
Ages 4-75 inclusive. Note: a pediatric family member will only be considered as a donor if a suitable adult haplo-identical donor is not available
Weight > 15 kg
For adults: Ability to comprehend the investigational nature of the study and provide informed consent. For minors: Written informed consent from one parent or guardian who is not the recipient of the transplant and informed assent. The process will be explained to the minor on a level of complexity appropriate for their age and ability to comprehend
Genetic testing for genes associated with bone marrow failure syndromes (BMFS) performed at a CLIA- certified laboratory. If there is a suspicion of familial BMFS in the recipient, then the haplo donor must have undergone genetic testing for genes associated with BMFS - performed at a CLIA-certified laboratory, prior to enrolling in this protocol

Exclusion Criteria

Pregnant or lactating
A pediatric haplo-identical donor will be excluded if a suitable adult haplo-identical donor is available
Unfit to receive filgrastim (G-CSF) and undergo apheresis (history of stroke, MI, unstable angina, uncontrolled hypertension, severe heart disease or palpable spleen)
HIV positive (Donors who are positive for HBV, HCV or HTLV I/II, T.cruzi [Chagas] may be used at the discretion of the investigator following counseling and approval from the recipient)
Sickling hemoglobinopathies including HbSS or HbSC. Donors with HbAS are acceptable
Psychiatric illness that would limit the patient s ability to tolerate and/or comply with study requirements
Screening test positive for Chagas disease (Trypanosoma cruzi /T. cruzi/trypanosomiasis) confirmed by the Center for Disease Control (CDC)
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer  to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact


Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider


Browse trials for

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 



Reply by • Private

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note