Nonmyeloablative Haploidentical Peripheral Blood Mobilized Hematopoietic Precursor Cell Transplantation for Sickle Cell Disease

Updated on 22 December 2020
cell transplantation
sickle cell disease
red blood cell disorder



  • Peripheral blood stem cell transplantation procedures are used for people with sickle cell disease. Researchers want to improve the success and reduce the complications for these procedures. This might allow more people to have a transplant.


  • To see if a new transplant regime is effective, safe and well tolerated in people with sickle cell disease.


  • Adults at least 18 years old with sickle cell disease and certain complications.
  • A relative who is a half tissue match.


  • Participants will be screened with medical history, physical exam, and blood tests. Recipients will also have:
    • Heart, lung, and mental health tests
    • Chest x-rays
    • Bone marrow taken from the pelvic bone
    • Eyes and teeth checked
  • Recipients will have a large central line inserted into a vein for up to 6 months.
  • Donors will have their veins tested and have an IV inserted for 1 day or on rare occasions 2 days.
  • Donors will get a drug to activate bone marrow. It will be injected for about 6 days.
  • Donors will have at least 1 five-hour procedure where bone marrow stem cells will be collected. Blood will be taken from a vein in one arm or in rare cases from a groin vein and put through a machine. Some blood will be saved and the rest will be returned. Stem cells will be taken from the saved blood in a lab and frozen until ready to give to the recipient.
  • Recipients will have:
    • Stems cells collected and frozen
    • Hygiene lessons
    • Bone density scans
    • Low-dose radiation
    • Drugs for their immune system
    • Donor cells infused through their central line
    • Transfusions

After about 30 days, recipients will leave the hospital. They must stay near NIH for 3 months after the transplant and have frequent visits. After returning home, they will have 8 visits over 5 years, then be contacted yearly.



Nonmyeloablative allogeneic peripheral blood stem cell (PBSC) transplants are currently being investigated in phase I/II trials assessing engraftment, efficacy, and toxicity at a number of transplant centers. Our ongoing protocol for patients with severe congenital anemias, particularly sickle cell disease (SCD), and an HLA-matched sibling donor has had excellent preliminary results. None of the patients who engrafted had sickle-related events or any evidence of graft versus host disease (GVHD). There was no significant toxicity associated with the conditioning regimen. An additional protocol is ongoing for patients with high risk of graft rejection which employs pentostatin and oral cyclophosphamide (PC) pre-transplant to further deplete recipient lymphocytes in an attempt to decrease the rate of graft rejection. Four of 4 patients transplanted remain free of SCD.

Our main limitation has been a lack of HLA-matched sibling donors in the majority of patients. We performed a study in which patients with severe SCD who lacked a suitable donor underwent a search for a matched unrelated donor or umbilical cord donor. The vast majority of patients were not found to have an appropriate alternative donor. We therefore seek to develop a safe nonmyeloablative regimen to be applied to the haploidentical setting so that family members can serve as donors and greatly expand the donor pool.

We developed a nonmyeloablative haploidentical PBSC transplant protocol which included 3 cohorts, with stopping rules built in for regimen failure, defined as graft rejection or severe GVHD. All included 400 cGy total body irradiation (TBI), alemtuzumab, and sirolimus. The first cohort included no cyclophosphamide. The 2nd included one dose of cyclophosphamide given at 50mg/kg on day 3 post-transplant, and the 3rd included 100mg/kg cyclophosphamide given in divided doses on days 3 and 4 post-transplant. The engraftment rate and percentage of patients who remained free of SCD improved with each successive cohort. However, the graft rejection rate in the 3rd cohort remained high at 50%. To attempt to reduce the rate of graft rejection in the haploidentical setting, this protocol will add PC to the conditioning regimen.

In this protocol, we propose PBSC transplantation in patients with SCD considered at high risk for complications from or ineligible for standard bone marrow transplantation, with allogeneic peripheral blood stem cells from a haploidentical donor using a novel immunosuppressive regimen without myeloablation in an attempt to further decrease the transplant-related morbidity/mortality. The low intensity nonmyeloablative conditioning regimen will consist of a relatively low radiation dose for therapeutic radiation, Alemtuzumab (Campath ), Sirolimus (Rapamune ), Cyclophosphamide (Cytoxan ), and pentostatin (Nipent ) as a strategy to provide adequate immunosuppression to allow sufficient engraftment for clinical remission with a lower risk of GVHD development. T-cell replete, donor-derived, granulocyte colony-stimulating factor (G-CSF)-mobilized PBSC will be used to establish hematopoietic and lymphoid reconstitution.

The primary endpoint of this study is the percentage of patients at 100 days post-transplant who have not rejected their grafts, and who are without severe GVHD (defined as grade 3 and higher acute GVHD and moderate to severe chronic GVHD). Other endpoints include degree of donor-host chimerism necessary for long-term graft survival and disease amelioration, incidence of acute and chronic GVHD, incidence of graft rejection, transplant-related morbidity, as well as disease-free and overall survival.


Condition Red Blood Cell Disorders, Sickle Cell Disease, Sickle Cell Disease SCD
Clinical Study IdentifierTX218178
Last Modified on22 December 2020


Yes No Not Sure

Inclusion Criteria

Haploidentical relative donor
Weight > 20 kg (insofar that the weight difference between recipient and donor does not exceed a reasonable likelihood of being able to obtain an adequate cell dose from the donor within two aphereses)
Fit to receive filgrastim (G-CSF) and to give peripheral blood stem cells (blood counts and blood pressure within DTM standards)
No history of congestive heart failure or unstable angina, and no history of stroke
Ability to comprehend and willing to sign an informed consent; assent obtained from minors

Exclusion Criteria

Any of the following would exclude the donor from participating
Pregnant or breastfeedingl
HIV positive
Hemoglobin S > 50%
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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.

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