Nonmyeloablative Haploidentical Peripheral Blood Mobilized Hematopoietic Precursor Cell Transplantation for Severe Congenital Anemias Including Sickle Cell Disease and Beta-Thalassemia


1 United States site


2 to 80 Years




Phase 1/Phase 2

Study type









About the study


Bone marrow transplantation (BMT), which involves transplanting a donor’s marrow stem cells,
is capable of curing some congenital anemias. BMT usually involves high-intensity treatment
with chemotherapy and radiation to kill abnormal cells, which affects all systems of the

People with anemias often have damage to other organs such as the kidneys, which can be
further damaged by the chemotherapy. Only approximately 20 percent of patients have a
full-matched donor, making treatment for many people with anemias unavailable. However, 90
percent of patients may have a half-matched donor, but using a half-matched donor increases
the toxicity of BMT.


To determine if a research BMT with half-matched donor cells, low-intensity radiation,
immunosuppressant drugs, and no chemotherapy will be effective in patients with sickle cell
disease and Beta-thalassemia.

To determine the effectiveness of cyclophosphamide, an immunosuppressant drug, in preventing
rejection of the donor cells.


Recipients are individuals at least 18 years of age who have been diagnosed with sickle cell
disease and Beta-thalassemia, and who have a family member who is a haploidentical (i.e.,
half match) tissue match.

Donors are healthy individuals between the ages of 2 and 80 who are found to be suitable


Donors will undergo apheresis, which involves withdrawing blood from one arm vein, passing it
through a machine that removes bone marrow stem cells, and returning the remaining blood
through the vein in the other arm. Donors will receive a drug that causes the stem cells to
be released into the bloodstream prior to the apheresis procedure.

Recipients will undergo routine physical and laboratory examinations, including bone marrow
sampling at the beginning of the study. After transplantation, physical and laboratory
examinations will occur on a weekly or twice weekly basis at the outpatient clinic.
Recipients will be examined every 6 months starting 100 days posttransplant for 5 years.

Recipients will receive low-dose radiation in two treatments 1 and 2 days before the
transplant. They will also be given immunosuppressant therapy with alemtuzumab and sirolimus.
Another immunosuppressant drug, cyclophosphamide, will be given in the future as needed to
subsets of the recipients to prevent rejection of donor cells.

Recipients will receive the donor stem cells through a previously inserted central line. The
process takes up to 8 hours.

Recipients will receive blood transfusions as necessary to prevent anemia and bleeding during
the posttransplant period. They may also receive intravenous antibiotics to prevent

participation requirements

Recipients (must fulfill one disease category in 5.1.1 and all of 5.1.2)

5.1.1 Disease specific Patients with sickle cell disease (HB SS, SC, or SBeta(0)-thal) at high risk for
disease-related morbidity or mortality, defined by having severe end-organ damage (A, B, C,
or D) or potentially modifiable complication(s) not ameliorated by hydroxyurea (E):

A. Stroke defined as a clinically significant neurologic event that is accompanied by an
infarct on cerebral MRI or cerebral arteriopathy requiring chronic transfusion therapy; OR

B. Sickle cell-related renal insufficiency defined by a creatinine level greater than or
equal to 1.5 times the upper limit of normal and kidney biopsy consistent with sickle cell
nephropathy OR nephrotic syndrome OR creatinine clearance less than 50mL/min OR requiring
peritoneal or hemodialysis; OR

C. Pulmonary hypertension defined as tricuspid regurgitant jet velocity (TRV) of greater
than or equal to 2.5 m/s at baseline (without vaso-occlusive crisis); OR

D. Sickle hepatopathy defined as EITHER ferritin greater than 1000mcg/L OR direct bilirubin
greater than 0.4 mg/dL AND platelet count less than 250,000/microL at baseline (without
vaso-occlusive crisis)

E. Any one of the below complications:

-Complication: Vaso-occlusive crises;

Eligible for hydroxyurea*: At least 3 hospital admissions in the last year.

Eligible for HSCT: More than 1 hospital admission per year while on maximal tolerated dose
of hydroxyurea*

-Complication: Acute chest syndrome

Eligible for hydroxyurea*: 2 prior ACS

Eligible for HSCT: any ACS while on hydroxyurea*

*hydroxyurea at maximum tolerated dose for at least 6 months Patients with thalassemia who have grade 2 or 3 iron overload, determined by the
presence of 2 or more of the following:

– portal fibrosis by liver biopsy

– inadequate chelation history (defined as failure to maintain adequate compliance with
chelation with deferoxamine initiated within 18 months of the first transfusion and
administered subcutaneously for 8-10 hours at least 5 days each week)

– hepatomegaly of greater than 2cm below the costochondral margin

5.1.2 Non-disease specific: Age greater than or equal to 18 years Haploidentical relative donor available Ability to comprehend and willing to sign an informed consent Negative Beta-HCG

participation restrictions

Recipient (any of the following would exclude the subject from participating)

5.2.1 6/6 HLA-matched with or without an ABO minor mismatched sibling donor

5.2.2 ECOG performance status of 3 or more

5.2.3 Evidence of uncontrolled bacterial, viral, or fungal infections (currently taking
medication and progression of clinical symptoms) within one month prior to starting the
conditioning regimen. Patients with fever or suspected minor infection should await
resolution of symptoms before starting the conditioning regimen.

5.2.4 Major anticipated illness or organ failure incompatible with survival from PBSC

5.2.5 Pregnant or lactating

5.2.6 Major ABO mismatch


  • Bethesda, Maryland, United States, National Institutes of Health Clinical Center, 9000 Rockville Pike, 20892