Nonmyeloablative Peripheral Blood Mobilized Hematopoietic Precursor Cell Transplantation for Sickle Cell Disease and Beta-Thalassemia in Individuals With Higher Risk of Transplant Failure

About the study


– Some sickle cell disease or beta-thalassemia can be cured with transplant. Researchers want
to test a variation of transplant that uses low dose radiation and a combination of
immunosuppressive drugs. They want to know if it helps a body to better accept donor stem


– To see if low dose radiation (300 rads), oral cyclophosphamide, pentostatin, and sirolimus
help a body to better accept donor stem cells.


– People 4 and older with beta-thalassemia or sickle cell disease that can be cured with
transplant, and their donors.


– Participants and donors will be screened with medical history, physical exam, blood
test, tissue and blood typing, and bone marrow sampling. They will visit a social

– Donors:

– may receive an intravenous (IV) tube in their groin vein.

– will receive a drug injection daily for 5 or 6 days to move the blood stem cells from
the bone marrow into general blood circulation.

– will undergo apheresis: an IV is put into a vein in each arm. Blood is taken from one
arm, a machine removes the white blood cells that contain blood stem cells, and the rest
is returned through the other arm.

– Participants:

– may undergo red cell exchange procedure.

– will remain in the hospital for about 30 days.

– will receive a large IV line that can stay in their body from transplant through

– will receive a dose of radiation, and transplant related drugs by mouth or IV.

– will receive blood stem cells over 8 hours by IV.

– will take neuropsychological tests and may complete questionnaires throughout the
transplant process.

– must stay near NIH for 4 months. They will visit the outpatient clinic weekly.

– will have 5 follow-up visits for 3 years after transplant, then annually.

Study point of contact

Matthew M Hsieh, M.D.
(301) 402-7687
Priscilla S Pollack, R.N.
(301) 496-1781


1 United States site


> 4 Years




Phase 2

Study type









participation requirements

– recipients (must fulfill one disease category in 1 and all of 2)

1. Disease specific

Patients with severe sickle cell disease (not limited to Hb SS, SC, or S
beta-thal) at high risk for disease-related morbidity or mortality, defined by
having severe end-organ damage (A, B, C, D, or E) or potentially modifiable
complication(s) not ameliorated by hydroxyurea or sickle specific therapy (F):

– 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. Tricuspid regurgitant jet velocity (TRV) of greater than or equal to 2.5 m/s 40, 41 at baseline; OR - D. Recurrent priapism defined as at least 2 episodes of an erection lasting >4 hours involving the corpora cavernosa and corpus spongiosa; OR

– E. Sickle hepatopathy defined as EITHER ferritin >1000mcg/L OR direct
bilirubin >0.4 mg/dL at baseline

– F. Any one of the below complications:

—Complication/ Eligible for hydroxyurea*/ Eligible for HSCT

– Vaso-occlusive crises/ At least 3 hospital admissions in the last year/
More than one hospital admission in the last year while on therapeutic
dose of hydroxyurea or sickle cell therapy

– Acute chest syndrome/ 2 prior ACS/ any ACS while on hydroxyurea

– Osetonecrosis of 2 or more joints/ And significantly affecting their
quality of life by Karnofsky score 50-60/ And on hydroxyurea where
total hemoglobuin increases less than 1 g/dL or fetal hemoglobin
increases less than 2.5 times the baseline level

– Red cell alloimmunization/ Transfusion dependent/ Total hemoglobin
increases less than 1g/dL while on hydroxurea

2. Patients with beta-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

Non-disease specific:

– Age greater than or equal to 4 years

– 6/6 HLA matched family donor available

– Ability to comprehend and willing to sign an informed consent

– Negative beta-HCG, when applicable

participation restrictions

– recipient (any of the following would exclude the subject from

– ECOG performance status of 3 or more

– 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.

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

– Pregnant or lactating


  • Bethesda, Maryland, United States, National Institutes of Health Clinical Center, 9000 Rockville Pike, 20892 [Recruiting]
Last updated 2021-09-04