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Protocol Details

Nonmyeloablative Allogeneic Peripheral Blood Mobilized Hematopoietic Precursor Cell Transplantation for Severe Congenital Anemias Including Sickle Cell Disease (SCD) and B-Thalassemia

This study is NOT currently recruiting participants.

Summary | Eligibility | Citations | Contacts




Sponsoring Institute

National Heart, Lung and Blood Institute (NHLBI)

Recruitment Detail

Type: No longer recruiting/follow-up only
Gender: Male & Female
Min Age: 2 Years
Max Age: 80 Years

Referral Letter Required


Population Exclusion(s)

Pregnant Women


Stem Cell Transplant;
Low Dose Radiation;
Alemtuzumab (Campath);
Sirolimus (Rapamune);
Donor Apheresis;
Sickle Cell Anemia (SCA)

Recruitment Keyword(s)

Sickle Cell Anemia;
Diamond-Blackfan Anemia;


Congenital Hemolytic Anemia;
Sickle Cell Disease

Investigational Drug(s)


Investigational Device(s)



Procedure/Surgery: Peripheral blood hematopoietic progenitor cell (PBPC) transplant
Drug: Alemtuzumab
Procedure/Surgery: Peripheral blood hematopoietic progenitor cell Apheresis
Drug: Sirolimus

Supporting Site

National Heart, Lung, and Blood Institute

People with severe congenital anemias, such as sickle cell anemia and beta-thalassemia, have been cured with bone marrow transplantation (BMT). The procedure, however, is limited to children younger than the age of 16 because the risks are lower for children than for adults.

The purpose of this study is to explore the use of a BMT regimen that, instead of chemotherapy, uses a low dose of radiation, combined with two immunosuppressive drugs. This type BMT procedure is described as nonmyeloablative, meaning that it does not destroy the patient s bone marrow. It is hoped that this type of BMT will be safe for patients normally excluded from the procedure because of their age and other reasons.

To participate in this study, patients must be between the ages of 18 and 65 and have a sibling who is a well-matched stem-cell donor. Beyond the standard BMT protocol, study participants will undergo additional procedures. The donor will receive G-CSF by injection for five days; then his or her stem cells will be collected and frozen one month prior to BMT. Approximately one month later, the patient will be given two immune-suppressing drugs, Campath 1-H and Sirolimus, as well as a single low dose of total body irradiation and then the cells from the donor will be infused.

Prior to their participation in this study, patients will undergo the following evaluations: a physical exam, blood work, breathing tests, heart-function tests, chest and sinus x-rays, and bone-marrow sampling.

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Must fulfill one disease category from below:


Patients with sickle cell disease at high risk for disease related morbidity or mortality, defined by having irreversible end organ damage (A, B, C, D or E) or potentially reversible complication(s) not ameliorated by hydroxyurea (F):

A. Stroke defined as a clinically significant neurologic event that is accompanied by an infarct on cerebral MRI


an abnormal trans-cranial Doppler examination ( greater than or equal to 200m/s);


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 60mL/min/1.73m^2 for patients less than or equal to 16 years of age or less than 50mL/min for patients greater than or equal to 16 years of age OR requiring peritoneal or hemodialysis.


Age is less than or equal to 5 years of age with the upper limit of normal serum creatinine 0.8mg/dl

Age is greater than 5 years or less than or equal to 10 years of age with the upper limit of normal serum creatinine 1.0mg/dl

Age is greater than 10 years and less than or equal to 15 years of age the upper limit of normal serum creatinine 1.2mg/dl

Age greater than 15 years of age with the upper limit of normal serum creatinine 1.3mg/dl

C. Tricuspid regurgitant jet velocity (TRV) of greater than or equal to 2.5m/s in patients greater than or equal to 18 years of age at least 3 weeks after a vaso-occlusive crisis, OR

D. Recurrent tricorporal priapism defined as at least two episodes of an erection lasting greater than or equal to 4 hours involving the corpora cavernosa and corpus spongiosa, OR

E. Sickle hepatopathy defined as EITHER ferritin greater than 1000mcg/L OR direct bilirubin greater than 0.4 mg/dL at baseline in patients greater than or equal to 18 years of age; OR

F. Any one of the below complications:

a. Vaso-occlusive crisis:

-Eligible for hydroxyurea; At least 3 hospital admissions in the last year

-Eligible for HSCT; More than 1 hospital admission per year while on therapeutic dose of hydroxyurea

b. Acute Chest Syndrome (ACS):

-Eligible for hydroxyurea*: 2 prior ACS while greater than 3 years of age and adequately treated for asthma

-Eligible for HSCT: any ACS while on hydroxyurea*

c. Osteonecrosis of 2 or more joints:

- Eligible for hydroxyurea*: And significantly affecting their quality of life by Karnofsky score 50-60

- Eligible for HSCT: And on hydroxyurea* where total hemoglobin increase less than 1g/dL or fetal hemoglobin increases less than 2.5 times the baseline level

d. Red cell alloimmunization:

- Eligible for hydroxyurea*: Transfusion-dependent

- Eligible for HSCT: Total hemoglobin increase less than 1g/dL while on hydroxyurea*

*hydroxyurea at therapeutic dose

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 2 cm below the costochondral margin


-Ages greater than or equal to 4 years

-6/6 HLA matched family donor available

-Ability to comprehend and willing to sign an informed consent, assent obtained from minors

-Negative serum beta-HCG, when applicable

-Pediatric patients less than 16 years of age must decline myeloablative bone marrow transplantation


Donor deemed suitable and eligible, and willing to donate per clinical evaluations, who are additionally willing to donate blood for research and undergo a neuropsychological test. Donors will be evaluated in accordance with existing Standard NIH Policies and Procedures for determination of eligibility and suitability for clinical donation under a separate NHLBI protocol. Note that participation in this study is offered to all donors, but is not required for a donor to make a stem cell donation, so it is possible that not all donors will enroll onto this study.



(Any of the following would exclude the subject from participating)

ECOG performance status of 3 or more, or Lanksy performance status of less than 40.

Diffusion capacity of carbon monoxide (DLCO) less than 35% predicted. (corrected for hemoglobin and alveolar volume).

Baseline oxygen saturation of less than 85% or PaO2 less than 70

Left ventricular ejection fraction: less than 35% estimated by ECHO.

Transaminases greater than 5 times the upper limit of normal for age

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

Major anticipated illness or organ failure incompatible with survival from PBSC transplant.

Pregnant or lactating

Major ABO mismatch



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Wayne AS, Schoenike SE, Pegelow CH. Financial analysis of chronic transfusion for stroke prevention in sickle cell disease. Blood. 2000 Oct 1;96(7):2369-72.

Platt OS, Brambilla DJ, Rosse WF, Milner PF, Castro O, Steinberg MH, Klug PP. Mortality in sickle cell disease. Life expectancy and risk factors for early death. N Engl J Med. 1994 Jun 9;330(23):1639-44.

Charache S, Terrin ML, Moore RD, Dover GJ, Barton FB, Eckert SV, McMahon RP, Bonds DR. Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia. Investigators of the Multicenter Study of Hydroxyurea in Sickle Cell Anemia. N Engl J Med. 1995 May 18;332(20):1317-22.

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Principal Investigator

Referral Contact

For more information:

John F. Tisdale, M.D.
National Heart, Lung and Blood Institute (NHLBI)
(301) 402-6497

Priscilla S. Pollack, R.N.
National Heart, Lung and Blood Institute (NHLBI)
National Institutes of Health
Building 10
Room 3-2473
10 Center Drive
Bethesda, Maryland 20892
(301) 496-1781

Office of Patient Recruitment
National Institutes of Health Clinical Center (CC)
Building 61, 10 Cloister Court
Bethesda, Maryland 20892
Toll Free: 1-800-411-1222
Local Phone: 301-451-4383
TTY: TTY Users Dial 7-1-1

Clinical Trials Number:


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