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Protocol Details

Co-Infusion of Umbilical Cord Blood and Haploidentical CD34+ Cells Following Nonmyeloablative Conditioning as Treatment for Severe Aplastic Anemia and MDS Associated with Severe Neutropenia Refractory to Immunosuppressive Therapy

This study is NOT currently recruiting participants.

Summary | Eligibility | Citations | Contacts




Sponsoring Institute

National Heart, Lung and Blood Institute (NHLBI)

Recruitment Detail

Type: Completed Study; data analyses ongoing
Gender: Male & Female
Min Age: 4 Years
Max Age: 75 Years

Referral Letter Required


Population Exclusion(s)



Umbilical Cord Blood;

Recruitment Keyword(s)

Severe Aplastic Anemia;
Myelodysplastic Syndrome;


Myelodysplastic Syndrome (MDS) with Refractory Anemia (RA);
Severe Aplastic Anemia

Investigational Drug(s)


Investigational Device(s)



Biological/Vaccine: Umbilical Cord Blood

Supporting Site

National Heart, Lung, and Blood Institute

This study will evaluate the safety and effectiveness of treating patients with severe aplastic anemia (SAA) or myelodysplastic syndrome (MDS) with both peripheral blood stem cells from a family member and umbilical cord blood stem cells from an unrelated donor.

Patients with SAA or MDS for whom other treatments have failed or are not available may be eligible for this study. Candidates may not have a tissue-matched sibling or matched unrelated donor and must have a family member who is a partial tissue type match.

Participants undergo the following tests and procedures:

-Insertion of a central intravenous (IV) line (plastic tube) into a large vein. The tube is used for giving the donated stem cells and antibiotics and other medicines, for transfusions of red blood cells and platelets, and for collecting blood samples.

-Preparatory chemotherapy (fludarabine, cyclophosphamide and anti-thymocyte globulin) and total body irradiation to suppress immunity and prevent rejection of the donated cells.

-Infusion of the donated stem cells and umbilical cord cells.

-Immune suppression with the drugs tacrolimus, mycophenolate mofetil and prednisone to prevent rejection of the donated cells and to prevent graft-versus-host disease (GVHD), a complication of stem cell transplants in which the donors immune cells destroy the patients healthy tissues.

The average hospital stay after stem cell transplantation is 3 to 4 weeks. Patients return for frequent follow-up visits for the first 2 to 4 months after transplantation. Once the patient returns home, his or her referring physician is asked to send results of any laboratory testing to the NIH researchers at least every 3 months for the first 3 years and annually thereafter. Patient follow-up visits are scheduled at NIH at 1, 2, 3, 4 and 5 years after transplantation to monitor for signs of disease or post-transplantation complications, such as infection or GVHD. After 5 years, participants are offered the opportunity to enroll in NHLBIs long-term evaluation and follow-up care protocol.

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-Diagnosed with severe aplastic anemia characterized by all of the following:

a) Bone marrow cellularity less than 30 percent (excluding lymphocytes)

b) Transfusion dependence for platelets and/or RBCs

c) Neutropenia (absolute neutrophil count less than 500 cells/microL) OR for patients receiving granulocyte transfusions, absolute neutrophil count < 500 cells/microL before beginning granulocyte transfusions].)


-Diagnosed with myelodysplastic syndrome characterized by refractory anemia OR refractory anemia with ringed sideroblasts (RARS and at least one of the following:

a) Neutropenia [(absolute neutrophil count < 500 cells/microL) OR for patients receiving granulocyte transfusions, absolute neutrophil count < 500 cells/microL before beginning granulocyte transfusions]) and history of 1 or more opportunistic infections related to neutropenia. OR

b) History of severe aplastic anemia transformed to MDS

-Intolerance of or failure to respond standard immunosuppressive therapy.

-Availability of at least one HLA-haploidentical (i.e. greater than or equal to 5/10 and less than or equal to 8/10 HLA match) related donor (HLA-A, B, C, DR, and DO loci) who is available to donate CD34+ cells (4-75 years old).

-Availability of at least one 4/6 HLA-matched (HLA-A, B, and DR loci) cord blood unit from the National Marrow Donor Program (NMDP). The cord blood unit must contain a minimum TNC (prior to thawing) of at least 1.5 x 10(7) cells per kilogram of recipient body weight with the following exception: if the minimum criterion of TNC is not met the cord unit must contain at least 1.7 x 10(5) CD34 plus cells/kg (prior to thawing).

-Ages 4-55 years inclusive.

-Ability to comprehend the investigational nature of the study and provide informed consent. The procedure will be explained to subjects aged 4-17 years with formal consent being obtained from parents or legal guardian.

--Telomere Length Testing

--In patients where a suspicion for a familial bone marrow failure syndromes (BMFS) exists, TERC and TERT mutation testing will be performed on protocol 04-H-0012 or performed elsewhere prior to enrolling on 04-H-0012.


-Availability of an HLA identical or 9/10 HLA matched(HLA A, B, C, DR, and DO loci-relative to serve as a stem cell donor.

-The patient is deemed to be a candidate for a 6/6 HLA matched unrelated stem cell transplant (availability of a donor and resources required for such a transplant).

-ECOG performance status of 2 or more.

-Major anticipated illness or organ failure incompatible with survival from transplant

-Severe psychiatric illness. Mental deficiency sufficiently severe as to make compliance with the transplant treatment unlikely and making informed consent impossible.

-Positive pregnancy test for women of childbearing age.

-HIV positive

-Diagnosis of Fanconi anemia (by chromosome breakage study).

-Diffusion capacity of carbon monoxide (DLCO) less than 40 percent using DLCO corrected for Hgb or lung volumes (patients under the age of 10 may be excluded from this criterion if they have difficulty performing the test correctly and thus are unable to have their DLCO assessed) using DL Adj and DL/VA/Adj.

-Left ventricular ejection fraction less than 40 percent (evaluated by ECHO)

-Transaminases greater than 5x upper limit of normal (when transaminases are elevated, the subject may be excluded at the discretion of the PI).

-Serum bilirubin greater than 4 mg/dl

-Creatinine clearance less than 50 cc/min by 24 hr urine collection (adjusted for body surface area, i.e.50 ml/min/1.73m(2))

-Serum creatinine > 2.5 mg/dl

-Failure to collect an adequate number of CD34+ cells (i.e. greater than or equal 2 x 10(6) CD34+ cells/kg) for transplantation from the subject s haploidentical relative.

-Presence of an active infection not adequately responding to appropriate therapy

-History of a malignant disease liable to relapse or progress within 5 years


-HLA mismatched family donor (greater than or equal to 5/10 and less than or equal to 8/10 HLA matched (HLA-A, B, C, DR and DO loci) who is available to donate CD34+ cells.

-Ages 4-75 inclusive

-Weight greater than or equal to 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.

-If there is a suspicion of familial BMFS in the recipient, then the donor must have undergone genetic testing for genes associated with BMFS - performed at a CLIA-certified laboratory, prior to enrolling in this protocol.


-Pregnant or breastfeeding.

-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, HbAS, HbSC. Donors with HbAS are acceptable.

-Severe psychiatric illness. Mental deficiency sufficiently severe as to make compliance with the BMT treatment unlikely and making informed consent impossible.

-Screening test positive for Chagas disease (Trypanosoma cruzi /T. cruzi/trypanosomiasis) confirmed by the Center for Disease Control (CDC).

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Young NS, Barrett AJ. The treatment of severe acquired aplastic anemia. Blood. 1995 Jun 15;85(12):3367-77.

Young NS, Maciejewski J. The pathophysiology of acquired aplastic anemia. N Engl J Med. 1997 May 8;336(19):1365-72.

Zoumbos NC, Gasc(SqrRoot)>=n P, Djeu JY, Trost SR, Young NS. Circulating activated suppressor T lymphocytes in aplastic anemia. N Engl J Med. 1985 Jan 31;312(5):257-65.

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Principal Investigator

Referral Contact

For more information:

Richard W. Childs, M.D.
National Heart, Lung and Blood Institute (NHLBI)

Melissa M. Spencer, R.N.
National Heart, Lung and Blood Institute (NHLBI)
National Institutes of Health
Building 10
Room 3485
10 Center Drive
Bethesda, Maryland 20892
(301) 402-5609

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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