T-Cell Depleted Alternative Donor Bone Marrow Transplant for Sickle Cell Disease (SCD) and Other Anemias

  • End date
    Aug 1, 2025
  • participants needed
  • sponsor
    Paul Szabolcs
Updated on 15 May 2022
stem cell transplantation
graft versus host disease
bone marrow transplant
ejection fraction
hemoglobin s
transplant conditioning
shortening fraction
blood transfusion
conditioning regimen
iron overload
diamond-blackfan anemia
acute chest syndrome
chest syndrome
sickle cell anemia
transcranial doppler ultrasonography
red blood cell transfusions


The purpose of this study is to evaluate what effect, if any, mismatched unrelated volunteer donor and/or haploidentical related donor stem cell transplant may have on severe sickle cell disease and other transfusion dependent anemias. By using mismatched unrelated volunteer donor and/or haploidentical related donor stem cells, this study will increase the number of patients who can undergo a stem cell transplant for their specified disease. Additionally, using a T-cell depleted approach should reduce the incidence of graft-versus-host disease which would otherwise be increased in a mismatched transplant setting.


CD3/CD19 depletion of mismatched donor grafts in the setting of reduced intensity, immune-ablative conditioning for patients with sickle cell disease and other transfusion-dependent anemias should sufficiently achieve engraftment while decreasing the incidence of treatment-related toxicities and achieving an acceptable incidence of graft versus host disease. Utilizing mismatched unrelated volunteer donors and haploidentical related donors will increase the number of patients able to undergo hematopoietic stem cell transplant (HSCT) for these diseases. Additionally, the institutional availability of virus-specific, donor-derived cytotoxic T lymphocytes should address complicated viral infections refractory to standard anti-viral therapy.

The purpose is to:

  • To provide alternate donor transplantation from cryopreserved stem cell grafts that are fully characterized for safety and potency to patients with severe sickle cell disease, beta-thalassemia major, or Diamond-Blackfan anemia who do not have matched sibling donor, matched unrelated donor or cord blood donor options.
  • To utilize a reduced-intensity conditioning regimen to achieve minimal treatment-related morbidity and mortality while attaining sustained donor engraftment and donor chimerism >20% in order to rescue disease phenotype, specifically in SCD patients.
  • To utilize ex-vivo T-cell depletion methods to prevent graft-versus-host disease in the setting of mismatched donor transplantation.
  • To utilize additional donor cell products to ensure sufficient immune reconstitution in the immediate post-transplant period, to improve mixed chimerism or provide non-specific anti-viral activity in patients with virus reactivation in the post-transplant period.
  • To utilize calcineurin inhibitor-free regimen in an effort to minimize/prevent central nervous system toxicity

Condition Sickle Cell Anemia, Beta-thalassemia Major, Diamond-blackfan Anemia
Treatment Rituximab, hydroxyurea, Fludarabine, alemtuzumab, thiotepa, CD3/CD19 depleted leukocytes, CD45RA depleted leukocytes
Clinical Study IdentifierNCT03653338
SponsorPaul Szabolcs
Last Modified on15 May 2022


Yes No Not Sure

Inclusion Criteria

Patient, parent, or legal guardian must have given written informed consent and/or assent according to FDA guidelines
Ages 5 years to 40 years, at time of consent
Diagnosis of Sickle Cell Disease (Hemoglobin SS, Sβ0-thalassemia) complicated by any of the following
Recurrent acute painful episodes (also known as vaso-occlusive crises; VOC) despite supportive care, minimum of 2 new pain events per year requiring hospitalization for parenteral pain management in the previous 2 years
Recurrent acute chest syndrome (ACS) despite supportive care, minimum of 2 episodes in preceding 2-year period
Stroke or neurologic event lasting > 24 hours with an accompanying infarct on MRI in any patient for all ages; Brain MRI with silent infarct without clinical event in patients ≤ 16 years
Chronic transfusion therapy defined as > 8 packed red blood cell transfusions per year in the year prior to enrollment and/or evidence of red blood cell alloimmunization
Elevated transcranial Doppler velocities - > 200 cm/s, via the non-imaging technique or > 185 cm/s by the imaging technique measured on 2 separate occasions ≥ 1-month apart
Elevated TRV > 2.6m/s in patients ≥ 16 years old
Sickle-related renal insufficiency and/or sickle hepatopathy and/or any irreversible end-organ damage in patients ≥ 16 years old
OR Diagnosis of beta-thalassemia or Diamond-Blackfan anemia complicated by transfusion
dependence with evidence of iron overload
A minimum donor match of 4/8 via high resolution HLA typing at HLA-A, -B, -C, -DRB1
loci in the related setting or minimum donor match of 6/8 via high resolution HLA
typing at HLA-A, -B, -C, -DRB1 loci (with the DRB1 locus as a full match requirement)
An unrelated donor and cord blood search must have been completed without an eligible
8 matched unrelated donor or 6/8 cord blood unit available. Patients who may have
acceptable cord blood donor options (4/6 or better) but are limited by cell dose of a
single cord will also be eligible for the proposed study
Adequate function of other organ systems as measured by
Creatinine clearance or GFR ≥ 45 ml/min/1.73m
Hepatic transaminases (ALT/AST) ≤ 3 x upper limit of normal
Liver MR imaging for iron content should be performed in all patients with
Ferritin > 500 ng/mL. If hepatic iron content > 10mg Fe/g liver should have
hepatology consultation and liver biopsy to confirm absence of cirrhosis
fibrosis or hepatitis
Adequate cardiac function as measure by echocardiogram (shortening fraction > 26%
Cardiology clearance to proceed with conditioning regimen and HSCT
or ejection fraction > 40% or >80% of age-specific normal)
Pulmonary evaluation testing demonstrating FEV1/FVC ≥ 60% of predicted for age
and/or resting pulse oximeter ≥ 92% on room air
Pulmonology clearance to proceed with conditioning regimen and HSCT
Subjects must be human immunodeficiency virus (HIV) negative by PCR
Negative pregnancy test for females ≥10 years old or who have reached menarche, unless
surgically sterilized
All females of childbearing potential and sexually active males must agree to use an
FDA approved method of birth control for up to 24 months after BMT or for as long as
they are taking any medication that may harm a pregnancy, an unborn child or may cause
a birth defect
Subject and/or parent guardian will also be counseled regarding the potential risks of
infertility following BMT and advised to discuss sperm banking or oocyte harvesting
(Refer to section
Hydroxyurea must have been trialed and failed in patients with sickle cell disease

Exclusion Criteria

Patients who are pregnant or lactating
Patients with uncontrolled bacterial, viral or fungal infection
Patients with alternate, superior donor options (matched sibling donor or matched
unrelated donor)
Patients who have undergone stem cell transplantation in the 6 months prior to
anticipated conditioning
Patients with history of a central nervous system (CNS) event within six months prior
to start of conditioning (patient will be delayed until eligible)
Past or current medical problems or findings from physical examination or laboratory
testing that are not listed above, which, in the opinion of the investigator, may pose
additional risks from participation in the study, may interfere with the participant's
ability to comply with study requirements or that may impact the quality or
interpretation of the data obtained from the study
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