Donor Stem Cell Transplant in Treating Young Patients With Myelodysplastic Syndrome, Leukemia, Bone Marrow Failure Syndrome, or Severe Immunodeficiency Disease

Conditions:Blood Cancer, HIV / AIDS, Hematology, Leukemia
Therapuetic Areas:Hematology, Immunology / Infectious Diseases, Oncology
Age Range:Any
Start Date:April 2005

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Stem Cell Enriched, T Cell Depleted Haplocompatible Peripheral Blood Transplantation for Children With Myelodysplastic Disease, Leukemia, Marrow Failure Syndromes, or Severe Immunodeficiency Diseases

RATIONALE: Giving chemotherapy and total body irradiation before a donor bone marrow
transplant or peripheral blood stem cell transplant helps stop the growth of cancer cells.
It also helps stop the patient's immune system from rejecting the donor's stem cells. When
the healthy stem cells from a donor are infused into the patient they may help the patient's
bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes
the transplanted cells from a donor can make an immune response against the body's normal
cells. Giving antithymocyte globulin and removing the T cells from the donor cells before
transplant may stop this from happening.

PURPOSE: This phase I trial is studying the side effects and best dose of donor T cells and
antithymocyte globulin when given together with chemotherapy and total-body irradiation in
treating young patients who are undergoing T-cell depleted donor stem cell transplant for
myelodysplastic syndrome, leukemia, bone marrow failure syndrome, or severe immunodeficiency


- Determine the efficacy and toxicity of stem cell-enriched, T-cell-depleted,
haplocompatible allogeneic hematopoietic stem cell transplantation in children with
high-risk myelodysplastic syndromes, high-risk leukemia, severe acquired or congenital
cytopenias, or primary immunodeficiency diseases.

- Determine the toxicity of a fludarabine and thiotepa-containing regimen in combination
with lower doses of antithymocyte globulin in these patients.

- Determine the engraftment rate in patients treated with this regimen.

- Define T-cell reconstitution in these patients.

- Determine the toxicity and effects of administering stem cell and T-cell boosts after
transplantation on hematopoiesis and immune reconstitution in these patients.

OUTLINE: This is a dose-escalation study of donor CD3+ cells and antithymocyte globulin

- Cytoreductive regimen: Patients undergo total body irradiation twice daily on days -9
to -7. Patients also receive fludarabine IV on days -6 to -2, thiotepa IV every 12
hours on day -6, and ATG IV on days -5 to -2.

- Transplantation: Patients undergo CD34-enriched, T-cell-depleted, haplocompatible
allogeneic peripheral blood stem cell or bone marrow transplantation on day 0.

- Donor T-cell infusion:Patients with no active graft-vs-host disease and evidence of
engraftment but low absolute CD34+ lymphocyte count at 12 weeks post transplant may
receive donor CD3+ cells at 4-week intervals.

- Donor stem cell boost: Patients with engraftment but either cytokine or transfusion
dependent at 12 weeks post transplant may receive a boost of donor CD34+ cells.

Cohorts of 3-6 patients receive escalating doses of donor CD3+ cells and ATG until the
optimum is determined. The optimum dose is defined as the dose at which both engraftment and
T-cell recovery occur, without dose-limiting toxicity, in ≥ 5 of 6 patients.

After the completion of study treatment, patients are followed periodically for 5 years and
then every 5 years thereafter.

PROJECTED ACCRUAL: A total of 21 patients will be accrued for this study.


- Diagnosis of one of the following:

- Acute lymphoblastic leukemia in ≥ 2nd remission or delayed remission induction

- High-risk myelodysplastic syndromes

- Refractory anemia with excess blasts (RAEB)

- RAEB in transformation

- Chronic myelogenous leukemia in second chronic phase

- No accelerated phase (> 5% blasts in marrow)

- Juvenile myelomonocytic leukemia

- Acute nonlymphoblastic leukemia in > 1st remission or induction failure and <
30% blasts in marrow

- Severe aplastic anemia, defined as absolute neutrophil count < 500/mm^3 and
platelet and/or red blood cell transfusion dependent

- Unresponsive to immunosuppressive therapy

- No Fanconi's anemia

- Congenital marrow aplasias unresponsive to cytokines and transfusion dependent

- Inherited immunodeficiency disease involving neutrophils or lymphocytes,
including any of the following:

- Chediak-Higashi disease

- Wiskott-Aldrich syndrome

- Combined immunodeficiency disease (Nezelof's)

- Hyper IgM syndrome

- No relapsed disease

- Haplocompatible related donor, including parent, cousin, aunt, uncle, grandparent,
half-sibling, or sibling (≥ 12 years of age), available

- 2 or 3 HLA antigen mismatch

- At least a 3 HLA antigen genotypic match

- No closely matched related or unrelated donor available in sufficient time to do
the transplant


- No active hepatitis or cytomegalovirus infection

- Cardiac ejection fraction ≥ 30%

- Creatinine clearance ≥ 70 mL/min

- DLCO ≥ 70% of predicted

- No active infection

- No HIV positivity


- See Disease Characteristics
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101 Manning Drive
Chapel Hill, North Carolina 27514
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Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill One of the...
Chapel Hill, NC
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