Myelodysplastic Syndrome Clinical Trial
Donor Stem Cell Transplant in Treating Young Patients With Myelodysplastic Syndrome, Leukemia, Bone Marrow Failure Syndrome, or Severe Immunodeficiency Disease
Summary
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 disease.
Full Description
OBJECTIVES:
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 (ATG).
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.
Eligibility Criteria
DISEASE CHARACTERISTICS:
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
PATIENT CHARACTERISTICS:
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
PRIOR CONCURRENT THERAPY:
See Disease Characteristics
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There are 2 Locations for this study
San Francisco California, 94115, United States
Chapel Hill North Carolina, 27599, United States
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