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

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.

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