RATIONALE: Giving total-body irradiation and chemotherapy, such as thiotepa and fludarabine, before a donor stem cell transplant helps stop the growth of cancer or abnormal 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 methylprednisolone and antithymocyte globulin before transplant and peripheral blood cells that have been treated in the laboratory after transplant may stop this from happening.

PURPOSE: This phase I trial is studying the side effects and best dose of laboratory-treated peripheral blood cell infusion after donor stem cell transplant in treating patients with hematologic cancers or other diseases.

OBJECTIVES:

Primary

• Establish the feasibility of delayed infusion of ex vivo anergized donor peripheral blood mononuclear cells (PBMC) after CD34 (cluster designation 34)-selected megadose haploidentical hematopoietic stem cell transplantation (HSCT) in patients with hematopoietic cancers or other diseases.
• Determine the feasibility of collecting parental allogeneic stimulator cells to induce anergy to the nonshared donor-recipient haplotype in these patients.
• Determine the feasibility of collecting donor PBMC as a source of T cells for ex vivo anergization.
• Determine the number of transplanted individuals who meet the criteria for proceeding to delayed infusion of ex vivo anergized donor PBMC.
• Establish the safety of delayed infusion of ex vivo anergized donor PBMC by establishing the maximum number of donor T cells that can be infused without unacceptable graft-versus-host disease.

Secondary

• Evaluate, in vitro, the induction and specificity of alloantigen hyporesponsiveness in donor PBMC after ex vivo anergization.
• Assess, in vitro, the function of immune cells engrafted in these patients.
• Assess, in vitro, whether alloantigen hyporesponsive donor T cells are present in these patients.
• Develop, preliminarily, in vitro data on the extent of pathogen-specific immunity and its rate of recovery.
• Describe the patterns of opportunistic infections in these patients.

OUTLINE: This is a multicenter, dose-escalation study of ex vivo anergized allogeneic peripheral blood mononuclear cells (PBMC). Patients who are treated on any dose level except dose level 1 are stratified according to age (under 17 [pediatric] vs 17 and over [adult]).

• Myeloablative conditioning regimen: Patients undergo total-body irradiation twice daily on days -11 to -9. Patients also receive thiotepa IV over 4 hours on days -8 and -7, fludarabine phosphate IV over 30 minutes on days -7 to -3, and anti-thymocyte globulin IV over 8 hours and methylprednisolone IV over 15-30 minutes on days -6 to -3.
• Allogeneic peripheral blood stem cell transplantation (PBSCT): Patients undergo CD34-selected PBSCT on day 0.
• Ex vivo anergized allogeneic PBMC infusion: If cells have engrafted and patients are free of active uncontrolled infection and graft-vs-host disease, patients undergo allogeneic or autologous PBMC infusion on day 35 or 42.

Cohorts of 3-8 patients receive escalating doses of ex vivo anergized allogeneic PBMCs until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 2 of 5 or 3 of 8 patients experience dose-limiting toxicity.

After completion of study, patients are followed periodically for 2 years.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Diagnosis of 1 of the following:

  • Acute lymphocytic leukemia

    • In ≥ second complete remission (CR), defined as < 5% blasts in bone marrow (BM) and no active extramedullary disease OR in first CR with any of the following high risk features:

      • History of induction failure
      • Philadelphia chromosome positive
      • t(4;11) by cytogenetic analysis
      • Any infant with MLL rearrangements on cytogenetic analysis

    • No relapse with isolated extramedullary disease after completion of prior treatment

  • Acute myeloid leukemia

    • Failed induction therapy after < 3 courses

    • In ≥ second CR, defined as < 5% blasts in BM and no active extramedullary disease OR in first CR with any of the following high-risk features:

      • History of induction failure = 5q- or monosomy 7 cytogenetic findings

  • Any of the following myelodysplastic syndromes:

    • Refractory anemia (RA) with excess blasts (RAEB) with a high International Prognostic Scoring System (IPSS) score or score of intermediate-1(INT-1) or intermediate-2 (INT-2)
    • RAEB in transformation with INT-1, INT-2, or high IPSS score
    • RA with INT-2 score

• Patients must have a healthy, related donor who is at least genotypically HLA-A, B, C, and DR haploidentical to the patient

  • No suitably matched family donor defined by genotypic or phenotypic identity for ≥ 5/6 A, B, or DR loci
  • No immediately available genotypically matched (6/6) unrelated marrow donor
  • No immediately available umbilical cord blood donor with suitable cell dose after a search ≥ 2 months
  • Patients whose medical condition is at high risk of deteriorating or whose disease is at high risk of progression during a donor search are eligible

• Has a parent with a haplotype that is disparate from that of the donor for the haplotype shared by the patient and parent, but not shared by the patient and donor OR patient is able to donate sufficient autologous cells by peripheral blood draw or unstimulated leukapheresis

• No active CNS disease

PATIENT CHARACTERISTICS:

• Room air O_2 saturation > 95% unless the lungs are involved with disease
• No clinical evidence of pulmonary insufficiency unless the lungs are involved with disease
• AST and ALT < 3 times upper limit of normal (ULN)*
• Bilirubin < 2.0 mg/dL*
• Creatinine < 2 times ULN OR creatinine clearance or glomerular filtration rate > 50% of the lower limit of normal
• LVEF > 45% OR shortening fraction > 20%
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No active infection, defined as absence of an infectious diagnosis or (in patients who have had a recent positive infectious diagnosis) the resolution of fever, documentation of negative cultures or antigen testing, continuation or completion of a course of appropriate therapy, and presence of stable to resolving clinical symptoms
• No evidence of HIV infection OR known HIV positivity NOTE: *Does not apply if liver is involved with disease

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No prior stem cell transplantation
• No other concurrent immunosuppressive therapy