Donor Stem Cell Transplant in Treating Patients With Myeloid Cancer or Other Disease

RATIONALE: Giving total-body irradiation and chemotherapy, such as fludarabine and thiotepa, 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 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 II trial is studying how well a donor stem cell transplant works in treating patients with myeloid cancer or other disease.

OBJECTIVES:

Primary

* Determine the incidence of disease-free survival at 1 year in patients with acute or chronic myeloid leukemias undergoing T-cell-depleted hematopoietic stem cell transplantation from HLA-C mismatched, unrelated donors.

Secondary

* Determine the incidence of disease relapse at 1 year in patients treated with this regimen.
* Determine the incidence and severity of acute graft-vs-host disease (GVHD) at 100 days and chronic GVHD at 1 year in these patients.
* Determine the incidence of graft failure at day 100.
* Determine the transplant-related mortality of these patients at 1 year.
* Determine the overall survival of these patients at 1 year.

OUTLINE: This is a prospective, multicenter study. Patients are stratified according to killer-cell immunoglobulin-like receptors (KIR) epitope mismatch (yes \[experimental\] vs no \[control\]).

* Myeloablative preparative regimen: Patients undergo total body irradiation twice daily on days -10 and -9 and receive thiotepa intravenously (IV) over 4 hours on days -8 and -7, fludarabine phosphate IV over 30-60 minutes on days -7 to -3, and antithymocyte globulin IV over 4-6 hours on days -5 to -2.
* Allogeneic peripheral blood stem cell (PBSC) transplantation: Patients undergo filgrastim (G-CSF)-mobilized, T-cell-depleted, CD34+-selected allogeneic PBSC transplantation on day 0.

After completion of study treatment, patients are followed periodically for at least 1 year.

Eligibility Criteria:
Inclusion Criteria:

* Primary acute myeloid leukemia (AML)

  * First complete remission (CR) with high risk features as defined by: failure to achieve remission by day 21 after induction chemotherapy, or the presence of chromosomal abnormalities involving any of the following: -5/de (5q), -7/del(7q), inversion 3q, abnormalities of 11q23, 20q, 21q, del(9q), translocation 6;9, translocation 9;22, abnormalities of 17p, or complex karyotype with \> or = 3 abnormalities. Complete remission is defined as \< 5% blasts in the marrow.
  * Second CR or subsequent in remission
  * Refractory or relapsed disease with absolute peripheral blood blasts \< 2000/mcL
* Secondary AML in remission or relapse
* Chronic myelogenous leukemia (CML) in accelerated or blast phase

  * Accelerated phase is defined by any one of the following:

    * Blasts 10% to 19% of peripheral blood white cells or bone marrow cells
    * Peripheral blood basophils at least 20%
    * Persistent thrombocytopenia (\<100 x 10\^9/L) unrelated to therapy, or persistent thrombocytosis (\>1000 x 10\^9/L) unresponsive to therapy
    * Increasing spleen size and increasing white blood cell (WBC) count unresponsive to therapy
    * Cytogenetic evidence of clonal evolution (i.e., the appearance of an additional genetic abnormality that was not present in the initial specimen at the time of diagnosis of chronic phase CML)
    * Resistance to tyrosine kinase inhibitors (imatinib or other) defined as no complete cytogenetic response even if the above criteria are not met.
  * Blast phase is defined by either of the following:

    * Blasts 20% or more of peripheral blood white cells or bone marrow cells
    * Extramedullary blast proliferation
    * Large foci or clusters of blasts in bone marrow biopsy
* Primary myelodysplastic syndrome (MDS) with an IPSS score \>1
* Secondary MDS with any international prostate symptom score (IPSS)
* Age ≤60 years
* Co-Morbidity score 0-2
* At least 35 days following start of preceding leukemia induction therapy

Exclusion Criteria:

* Patients for whom a suitable HLA genotypically identical sibling or fully matched HLA-A, -B, -C, and -DRB1 unrelated donor is available.
* Patients greater than 60 years of age.
* Hypersensitivity to thymoglobulin.
* Symptomatic uncontrolled coronary artery disease or congestive heart failure.
* Hepatic disease with transaminases or bilirubin \> 2 times upper limit of normal (ULN) except for isolated hyperbilirubinemia attributed to Gilbert's syndrome.
* Severe hypoxemia with room air - Partial Pressure of Oxygen in Arterial Blood - (PAO2) \< 70, supplemental oxygen-dependence, or carbon monoxide diffusing capacity (DLCO) \< 50% predicted.
* Impaired renal function with creatinine \> 2 times upper limit of normal (ULN) or creatinine clearance measured by 24-hour urine collection \< 50% normal for age, gender, and weight.
* Patients with central nervous system (CNS) involvement with disease refractory to intrathecal chemotherapy.
* Patients who are human immunodeficiency virus (HIV) seropositive.
* Patients who are pregnant or breast-feeding.
* Patients with active infections that are untreated, or failing to respond to appropriate therapy.
* Karnofsky performance status \< 50%.
* Prior allogeneic or autologous bone marrow, peripheral blood stem cell, or umbilical cord blood transplant.
* Inability to provide informed consent.
* Co-morbidity score \>2
* Less than 35 days from start of previous leukemia induction therapy