Chemotherapy and a Donor Natural Killer Cell Infusion in Treating Patients With Relapsed or Persistent Leukemia or Myelodysplastic Syndrome After a Donor Stem Cell Transplant

Subject Inclusion Criteria:

Diagnosis and Status

* Patients with a pathologically confirmed diagnosis of relapsed or persistent resistant AML, MDS, or blastic CML following HSCT and who have been deemed ineligible for second HSCT after consideration of adequacy of their physical function, extent of disease, and prior treatment-related toxicities.

Eligible patients have evidence of disease with ≥5% bone marrow involvement detected by morphology or abnormal cytogenetics (by karyotype or FISH). Patients with molecular detection of markers characteristic of the patient's disease from two consecutive bone marrow biopsies are also eligible. Following diagnosis of relapsed disease, treatment to reduce leukemic burden is allowed prior to protocol therapy without the need for additional disease documentation prior to cyclophosphamide and fludarabine.

* Patients with extramedullary relapse are eligible except for those with CNS involvement.
* Patients must have received an allogeneic HSCT.
* Patient must not be pregnant and must be using adequate form of birth control.
* Patients must have a Karnofsky (adult) or Lansky (pediatric) Performance Status ≥ 60%.
* Hospitalization does not preclude enrollment, as long as the patient's performance status is ≥ 60% according to the KPS grading scale.
* Patients must have adequate physical function measured by :

Cardiac: asymptomatic and LVEF at rest must be \> 50%. Hepatic: \< 2x ULN ALT and \< 1.5 total serum bilirubin, unless liver is involved with disease, there is congenital benign hyperbilirubinemia, or other reversible causes of hepatic abnormalities are documented.

Renal: serum creatinine \<1.5 mg/dl or if serum creatinine is outside the normal range, then CrCl \> 50 ml/min Pulmonary: Patient cannot be oxygen-dependent.

* Patients with documented GVHD are not excluded from this trial, but either must not have used systemic immunosuppression for two weeks, or during immunosuppression taper have documented two subtherapeutic levels at least one week apart. Immunosuppressive agents include but are not limited to systemic steroids, calcineurin inhibitors, MTOR-inhibitors, Budesonide, anti-thymocyte globulin. The maximal allowable dose of corticosteroids is the equivalent of 10 mg/day prednisone.
* Patients with grade I/II acute GVHD or limited chronic GVHD and receiving localized GVHD therapy (e.g. topical steroids) are not excluded from this trial.
* Patients having received previous adoptive cellular therapy such as donor lymphocyte infusion (DLI) are not excluded from this trial as long as their disease has been documented to progress within two months of receiving DLI or if the patient has not received DLI within two months of NK cell infusion.
* Patients who have received cytoreductive therapy following documentation of relapse and prior to enrollment are not excluded from this trial. The interval between standard reinduction chemotherapy and start of protocol chemotherapy should be a minimum of 2 weeks, and all induction chemotherapy-related toxicities should be documented to be completely resolved. For patients receiving nonintensive chemotherapies such as hydroxyurea or low-dose cytarabine, nonintensive chemotherapies should be discontinued upon initiation of protocol chemotherapy.
* Each patient must be willing to participate as a research subject and must sign an informed consent form. Parents or legal guardians of patients who are minors may sign the informed consent form
* Patients must have an eligible NK donor.
* There are no age restrictions to this protocol.

NK Cell Donor Eligibility

* Donor is blood-related and HLA-haploidentical to the recipient.
* Donor has undergone serologic testing for transmissible diseases as per blood banking guidelines for organ and tissue donors. Tests include but are not limited to: HepBsAg, HepBsAb, HepBcAb, HepC antibody, HIV, HTLV I and II, VZV, CMV and VDRL, and West Nile Virus . Donor must have normal negative test results for HIV, HTLV I and II, and West Nile Virus. Donor exposure to other viral pathogens will be discussed on a case-by-case basis by the Transplant team.
* Donor has a CXR and EKG performed.
* Donor must be able to undergo leukopheresis for total volume of 10-15 liters.
* Donor is not pregnant.
* Donor does not have concurrent malignancy or autoimmune disease.
* There is no age restriction for the donor.

Subject Exclusion Criteria:

* Patients on systemic immunosuppression with therapeutic drug levels. Patients whose immunosuppression is being actively tapered and have documentation of subtherapeutic drug levels one week apart are not excluded from enrollment. For patients receiving corticosteroids, the maximal allowable dose of corticosteroids is the equivalent of 10 mg/day prednisone.
* Patients with untreated or uncontrolled active infection. Infections that are controlled or being appropriately treated does not exclude a patient from enrollment.

NK Cell Donor Exclusion

* Donor has cardiac risk factors precluding ability to undergo leukopheresis.
* Donor has evidence of concurrent malignancy or autoimmune disease.
* Donor is pregnant.