Post T-plant Infusion of Allogeneic Cytokine Induced Killer Cells as Consolidate Therapy in Myelodysplastic Syndromes/Myeloproliferative Disorders

Inclusion Criteria:

4.1.1 Recipient Inclusion Criteria to start ATG/TLI:

Diagnosis Myelodysplastic Syndrome Criteria

(A) Diagnosis of MDS classifiable by the WHO system as

• Refractory Anemia
• Refractory Cytopenia with Multilineage Dysplasia
• MDS-unclassified
• Refractory Cytopenias with Multilineage Dysplasia and Ringed Sideroblasts, Refractory Anemia with Excess Blasts-1
• Refractory Anemia with Excess Blasts-2
• Chronic myelomonocytic leukemia (CMML)
• MDS transformed to acute leukemia.

Patients with advanced MDS must have < 10% marrow blasts prior to receiving conditioning with TLI/ATG. Less than 10% marrow blasts must be documented by marrow examination within 1 month of starting conditioning. If necessary, a cytoreductive regimen will be determined by referring centers.

Patients with evolution to AML are required to be in a morphologic leukemia free-state with blasts <5% (50).

Myeloproliferative Disorders

B) Myeloproliferative disorders to be included:

• Idiopathic Myelofibrosis
• Polycythemia vera
• Essential Thrombocythemia
• Chronic Myelomonocytic Leukemia
• Chronic Neutrophilic Leukemia
• Chronic Eosinophilic Leukemia
• Philadelphia chromosome-negative CML.
• Hypereosinophilic Syndrome
• Systemic Mastocytosis

Patients with MPD must have < 10% marrow blasts prior to receiving conditioning with TLI/ATG. Less than 10% marrow blasts must be documented by marrow examination within 1 month of starting conditioning. If necessary, a cytoreductive regimen will be determined by referring centers.

Patients with evolution to AML are required to be in a morphologic leukemia-free state less than 5% in a marrow aspirate. Presence of residual dysplastic features following cytoreductive therapy is acceptable.

Therapy-related myeloid neoplasms

Patients with t-MDS must have < 10% marrow blasts prior to receiving conditioning with TLI/ATG. Less than 10% marrow blasts must be documented by marrow examination within 1 month of starting conditioning. If necessary, a cytoreductive regimen will be determined by referring centers.

Patients with t-AML are required to be in a morphologic leukemia free-state with blasts <5%.

2. Patient age > 50 years, or for patients <50 years of age but because of pre-existing medical conditions or prior therapy are considered to be at high risk for regimen-related toxicity associated with conventional myeloablative transplants.

3. A fully HLA matched or single antigen/allele mismatched sibling or unrelated donor is available.

4.2 Donor Eligibility

4.2.1 Inclusion Criteria - Related Donors

1. Donors must be HLA-matched or one allele mismatched.
2. Donor age < 75 unless cleared by the Principal Investigator
3. Donor must consent to peripheral blood stem cells (PBSC) mobilization with G-CSF and apheresis
4. Donor must consent to placement of a central venous catheter in the event that peripheral venous access is limited.

Exclusion Criteria:

4.1.2 Recipient Exclusion Criteria

1. Uncontrolled CNS involvement with disease
2. Females who are pregnant

3. Organ dysfunction defined as follows:

   • Cardiac function: ejection fraction (EF) <35% or uncontrolled cardiac failure
   • Pulmonary: DLCO <40% predicted
   • Liver function abnormalities: elevation of bilirubin to > 3 mg/dl and/or AST or ALT >3x the upper limit of normal
   • Estimated creatinine clearance < 50 ml/min
4. Karnofsky performance score (KPS) < 70% (Appendix F)
5. Documented fungal disease that is progressive despite treatment
6. Viral infections: HIV positive patients are not eligible for this protocol. Hepatitis B and C positive patients will be evaluated on a case-by-case basis
7. Patients with prior malignancies diagnosed > 5 years ago without evidence of disease are eligible. Patients with a prior malignancy treated < 5 years ago but have a life expectancy of > 5 years for that malignancy are eligible.

4.1.3 Recipient Exclusion Criteria to proceed to CIK infusion 1. Uncontrolled infection 2. Evidence of disease relapse 3. Grade 2 or above GVHD (Grade 1 GVHD to be evaluated by Principal Investigator) 4. Does not meet release criteria for CIK cells

.2.2 Exclusion Criteria - Related Donor

1. Identical twin
2. Pregnant or lactating females
3. Prior malignancy within the preceding five years, with the exception of non-melanoma skin cancers.
4. HIV seropositivity

4.2.3 Unrelated Donor Inclusion Criteria

1. Donors must be HLA-matched or one allele or antigen mismatched.
2. Donor must consent to PBSC mobilization with G-CSF and apheresis as well as collection and donation of plasma. Bone marrow unrelated donors are not eligible for this protocol.