Reduced-Intensity Conditioning Before Donor Stem Cell Transplant in Treating Patients With High-Risk Hematologic Malignancies

Inclusion Criteria:

1. Any patient with a high-risk hematologic or oncologic diagnosis in which allogeneic HSCT is thought to be beneficial, and in whom front-line therapy has already been applied. High risk is defined as:

   1. Acute myeloid leukemia with high risk features as defined by:

      • Age greater than or equal to 60
      • Secondary AML (prior therapy or hematologic malignancy)
      • Normal cytogenetics but FLT3/ITD positive
      • Any relapse or primary refractory disease
      • Greater than 3 cytogenetic abnormalities or any one of the following cytogenetic abnormalities: -5/del(5q), -7/del(7q), Abn(9q),(11q),(3q),(21q),(17p),t(6;9), t(6;11), t(11;19), +8,del(12p),inv(3),t(10;11),-17, 11q 23
      • Any single autosomal monosomy
   2. Acute lymphoid leukemia in 1st or 2nd morphological remission. ALL with any morphological evidence of disease will not be eligible.
   3. Myelodysplasia (MDS) other than refractory anemia (RA), refractory anemia with rare sideroblasts (RARS), or isolated 5q- syndrome subtypes.
   4. Hodgkin's or Non-Hodgkin's lymphoma in 2nd or greater remission or with persistent disease.
   5. Myeloma with evidence of persistent disease after front-line therapy.
   6. Chronic myeloid leukemia (CML) resistant to signal transducer inhibitor (STI) therapy
   7. Myelofibrosis and CMML
   8. Essential Thrombocytopenia or Polycythemia Vera with current or past evidence of evolution to acute leukemia
   9. Any hematological malignancy not cited above which is thought to be high-risk with increased chance of post HSCT relapse. Patients in this category require specific approval of the PI and the TJU BMT attending physician group for entrance.
2. Patients must have a related donor who is at least a 4 antigen match at the Human Leukocyte Antigen (HLA)-A; B; C; DR loci.

3. Patients must adequate organ function:

   1. Left ventricular end diastolic function (LVEF) of >50%
   2. Diffusion Lung Capacity of Oxygen (DLCO) >50% of predicted corrected for hemoglobin
   3. Adequate liver function as defined by a serum bilirubin <1.8, aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 2.5X upper limit of normal
   4. Creatinine Clearance of ≥ 60 mL/min
4. Performance status ≥ 80% (TJU Karnofsky) for patients ≥ 60 years old or ≥70% for patients < 60.
5. Hematopoietic cell transplant-comorbidity index (HCT-CI) Score ≤ 4 points for patients ≥ 60 years old or ≤ 5 points for patients < 60.
6. Patients must be willing to use contraception if they have childbearing potential
7. Able to give informed consent
8. No previous radiation history that negates the ability to safely receive 2 Gy of TBI as determined by the radiation oncologist and the study co-investigator responsible for the patient

Exclusion Criteria:

1. Performance status < 80% (TJU Karnofsky) for patients ≥ 60 years old or <70% for patients < 60.
2. HCT-CI Score > 4 points for patients ≥ 60 years old or > 5 points for patients < 60.
3. HIV positive
4. Active involvement of the central nervous system with malignancy
5. Inability to obtain informed consent
6. Pregnancy
7. Patients with life expectancy of < 6 months for reasons other than their underlying hematologic/oncologic disorder
8. Patients who have received alemtuzumab within 8 weeks of the transplant admission, or who have recently received horse or rabbit ant-thymocyte globulin and have an ATG level of > 2 ugm/ml
9. Patients with evidence of another malignancy, exclusive of a skin cancer that requires only local treatment, should not be enrolled on this protocol