• Assess safety and feasibility of monoclonal abs directed to CD45 and CD52 antigens, Fludarabine and low dose TBI, as a non-myeloablative preparatory regimen for allo HSCT. This will be determined by 100d Non-relapse mortality and 100d Graft rejection [ Time Frame: 100 days post transplant ] [ Designated as safety issue: Yes ]
  

• To obtain a preliminary estimate of the efficacy of this therapy as defined by: Complete remission at day 100 and One-year disease free survival. [ Time Frame: 100 days and 1 year post transplant ] [ Designated as safety issue: No ]
  

CAMPATH-1H will be given as a daily IV infusion for three days. Fludarabine will be given as a daily IV infusion for four days. Anti-CD45 will be given as a daily IV infusion for 4 days. Patients will then receive radiotherapy (also known as Total Body Irradiation or TBI) for one day. A summary of the treatment follows:

• Day - 8: CAMPATH-1H and Fludarabine
• Day - 7: CAMPATH-1H and Fludarabine
• Day - 6: CAMPATH-1H and Fludarabine
• Day - 5: Anti-CD45 and Fludarabine
• Day - 4: Anti-CD45
• Day - 3: Anti-CD45
• Day - 2: Anti-CD45
• Day - 1: TBI
• Day 0: Stem Cell Infusion (transplant)

To help prevent the body from developing GVHD, patients will also receive the drug FK506, starting two days before the transplant and continuing for at least one month.

Both the CAMPATH-1H and the Anti-CD45 can cause allergic reactions so patients will be given drugs to help prevent those reactions before receiving daily doses.

To see how CAMPATH-1H works in patients with hematologic malignancies, some patients will be asked to participate in pharmacokinetic studies. For this, approximately 13 blood samples will be taken from the central line scheduled before each infusion on Day -8 to Day -6, daily thereafter until Day 0, and then approximately once per week on days 7, 14, 21 and 28 post transplant. No more than 5 teaspoonfuls total will be drawn.

To see how Anti-CD45 works in patients with hematologic malignancies some patients will be asked to participate in pharmacokinetic studies. Approximately 22 blood samples will be taken from the central line scheduled before, during and after each infusion and after the end of the last infusion of Anti-CD45. No more than 10 teaspoonfuls total will be drawn over the course of the four anti-CD45 infusions.

Inclusion criteria:

1. Patients with one of the following high risk diseases needing allogeneic hemopoietic stem cell transplantation:

   • Acute myeloid leukemia either a) Primary refractory, or b) Beyond first complete remission(CR1), or c) In CR1 with high risk of relapse
   • Acute lymphoblastic leukemia either a) Primary refractory, or b) Beyond first complete remission(CR1), or c) In CR1 with high risk of relapse
   • Chronic myeloid leukemia, either a) Accelerated phase, or b) Blast crisis, or c) Chronic phase and not achieving major cytogenetic response despite standard therapy
   • Chronic lymphocytic leukemia, either a) Primary refractory, or b) Beyond first complete remission(CR1),
   • Non Hodgkin's lymphoma, either a) Primary refractory, or b) Beyond first complete remission(CR1)
   • Hodgkin's disease a) Primary refractory, or b) Beyond first complete remission(CR1),
   • Myelodysplastic syndrome with IPSS score > 0.
   • Myeloproliferative disorders (with the exclusion of chronic myeloid leukemia) a) Primary Myelofibrosis with Lile score of 1 or 2 b) Polycythemia Vera or Essential Thrombocythemia transformed to AML or Myelofibrosis and PV "spent phase"
   • Multiple Myeloma with stage II or III disease
   • Severe aplastic anemia

2. Conditions that increase Treatment Related Mortality (need one or more to be eligible):

   • Greater or equal to 35 years of age;
   • Ejection Fraction of less than 50%;
   • DLCO less than 50% or FEV1/FVC < 80% of predicted value;
   • Diabetes Mellitus;
   • Renal insufficiency (serum creatinine abnormal);
   • Hepatic dysfunction-transaminases, or alkaline phosphatase, or bilirubin twice the upper limit of normal;
   • Prior recent history of systemic fungal infection;
   • Multiple prior treatment regimens (equal to or more than 3);
   • Significant Grade III or IV neurologic, cardiac, pulmonary, renal or hepatic toxicity from previous treatment;
   • Prior Autologous or Allogeneic Stem Cell transplantation;
3. Available Healthy Donor without any contraindications for donation. 5/6 or 6/6 related or unrelated donor (molecular typing for DRB1);
4. Patient and/or responsible person able to understand and sign consent

Exclusion criteria:

• Pregnant and lactating women, or women unwilling to use contraception.
• HIV positive patient
• Unstable angina and uncompensated congestive heart failure (Zubrod of 3 or greater)
• Severe chronic pulmonary disease requiring oxygen (Zubrod of 3 or greater)
• Child's class C cirrhosis
• Unstable cerebral vascular disease or recent hemorrhagic stroke (less than 6 months)
• Patients with known allergy to rat serum products