1. To assess the treatment related mortality of allogeneic stem cell transplantation with non-myeloablative therapy incorporating the lymphodepleting MAb CAMPATH-1H, in patients with hematological diseases and renal cell carcinoma not eligible for conventional (myeloablative) therapy.
2. To assess the time to engraftment and incidence of graft failure in patients receiving this transplant regimen.
3. To assess the safety, pharmacokinetics and immunologic activity of CAMPATH-1H when used as part of a subablative conditioning regimen.

This is a two arm study in which outcomes will be assessed independently in recipients of HLA matched sibling transplants and recipients of unrelated or mismatched family donor transplants, although both groups will receive identical treatments.

The following will be given to the patient after admission:

Day - 6: Total body irradiation

Day - 5 to - 2: Fludarabine and Campath 1H

Day - 1: Day of rest

Day 0: Stem cell transplant (infusion)

• Myelodysplastic Disorders
• Leukemia
• Multiple Myeloma
• Plasma Cell Dyscrasia
• Lymphoproliferative Disorders

• Drug: FLUDARABINE
• Drug: CAMPATH 1H
• Drug: FK50
• Procedure: Stem Cell Collection and Infusion

Inclusion criteria

1. Diagnosis of myelodysplastic disorders, Acute Myelogenous Leukemia, Acute Lymphoblastic Leukemia, Multiple Myeloma, Plasma Cell Dyscrasia, Lymphoproliferative disorders (Non-Hodgkin Lymphoma, Hairy Cell Leukemia, Chronic Lymphocytic Leukemia and Hodgkins Disease) or Renal Cell Carcinoma.

2. Conditions that increase treatment related mortality (need one or more to be eligible):

   1. Greater to or equal to 50 years of age.
   2. EF of less than 45%
   3. DLCO less than 50% of FEV1 50-75% of predicted value.
   4. Diabetes Mellitus
   5. Renal Insufficiency (but creatine clearance not less than 25ml/min).
   6. Prior recent history of systemic fungal infection.
   7. 3rd or greater remission of AML or ALL
   8. More than 1 year of diagnosis (CML or Myeloma patients)
   9. Multiple types of treatment regimens. (equal to or more than 3)
   10. Prior autologous or allogeneic stem cell transplantation.
   11. Significant grade III or IV neurologic or hepatic toxicity from previous treatment.
   12. No matched sibling donor.
3. Available healthy donor without any contraindications for donation. 5/6 or 6/6 related donor. 5/6 or 6/6 unrelated donor (molecular typing for DRB1)
4. Patient and/or responsible person able to understand consent.
5. Age between birth and 70 years.
6. For women of childbearing potential, negative pregnancy test.

Exclusion criteria

1. Patient is pregnant, lactating or unwilling to use contraceptives
2. HIV positive patient
3. Uncontrolled intercurrent infection
4. Refractory AML, or ALL
5. Untreated Blast Crisis for CML
6. Uncontrolled High-grade lymphoproliferative disease/lymphoma.
7. Unstable angina and uncompensated congestive heart failure (Zubrod of 3 or greater)
8. Severe chronic pulmonary disease requiring oxygen (Zubrod of 3 or greater)
9. Hemodialysis dependent
10. Active Hepatitis or cirrhosis with total bilirubin, SGOT, and SGPT greater than 3 x normal.
11. Unstable Cerebral vascular disease and recent hemorrhagic stroke (less than 6 months)
12. Active CNS disease from hematological disorder.

• The Methodist Hospital System
• Texas Children's Hospital
• Center for Cell and Gene Therapy