Efficacy Study of T Cell Depleted Allogeneic Non-myeloablative Stem Cell Transplant

The central hypothesis of this study is that use of a less toxic chemotherapy preparative
regimen for allogeneic hematopoietic stem cell transplantation in combination with T cell
depletion with alemtuzumab for patients with high risk hematologic malignancies will allow
effective control of disease and improved disease free and overall survival compared with
historical expectations. Specifically, the objectives are to estimate toxicity, disease
free, progression free, event free and overall survival rates in patients treated with an
alemtuzumab T cell depleted, reduced intensity preparative regimen followed by allogeneic
hematopoietic transplantation; evaluate immune recovery following this reduced intensity
allogeneic immunotherapy; develop an in vitro assay to allow patient individualized targeted
dosing. The study population is HIV negative, adult patients who are not pregnant but have
confirmed diagnosis of disease; must have CALGB PS 0, 1, or 2; must have a 3-6/6 HLA-matched
related donor or 8/8 (A, B, C, DRB1, DQ are the primary determinants) or better HLA-matched
unrelated donor who is evaluated and deemed able to provide PBPCs and/or marrow by the
transplant team. The target population of patients is those with a high chance of
progressive lymphoid or myelomatous diseases, progressive myeloid diseases, marrow failure
syndromes or myeloproliferative disorders.

Inclusion Criteria:

- Patients must have their diagnosis confirmed at the transplant center.

- Performance status must be CALGB PS 0, 1, or 2.

- Patients must have a 3-6/6 HLA-matched related donor or 8/8 or better allele level
match MUD matched unrelated donor (at A,B, C, DRB1, DQ).

- HIV negative.

- Women of child bearing potential must have a negative pregnancy serum beta-HCG test
within 1 week of starting therapy.

- Patients > or equal to 18 years of age are eligible.

- Patients must have a MUGA and/or ECHO or cardiac MR and PFTs with DLCO performed
before transplant.

- Specific patient populations:

- Group A) Patients with a high chance of progressive lymphoid or myelomatous
diseases.

- Group B) Patients with a high chance of progressive myeloid diseases, marrow
failure syndromes or myeloproliferative disorders

Exclusion Criteria:

- Pregnant or lactating women.

- Patients with other major medical or psychiatric illnesses which the treating
physician feels could seriously compromise tolerance to this protocol.

- Patients with uncontrolled, progressive infections.

- Patients who are good candidates for long term disease control with standard
chemotherapy or radiation or high dose therapy and autologous support.

- Patients with active CNS disease.