Flu,Alemtuzumab,and TBI Followed By Donor Stem Cell Chronic Phase CML

Inclusion Criteria

• •Patients aged 4-75 with chronic myelogenous leukemia (CML) treatable by allogeneic hematopoietic stem cell transplant.
• •Patients with cytogenetically confirmed chronic phase CML.
• •o Hematologic parameters for chronic phase are: i) Percentage of blasts in peripheral blood or marrow \< 15% ii) Percentage of blasts + promyelocytes in the peripheral blood or bone marrow \< 30% iii) Percentage of basophils in blood or marrow \<20% iv) Platelet count \> 100 x 109/l
• •Patients must have demonstrated refractoriness/resistance to STI571 defined as follows:
• •i) Hematologically resistant- failure to achieve a complete hematologic remission (CHR) despite 3 months of STI571 therapy.
• •ii) Hematologically refractory - a rising WBC count \> 20 x 109/l confirmed by two samples taken two weeks apart in a patient with a previous CHR despite concurrent treatment with STI571 iii) Cytogenetically resistant - bone marrow cytogenetics showing \> 65% Philadelphia chromosome positivity (Ph+) after 6 months of STI571 based therapy.
• •iv) Cytogenetically refractory - An increase in the number of Philadelphia chromosome positive (Ph+) bone marrow cells by at least 30%, or an increase to \> 65%, confirmed by samples at least 1 month apart following a previous STI571 induced cytogenetic response, while continuing STI571 therapy.
• •Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
• •Patients with a human leukocyte antigen (HLA) matched sibling donor at the HLA-A, B, and DR loci.
• •Patients with an unrelated hematopoietic stem cell donor must be matched using high resolution typing for class II human leukocyte antigen (HLA-DR beta-1, 3, 4, 5 and DQ beta-1) and matched with intermediate to high resolution molecular typing at class I human leukocyte antigen (HLA-A, B, and C) loci.
• •Patients with accelerated or blast crisis of CML who have returned to chronic phase as described above are eligible.
• •Written informed, voluntary consent.
• •Sibling donors are permitted if matched at class I human leukocyte antigen (HLA-A, B), and class II human leukocyte antigen (DR) loci.
• •Unrelated donors must be matched for class II human leukocyte antigen(HLA-DR beta-1,2,3,4,5) and class II human leukocyte antigen (DQ beta-1) with high resolution typing and with intermediate resolution molecular typing at class I human leukocyte antigen(HLA-A, B, and C) loci.
• •Donors must be eligible to serve as a peripheral stem cell allograft donor. Bone marrow donors will not be permitted on this protocol.
• •Donors must be \>18 and \< 75 years of age.
• •Exclusions Criteria for Donors:
• •Volunteer donors who wish to serve as bone marrow donors only and refuse exogenous cytokines.
• •Donors who are Human immunodeficiency virus (HIV+), Human T-lymphotropic virus (HTLV-1+), or hepatitis Bs Ag+..
• •Donors with medical conditions that would result in increased risk for Granulocyte colony-stimulating factor (G-CSF) mobilization and harvest of peripheral blood stem cells (PBSC) including renal insufficiency with Cr \> 2.0, idiopathic splenomegaly, underlying coagulopathy, uncontrolled coronary artery disease, and major surgery within 28 days.