Total Marrow and Lymphoid Irradiation and Chemotherapy for High-Risk Acute Leukemia
Total Marrow and Lymphoid Irradiation and Chemotherapy for High-Risk Acute Leukemia
RATIONALE: Giving chemotherapy and total marrow and lymphoid irradiation before allogeneic
 hematopoietic cell transplant helps stop the growth of leukemia cells. It may also stop the
 patient's immune system from rejecting the donor's stem cells. When the healthy stem cells
 from a donor are infused into the patient they may achieve brand new hematopoietic recovery.
 Sometimes the transplanted cells from a donor can make an immune response against the body's
 normal cells, resulting in graft versus-host disease.

 PURPOSE: This study is to evaluate the toxicity and efficacy of total marrow and lymphoid
 irradiation conditioning when given together with combination chemotherapy and allogeneic
 peripheral blood stem cell transplant in treating patients with high-risk acute leukemia.
Patient receives preparative therapy including cyclophosphamide and total body irradiation
 (TBI) of 10 Gy or total marrow and lymphoid irradiation (TMLI) of 12-20 Gy, and starts
 immunosuppressive therapy using cyclosporine or tacrolimus, methotrexate-based prophylaxes,
 followed by peripheral blood stem cell transplantation and granulocyte colony-stimulating
 factor administration.
Inclusion Criteria:

 1. High-risk acute myelogenous leukemia or acute lymphocytic leukemia based on clinical
 and biological characteristics, which including but not limited to poor response to
 induction therapy and relapse or beyond second remission.

 2. Karnofsky performance status (KPS) >= 70%

 3. Women of child-bearing potential and men must agree to use adequate contraception
 (hormonal or barrier method of birth control or abstinence) prior to study entry and
 for six months following duration of study participation; should a woman become
 pregnant or suspect that she is pregnant while participating on the trial, she should
 inform her treating physician immediately

 4. All candidates for this study must have a prepared allogeneic stem cell donor,
 including human leukocyte antigen matched or partially mismatched donor

 5. A cardiac evaluation with an electrocardiogram showing no ischemic changes or abnormal
 rhythm and an ejection fraction of >= 50% established by multi gated acquisition scan
 (MUGA) or echocardiogram

 6. Patients must have a serum creatinine of less than or equal to 1.3 mg/dL or creatinine
 clearance >70 ml/min

 7. Hepatic: bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT),
 Alkaline phosphatase (ALP) < 5 x upper limit of normal (ULN)

 8. Pulmonary function: Carbon Monoxide Diffusing Capacity corrected (DLCOcorr) > 50% of
 normal, (oxygen saturation [>92%] can be used in child where pulmonary function tests
 (PFT's) cannot be obtained)

 9. The time from the end last induction or re-induction attempt should be greater than or
 equal to 14 days

 10. All subjects must have the ability to understand and the willingness to sign a written
 informed consent

 Exclusion Criteria:

 1. Active uncontrolled infection at time of enrollment or documented fungal infection
 within 3 months

 2. Evidence of Human immunodeficiency virus (HIV) infection

 3. Prior myeloablative transplant within the last 6 months

 4. Prior radiation therapy that would exclude the use of TMLI

 5. Relapsed patients who have undergone autologous or allogeneic hematopoietic stem cell
 transplantation previously