Busulfan Dose Escalation Study Based on AUC in the Setting of Busulfan/Fludarabine Conditioning Prior to Allogeneic Hematopoietic Cell Transplantation (HCT)

Inclusion Criteria

Inclusion Criteria - Recipient:

- HLA A, B, C, DRB1 8/8 or 7/8 matched related or unrelated donor. HLA-DQ mismatches
are not considered ie they are allowed in addition to these.

- Histologically confirmed diagnosis by pathologic review

- Diagnosis of any of the following:

1. AML, ALL, or NHL, in first remission with high risk of relapse, refractory to
primary chemotherapy, or after first relapse; acute biphenotypic or
undifferentiated leukemia is also included

2. MDS, with IPSS >1

3. CML, with GleevecR-refractory or intolerant chronic phase, or beyond chronic
phase by morphology or cytogenetics

4. Myeloproliferative disorders, including Ph-negative CML, myelofibrosis and
chronic myelomonocytic leukemia (CMML)

5. Multiple myeloma, refractory to two or more lines of therapy.

6. CLL, refractory to fludarabine

7. Hodgkin's disease, refractory to primary chemotherapy or after first relapse

8. Karnofsky performance status 70-100%

- Organ function:

1. Pulmonary: DLCO greater than 50%

2. Cardiac: left ventricular ejection fraction greater than 45%

3. Renal: creatinine clearance (measured or calculated) equal or greater than 50
ml/min

4. Hepatic: total bilirubin less than or equal to 2mg/dL, (Gilbert and other
syndromes with increased indirect bilirubin should be allowed); serum
transaminases less than two times the upper limit of normal.

- Signed informed consent form in accordance with institutional policies

Exclusion Criteria - Recipient:

- Pregnant or lactating women

- HIV or seropositive, confirmed by NAT

- Active CNS malignancy

- Patients with current uncontrolled bacterial, viral or fungal infection (currently
taking medication with evidence of progression of clinical symptoms or radiologic
findings) are ineligible.

- Unfavorable psychosocial evaluation or history of poor compliance to prescribed
medical care

- Current use of metronidazole or acetominophen, unless medically necessary; patients
must discontinue use of these agents at least 7 days prior to the start of BusulfexR
administration

- Prior use of MylotargR (gemtuzumab ozogamicin)

- Prior HCT

- Prior chest or abdominal irradiation with greater than 1800 cGy

- Presence of any of the following comorbid conditions:

1. History of myocardial infarction or coronary artery disease requiring
catheterization or stent placements less than six months prior to enrollment.
All subjects with history of myocardial infarction or coronary artery disease
must have clearance by a cardiologist to be enrolled

2. Congestive heart failure (even if symptomatically controlled)

3. Peripheral vascular disease (including intermittent claudication or history of
bypass for arterial insufficiency)

4. Untreated thoracic or abdominal aneurysm (6cm or more)

5. History of any cerebrovascular accident including transient ischemic attacks

6. Dementia

7. Connective tissue/rheumatologic disorders with active disease

8. Diabetes uncontrolled by medication (including insulin)

9. Hemiplegia/paraplegia

10. History of prior malignancy (excluding nonmelanoma skin or cervical carcinoma
after curative resection) less than 5 years from enrollment with the following
exception. Cancer treated with curative intent less than 5 years will be
reviewed on a case-by-case basis by the Principal Investigator.

11. History of renal failure requiring renal replacement therapy (e.g.,
hemodialysis, peritoneal dialysis, etc)