Pre-transplant conditioning will include Fludarabine and dose-escalated Busulfan on days -6, -5, -4, and -3. Daily treatment doses will be adjusted to achieve target area under the plasma concentration time curve (AUC). Day 0 is the day of hematopoietic progenitor cell reinfusion. Supportive care will be based on institutional guidelines. Blood samples will be collected for dose modification based on the AUC levels. Dose escalation will proceed to determine the maximally tolerated level or AUC to evaluate the potential therapeutic benefit of higher doses of busulfan.

Patients will receive anti-seizure prophylaxis beginning on day -7. Pre-transplant conditioning will include Fludarabine and dose-escalated Busulfan on days -6, -5, -4, and -3. Daily treatment doses will be adjusted to achieve target AUCs (area under the plasma concentration time curve). Day 0 is the day of hematopoietic progenitor cell reinfusion.

Supportive care will be based on institutional guidelines. In an effort to prevent hepatotoxicity, ursodiol will be given to patients. During chemotherapy patients will not receive concurrent metronidazole, itraconazole, or be given acetaminophen.

Blood samples will be collected at specific times after Dose 1 and Dose 4 and dose modification will be determined or based on the desired AUC levels. Doses 3 and/or 4 will be adjusted to achieve an average daily Busulfan AUC over the 4 treatment days.

Dose escalation will proceed through 3 dose levels to determine the maximally tolerated level or AUC to evaluate the potential therapeutic benefit of higher doses of busulfan.

Graft assessment, processing, and characterization will be done as per institutional guidelines. Donor-recipient chimerism (two genetically distinct types of blood cells) will be characterized by samples obtained pre-transplant and on days 30+/- 7, 90+/-7 and 360+/-30 post-transplant.

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. Acute myelogenous leukemia (AML), Acute lymphoblastic leukemia (ALL), or Non-Hodgkin's Leukemia (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. Myelodysplastic Syndrome (MDS), with IPSS >1
  3. Chronic myelogenous leukemia (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. Chronic lymphocytic leukemia (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: Diffusing capacity of lung for carbon monoxide (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 2 mg/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 nucleic acid test (NAT)

• Active central nervous system (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 Hematopoietic Cell Transplantation (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 participants 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 (6 cm 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.)