Total Marrow Irradiation for Refractory Acute Leukemia

Inclusion Criteria:

Acute lymphoblastic leukemia

≥ Complete remission 2 (CR2) (adults ≥ 18 years and ≤ 55 years)
CR2 in pediatrics (defined as <18 years) and <12 months duration of first remission
≥ CR3 or not in remission (pediatric patients <18 years)
T cell leukemia ≥ CR2
Evidence of pre-transplant minimal residual disease (MRD) by flow cytometry, FISH or cytogenetics

Myelodysplastic syndrome

≤ 55 years of age and ≥ 10% blasts, not responsive to hypomethylating agents and/or conventional therapy

Acute myeloid leukemia

Not in remission (pediatric patients <18 years)
Not in remission (10-30% blasts in the bone marrow for adult patients ≥18 years and ≤ 55 years)
Evidence of pre-transplant minimal residual disease (MRD) by flow cytometry, FISH or cytogenetics

Multiple myeloma

No prior autologous transplant and fitting into one of the following disease categories:

Early disease stage (CR1/PR1) with high-risk molecular features
Early disease stage (CR1/PR1) with high-risk clinical features
Late disease stage (CR2/PR2+) with high-risk clinical features
Other high risk hematologic malignancies - to be approved by 2 or more hematology/oncology and BMT physicians
Patients with prior CNS involvement are eligible provided that it has been treated and is in remission. CNS therapy (chemotherapy or radiation) should continue as medically indicated during the protocol.

Have acceptable organ function within 14 days of study registration defined as:

Renal: glomerular filtration rate > 60ml/min/1.73m2
Hepatic: bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), Alkaline phosphatase (ALP) < 5 x upper limit of normal (ULN)
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)
Cardiac: left ventricular ejection fraction ≥ 45% by echocardiogram (ECHO) or multi gated acquisition scan (MUGA)
Karnofsky performance status (PS) >80% for ages 16 years and older or Lansky Play Score >50 for < 16 years

An acceptable source of stem cells according to current University of Minnesota BMT program guidelines:

UCB graft will be composed of two partially HLA matched units. Each unit must be matched at 4-6 HLA loci to the recipient and to each other. If two matched units are not available, then a single HLA 4-6 matched unit may be used if of adequate cell dose - total graft dose must be >3 x 107 MNC/kg
HLA-matched related donor (6/6 or 5/6 antigen match)
HLA-matched unrelated adult donor (if previously identified)
Women of childbearing potential must agree to use adequate contraception (diaphragm, birth control pills, injections, intrauterine device [IUD], surgical sterilization, subcutaneous implants, or abstinence, etc.) for the duration of treatment.
Voluntary written consent

Exclusion Criteria:

Active uncontrolled infection at time of enrollment or documented fungal infection within 3 months.
Evidence of Human immunodeficiency virus (HIV) infection
Pregnant or breast feeding. The agents used in this study may be teratogenic to a fetus and there is no information on the excretion of agents into breast milk. All females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy.
Prior myeloablative transplant within the last 6 months
Prior total body irradiation (TBI) making total marrow irradiation (TMI) not feasible