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