Treatments and/or Procedures

Study Criteria

Inclusion Criteria:

  -  Malignant conditions or other life threatening disorders correctable by transplant for
     which CD34+ selected, T-cell depleted allogeneic hematopoietic stem cell
     transplantation is indicated such as:

  -  AML in 1st remission - for patients whose AML does not have 'good risk' cytogenetic
     features (i.e. t 8;21, t15;17, inv 16).

  -  Secondary AML in 1st remission

  -  AML in 1st relapse or > than or = to 2nd remission

  -  ALL/CLL in 1st remission clinical or molecular features indicating a high risk for
     relapse; or ALL/CLL > than or = to 2nd remission

  -  CML failing to respond to or not tolerating Imatinib or dasatinib in first chronic
     phase of disease; CML in accelerated phase second chronic phase or in CR after
     accelerated phase or blast crisis.

  -  Non-Hodgkins lymphoma with chemoresponsive disease in any of the following categories:

       1. intermediate or high grade lymphomas who have failed to achieve a first CR or
          have relapsed following a 1st remission who are not candidates for autologous
          transplants.

       2. any NHL in remission which is considered not curable with chemotherapy alone and
          not eligible/appropriate for autologous transplant.

  -  Myelodysplastic syndrome (MDS): RA//RARS/RCMD with high risk cytogenetic features or
     transfusion dependence as well as RAEB-1 and RAEB-2 and Acute myelogenous leukemia
     (AML) evolved from MDS, who are not eligible for transplantation and/or unable to
     enroll onto protocol IRB 08-008.

  -  Chronic myelomonocytic leukemia: CMML-1 and CMML-2.

  -  Multiple Myeloma with disease in the following categories:

       1. Patients with relapsed multiple myeloma following autologous stem cell
          transplantation who have achieved at least partial response following additional
          chemotherapy.

       2. Patients with high risk cytogenetics at diagnosis must have achieved a partial
          response following autologous stem cell transplantation. Patients must have
          complex karyotype, del17p, t4;14 and/or t14;16 by FISH and/or del13 by
          karyotyping.

  -  Other rare lethal disorders of Hematopoiesis and Lymphopoiesis for which a T-cell
     depleted transplant is indicated (e.g. hemophagocytic lymphohistiocytosis; refractory
     aplastic anemia or congenital cytopenias; non-SCID lethal genetic immunodeficiencies
     such as Wiskott Aldrich Syndrome, CD40 ligand deficiency, or ALPS, as well as
     refractory autoimmune cytopenias, PNH, metabolic storage diseases or heavily
     transfused congenital hemoglobinopathies).

  -  Accrual to each treatment arm will include up to 30 standard risk and 30 poor risk
     patients (60 patients/treatment arm) except for Regimen D, which will include 30
     patients/treatment arm, all of which will be poor risk by virtue of risks of relapse
     and/or transplant related mortality.

  -  Standard risk patients will include eligible patients, as defined above, who are
     receiving transplants as treatment for MDS in RA//RARS/RCMD, AML in 1st or 2nd
     remission, ALL in 1st CR, NHL in 1st remission, MM in 1st remission, Very Good Partial
     Response, or 1st Partial Response or CML in the first chronic phase or 1st remission.

  -  All other patients, including those with treatment related malignancies and/or those
     who have AML derived from MDS, will have received extensive prior chemo/radiotherapy
     and, therefore, will be considered to be at poor risk of conditioning and transplant
     related morbidities, and potentially transplant related mortality. Patients with life
     threatening non-malignant genetic and acquired disorders will also, by virtue of their
     history of, optional transfusions and/or infection be considered poor risk. Stopping
     rules for non-relapse related mortality in these heavily treated patients are,
     therefore, slightly less stringent than patients in the poor risk transplant groups.
     Stopping rules for the principal endpoints of graft failure and GvHD are the same for
     all groups.

The following inclusion criteria are also required:

  -  Patient's age includes from birth on to < 70 years old.

  -  Patients may be of either gender or any ethnic background.

  -  Patients must have a Karnofsky (adult) or Lansky (pediatric) Performance Status > or =
     to 70%

  -  Patients must have adequate organ function measured by:

Cardiac: asymptomatic or if symptomatic then LVEF at rest must be > or = to 50% and must
improve with exercise.

Hepatic: < 3x ULN AST and ≤ to 1.5 total serum bilirubin, unless there is congenital benign
hyperbilirubinemia or if the hyperbilirubinemia is directly caused by the disease in which
the patient is receiving a transplant (e.g. AML Chloroma obstructing the biliary tree).
Patients with higher bilirubin levels due to causes other than active liver disease are
also eligible with PI approval e.g. patients with PNH, Gilbert's disease or other hemolytic
disorders.

Renal: serum creatinine < than or = to 1.2 mg/dl or if serum creatinine is outside the
normal range, then CrCl > 40 ml/min (measured or calculated/estimated) Pulmonary:
asymptomatic or if symptomatic, DLCO > or = to 50% of predicted (corrected for hemoglobin)

  -  Each patient must be willing to participate as a research subject and must sign an
     informed consent form.

Exclusion Criteria:

  -  Female patients who are pregnant or breast-feeding

  -  Active viral, bacterial or fungal infection

  -  Patient seropositive for HIV-I/II; HTLV -I/II

  -  Presence of leukemia in the CNS.

Donor Inclusion Criteria:

  -  Each donor must meet criteria outlined by institutional guidelines

  -  Donor should agree to undergo general anesthesia and bone marrow harvest collection if
     PBSC yield is inadequate or otherwise not transplantable for whatever reason.

Donor Exclusion Criteria

  -  If donors do not meet institutional guidelines, exclusion will be considered.