Ex Vivo T-Cell Depletion of Mobilized Peripheral Blood Stem Cells Via CD34-Selection

Participation in this project will last approximately one year with follow-up exams.

Before treatment can begin, stem cells will be collected from the donor (a close relative) that has been selected as the best match for the participant. White blood cells will be collected from the donor. The cells will then be mixed with a special protein, called a CD34 antibody, that binds to the stem cells, which will then be separated out from the white blood cells by a special machine- called a CliniMACS CD34 Reagent System in the laboratory. This is an investigational device that is not approved by the FDA. Although this device is not approved for use in this country, it has been in use for years and is approved in other countries. The stem cells will be collected and given fresh or they can be frozen before they will be given to the participant.

On about days 28, 60, 100, 180 and 365 after the transplant, the participant will have the same tests/evaluations since the time of transplant. For patients who do not develop GvHD, they are not required to have these tests/evaluations.

In addition, for purposes of the study, health-related information will be collected for a year from the time of stem cell infusion. This will be used to determine survival, relapse, infections and GvHD that may occur following transplant.

Inclusion criteria

for Stem Cell Transplant WITH Conditioning (COHORT 1)

• Patient requiring allogeneic SCT
• Age between birth and 70 years
• Patient and/or responsible person able to understand and sign consent

Exclusion criteria

for Stem Cell Transplant WITH Conditioning (COHORT 1)

• Active, acute GvHD > grade II or extensive, chronic GvHD
• Severe life, threatening infection
• Pulmonary dysfunction (FEV1, FVC or DLCO 40% of predicted or 3 SD below normal)
• Cardiac dysfunction (LVSF less than 25%)
• Psychiatric disturbance
• Lansky or Karnofsky score < 50%
• The presence of severe hepatic disease (direct bilirubin >3x upper limit of normal and AST > 5x upper limit of normal).
• Creatinine > 3x normal
• Known HIV Positivity
• Pregnancy

Inclusion criteria

for CD34+ Topoff WITHOUT conditioning (COHORT 2)

• Allogeneic SCT Recipient requiring additional cellular therapy
• Age between birth and 70 years
• Patient and/or responsible person able to understand and sign consent
• At least ONE of the following must be answered YES for a patient to be eligible to receive CD34+ topoff:

• Evidence of mixed chimerisms (less than 95% donor cells)
• Evidence of poor bone marrow function (bone marrow cellularity less than 50% with at least one cytopenia)
• Relapsed or persistent disease

Exclusion criteria

for CD34+ Topoff WITHOUT conditioning (COHORT 2)

• Active, acute GvHD > grade II or extensive, chronic GvHD
• Severe life, threatening infection
• Known HIV positivity
• Pregnancy

Inclusion criteria

for CD34+ Topoff WITH conditioning (COHORT 3)

• Allogeneic SCT Recipient requiring additional cellular therapy
• Age between birth and 70 years
• Patient and/or responsible person able to understand and sign consent
• At least ONE of the following must be answered YES for a patient to be eligible to receive CD34+ topoff:

• Evidence of mixed chimerisms (less than 95% donor cells)
• Evidence of poor bone marrow function (bone marrow cellularity less than 50% with at least one cytopenia)
• Relapsed or persistent disease

Exclusion criteria

for CD34+ Topoff WITH Conditioning (COHORT 3)

• Active, acute GVHD > grade II or extensive, chronic GvHD
• Severe life, threatening infection
• Pulmonary disfunction (FEV1, FVC or DLCO 40% of predicted or 3 SD below normal)
• Cardiac dysfunction (LVSF less than 25%)
• Psychiatric disturbance
• Lansky or Karnofsky score < 50%
• The presence of severe hepatic disease (direct bilirubin > 3x upper limit of normal and AST > 5x upper limit of normal)
• Creatinine > 3x normal
• Known HIV positivity
• Pregnancy