Donor Stem Cell Processing for Mismatched Donors: Harvested peripheral blood stem cells will be enriched for CD34 cells using the CliniMACS CD34 Reagent system, according to Center for Cell and Gene Therapy (CAGT) SOPs.
Stem Cell Transplant Conditioning
Campath-1H will be given as 3 daily intravenous infusions and will be followed by Anti-CD45 which will be given as four daily intravenous infusions that will be completed two days prior to stem cell infusion. Diphenydramine will be administered i.v. q4h during the period of the course of the Campath and Anti-CD45 infusions.
Day
8 Campath 1H as per CAGT SOP Fludarabine 10 kg or less: 1 mg/kg; \> 10 kg: 30 mg/m2
7 Campath 1H as per CAGT SOP Fludarabine 10 kg or less: 1 mg/kg; \> 10 kg: 30 mg/m2
6 Campath 1H as per CAGT SOP Fludarabine 10 kg or less: 1 mg/kg; \> 10 kg: 30 mg/m2
5 YTH 24/54 400ug/kg over 6 hr Fludarabine 10 kg or less: 1 mg/kg; \> 10 kg: 30 mg/m2
4 YTH 24/54 400ug/kg over 6 hr Fludarabine 10 kg or less: 1 mg/kg; \> 10 kg: 30 mg/m2
3 YTH 24/54 400ug/kg over 6 hr
2 YTH 24/54 400ug/kg over 6 hr
1 rest
0 Stem Cell Infusion
Campath 1H Infusion- Campath dose is weight based: for patients less than 15 killograms (kg) administer Campath 3 mg; for patients \>15 kg to 30 kg administer Campath 5 mg; for patients \> 30 kg administer Campath 10 mg. Campath will be dosed and administered as per CAGT SOP.
Anti-CD45- Infusion Anti-CD45 infusion will be administered according to CAGT SOPs. 3 ml of heparinized blood will be drawn 48 hr post Anti-CD45 to evaluate for free Anti-CD45 levels in the plasma. This estimation will be used to determine whether treatment with irradiated leukocytes is required before the bone marrow is infused.
GVHD Prophylaxis- GVHD prophylaxis will be achieved through positive selection for CD34 resulting in \> 3 log T cell depletion. Previous reports have indicated that there is a low frequency of severe (Grade II/IV) GVHD after haploidentical transplants if recipients receive stem cell populations containing \<5 x 10 CD3 positive T cells. We hope to achieve such levels with our CD34 enrichment protocol. However, pharmacologic prophylaxis will be added if the CD34 selected product contains more than 5 x 10 CD3+ve T cells/kg recipient weight. In addition, Campath 1H persists in the recipient circulation through the immediate transplant period and will contribute anti-GVHD activity, in vivo. Patients who develop acute or chronic GVHD will be managed according to CAGT SOPs.
