• Determine # of donor lymphocytes that can be given to recipients of haplo-SCT with FA after depletion of recipient-reactive T lymphocytes by ex-vivo tx with a fixed dose of RFT5-dgA immunotoxin, and will result in Grade III/IV GVHD of < / = 25%. [ Time Frame: 1 yr ] [ Designated as safety issue: Yes ]
  

• To analyze immune reconstitution in these patients. [ Time Frame: 1 yr ] [ Designated as safety issue: No ]
  
• To measure their overall and disease free survival, at 100 days and at 1 year after transplant. [ Time Frame: 1 yr ] [ Designated as safety issue: No ]
  

Procedure: CD34 selected haploidentical PBSCT
Infusion of CD34 selected haploidentical PBSCT
Drug: Fludarabine
day -8 through day -4 Fludarabine 30 mg/m^2
Biological: T cell infusion

At least 30 days after the stem cell infusion, patients will be dosed with T cells. This study will begin with a dose of T cells known not to cause GvHD even in haploidentical recipients, even when the T cells administered have not first been allodepleted. Dose escalation will follow a traditional up and down method, but as results become available they will be used to determine subsequent dose levels by the continual reassessment method. Initially, 2 patients will be entered beginning at dose level 1. Each and every patient will receive up to three additional injections of T cells at the same dose, at monthly intervals, provided there is no evidence of grade 2 or higher GVHD, until total T cell numbers are > 1000/ul.

Dose level -1 (1 x 10^3 T cells/Kg); Dose level 1 (1 x 10^4 T cells/Kg); Dose level 2 (1 x 10^5 T cells/Kg); Dose level 3 (1 x 10^6 T cells/Kg); Dose level 4 (5 x 10^6 T cells/Kg)

Biological: Campath 1h
10 mg iv over 4 hours day-8 through day-6
Biological: anti-CD45
anti-CD45 400 ug/kg over 6 hours day -5 through day -2

Patients will have received a haplo-identical stem cell transplant on our on-going study "CD45 (YTH-24 and YTH-54) and CD52 (Campath 1H) Monoclonal Antibody Conditioning Regimen for Allogeneic Donor Stem Cell Transplantation of Patients with Fanconi Anemia" (H-9938 IND# 7233) and will become eligible to receive allodepleted T Cells following engraftment. What follows is a summary of the treatment plan including initial transplant phase as well as generation and infusion of allodepleted T cells.

Preparative Regimen for Patients with Fanconi Anemia:

The study will be open to patients who received a haploidentical PBSCT on the MAFIA protocol and for patients who failed to engraft and receive a second haploidentical transplants with alternate conditioning consisting of ATG, Fludarabine, TBI (450cGY single dose) and Cytoxan.

In Outline MAFIA conditioning (primary conditioning regimen)

Day 8 Campath 1H 10mg iv over 4hr Fludarabine 30 mg/m2 7 Campath 1H 10mg iv over 4hr Fludarabine 30 mg/m2 6 Campath 1H 10mg iv over 4hr Fludarabine 30 mg/m2 5 YTH 24/54 400ug/kg over 6 hr Fludarabine 30 mg/m2

• 4 YTH 24/54 400ug/kg over 6 hr Fludarabine 30 mg/m2
• 3 YTH 24/54 400ug/kg over 6 hr
• 2 YTH 24/54 400ug/kg over 6 hr
• 1 Rest
• 0 CD34-selected PBSC infusion

Stem Cell Infusion: One day after the completion of pretransplant conditioning therapy (day 0), CD34+ cells will be infused through a central venous catheter as outlined in CAGT SOPs.

This study will begin with a dose of T cells known not to cause GvHD even in haploidentical recipients, even when the T cells administered have not first been allodepleted. Dose escalation will follow a traditional up and down method, but as results become available they will be used to determine subsequent dose levels by the continual reassessment method. Initially, 2 patients will be entered beginning at dose level 1. Each and every patient will receive up to three additional injections of T cells at the same dose, at monthly intervals, provided there is no evidence of grade 2 or higher GVHD, until total T cell numbers are > 1000/ul.

Dose level -1 (1 x 10^3 T cells/Kg); Dose level 1 (1 x 10^4 T cells/Kg); Dose level 2 (1 x 10^5 T cells/Kg); Dose level 3 (1 x 10^6 T cells/Kg); Dose level 4 (5 x 10^6 T cells/Kg)

Inclusion Criteria:

• At the time of eligibility for infusion of allodepleted T -cells patients must satisfy the criteria below:
• Patients with Fanconi anemia of all ages with severe aplasia (as evidenced by hypocellular bone marrow) who lack a suitable conventional related (i.e. 5/6 or 6/6 related) or 5/6 or 6/6 unrelated donor with at least 2 out of 3 of the following: a) ANC < 500/mm3, b) reticulocytes < 1% c) platelets < 50,000/mm3
• Diagnosis of Fanconi anemia confirmed by studies of peripheral blood or bone marrow sensitivity to mitomycinC or DEB prior to stem cell transplant. Have received a related haploidentical CD34-selected peripheral blood stem cell transplant with evidence of a full or partial hematopoietic donor chimerism (> 50%) in the peripheral blood.

Exclusion Criteria:

• Patients with a life expectancy (< 6 weeks) limited by diseases other than FA
• Patients with active GVHD > / = Grade II
• Patients with severe renal disease (i.e. creatinine greater than 3 X normal for age)
• Patients with severe hepatic disease (direct bilirubin greater than 3ug/dl or SGPT greater than 500ug/dl)
• Patients with a severe intercurrent infection
• Lansky scale < 60 or Karnofsky < 60