Pentostatin and Lymphocyte Infusion in Preventing Graft Rejection in Patients Who Have Undergone Donor Stem Cell Transplant

PRIMARY OBJECTIVES:

I. To assess the safety and efficacy of the combined use of pentostatin and donor lymphocyte
infusion (DLI) in patients with low or falling donor T-cell chimerism to prevent graft
rejection after transplantation both from matched related donors (MRDs) or unrelated donors
(URDs).

SECONDARY OBJECTIVES:

I. To determine the incidence of graft-versus-host disease (GvHD) infections and disease
response, if persistent disease is present.

OUTLINE: This is a dose-escalation study of donor lymphocyte infusion.

GROUP I: Patients receive pentostatin intravenously (IV) over 20-30 minutes on day -2 and DLI
over 15-30 minutes on day 0. Treatment may repeat once beginning with an escalated or same
cluster of differentiation (CD)3-dose at least 4 weeks if persistent donor T-cells are
documented, no GvHD has developed, and the chimerism status worsens or, if chimerism status
is unchanged after at least 8 weeks with two subsequent tests of chimerism 4 weeks apart.

GROUP II (initiated if patients in group I do not achieve sustained engraftment and improved
chimerism): Patients receive treatment as in group I. Patients also receive cyclosporine
orally (PO) twice daily (BID) on days -3 to 56 and mycophenolate mofetil PO once daily (QD)
on days 0 to 27. Treatment continues in the absence of GvHD.

After completion of study treatment, patients are followed up every 6 months for 2 years and
then annually thereafter.

Inclusion Criteria:

- Patients having received a preceding allogeneic transplantation from either a human
leukocyte antigen (HLA)-matched related or unrelated donor are eligible for this
protocol

- Related donor: HLA genotypically identical at least at one haplotype and may be
phenotypically or genotypically identical at the allele level at HLA A, B, C,
DRB1, and DQB1

- Unrelated donor who are prospectively:

- Matched for HLA-A, B, C, DRB1 and DQB1 by high resolution typing; OR

- Only a single allele disparity will be allowed for HLA-A, B, or C as defined
by high resolution typing

- Patients with less than 50% donor CD3 peripheral blood chimerism on two separate,
consecutive evaluations; the two evaluations must be at least 14 days apart OR
patients with absolute decreases of donor CD3 peripheral blood chimerism of >= 20% if
the second test shows < 50% donor CD3 cells; the two evaluations must be at least 14
days apart

- Patients with evidence of disease are only eligible if the disease is stable (or
persistent) in comparison to the status prior to transplantation

- Patients must be tapered off systemic steroids to a dosage of less than or equal to
0.25 mg/kg/day

- Patients must have persistent donor CD3 cells (>= 5% donor CD3 cells by a
deoxyribonucleic acid [DNA]-based assay that compares the profile of amplified
fragment length polymorphisms [ampFLP] [or fluorescent in situ hybridization (FISH)
studies or variable number of tandem repeats (VNTR)])

- DONOR: Alternatively to a fresh unmodified leukapheresis product, previously collected
cryopreserved peripheral blood stem cells (PBSC) after mobilization with G-CSF or
cryopreserved unmodified leukapheresis product from the original donor can be used; if
cryopreserved product is not available, the following criteria apply for the DLI
product:

- DONOR: Original donor of hematopoietic cell transplantation

- DONOR: Donor must give consent to leukapheresis

- DONOR: Donor must have adequate veins for leukapheresis or agree to placement of
central venous catheter (femoral or subclavian)

- DONOR: Donor must be medically fit to undergo the apheresis procedure (institutional
guidelines for apheresis)

Exclusion Criteria:

- Current grade II to IV acute GVHD or extensive chronic GVHD

- Karnofsky score < 50%

- Pediatric criteria

- Lansky play-performance score < 40

- Evidence of relapse or progression of disease after transplantation

- Prior recipient of cord blood

- DONOR: Donors who are not suitable for medical reasons to donate peripheral blood
mononuclear cells (PBMC) by continuous centrifugation according to the criteria of the
American Association of Blood Banks (AABB)

- DONOR: Pregnancy

- DONOR: Human immunodeficiency virus (HIV) or human T-lymphotrophic virus (HTLV)
infection

- DONOR: Recent immunization may require a delay