Pentostatin and Lymphocyte Infusion in Preventing Graft Rejection in Patients Who Have Undergone Donor Stem Cell Transplant
Pentostatin and Lymphocyte Infusion in Preventing Graft Rejection in Patients Who Have Undergone Donor Stem Cell Transplant
This phase II trial studies pentostatin and donor lymphocyte infusion in preventing graft
 rejection in patients who have undergone donor stem cell transplant. Giving pentostatin and
 an infusion of the donor's T cells (donor lymphocyte infusion) after a donor stem cell
 transplant may stop the patient's immune system from rejecting the donor's stem cells. The
 donated stem cells may replace the patient's immune cells and help destroy any remaining
 cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can
 also make an immune response against the body's normal cells. Giving pentostatin before donor
 lymphocyte infusion may stop this from happening.
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