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

• Safety of the combined use of pentostatin and DLI as defined by an acceptable rate of grade IV acute GVHD [ Time Frame: Within 100 days after the last DLI ] [ Designated as safety issue: Yes ]
  Reported following the Fred Hutchinson Cancer Research Center (FHCRC) Guidelines for serious adverse event (SAE) reporting.
  
  
• Efficacy of the combined use of pentostatin and DLI defined as an increase of at least 10 percentage points in donor T-cell chimerism [ Time Frame: From the time of enrollment maintained to day 56 after the last DLI ] [ Designated as safety issue: No ]
  A regimen will be considered successful if 20 patients are enrolled, at least 13 demonstrate improved chimerism. If fewer than 5 patients have shown improvement in chimerism then we can be at least 75% confident that the true rate of improvement is less than 0.53. Enrollment to the regimen will stop and the next regimen will be opened. Enrollment to a regimen may also be stopped at any time it becomes impossible to achieve 5 of 10 or 13 of 20 successful improvements.
  
  

• Incidence of grade II-IV acute GVHD infection [ Time Frame: Day 84 ] [ Designated as safety issue: No ]
  Reported following the FHCRC Guidelines for SAE reporting. Accrual to a regimen will stop at any time there is reasonable evidence that the rate of grade IV acute GVHD exceeds 0.15.
  
  
• Incidence of grade II-IV acute GVHD infection [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  Reported following the FHCRC Guidelines for SAE reporting. Accrual to a regimen will stop at any time there is reasonable evidence that the rate of grade IV acute GVHD exceeds 0.15.
  
  
• Incidence of chronic GVHD infection [ Time Frame: Day 84 ] [ Designated as safety issue: No ]
  Reported following the FHCRC Guidelines for SAE reporting.
  
  
• Incidence of chronic GVHD infection [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  Reported following the FHCRC Guidelines for SAE reporting.
  
  
• Disease response of the combined use of pentostatin and DLI [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
  

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 nonmyeloablative marrow 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. Patients are assigned to 1 of 2 treatment groups.

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 on days -3 to 56 and mycophenolate mofetil PO once daily 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.