Donor Lymphocyte Infusion in Treating Patients With Persistent, Relapsed, or Progressing Cancer After Donor Hematopoietic Cell Transplant

PRIMARY OBJECTIVES:

I. To assess the safety of donor lymphocyte infusion (DLI) as adoptive immunotherapy for
persistent or relapsed malignant diseases in patients after related or unrelated
nonmyeloablative transplantation.

SECONDARY OBJECTIVES:

I. To determine disease response, progression free and overall survival, chimerism, grade of
graft-versus-host disease (GVHD), and infections.

OUTLINE:

Patients undergo unirradiated DLI over 15-30 minutes on day 0. Patients then undergo
restaging on day 28 and may undergo a second DLI after at least 4 weeks if no significant
GVHD develops and disease status worsens or after at least 8 weeks if disease status is
unchanged and persistent donor T-cells are documented.

After completion of study treatment, patients are followed up periodically.

Inclusion Criteria:

- Only patients having received a preceding nonmyeloablative allogeneic transplantation
with fludarabine/2 Gy total-body irradiation (TBI) - 4 Gy TBI or 2 Gy TBI - 4 Gy TBI
conditioning from either a related or unrelated donor are eligible for this protocol

- Patients with persistent, relapsed or progressing malignancy after nonmyeloablative
allogeneic transplantation; persistent disease will be defined as a failure to achieve
a response as compared to baseline

- Patients with rapidly progressing malignancies (acute myeloid leukemia [AML], acute
lymphocytic leukemia [ALL], blastic phase chronic myelogenous leukemia [CML-BC]
intermediate-high-grade non-Hodgkin lymphoma [NHL], Hodgkin's lymphoma or aggressive
multiple myeloma [MM]) should receive salvage chemotherapy or radiation before DLI
according to the recommendation made in this protocol; any form of salvage
chemotherapy should be discontinued no less than 3 weeks before DLI; therapy with
Gleevec or interferon (IFN)-alpha should be discontinued prior to DLI; after salvage
chemotherapy restaging is performed, patients with progressive disease and patients
not meeting the inclusion criteria of the study after chemotherapy will be excluded
from the study; patients are allowed to receive further doses of chemotherapy after
DLI administration if they are scheduled for further DLI; after additional therapy the
patients must be restaged and must again meet inclusion criteria to receive further
DLI

- Patients must be able to tolerate a taper of systemic steroids to a dosage of less
than or equal to 0.25 mg/kg/day; all other immunosuppressive therapy must have been
discontinued for at least two weeks without significant flares in GVHD (i.e., increase
of acute GVHD by one or more grades)

- Patients must have persistent donor cluster of differentiation (CD)3 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 tandem repeat (VNTR)])

- DONOR: Alternatively to a fresh unmodified leukapheresis product, previously collected
cryopreserved peripheral blood stem cells (PBSC) after mobilization with granulocyte
colony-stimulating factor (G-CSF) or cryopreserved unmodified leukapheresis product
from the original donor can be used; if cryopreserved product is not available, the
DLI product must be from the original donor of hematopoietic cell transplantation

- 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%

- Lansky Play-Performance Score < 40 for pediatric patients

- 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