A Phase I/II Study of Autologous Stem Cell Transplantation Followed by Nonmyeloablative Allogeneic Stem Cell Transplantation for Patients With Relapsed or Refractory Lymphoma - A Multi-Center Trial

Inclusion Criteria:

- Patients with lymphoma (non-Hodgkin lymphoma [NHL], chronic lymphocytic
leukemia/small lymphocytic lymphoma [CLL/SLL] or Hodgkin lymphoma) with primary
refractory or relapsed disease after standard chemotherapy at high risk of relapse
with conventional autografting; patients with a diagnosis of CLL (or small
lymphocytic lymphoma) or diagnosis of CLL that progresses to prolymphocytic leukemia
(PLL), or T-cell CLL or PLL

- Must have an HLA genotypically or phenotypically identical related donor or, at a
minimum, a high likelihood of identifying an HLA-matched unrelated donor; the
determination of availability of a suitable unrelated donor may be based on a
World-Book search

- Cross-over to other tandem autologous-allogeneic research protocol (#2241) will be
allowed if the patient loses the suitable HLA-matched related or unrelated donor but
has an available HLA-haploidentical donor before receiving the allogeneic
transplantation and if the patient meets the eligibility criteria of the subsequent
study

- Cross-over from other tandem autologous-allogeneic research protocol (#2241) will be
allowed if a suitable HLA-matched related or unrelated donor is identified before
receiving the allogeneic transplantation and if the patient meets the eligibility
criteria of the subsequent study

- Signed informed consent

- Detectable tumor on radiographic studies or bone marrow biopsy prior to mobilization
regimen

- Expected survival >= 3 months from study entry

- DONOR: HLA genotypically or phenotypically identical related donor

- DONOR: must consent to G-CSF administration and leukapheresis for both PBSC allograft
and subsequent donor lymphocyte infusion (DLI)

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

- DONOR: Age < 75 yrs, older donors may be considered after review at Patient Care
Conference

- DONOR: Fred Hutchinson Cancer Research Center (FHCRC) matching allowed will be Grades
1.0 to 2.1; unrelated donors who are prospectively: Matched for HLA-A, B, C, DRB1 and
DQB1 by high resolution typing; only a single allele disparity will be allowed for
HLA-A, B, or C as defined by high resolution typing

- DONOR: Donors are excluded when preexisting immunoreactivity is identified that would
jeopardize donor hematopoietic cell engraftment; this determination is based on the
standard practice of the individual institution; the recommended procedure for
patients with 10 of 10 HLA allele level (phenotypic) match is to obtain a panel
reactive antibody (PRA) screens to class I and class II antigens for all patients
before HCT; if the PRA shows > 10% activity, then flow cytometric or B and T cell
cytotoxic cross matches should be obtained; the donor should be excluded if any of
the cytotoxic cross match assays are positive; for those patients with an HLA Class I
allele mismatch, flow cytometric or B and T cell cytotoxic cross matches should be
obtained regardless of the PRA results; a positive anti-donor cytotoxic crossmatch is
an absolute donor exclusion

- DONOR: patient and donor pairs homozygous at a mismatched allele in the graft
rejection vector are considered a two-allele mismatch, i.e., the patient is A*0101
and the donor is A*0102, and this type of mismatch is not allowed

- DONOR: Only G-CSF mobilized peripheral blood mononuclear cells (PBMC) only will be
permitted as a hematopoietic stem cell (HSC) source on this protocol

Exclusion Criteria:

- Life expectancy severely limited by disease other than lymphoma

- Prior autologous hematopoietic stem cell transplant

- Patients at high risk of veno-occlusive disease of the liver (criteria not yet
rigorously defined but includes bilirubin > 2.0 mg and serum glutamic oxaloacetic
transaminase [SGOT] or serum glutamic pyruvate transaminase [SGPT] > 2 x normal);
patients may be accepted outside of this range if cleared by gastrointestinal (GI)
consult

- Cardiac ejection fraction (EF) < 40% on multi-gated acquisition (MUGA) scan or
cardiac echo (or if unable to obtain ejection fraction, shortening fraction of <
26%); patients with active or a history of cardiac disease should be evaluated with
appropriate cardiac studies and/or consult; ejection fraction is required if age > 50
years or there is a history of anthracyclines or history of cardiac disease; patients
with a shortening fraction < 26% may be enrolled if approved by a cardiologist

- Baseline serum-creatinine > 2.0 mg/dl and a calculated or measured creatinine
clearance of < 50 ml/minute

- Seropositive for the human immunodeficiency virus (HIV)

- Pulmonary dysfunction as measured by a corrected diffusing capacity of the lung for
carbon monoxide (DLCO) < 50% of predicted total lung capacity (TLC) < 30%, forced
expiratory volume in 1 second (FEV1) < 30% and/or receiving supplementary continuous
oxygen; the FHCRC primary investigator (PI) of the study must approve enrollment of
all patients with pulmonary nodules

- Pregnancy or breast-feeding

- Radiation therapy to mediastinum within 3 months prior to enrollment

- Patients with poorly controlled hypertension despite hypertensive medication

- Karnofsky score < 60; pediatric criteria: Lansky Play-Performance Score < 40

- Patients with cluster of differentiation (CD)34 selected auto grafts

- Patients with active non-hematologic malignancies (except nonmelanoma skin cancers);
this exclusion does not apply to patients with non-hematologic malignancies that do
not require therapy

- Patients with a history of non-hematologic malignancies (except nonmelanoma skin
cancers) currently in a complete remission, who are less than 5 years from the time
of complete remission, and have a > 20% risk of disease recurrence; this exclusion
does not apply to patients with non-hematologic malignancies that do not require
therapy

- DONOR: Identical twin

- DONOR: Age less than 12 years

- DONOR: Pregnancy

- DONOR: HIV seropositivity

- DONOR: Inability to achieve adequate venous access

- DONOR: Known allergy to G-CSF

- DONOR: Current serious systemic illness

- DONOR: Failure to meet FHCRC criteria for stem cell donation

- DONOR: Donor (or centers) who will exclusively donate marrow